The Impact of the Gut Microbiome, Environment, and Diet in Early-Onset Colorectal Cancer Development.

Traditionally considered a disease common in the older population, colorectal cancer is increasing in incidence among younger demographics. Evidence suggests that populational- and generational-level shifts in the composition of the human gut microbiome may be tied to the recent trends in gastrointestinal carcinogenesis. This review provides an overview of current research and putative mechanisms behind the rising incidence of colorectal cancer in the younger population, with insight into future interventions that may prevent or reverse the rate of early-onset colorectal carcinoma.

Causes of death in patients operated for colorectal cancer.

BACKGROUND: Colorectal cancer remains the third leading cause of cancer-related mortality in the United States. This study evaluates the causes of death in patients operated on for colorectal cancer and their determinants. METHODS: An Instructional Review Board-approved database containing patients who underwent surgical resection for colorectal cancer from 2004 to 2018 (last followed up in December 2020) in a tertiary care institution. Data on the underlying cause of death was extracted from the Registry of Vital Records and Statistics in Massachusetts. RESULTS: A total of 576 deaths were recorded in the database, of which 290 (50.35%) patients died of colorectal cancer. Deaths from colorectal cancer gradually decreased over time, whereas deaths from other cancers increased, and deaths from cardiovascular diseases remained stable. Patients who died from colorectal cancer were younger, died earlier in the disease course, had fewer comorbidities, higher rates of stage IV disease, rectal cancer, neoadjuvant therapy, extramural vascular invasion, perineural invasion, R0 resection, and preserved mismatch repair protein status. On multivariate analysis, age (adjusted odds ratio for 10-year increase = 0.79, 95% confidence interval 0.65-0.95), American Society of Anesthesiologists score (adjusted odds ratio = 0.64, confidence interval 0.42-0.98), stage IV disease (adjusted odds ratio = 3.02, confidence interval 1.59-5.9), neoadjuvant therapy (adjusted odds ratio = 7.91, confidence interval 2.64-28.13), extramural vascular invasion (adjusted odds ratio = 2.3, confidence interval 1.36-3.91) & time from diagnosis to death (adjusted odds ratio = 0.76, confidence interval 0.68-0.83) predicted death due to colorectal cancer versus other causes, whereas tumor location, perineural invasion, R0 resection, and mismatch repair protein status did not. CONCLUSION: There is a declining trend of deaths from colorectal cancer, presumably reflecting advances in colorectal cancer management strategies and better screening over time. However, younger patients disproportionately contribute to death due to colorectal cancer and need aggressive screening and management strategies.

Metformin Does not Affect Outcomes in Patients With Locally Advanced Rectal Cancer Treated With Neoadjuvant Therapy and Resection.

INTRODUCTION: There is emerging evidence that metformin may have a protective effect in patients with cancer. However, its current evidence in locally advanced rectal cancer (LARC) is inconclusive. We aim to assess the effect of metformin on long-term outcomes in patients with LARC who received neoadjuvant therapy and surgical resection. METHODS: A retrospective review of 324 patients with nonmetastatic LARC who received neoadjuvant therapy and major surgical resection from 2004 to 2018. There were 27 patients who received metformin before surgery and 297 patients who did not receive metformin. RESULTS: Metformin users were associated with a significantly higher age, BMI, ASA score, and 30-day readmissions (P < .05). There was no difference in overall survival (OS, P = .18) or disease-free survival (DFS, P = .33) between the two groups. On Cox regression, metformin intake did not predict OS (HR 0.85, 95% CI 0.4-1.77) when controlled for age (HR 1.04, 1.02-1.06), sex (HR 1.13, 0.69-1.85), BMI (HR 0.97, 0.92-1.02), ASA score (HR: 1.7, 1.06-2.73), TNT (HR 0.31, 0.1-0.92), pathological Stage III disease (HR 2.55, 1.51-4.32), extramural vascular invasion (EMVI) (HR 3.06, 1.7-5.5), and adjuvant therapy (HR 0.1, 0.04-0.27 for <25 months OS and HR 0.3, 0.15-0.59 for ≥25 months). Disease-free survival showed a similar trend with no significant effect of metformin (HR 0.77, 0.39-1.52) when controlled for age, sex, BMI, ASA, TNT, Stage III disease, EMVI, and adjuvant therapy. CONCLUSION: Metformin does not affect long-term survival in LARC treated with neoadjuvant therapy followed by surgical resection. Studies with larger sample sizes are needed to validate the findings further.

