A comparative analysis of whole genome sequencing of esophageal adenocarcinoma pre- and post-chemotherapy.

The scientific community has avoided using tissue samples from patients that have been exposed to systemic chemotherapy to infer the genomic landscape of a given cancer. Esophageal adenocarcinoma is a heterogeneous, chemoresistant tumor for which the availability and size of pretreatment endoscopic samples are limiting. This study compares whole-genome sequencing data obtained from chemo-naive and chemo-treated samples. The quality of whole-genomic sequencing data is comparable across all samples regardless of chemotherapy status. Inclusion of samples collected post-chemotherapy increased the proportion of late-stage tumors. When comparing matched pre- and post-chemotherapy samples from 10 cases, the mutational signatures, copy number, and SNV mutational profiles reflect the expected heterogeneity in this disease. Analysis of SNVs in relation to allele-specific copy-number changes pinpoints the common ancestor to a point prior to chemotherapy. For cases in which pre- and post-chemotherapy samples do show substantial differences, the timing of the divergence is near-synchronous with endoreduplication. Comparison across a large prospective cohort (62 treatment-naive, 58 chemotherapy-treated samples) reveals no significant differences in the overall mutation rate, mutation signatures, specific recurrent point mutations, or copy-number events in respect to chemotherapy status. In conclusion, whole-genome sequencing of samples obtained following neoadjuvant chemotherapy is representative of the genomic landscape of esophageal adenocarcinoma. Excluding these samples reduces the material available for cataloging and introduces a bias toward the earlier stages of cancer.

Common and Less Well-known Upper-limb Injuries in Elite Tennis Players.

A recent increase in epidemiology studies on injuries in elite tennis players has helped to shed light on the types of injuries these athletes sustain. This article reviews the common upper-limb injuries in elite players and includes less well known, but important, injuries. A search was conducted to identify current relevant studies involving elite tennis players. Injury frequency rates, injuries by regions, and types of injuries together with a list of commonly reported injuries in the upper limb were established. This list was then reviewed and refined by a sports medicine physician who cares for elite tennis players to include both those injuries of the upper limb that are common and those that are less well known but still important and frequently encountered. Common injuries include internal shoulder impingement, rotator cuff pathology, labral tears, elbow tendinopathies, as well as extensor carpi ulnaris tendinopathies and subluxation. Posterior shoulder instability, distal humeral bone stress, elbow medial collateral ligament, and nondominant wrist ulnar collateral ligament injuries are not commonly reported injuries, but they are of significant clinical importance.

P.R.O.P.S. - A novel Pre-Operative Predictive Score for unresectability in patients with colorectal peritoneal metastases being considered for cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC).

BACKGROUND: Twenty to thirty percent of planned cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS and HIPEC) procedures are abandoned intra-operatively. Pre-operative factors associated with unresectability identified previously were used to develop a Pre-Operative Predictive Score (PROPS), which was compared with current selection criteria-Peritoneal Surface Disease Severity Score (PSDSS), Verwaal's Prognostic Score (PS) and Colorectal Peritoneal Metastases Prognostic Surgical Score (COMPASS), to determine which score provides the best prediction for unresectability. METHODS: Fifty-six patients with peritoneal metastases of colorectal origin were included. Beta-coefficient values of significant variables (p < 0.05) were determined from multivariate analysis to develop PROPS. PROPS, PSDSS, PS and COMPASS were compared using a receiver operating characteristic curve to calculate its accuracy, sensitivity and specificity. RESULTS: PROPS consisted of nine patient and tumour factors which were categorised into three groups: (i) poor tumour biology: previous inadequate resection, underwent multiple lines of chemotherapy and poorly differentiated or signet cell histology; (ii) heavy tumour burden: abdominal distension, palpable abdominal mass and computed tomography findings of ascites, small bowel disease and/or omental thickening; and (iii) active tumour proliferation: elevated tumour markers. Overall, PROPS achieved 86% accuracy with 100% sensitivity and 68% specificity, PSDSS achieved 85% accuracy with 100% sensitivity and 63% specificity, PS achieved 73% accuracy with 100% sensitivity and 68% specificity and COMPASS achieved 61% accuracy with 27% sensitivity and 100% specificity. CONCLUSIONS: PROPS is more effective in predicting unresectability as compared to PSDSS, PS and COMPASS, and has the added advantage of using solely pre-operative factors.

CA-125: an inaccurate surveillance tool immediately after cytoreductive surgery and hyperthermic intraoperative chemotherapy (CRS-HIPEC)?

