Mass Spectrometry Proteomics Characterization of Plasma Biomarkers for Colorectal Cancer Associated With Inflammation.

Background: Colorectal cancer (CRC) prognosis is determined by the disease stage with low survival rates for advanced stages. Current CRC screening programs are mainly using colonoscopy, limited by its invasiveness and high cost. Therefore, non-invasive, cost-effective, and accurate alternatives are urgently needed. Objective and design: This retrospective multi-center plasma proteomics study was performed to identify potential blood-based biomarkers in 36 CRC patients and 26 healthy volunteers by high-resolution mass spectrometry proteomics followed by the validation in an independent CRC cohort (60 CRC patients and 44 healthy subjects) of identified selected biomarkers. Results: Among the 322 identified plasma proteins, 37 were changed between CRC patients and healthy volunteers and were associated with the complement cascade, cholesterol metabolism, and SERPIN family members. Increased levels in CRC patients of the complement proteins C1QB, C4B, and C5 as well as pro-inflammatory proteins, lipopolysaccharide-binding protein (LBP) and serum amyloid A4, constitutive (SAA4) were revealed for first time. Importantly, increased level of C5 was verified in an independent validation CRC cohort. Increased C4B and C8A levels were correlated with cancer-associated inflammation and CRC progression, while cancer-associated inflammation was linked to the acute-phase reactant leucine-rich alpha-2-glycoprotein 1 (LRG1) and ceruloplasmin. Moreover, a 4-protein signature including C4B, C8A, apolipoprotein C2 (APO) C2, and immunoglobulin heavy constant gamma 2 was changed between early and late CRC stages. Conclusion: Our results suggest that C5 could be a potential biomarker for CRC diagnosis. Further validation studies will aid the application of these new potential biomarkers to improve CRC diagnosis and patient care.

Integrative genomic analyses of European intrahepatic cholangiocarcinoma: Novel ROS1 fusion gene and PBX1 as prognostic marker.

BACKGROUND: Cholangiocarcinoma (CCA) is a fatal cancer of the bile duct with a poor prognosis owing to limited therapeutic options. The incidence of intrahepatic CCA (iCCA) is increasing worldwide, and its molecular basis is emerging. Environmental factors may contribute to regional differences in the mutation spectrum of European patients with iCCA, which are underrepresented in systematic genomic and transcriptomic studies of the disease. METHODS: We describe an integrated whole-exome sequencing and transcriptomic study of 37 iCCAs patients in Germany. RESULTS: We observed as most frequently mutated genes ARID1A (14%), IDH1, BAP1, TP53, KRAS, and ATM in 8% of patients. We identified FGFR2::BICC1 fusions in two tumours, and FGFR2::KCTD1 and TMEM106B::ROS1 as novel fusions with potential therapeutic implications in iCCA and confirmed oncogenic properties of TMEM106B::ROS1 in vitro. Using a data integration framework, we identified PBX1 as a novel central regulatory gene in iCCA. We performed extended screening by targeted sequencing of an additional 40 CCAs. In the joint analysis, IDH1 (13%), BAP1 (10%), TP53 (9%), KRAS (7%), ARID1A (7%), NF1 (5%), and ATM (5%) were the most frequently mutated genes, and we found PBX1 to show copy gain in 20% of the tumours. According to other studies, amplifications of PBX1 tend to occur in European iCCAs in contrast to liver fluke-associated Asian iCCAs. CONCLUSIONS: By analyzing an additional European cohort of iCCA patients, we found that PBX1 protein expression was a marker of poor prognosis. Overall, our findings provide insight into key molecular alterations in iCCA, reveal new targetable fusion genes, and suggest that PBX1 is a novel modulator of this disease.

Pan-cancer analysis and in vitro validation of the oncogenic and prognostic roles of AURKA in human cancers.

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.

Impact of home-based training and nutritional behavior on body composition and metabolic markers in cancer patients: data from the CRBP-TS study.