Association Between Coronavirus Disease 2019 Vaccination and Mortality After Major Operations.

OBJECTIVE: The objective of this study was to compare postoperative 90-day mortality between (1) fully vaccinated patients with COVID-19-positive and negative diagnosis, and (2) vaccinated and unvaccinated patients with COVID-19 positive diagnosis. BACKGROUND: Societal guidelines recommend postponing elective operations for at least 7 weeks in unvaccinated patients with preoperative coronavirus disease 2019 (COVID-19) infection. The role of vaccination in this infection-operation time risk is unclear. METHODS: We conducted a national US multicenter retrospective, matched cohort study spanning July 2021 to October 2022. Participants were included if they underwent a high-risk general, vascular, orthopedic, neurosurgery, or genitourinary surgery. All-cause mortality occurring within 90 days of the index operation was the primary outcome. Inverse probability treatment weighted propensity scores were used to adjust logistic regression models examining the independent and interactive associations between mortality, exposure status, and infection proximity. RESULTS: Of 3401 fully vaccinated patients in the 8-week preoperative period, 437 (12.9%) were COVID-19-positive. Unadjusted mortality rates were not significantly different between vaccinated patients with COVID-19 (22, 5.0%) and vaccinated patients without COVID-19 (99, 3.3%; P = 0.07). After inverse probability treatment weighted adjustment, mortality risk was not significantly different between vaccinated COVID-19-positive patients compared to vaccinated patients without COVID-19 (adjusted odds ratio = 1.38, 95% CI: 0.70, 2.72). The proximity of COVID-19 diagnosis to the index operation did not confer added mortality risk in either comparison cohort. CONCLUSIONS: Contrary to risks observed among unvaccinated patients, postoperative mortality does not differ between patients with and without COVID-19 when vaccinated against the severe acute respiratory syndrome coronavirus 2 virus and receiving a high-risk operation within 8 weeks of the diagnosis, regardless of operation timing relative to diagnosis.

Trends and Determinants of Location of Death Due to Colorectal Cancer in the United States : A Nationwide Study.

BACKGROUND: Colorectal cancer (CRC) is the second leading cause of cancer-related mortality in the United States (US); however, there are limited data on location of death in patients who die from CRC. We examined the trends in location of death and determinants in patients dying from CRC in the US. METHODS: We utilized the Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research database to extract nationwide data on underlying cause of death as CRC. A multinomial logistic regression was performed to assess associations between clinico-sociodemographic characteristics and location of death. RESULTS: There were 850,750 deaths due to CRC from 2003 to 2019. There was a gradual decrease in deaths in hospital, nursing home, or outpatient facility/emergency department over time and an increase in deaths at home and in hospice. Relative to White decedents, Black, Asian, and American Indian/Alaska Native decedents were less likely to die at home and in hospice compared with hospitals. Individuals with lower educational status also had a lower risk of dying at home or in hospice compared with in hospitals. CONCLUSIONS: The gradual shift in location of death of patients who die of CRC from institutionalized settings to home and hospice is a promising trend and reflects the prioritization of patient goals for end-of-life care by healthcare providers. However, there are existing sociodemographic disparities in access to deaths at home and in hospice, which emphasizes the need for policy interventions to reduce health inequity in end-of-life care for CRC.

Incidence of Secondary Cancers After Neoadjuvant Therapy for Locally Advanced Rectal Cancer.

INTRODUCTION: Whether neoadjuvant chemoradiation for locally advanced rectal cancer (LARC) induces secondary cancers is controversial. This retrospective cohort study describes the incidence of secondary cancers in LARC patients. METHODS: We compared 364 LARC patients who received conventional (50.4 Gy) or short course neoadjuvant radiation (25 Gy x 5 fractions) followed by resection to 142 patients with surgically resected rectal cancer who did not receive radiation at a single institution from 2004 to 2018. Secondary cancer was defined as any nonmetastatic noncolorectal malignancy diagnosed via biopsy or definitive imaging criteria at least 6 mo after completion of neoadjuvant therapy or after resection in the comparison group. RESULTS: Among the neoadjuvant radiation group (364 patients, 40% female, age 61 ± 13 y), 32 patients developed 34 (9.3%) secondary cancers. Three cases involved a pelvic organ. Among the comparison group (142 patients, 39% female, age 64 ± 15 y), 15 patients (10.6%) developed a secondary cancer. Five cases involved pelvic organs. Secondary cancer incidence did not differ between groups. Latency period to secondary cancer diagnosis was 6.7 ± 4.3 y. Patients who received radiation underwent longer median follow-up (6.8 versus 4.5 y, P < 0.01) and were significantly less likely to develop a pelvic organ cancer (odds ratio 0.18; 95% confidence interval, 0.04-0.83; P = 0.02). No genetic mutations or cancer syndromes were identified among patients with secondary cancers. CONCLUSIONS: Neoadjuvant chemoradiation is not associated with increased secondary cancer risk in LARC patients and may have a local protective effect on pelvic organs, especially prostate. Ongoing follow-up is critical to continue risk assessment.