OBJECTIVE: This study seeks to evaluate pre and post-operative CA-125 in patients undergoing complete cytoreduction surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC), and understand the time frame before values normalise allowing use as a surveillance tool to resume. METHODS: A retrospective review was carried out of 94 patients undergoing CRS-HIPEC to compare pre-operative CA-125 values, measured within one week prior to surgery to post-operative readings within the first 30 d. Raised CA-125 was defined using as a value >35 U/ml. RESULTS: Of 63 (67%) patients with normal pre-operative CA-125, 22 (35%) had raised post-operative CA-125, and consisted of patients with colorectal (n = 8), appendiceal (n = 6), ovarian (n = 4) or other (n = 4) cancers. The average peak CA-125 was 80 U/ml occurring on median 10th post-operative day (POD) (range 7-30). The median day of normalisation for patients with normal pre-operative and raised post-operative CA-125 was 57 (range 28-115). The median day of normalisation for patients with raised pre-operative CA-125 was POD 41 (range 1-114). Notably 10 patients had initial normalisation (median POD 1, range 1-6), followed by subsequent raised value (median POD 10, range 5-40) and re-normalisation (median POD 47, range 19-104). DISCUSSION: For patients with raised pre-operative CA-125 an immediate post-operative CA-125 within 3 d may be useful to assess normalisation following surgery. Aside from immediate measurement CA-125 is misleading and should not be measured post-operatively within the first 3 months after surgery following which its use as a surveillance marker can resume.

Does having a gastrectomy delay time to feeding and prolong hospital stay in patients undergoing cytoreductive surgery and hyperthermic intraperitoneal chemotherapy?

AIM: Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) is routinely used to treat selected patients with peritoneal carcinomatosis, but can be associated with prolonged hospital stay, significant morbidity and mortality. Our objective was to assess whether patients undergoing gastrectomy as part of CRS/HIPEC were at increased risk of delayed feeding time and prolonged hospital stay. METHODS: Two hundred and fourteen consecutive patients with peritoneal carcinomatosis treated with CRS/HIPEC between 2001 and 2016 were stratified by whether CRS included gastrectomy (n = 19, 9%) and compared. Primary outcomes were time to full feeds and rate of serious morbidity (Clavien-Dindo grades III-V). Secondary outcomes were durations of ICU and hospital stays. RESULTS: Of 214 patients undergoing CRS/HIPEC, those undergoing gastrectomy (19, 8.9%) had increased time to full feeds (8 vs. 5 days, p < 0.01), and duration of ICU (2 vs. 1 days, p < 0.01) and total hospital stays (16 vs. 14 days, p = 0.013). There was no significant increase in serious complications, although increased risk of pneumonia was noted (21% vs. 4.1%, p = 0.011). Undergoing gastrectomy was not independently prognostic in multivariable analysis including high peritoneal tumour load (PCI >12), multiple CRS procedures (number >2) and operation duration (>480 min) in which operative duration remained independently prognostic (p < 0.01). CONCLUSIONS: After surgery, early oral refeeding may be beneficial in the majority of patients undergoing CRS/HIPEC. However, patients found to have high peritoneal tumour load with extended surgery and those who underwent gastrectomy should be considered for early post-operative TPN due to the significant risk of delayed time to full feeds.

Platinum agents and mitomycin C-specific complications in cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC).

INTRODUCTION: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) have been found to prolong survival in patients with peritoneal disease but is associated with significant morbidity. We evaluate the perioperative complications and the association with the chemotherapy agent used for HIPEC. METHODS: Retrospective analysis of a prospectively collected database of CRS-HIPEC cases between April 2001 and February 2016 was performed. Patients were stratified by the chemotherapy used, and perioperative complications were compared. RESULTS: Out of 214 CRS-HIPEC cases, 113 procedures used Mitomycin-C(MMC), 92 used cisplatin, 8 used oxaliplatin and the HIPEC regimen for one procedure was not recorded and excluded. 94 patients (44%) suffered low-grade complications (grade I-II), and 49 patients (23%) suffered high-grade complications (grade III-V). The frequency of low-grade complications for the cisplain, oxaliplatin and MMC groups were 49%, 50% and 40%, respectively, whereas that of high-grade complications were 24%, 50% and 20%, respectively. HIPEC with platinum agents was associated with a higher rate of acute renal impairment (ARI) compared to MMC (32% and 62% for cisplatin and oxaliplatin vs. 5.6% for MMC), whereas grade IV ARI requiring dialysis occurred only in the cisplatin group (5.6%). HIPEC with oxaliplatin was associated with higher rates of post-operative bleeding (25% vs. 1.1% and 0.88%). Rates of other complications did not differ significantly between the groups receiving different HIPEC regimens. CONCLUSIONS: The overall complication rates do not significantly differ after HIPEC with MMC and platinum based agents. Renal impairment tends to be more common and of greater severity when a platinum agent is used, whereas oxaliplatin is associated with significant post-operative bleeding.