Introduction: Obesity and physical inactivity are known to affect cancer's development and prognosis. In this context, physical aerobic and resistance training as well as a Mediterranean nutrition have been proven to have many positive health effects. The aim of this study was therefore to investigate the effect of home-based training on body composition and certain metabolic laboratory parameters. Methods: Patients with breast, colorectal and prostate cancer who underwent curative surgery at stages T1N0M0-T3N3M0 were eligible for this trial and randomized to an intervention and control group. In the intervention group the patients carried out online-based strength-endurance home training during the 6-month study period. Body composition was assessed via bioelectrical impedance analysis (baseline, 3 months and 6 months). Metabolic blood parameters were also analyzed and nutrition behavior determined using the Mediterranean Diet Adherence Screener (MEDAS). Results: The intervention group's fat mass decreased while their lean body mass increased (time effect p = 0.001 and p = 0.001, respectively). We found no interaction effect in body weight (p = 0.19), fat mass [p = 0.06, 6-months estimates -0.9 (95% CI -1.8 to -0.1)] and lean body mass (p = 0.92). Blood samples also failed to show a statistically significant interaction effect between time × group for HbA1c% (p = 0.64), Insulin (p = 0.33), Adiponectin (p = 0.87), Leptin (p = 0.52) and Triglycerides (p = 0.43). Only Adiponectin revealed significance in the time effect (p < 0.001) and Leptin in the group effect (p = 0.03). Dietary behavior during the study period was similar in patients in the intervention and control groups (interaction p = 0.81; group p = 0.09 and time p = 0.03). Discussion: Individualized online-based home training in postoperative cancer patients revealed only minor changes, with no group differences in body composition or metabolic laboratory parameters, which were predominantly in the reference range at baseline. More studies investigating effects of online-based home training on body composition and nutrition behavior are needed. Trial registration: https://drks.de/search/en/trial/DRKS00020499, DRKS-ID: DRKS00020499.

Descriptive review of current practices and prognostic factors in patients with ovarian cancer treated by pressurized intraperitoneal aerosol chemotherapy (PIPAC): a multicentric, retrospective, cohort of 234 patients.

Introduction: Ovarian cancer (OC) is the primary cause of mortality in women diagnosed with gynecological cancer. Our study assessed pressurized intraperitoneal aerosol chemotherapy (PIPAC) as treatment for peritoneal surface metastases (PSM) from recurrent or progressive OC and conducted survival analyses to identify prognostic factors. Material and methods: This retrospective cohort study, conducted across 18 international centers, analyzed the clinical practices of patients receiving palliative treatment for PSM from OC who underwent PIPAC. All patients were initially treated appropriately outside any clinical trial setting. Feasibility, safety, and morbidity were evaluated along with objective endpoints of oncological response. Multivariate analysis identified prognostic factors for OS and PFS. Results: From 2015-2020, 234 consecutive patients were studied, from which 192 patients were included and stratified by platinum sensitivity for analysis. Patients with early recurrence, within one postoperative month, were excluded. Baseline characteristics were similar between the groups regarding platinum sensitivity (platinum sensitive (PS) and resistant (PR)), but chemotherapy frequency differed, as did PCI before PIPAC. Median PCI decreased in both groups after three cycles of PIPAC (PS 16 vs. 12, p < 0.001; PR 24 vs. 20, p = 0.009). Overall morbidity was 22%, with few severe complications (4-8%) or mortality (0-3%). Higher pathological response and longer OS (22 vs. 11m, p = 0.012) and PFS (12 vs. 7m, p = 0.033) were observed in the PS group. Multivariate analysis (OS/PFS) identified ascites (HR 4.02, p < 0.001/5.22, p < 0.001), positive cytology at first PIPAC (HR 3.91, p = 0.002/1.96, p = 0.035), and ≥ 3 PIPACs (HR 0.30, p = 0.002/0.48, p = 0.017) as independent prognostic factors of overall survival/progression-free survival. Conclusions: With low morbidity and mortality rates, PIPAC is a safe option for palliative treatment of advanced ovarian cancer. Promising results were observed after 3 PIPAC, which did improve the peritoneal burden. However, further research is needed to evaluate the potential role of PIPAC as an independent prognostic factor.

Effect of home-based online training and activity feedback on oxygen uptake in patients after surgical cancer therapy: a randomized controlled trial.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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. TRIAL REGISTRATION: DRKS-ID: DRKS00020499 ; Registered 17 March 2020.

[Therapy of esophageal motility disorders]. / Therapieoptionen von primären Motilitätsstörungen des Ösophagus.

Esophageal motility disorders are diseases in which there are malfunctions of the act of swallowing due to a change in neuromuscular structures. The main symptom is therefore dysphagia for solid and/or liquid foods, often accompanied by symptoms such as chest pain, regurgitation, heartburn, and weight loss. Esophageal manometry is the gold standard in diagnostics. Endoscopy and radiology serve to exclude inflammatory or malignant changes. With the introduction of high-resolution esophageal manometry (HRM), the diagnosis of esophageal motility disorders has improved and led to a new classification with the Chicago Classification, which has been modified several times in the last decade, most recently in 2020 with the Chicago Classification v4.0. Compared to the previous version 3.0, there are some important changes that are presented based on the most important esophageal motility disorders in everyday clinical practice.