Stratification of Stage II Colon Cancer Using Recurrence Prediction Value: A Multi-institutional International Retrospective Study.

OBJECTIVE: To create a recurrence prediction value (RPV) of high-risk factor and identify the patients with high risk of cancer recurrence. SUMMARY BACKGROUND DATA: There are several high-risk factors known to lead to poor outcomes. Weighting each high-risk factor based on their association with increased risk of cancer recurrence can provide a more precise understanding of risk of recurrence. METHODS: We performed a multi-institutional international retrospective analysis of patients with Stage II colon cancer patients who underwent surgery from 2010 to 2020. Patient data from a multi-institutional database were used as the Training data, and data from a completely separate international database from two countries were used as the Validation data. The primary endpoint was recurrence-free survival (RFS). RESULTS: A total of 739 patients were included from Training data. To validate the feasibility of RPV, 467 patients were included from Validation data. Training data patients were divided into RPV low (n = 564) and RPV high (n = 175). Multivariate analysis revealed that risk of recurrence was significantly higher in the RPV high than the RPV low (Hazard ratio (HR) 2.628; 95% confidence interval (CI) 1.887-3.660; P < 0.001). Validation data patients were divided into two groups (RPV low, n = 420) and RPV high (n = 47). Multivariate analysis revealed that risk of recurrence was significantly higher in the RPV high than the RPV low (HR 3.053; 95% CI 1.962-4.750; P < 0.001). CONCLUSIONS: RPV can identify Stage II colon cancer patients with high risk of cancer recurrence world-wide.

Immune microenvironment and lymph node yield in colorectal cancer.

BACKGROUND: Lymph node (LN) harvesting is associated with outcomes in colonic cancer. We sought to interrogate whether a distinctive immune milieu of the primary tumour is associated with LN yield. METHODS: A total of 926 treatment-naive patients with colorectal adenocarcinoma with more than 12 LNs (LN-high) were compared with patients with 12 or fewer LNs (LN-low). We performed immunohistochemistry and quantification on tissue microarrays for HLA class I/II proteins, beta-2-microglobulin (B2MG), CD8, CD163, LAG3, PD-L1, FoxP3, and BRAF V600E. RESULTS: The LN-high group was comprised of younger patients, longer resections, larger tumours, right-sided location, and tumours with deficient mismatch repair (dMMR). The tumour microenvironment showed higher CD8+ cells infiltration and B2MG expression on tumour cells in the LN-high group compared to the LN-low group. The estimated mean disease-specific survival was higher in the LN-high group than LN-low group. On multivariate analysis for prognosis, LN yield, CD8+ cells, extramural venous invasion, perineural invasion, and AJCC stage were independent prognostic factors. CONCLUSION: Our findings corroborate that higher LN yield is associated with a survival benefit. LN yield is associated with an immune high microenvironment, suggesting that tumour immune milieu influences the LN yield.

Colitis-Associated Colorectal Cancer Survival is Comparable to Sporadic Cases after Surgery: a Matched-Pair Analysis.