Selective insulin resistance in hepatocyte senescence.

Insulin resistance has been described in association with chronic liver disease for decades. Hepatocyte senescence has been demonstrated in chronic liver disease and as many as 80% of hepatocytes show a senescent phenotype in advanced liver disease. The aim of this study was to understand the role of hepatocyte senescence in the development of insulin resistance. Senescence was induced in HepG2 cells via oxidative stress. The insulin metabolic pathway was studied in control and senescent cells following insulin stimulation. GLUT2 and GLUT4 expressions were studied in HepG2 cells and human liver tissue. Further, GLUT2 and GLUT4 expressions were studied in three independent chronic liver disease cohorts. Signalling impairment distal to Akt in phosphorylation of AS160 and FoxO1 was evident in senescent HepG2 cells. Persistent nuclear localisation of FoxO1 was demonstrated in senescent cells despite insulin stimulation. Increased GLUT4 and decreased GLUT2 expressions were evident in senescent cells, human cirrhotic liver tissue and publically available liver disease datasets. Changes in GLUT expressions were associated with a poor clinical prognosis. In conclusion, selective insulin resistance is evident in senescent HepG2 cells and changes in GLUT expressions can be used as surrogate markers of hepatocyte senescence.

A systematic approach to therapeutic target selection in oesophago-gastric cancer.

OBJECTIVE: The success of personalised therapy depends on identification and inhibition of the oncogene(s) on which that tumour is dependent. We aimed to determine whether a receptor tyrosine kinase (RTK) array could be used to select the most effective therapeutic strategies in molecularly heterogeneous oesophago-gastric adenocarcinomas. DESIGN: Gene expression profiling from oesophago-gastric tumours (n=75) and preinvasive stages (n=57) identified the active signalling pathways, which was confirmed using immunohistochemistry (n=434). RTK arrays on a cell line panel (n=14) determined therapeutic targets for in vitro cytotoxic testing. Feasibility of this personalised approach was tested in tumour samples (n=46). RESULTS: MAPK was the most frequently activated pathway (32/75 samples (42.7%)) with progressive enrichment in preinvasive disease stages (p<0.05) and ERK phosphorylation in 148/434 (34.3%) independent samples. Cell lines displayed a range of RTK activation profiles. When no RTKs were activated, tyrosine kinase inhibitors (TKIs) and a Mek inhibitor were not useful (MKN1). In lines with a dominant phosphorylated RTK (OE19, MKN45 and KATOIII), selection of this TKI or Mek in nM concentrations induced cytotoxicity and inhibited Erk and Akt phosphorylation. In cells lines with complex activation profiles (HSC39 and OE33), a combination of TKIs or Mek inhibition (in nM concentrations) was necessary for cytotoxicity and inhibition of Erk and Akt phosphorylation. Human tumours demonstrated diverse activation profiles and 65% of cases had two or more active RTKs. CONCLUSIONS: The MAPK pathway is commonly activated in oesophago-gastric cancer following activation of a variety of RTKs. Molecular phenotyping can inform a rational choice of targeted therapy.

Unveiling Liquid Gold: Lymph as an HPV Marker in OPSCC to Guide Treatment Decisions.

Distinguishing low- versus high-risk HPV-associated oropharyngeal squamous cell carcinoma (OPSCC) is pivotal for tailoring treatment. Liquid biopsy, measuring cell-free HPV-DNA in serum and saliva, assesses treatment response and early-recurrence risk. Postoperative lymphatic fluid may better guide future adjuvant therapy decisions due to its proximity to primary lesions and lymph nodes. See related article by Earland et al., p. 1409.

The immunomodulatory role of paracrine signalling factor VSIG4 in peritoneal metastases.