[Diagnosis of esophageal motility disorders - Significance of the new Chicago classification v4.0]. / Diagnostik von Motilitätsstörungen des Ösophagus ­ Bedeutung der neuen Chicago-Klassifikation v4.0.

Esophageal motility disorders are diseases in which there are malfunctions of the act of swallowing due to a change in neuromuscular structures. The main symptom is therefore dysphagia for solid and/or liquid foods, often accompanied by symptoms such as chest pain, regurgitation, heartburn, and weight loss. Esophageal manometry is the gold standard in diagnostics. Endoscopy and radiology serve to exclude inflammatory or malignant changes. With the introduction of high-resolution esophageal manometry (HRM), the diagnosis of esophageal motility disorders has improved and led to a new classification with the Chicago Classification, which has been modified several times in the last decade, most recently in 2021 with the Chicago Classification v4.0. Compared to the previous version 3.0, there are some important changes that are presented based on the most important esophageal motility disorders in everyday clinical practice.

Dissecting the genetic heterogeneity of gastric cancer.

BACKGROUND: Gastric cancer (GC) is clinically heterogenous according to location (cardia/non-cardia) and histopathology (diffuse/intestinal). We aimed to characterize the genetic risk architecture of GC according to its subtypes. Another aim was to examine whether cardia GC and oesophageal adenocarcinoma (OAC) and its precursor lesion Barrett's oesophagus (BO), which are all located at the gastro-oesophageal junction (GOJ), share polygenic risk architecture. METHODS: We did a meta-analysis of ten European genome-wide association studies (GWAS) of GC and its subtypes. All patients had a histopathologically confirmed diagnosis of gastric adenocarcinoma. For the identification of risk genes among GWAS loci we did a transcriptome-wide association study (TWAS) and expression quantitative trait locus (eQTL) study from gastric corpus and antrum mucosa. To test whether cardia GC and OAC/BO share genetic aetiology we also used a European GWAS sample with OAC/BO. FINDINGS: Our GWAS consisting of 5816 patients and 10,999 controls highlights the genetic heterogeneity of GC according to its subtypes. We newly identified two and replicated five GC risk loci, all of them with subtype-specific association. The gastric transcriptome data consisting of 361 corpus and 342 antrum mucosa samples revealed that an upregulated expression of MUC1, ANKRD50, PTGER4, and PSCA are plausible GC-pathomechanisms at four GWAS loci. At another risk locus, we found that the blood-group 0 exerts protective effects for non-cardia and diffuse GC, while blood-group A increases risk for both GC subtypes. Furthermore, our GWAS on cardia GC and OAC/BO (10,279 patients, 16,527 controls) showed that both cancer entities share genetic aetiology at the polygenic level and identified two new risk loci on the single-marker level. INTERPRETATION: Our findings show that the pathophysiology of GC is genetically heterogenous according to location and histopathology. Moreover, our findings point to common molecular mechanisms underlying cardia GC and OAC/BO. FUNDING: German Research Foundation (DFG).

The role of intraoperative hyperspectral imaging (HSI) in colon interposition after esophagectomy.

BACKGROUND: Colon conduit is an alternative approach to reconstructing the alimentary tract after esophagectomy. Hyperspectral imaging (HSI) has been demonstrated to be effective for evaluating the perfusion of gastric conduits, but not colon conduits. This is the first study to describe this new tool addressing image-guided surgery and supporting esophageal surgeons to select the optimal colon segment for the conduit and anastomotic site intraoperatively. PATIENTS AND METHODS: Of 10 patients, eight who underwent reconstruction with a long-segment colon conduit after esophagectomy between 01/05/2018 and 01/04/2022 were included in this study. HSI was recorded at the root and tip of the colon conduit after clamping the middle colic vessels, allowing us to evaluate the perfusion and appropriate part of the colon segment. RESULTS: Anastomotic leak (AL) was detected in only one (12.5%) of all the enrolled patients (n = 8). None of the patients developed conduit necrosis. Only one patient required re-anastomosis on postoperative day 4. No patient needed conduit removal, esophageal diversion, or stent placement. There was a change in the anastomosis site to proximal in two patients intraoperatively. There was no need to change the side of colon conduit intraoperatively in any patient. CONCLUSION: HSI is a promising and novel intraoperative imaging tool to objectively assess the perfusion of the colon conduit. It helps the surgeon to define the best perfused anastomosis site and the side of colon conduit in this type of operation.