BACKGROUND: Inflammatory bowel disease (IBD) confers an increased lifetime risk of colorectal cancer (CRC). The pathogenesis of colitis-associated CRC is considered distinct from sporadic CRC, but existing is mixed on long-term oncologic outcomes. This study aims to compare clinicopathological characteristics and survival between colitis-associated and sporadic CRC. METHODS: Data was retrospectively extracted and analyzed from a single institutional database of patients with surgically resected CRC between 2004 and 2015. Patients with IBD were identified as having colitis-associated CRC. The remainder were classified as sporadic CRC. Propensity score matching was performed. Univariate and survival analyses were carried out to estimate the differences between the two groups. RESULTS: Of 2275 patients included in this analysis, 65 carried a diagnosis of IBD (2.9%, 33 Crohn's disease, 29 ulcerative colitis, 3 indeterminate colitis). Average age at CRC diagnosis was 62 years for colitis-associated CRC and 65 for sporadic CRC. The final propensity score matched cohort consisted of 65 colitis-associated and 130 sporadic CRC cases. Patients with colitis-associated CRC were more likely to undergo total proctocolectomy (p < 0.01) and had higher incidence of locoregional recurrence (p = 0.026) compared to sporadic CRC patients. There were no significant differences in time to recurrence, tumor grade, extramural vascular invasion, perineural invasion, or rate of R0 resections. Overall survival and disease-free survival did not differ between groups. On multiple Cox regression, IBD diagnosis was not a significant predictor of survival. CONCLUSIONS: Patients with colitis-associated CRC who undergo surgical resection have comparable overall and disease-free survival to patients with sporadic CRC.

Behaviour and stability of thermodilution signals in a closed extracorporeal circuit: a bench study.

Thermodilution is the gold standard for cardiac output measurement in critically ill patients. Its application in extracorporeal therapy is limited, as a portion of the thermal indicator is drawn into the extracorporeal circuit. The behaviour of thermodilution signals in extracorporeal circuits is unknown. We investigated thermodilution curves within a closed-circuit and assessed the impact of injection volume, flow and distance on the behaviour of the thermodilution signals and catheter constants. We injected 3, 5, 7 and 10 ml of thermal indicator into a heated closed circuit. Thermistors at distances of 40, 60, 80, and 100 cm from the injection port recorded the thermodilution signals (at flow settings of 0.5, 1, 1.5, and 2 L/min). Area under the curve (AUC), rise time, exponential decay and catheter constants were analysed. Linear mixed-effects models were used to evaluate the impact of circuit flow, distance and injection volume. Catheter positioning did not influence AUC (78 injections). Catheter constants were independent of flow, injection volume or distance to the injection port. The distance to the injection port increased peak temperature and rise time and decreased exponential time constant significantly. The distance to the injection port did not influence catheter constants, but the properties of the thermodilution signal itself. This may influence measurements that depend on the exponential decay of the thermodilution signal such as right ventricular ejection fraction.

Clinical, pathological, genetics and intratumoural immune milieu of micropapillary carcinoma of the colon.

AIM: Micropapillary carcinoma (MPC) is a recognised WHO variant of colonic carcinoma (CC), although little is known about its prognosis, immune microenvironment and molecular alterations. We investigated its clinical, pathological and immunological characteristics. METHODS: We assessed 903 consecutive CCs and used the WHO definition to identify MPC. We recorded serrated and mucinous differentiation and mismatch repair (MMR) status. We performed immunohistochemistry and quantification on tissue microarrays for HLA class I/II proteins, beta-2-microglobulin (B2MG), CD8, CD163, LAG3, PD-L1, FoxP3, PD-L1and BRAF V600E. RESULTS: We classified 8.6% (N=78) of CC as MPC. Relative to non-MPC, MPC was more often high grade (p=0.03) and showed serrated morphology (p<0.01); however, we found no association with extramural venous invasion (p=0.41) and American Joint Committee on Cancer stage (p=0.95). MPCs showed lower numbers of CD8 positive lymphocytes (p<0.01), lower tumour cell B2MG expression (p=0.04) and lower tumour cell PD-L1 expression (p<0.01). There was no difference in HLA class I/II, LAG3, FOXP3, CD163 and PD-L1 positive histiocytes. There was no association with MMR status or BRAF V600E relative to non-MPC. MPC was not associated with decreased disease-specific survival (p=0.36). CONCLUSION: MPCs are associated with high-grade differentiation and a less active immune microenvironment than non-MPC. MPC is not associated with inferior disease-specific survival.

Patient Factors Affecting Inpatient Mortality Following Colorectal Cancer Resection.