Peritoneal metastasis (PM), the regional progression of intra-abdominal malignancies, is a common sequelae of colorectal cancer (CRC). Immunotherapy is slated to be effective in generating long-lasting anti-tumour response as it utilizes the specificity and memory of the immune system. In the tumour microenvironment, tumour associated macrophages (TAMs) are posited to create an anti-inflammatory pro-tumorigenic environment. In this paper, we aimed to identify immunomodulatory factors associated with colorectal PM (CPM). A publicly available colorectal single cell database (GSE183916) was analysed to identify possible immunological markers that are associated with the activation of macrophages in cancers. Immunohistochemical analysis for V-set and immunoglobin containing domain 4 (VSIG4) expression was performed on tumour microarrays (TMAs) of tumours of colorectal origin (n = 211). Expression of VSIG4 in cell-free ascites obtained from CPM patients (n = 39) was determined using enzyme-linked immunosorbent assay (ELISA). CD163-positive TAMs cluster expression was extracted from a publicly available single cell database and evaluated for the top 100 genes. From these macrophage-expressed genes, VSIG4, a membrane protein produced by the M2 macrophages, mediates the up-regulation of anti-inflammatory and down-regulation of pro-inflammatory macrophages, contributing to an overall anti-inflammatory state. CRC TMA IHC staining showed that low expression of VSIG4 in stromal tissues of primary CRC are associated with poor prognosis (p = 0.0226). CPM ascites also contained varying concentrations of VSIG4, which points to a possible role of VSIG4 in the ascites. The contribution of VSIG4 to CPM development can be further evaluated for its potential as an immunotherapeutic agent.

Transcriptomic convergence despite genomic divergence drive field cancerization in synchronous squamous tumors.

Introduction: Field cancerization is suggested to arise from imbalanced differentiation in individual basal progenitor cells leading to clonal expansion of mutant cells that eventually replace the epithelium, although without evidence. Methods: We performed deep sequencing analyses to characterize the genomic and transcriptomic landscapes of field change in two patients with synchronous aerodigestive tract tumors. Results: Our data support the emergence of numerous genetic alterations in cancer-associated genes but refutes the hypothesis that founder mutation(s) underpin this phenomenon. Mutational signature analysis identified defective homologous recombination as a common underlying mutational process unique to synchronous tumors. Discussion: Our analyses suggest a common etiologic factor defined by mutational signatures and/or transcriptomic convergence, which could provide a therapeutic opportunity.

Stromal genes discriminate preinvasive from invasive disease, predict outcome, and highlight inflammatory pathways in digestive cancers.

The stromal compartment is increasingly recognized to play a role in cancer. However, its role in the transition from preinvasive to invasive disease is unknown. Most gastrointestinal tumors have clearly defined premalignant stages, and Barrett's esophagus (BE) is an ideal research model. Supervised clustering of gene expression profiles from microdissected stroma identified a gene signature that could distinguish between BE metaplasia, dysplasia, and esophageal adenocarcinoma (EAC). EAC patients overexpressing any of the five genes (TMEPAI, JMY, TSP1, FAPalpha, and BCL6) identified from this stromal signature had a significantly poorer outcome. Gene ontology analysis identified a strong inflammatory component in BE disease progression, and key pathways included cytokine-cytokine receptor interactions and TGF-beta. Increased protein levels of inflammatory-related genes significantly up-regulated in EAC compared with preinvasive stages were confirmed in the stroma of independent samples, and in vitro assays confirmed functional relevance of these genes. Gene set enrichment analysis of external datasets demonstrated that the stromal signature was also relevant in the preinvasive to invasive transition of the stomach, colon, and pancreas. These data implicate inflammatory pathways in the genesis of gastrointestinal tract cancers, which can affect prognosis.

Improving the accuracy of revised cardiac risk index with HbA1C: Hemoglobin ratio (HH ratio) - A retrospective cohort study.

Background: The current Lee's Revised cardiac risk index (RCRI) was created in 1999. Validation studies have found RCRI to be only moderately discriminant. The "Diabetes Mellitus on insulin" component of the score does not accurately reflect the severity of the disease. A previously studied HbA1C:Hemoglobin ratio shows an improved association with outcomes than individual components alone. Study design: A retrospective cohort study was performed in diabetic patients undergoing non-cardiac surgery. Ethics approval was obtained. The study compares the predictive value of RCRI and substitution of the "DM on insulin" component with HH ratio for 30- and 90-day mortality, and postoperative acute myocardial injury (AMI) and acute kidney injury (AKI). Results: A total of 20,099 adult patients were included in the final analysis. The incidence of 30- and 90-day mortality was at 4.2 and 6.5%, respectively. Substitution of HH ratio in RCRI resulted in 687 more patients being in the moderate to high-risk category. The substituted HH-RCRI score had better prediction for 30-day (AUC 0.66 vs. 0.69, p < 0.001) and 90-day mortality (AUC 0.67 vs. 0.70, p < 0.001), and postoperative AMI (AUC 0.69 vs. 0.71, p < 0.001) and AKI (AUC 0.57 vs. 0.62, p < 0.001). Conclusion: Although currently not an universal practice, substitution of "DM on insulin" with HbA1C:Hemoglobin ratio in RCRI score improves the accuracy of the RCRI risk prediction model in diabetic patients going for non-cardiac surgery.