In vivo evaluation of a hyperspectral imaging system for minimally invasive surgery (HSI-MIS).

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 (StO2), 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 StO2 orig. 17.2% (± 7.7%), NIR-PIorig. 16.0 (± 9.5), TWIorig. 18.1 (± 7.9), OHIorig. 14.4 (± 4.5). For the PLS calculation, they were StO2 PLS 12.6% (± 5.2%), NIR-PIPLS 10.3 (± 6.0), TWIPLS 10.6 (± 5.1), and OHIPLS 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.

Alternative intraoperative optical imaging modalities for fluorescence angiography in gastrointestinal surgery: spectral imaging and imaging photoplethysmography.

INTRODUCTION: Intraoperative near-infrared fluorescence angiography with indocyanine green (ICG-FA) is a well-established modality in gastrointestinal surgery. Its main drawback is the application of a fluorescent agent with possible side effects for patients. The goal of this review paper is the presentation of alternative, non-invasive optical imaging methods and their comparison with ICG-FA. MATERIAL AND METHODS: The principles of ICG-FA, spectral imaging, imaging photoplethysmography (iPPG), and their applications in gastrointestinal surgery are described based on selected published works. RESULTS: The main applications of the three modalities are the evaluation of tissue perfusion, the identification of risk structures, and tissue segmentation or classification. While the ICG-FA images are mainly evaluated visually, leading to subjective interpretations, quantitative physiological parameters and tissue segmentation are provided in spectral imaging and iPPG. The combination of ICG-FA and spectral imaging is a promising method. CONCLUSIONS: Non-invasive spectral imaging and iPPG have shown promising results in gastrointestinal surgery. They can overcome the main drawbacks of ICG-FA, i.e. the use of contrast agents, the lack of quantitative analysis, repeatability, and a difficult standardization of the acquisition. Further technical improvements and clinical evaluations are necessary to establish them in daily clinical routine.

[Therapy of esophageal motility disorders]. / Therapieoptionen von primären Motilitätsstörungen des Ösophagus.

Esophageal motility disorders are diseases in which there are malfunctions of the act of swallowing due to a change in neuromuscular structures. The main symptom is therefore dysphagia for solid and/or liquid foods, often accompanied by symptoms such as chest pain, regurgitation, heartburn, and weight loss. Esophageal manometry is the gold standard in diagnostics. Endoscopy and radiology serve to exclude inflammatory or malignant changes. With the introduction of high-resolution esophageal manometry (HRM), the diagnosis of esophageal motility disorders has improved and led to a new classification with the Chicago Classification, which has been modified several times in the last decade, most recently in 2020 with the Chicago Classification v4.0. Compared to the previous version 3.0, there are some important changes that are presented based on the most important esophageal motility disorders in everyday clinical practice.

[Diagnosis of esophageal motility disorders - Significance of the new Chicago classification v4.0]. / Diagnostik von Motilitätsstörungen des Ösophagus ­ Bedeutung der neuen Chicago-Klassifikation v4.0.

Esophageal motility disorders are diseases in which there are malfunctions of the act of swallowing due to a change in neuromuscular structures. The main symptom is therefore dysphagia for solid and/or liquid foods, often accompanied by symptoms such as chest pain, regurgitation, heartburn, and weight loss. Esophageal manometry is the gold standard in diagnostics. Endoscopy and radiology serve to exclude inflammatory or malignant changes. With the introduction of high-resolution esophageal manometry (HRM), the diagnosis of esophageal motility disorders has improved and led to a new classification with the Chicago Classification, which has been modified several times in the last decade, most recently in 2021 with the Chicago Classification v4.0. Compared to the previous version 3.0, there are some important changes that are presented based on the most important esophageal motility disorders in everyday clinical practice.

GWAS meta-analysis of 16 790 patients with Barrett's oesophagus and oesophageal adenocarcinoma identifies 16 novel genetic risk loci and provides insights into disease aetiology beyond the single marker level.