BACKGROUND: Our objective is to identify factors for inpatient death in patients undergoing resection for colorectal cancer (CRC). STUDY DESIGN: Unmatched 1:3 case-control study of surgically resected CRC at a tertiary care institution between 2004 and 2018. Variables for multivariate analysis were selected using tetrachoric correlation followed by a least absolute shrinkage and selection operator (LASSO) penalized regression model. RESULTS: A total of 140 patients were included (N = 35 patients who died inpatient, N = 105 patients who did not die). Patients who died were older, had higher Charlson Comorbidity Index (CCI), higher rates of preoperative anemia, hypoalbuminemia, emergency surgeries, blood transfusion, postoperative vasopressor requirement, anastomotic leak, and postoperative ICU admission than patients who underwent surgical resection without inpatient mortality. Anemia (aOR = 8.62, 1.44-91.58), emergency admission (aOR = 5.71, 1.46-24.36), and ICU admission (aOR 45.51, 8.31-448.4) significantly predicted inpatient mortality when controlled for CCI and hypoalbuminemia. CONCLUSIONS: Surprisingly, it appears that pre-existing anemia and perioperative factors are more important in predicting inpatient mortality of patients undergoing CRC surgery than baseline comorbidity or nutritional status.

Association of age with outcomes in locally advanced rectal cancer treated with neoadjuvant therapy followed by surgery.

INTRODUCTION: We aimed to assess the association of age with outcomes in patients with Locally Advanced Rectal Cancer (LARC) who received neoadjuvant therapy followed by major surgery. METHODS: Retrospective review of 328 patients with LARC, N = 99 < 70 years (younger) versus N = 229 ≥ 70 years (elderly) from 2004 to 2018. RESULTS: Elderly patients had a higher American Society of Anesthesiologists (ASA) score, Charlson Comorbidity Index (CCI), length of stay and 30-day readmissions (p < 0.05). They also had worse overall survival (OS) & disease-free survival (DFS) (p < 0.001), but similar disease-specific survival (DSS) compared to younger group. Age was not associated with hazard of death (HR 1.01, 0.98-1.03). Rather, CCI (HR 1.29, 1.01-1.5), extramural vascular invasion (HR 4.98, 2.84-8.74), and adjuvant therapy (0.37, 0.21-0.64) were significantly associated with the hazard of death; when controlled for stage, tumor distance from anal verge, and neoadjuvant completion. CONCLUSION: Comorbidities and lower rates of adjuvant therapy, and not chronologic age, are associated with poor OS of elderly patients with LARC treated with neoadjuvant therapy and major surgery.

Immunological and Clinico-Molecular Features of Tumor Border Configuration in Colorectal Cancer.

INTRODUCTION: Infiltrating tumor border configuration (ITBC) portends a poor prognosis compared with pushing tumor border configuration (PTBC) in colorectal cancer. The tumor and its surrounding immune microenvironment of tumor border configuration is not well-characterized. We aim to elucidate the differences in expression of molecular markers between the 2 groups using tissue microarray (TMA). STUDY DESIGN: Immunohistochemistry was performed on TMAs of surgical pathology specimens obtained from colorectal cancer patients consecutively operated at our institution from 2004 to 2015. TMAs were stained for immune cells (CD8, FOXP3, LAG3, PU1, CD163, and PDL1); HLA II, beta 2 microglobulin, and HC10 on tumor cells; BRAFV600E mutation; and DNA mismatch repair proteins (MMR) status. Patients who received neoadjuvant therapy were excluded. RESULTS: There were 646 tumors with ITBC and 310 tumors with PTBC. There was a significantly lower expression (p < 0.05) of immune components, namely CD8, FOXP3, LAG3, PU1, PDL1 immune cells, and Beta-2 Microglobulin on tumor cells in the tumors with ITBC compared with PTBC, except CD163 immune cells, and HC10 and HLAII on tumor cells. Tumors with ITBC were less likely to be associated with BRAFV600E mutations and deficient MMR proteins (p < 0.001). On analyzing MMR-proficient tumors separately, we could not find any difference in the expression of any molecular marker (including BRAF), except a lower expression of PDL1 immune cells in tumors with ITBC (p < 0.001). CONCLUSIONS: Colorectal tumors with ITBC are associated with a generalized low immune microenvironment and low rates of BRAFV600E mutation compared with tumors with PTBC. However, the molecular expression of tumor border configuration seems confounded by the MMR molecular signature. MMR-proficient colorectal tumors with ITBC are associated with a lower expression of only PDL1 immune cells among all immune markers examined.

Integral assessment of gas exchange during veno-arterial ECMO: accuracy and precision of a modified Fick principle in a porcine model.