Cost-effectiveness comparison of delayed versus immediate coloanal anastomosis following ultralow anterior resection for rectal cancer.

BACKGROUND: Following ultralow anterior resection for distal rectal cancers, a coloanal anastomosis is usually created along with a defunctioning ileostomy (DI). Recent evidence suggests that abdominoperineal pull-through with delayed coloanal anastomosis (DCAA) is a viable alternative to immediate coloanal anastomosis (ICAA), minimizing the risk of anastomotic leakage and avoiding the need for stoma creation with the risk of stoma-associated morbidity. However, DCAA requires a longer initial hospitalization. We aimed to perform a cost-effectiveness analysis to compare DCAA versus ICAA for elective rectal cancer surgery. METHODS: A decision tree model was used to compare the cost-effectiveness of the two strategies. Cost data were obtained from the 2019 to 2020 United Kingdom National Health Service reference costs. Model probabilities were derived from published studies. Univariate and probabilistic sensitivity analyses were used to evaluate the robustness of the results. RESULTS: DCAA was the overall cheaper strategy at £13 541 compared with £14 856 for ICAA in the base case analysis. This was explained by the decreased overall costs of hospitalization/surgery, reduction in costs associated with anastomotic or stoma-related complications, specifically dehydration-induced hospital readmissions and avoidance of stoma maintenance costs. Sensitivity analysis demonstrated that DCAA remained consistently more inexpensive except when the duration of total parenteral nutrition exceeded 14 days. CONCLUSION: Despite a longer index hospitalization with higher initial costs, this economic analysis demonstrates that DCAA without stoma is overall more cost-effective compared with ICAA with DI following ultralow anterior resection. Cost savings should be considered an additional benefit when selecting the DCAA approach for rectal cancer surgery.

Adherence to Multidisciplinary Tumor Board Recommendations in Patients With Curable Esophageal and Gastric Cancers.

BACKGROUND: Multidisciplinary tumor board (MDT) discussion is standard practice in the management of Upper Gastrointestinal (UGI) cancers. However, poor adherence to MDT recommendations may account for the lack of improved oncological outcomes with MDTs. We aim to quantify adherence rates and compare outcomes between adherent and non-adherent patients. METHODS: We included all patients with potentially curable primary UGI carcinomas who were discussed at UGI MDT from 2017 to 2018. MDT recommendations were compared to actual treatment received. Oncological and survival outcomes were compared between both groups. RESULTS: Amongst 153 patients, 64 (41.8%) were non-adherent to MDT recommendations. Reasons for non-adherence were patient refusal (50.0%), treatment-related complications (31.3%), disease factors (17.2%) and clinician decision (1.56%). Univariate analysis showed that non-adherent patients were older (71.6 vs 65.2 years, p < 0.001), with higher clinical stage at point of diagnosis (p = 0.028), pathological stage after resection (p < 0.001) and were more likely to be recommended for multimodal therapy. No significant factors were associated with non-adherence at multivariate analysis. Non-adherent patients had worse median overall survival (19.5 months) compared to adherent patients (not reached at follow-up) with both unmatched and propensity-score matched analysis. Patients who received only part of the intended adjuvant chemotherapy course had worse median overall survival and disease-free survival compared to patients who completed or did not initiate adjuvant chemotherapy. CONCLUSIONS: Non-adherence to MDT recommendations was associated with advanced age and tumor stage, and potentially contributes to the worse oncological outcomes in a group of patients already predisposed to poor outcomes.

Impact of COVID-19 on Public Interest in Breast Cancer Screening and Related Symptoms: Google Trends Analysis.