OBJECTIVE: Oesophageal cancer (EC) is the sixth leading cause of cancer-related deaths. Oesophageal adenocarcinoma (EA), with Barrett's oesophagus (BE) as a precursor lesion, is the most prevalent EC subtype in the Western world. This study aims to contribute to better understand the genetic causes of BE/EA by leveraging genome wide association studies (GWAS), genetic correlation analyses and polygenic risk modelling. DESIGN: We combined data from previous GWAS with new cohorts, increasing the sample size to 16 790 BE/EA cases and 32 476 controls. We also carried out a transcriptome wide association study (TWAS) using expression data from disease-relevant tissues to identify BE/EA candidate genes. To investigate the relationship with reported BE/EA risk factors, a linkage disequilibrium score regression (LDSR) analysis was performed. BE/EA risk models were developed combining clinical/lifestyle risk factors with polygenic risk scores (PRS) derived from the GWAS meta-analysis. RESULTS: The GWAS meta-analysis identified 27 BE and/or EA risk loci, 11 of which were novel. The TWAS identified promising BE/EA candidate genes at seven GWAS loci and at five additional risk loci. The LDSR analysis led to the identification of novel genetic correlations and pointed to differences in BE and EA aetiology. Gastro-oesophageal reflux disease appeared to contribute stronger to the metaplastic BE transformation than to EA development. Finally, combining PRS with BE/EA risk factors improved the performance of the risk models. CONCLUSION: Our findings provide further insights into BE/EA aetiology and its relationship to risk factors. The results lay the foundation for future follow-up studies to identify underlying disease mechanisms and improving risk prediction.

[Artificial intelligence and hyperspectral imaging for image-guided assistance in minimally invasive surgery]. / Künstliche Intelligenz und hyperspektrale Bildgebung zur bildgestützten Assistenz in der minimal-invasiven Chirurgie.

BACKGROUND: Intraoperative imaging assists surgeons during minimally invasive procedures. Hyperspectral imaging (HSI) is a noninvasive and noncontact optical technique with great diagnostic potential in medicine. The combination with artificial intelligence (AI) approaches to analyze HSI data is called intelligent HSI in this article. OBJECTIVE: What are the medical applications and advantages of intelligent HSI for minimally invasive visceral surgery? MATERIAL AND METHODS: Within various clinical studies HSI data from multiple in vivo tissue types and oncological resections were acquired using an HSI camera system. Different AI algorithms were evaluated for detection and discrimination of organs, risk structures and tumors. RESULTS: In an experimental animal study 20 different organs could be differentiated with high precision (> 95%) using AI. In vivo, the parathyroid glands could be discriminated from surrounding tissue with an F1 score of 47% and sensitivity of 75%, and the bile duct with an F1 score of 79% and sensitivity of 90%. Furthermore, ex vivo tumor tissue could be successfully detected with an area under the receiver operating characteristic (ROC) curve (AUC) larger than 0.91. DISCUSSION: This study demonstrates that intelligent HSI can automatically and accurately detect different tissue types. Despite great progress in the last decade intelligent HSI still has limitations. Thus, accurate AI algorithms that are easier to understand for the user and an extensive standardized and continuously growing database are needed. Further clinical studies should support the various medical applications and lead to the adoption of intelligent HSI in the clinical routine practice.

Effects and duration of exercise-based prehabilitation in surgical therapy of colon and rectal cancer: a systematic review and meta-analysis.

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.

Tumor cell identification and classification in esophageal adenocarcinoma specimens by hyperspectral imaging.

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.

New Intraoperative Imaging Tools and Image-Guided Surgery in Gastric Cancer Surgery.

Innovations and new advancements in intraoperative real-time imaging have gained significant importance in the field of gastric cancer surgery in the recent past. Currently, the most promising procedures include indocyanine green fluorescence imaging (ICG-FI) and hyperspectral imaging or multispectral imaging (HSI, MSI). ICG-FI is utilized in a broad range of clinical applications, e.g., assessment of perfusion or lymphatic drainage, and additional implementations are currently investigated. HSI is still in the experimental phase and its value and clinical relevance require further evaluation, but initial studies have shown a successful application in perfusion assessment, and prospects concerning non-invasive tissue and tumor classification are promising. The application of machine learning and artificial intelligence technologies might enable an automatic evaluation of the acquired image data in the future. Both methods facilitate the accurate visualization of tissue characteristics that are initially indistinguishable for the human eye. By aiding surgeons in optimizing the surgical procedure, image-guided surgery can contribute to the oncologic safety and reduction of complications in gastric cancer surgery and recent advances hold promise for the application of HSI in intraoperative tissue diagnostics.