BACKGROUND: The COVID-19 pandemic has led to a decrease in cancer screening due to the redeployment of health care resources and public avoidance of health care facilities. Breast cancer is the most common cancer diagnosed in female individuals, with improved survival rates from early detection. An avoidance of screening, resulting in late detection, greatly affects survival and increases health care resource burden and costs. OBJECTIVE: This study aimed to evaluate if a sustained decrease in public interest in screening occurred and to evaluate other search terms, and hence interest, associated with that. METHODS: This study used Google Trends to analyze public interest in breast cancer screening and symptoms. We queried search data for 4 keyword terms ("mammogram," "breast pain," "breast lump," and "nipple discharge") from January 1, 2019, to January 1, 2022. The relative search frequency metric was used to assess interest in these terms, and related queries were retrieved for each keyword to evaluate trends in search patterns. RESULTS: Despite an initial drastic drop in interest in mammography from March to April 2020, this quickly recovered by July 2020. After this period, alongside the recovery of interest in screening, there was a rapid increase in interest for arranging for mammography. Relative search frequencies of perceived breast cancer-related symptoms such as breast lump, nipple discharge, and breast pain remained stable. There was increase public interest in natural and alternative therapy of breast lumps despite the recovery of interest in mammography and breast biopsy. There was a significant correlation between search activity and Breast Cancer Awareness Month in October. CONCLUSIONS: Online search interest in breast cancer screening experienced a sharp decline at the beginning of the COVID-19 pandemic, with a subsequent return to baseline interest in arranging for mammography followed this short period of decreased interest.

Preoperative shock index in major abdominal emergency surgery.

Introduction: Major abdominal emergency surgery (MAES) patients have a high risk of mortality and complications. The time-sensitive nature of MAES necessitates an easily calculable risk-scoring tool. Shock index (SI) is obtained by dividing heart rate (HR) by systolic blood pressure (SBP) and provides insight into a patient's haemodynamic status. We aimed to evaluate SI's usefulness in predicting postoperative mortality, acute kidney injury (AKI), requirements for intensive care unit (ICU) and high-dependency monitoring, and the ICU length of stay (LOS). Method: We retrospectively reviewed 212,089 MAES patients from January 2013 to December 2020. The cohort was propensity matched, and 3960 patients were included. The first HR and SBP recorded in the anaesthesia chart were used to calculate SI. Regression models were used to investigate the association between SI and outcomes. The relationship between SI and survival was explored with Kaplan-Meier curves. Results: There were significant associations between SI and mortality at 1 month (odds ratio [OR] 2.40 [1.67-3.39], P<0.001), 3 months (OR 2.13 [1.56-2.88], P<0.001), and at 2 years (OR 1.77 [1.38-2.25], P<0.001). Multivariate analysis revealed significant relationships between SI and mortality at 1 month (OR 3.51 [1.20-10.3], P=0.021) and at 3 months (OR 3.05 [1.07-8.54], P=0.034). Univariate and multivariate analysis also revealed significant relationships between SI and AKI (P<0.001), postoperative ICU admission (P<0.005) and ICU LOS (P<0.001). SI does not significantly affect 2-year mortality. Conclusion: SI is useful in predicting postopera-tive mortality at 1 month, 3 months, AKI, postoperative ICU admission and ICU LOS.

Prehabilitation programs - a systematic review of the economic evidence.

Introduction: Prehabilitation, which involves improving a patient's physical and psychological condition before surgery, has shown potential benefits but has yet to be extensively studied from an economic perspective. To address this gap, a systematic review was conducted to summarize existing economic evaluations of prehabilitation interventions. Methods: The PRISMA Protocols 2015 checklist was followed. Over 16,000 manuscripts were reviewed, and 99 reports on preoperative interventions and screening tests were identified, of which 12 studies were included in this analysis. The costs are expressed in Pounds (GBP, £) and adjusted for inflation to December 2022. Results: The studies were conducted in Western countries, focusing on specific surgical subspecialties. While the interventions and study designs varied, most studies demonstrated cost savings in the intervention group compared to the control group. Additionally, all cost-effectiveness analysis studies favored the intervention group. However, the review also identified several limitations. Many studies had a moderate or high risk of bias, and critical information such as time horizons and discount rates were often missing. Important components like heterogeneity, distributional effects, and uncertainty were frequently lacking as well. The misclassification of economic evaluation types highlighted a lack of knowledge among physicians in prehabilitation research. Conclusion: This review reveals a lack of robust evidence regarding the economics of prehabilitation programs for surgical patients. This suggests a need for further research with rigorous methods and accurate definitions.