Assessment of native cardiac output during extracorporeal circulation is challenging. We assessed a modified Fick principle under conditions such as dead space and shunt in 13 anesthetized swine undergoing centrally cannulated veno-arterial extracorporeal membrane oxygenation (V-A ECMO, 308 measurement periods) therapy. We assumed that the ratio of carbon dioxide elimination (V̇co2) or oxygen uptake (V̇o2) between the membrane and native lung corresponds to the ratio of respective blood flows. Unequal ventilation/perfusion (V̇/Q̇) ratios were corrected towards unity. Pulmonary blood flow was calculated and compared to an ultrasonic flow probe on the pulmonary artery with a bias of 99 mL/min (limits of agreement -542 to 741 mL/min) with blood content V̇o2 and no-shunt, no-dead space conditions, which showed good trending ability (least significant change from 82 to 129 mL). Shunt conditions led to underestimation of native pulmonary blood flow (bias -395, limits of agreement -1,290 to 500 mL/min). Bias and trending further depended on the gas (O2, CO2) and measurement approach (blood content vs. gas phase). Measurements in the gas phase increased the bias (253 [LoA -1,357 to 1,863 mL/min] for expired V̇o2 bias 482 [LoA -760 to 1,724 mL/min] for expired V̇co2) and could be improved by correction of V̇/Q̇ inequalities. Our results show that common assumptions of the Fick principle in two competing circulations give results with adequate accuracy and may offer a clinically applicable tool. Precision depends on specific conditions. This highlights the complexity of gas exchange in membrane lungs and may further deepen the understanding of V-A ECMO.

The time Interval Between the End of Radiotherapy and Surgery Does Not Affect Outcomes in Rectal Cancer.

INTRODUCTION: The ideal time interval between the completion of chemoradiotherapy and subsequent surgical resection of advanced stage rectal tumors is highly debated. Our aim is to study the effect of the time interval between the completion of chemoradiotherapy and surgical resection on postoperative and oncologic outcomes in rectal cancer. METHODS: Patients who underwent neoadjuvant chemoradiotherapy for resected locally advanced rectal tumors between 2004 and 2015 were included in this analysis. The time interval was calculated from the date of radiation completion to date of surgery. Patients were split into 2 groups based on the time interval (<8 weeks and >8 weeks). Postoperative outcomes (anastomotic leak, pathologic complete response (pCR), and readmission) and survival were assessed with multivariable logistic regression and Cox regression models while adjusting for relevant confounders. RESULTS: 200 patients (62% male) underwent resection with a median time interval of 8 weeks from completion of radiotherapy. On multivariable logistic regression, there was no significant increase in odds between time interval to surgery and anastomotic leak (aOR = .8 [.27-2.7], P = .8), pCR (aOR = 1.2[.58-2.6] P = .6), or readmission (aOR = 1.02, 95% CI:0.49-2.24, P = .9). Time interval to surgery was not an independent prognostic factor for overall (HR = 1.04 CI = .4-2.65, P = .9) and disease-free survival (HR = 1.2 CI = .5-2.9, P = .6). CONCLUSION: The time interval between neoadjuvant radiotherapy completion and surgical resection does not affect anastomotic leak rate, achievement of pCR, or overall and disease-free survival in patients with rectal cancer. Extended periods of time to surgical resection are relatively safe.

Perioperative Doppler ultrasound assessment of portal vein flow pulsatility in high-risk cardiac surgery patients: a multicentre prospective cohort study.

BACKGROUND: Portal vein Doppler ultrasound pulsatility measured by transoesophageal echocardiography is a marker of the haemodynamic impact of venous congestion in cardiac surgery. We investigated whether the presence of abnormal portal vein flow pulsatility is associated with a longer duration of invasive life support and postoperative complications in high-risk patients. METHODS: In this multicentre cohort study, pulsed-wave Doppler ultrasound assessments of portal vein flow were performed during anaesthesia before initiation of cardiopulmonary bypass (before CPB) and after separation of cardiopulmonary bypass (after CPB). Abnormal pulsatility was defined as portal pulsatility fraction (PPF) ≥50% (PPF50). The primary outcome was the cumulative time in perioperative organ dysfunction (TPOD) requiring invasive life support during 28 days. Secondary outcomes included major postoperative complications. RESULTS: 373 patients, 71 (22.0%) had PPF50 before CPB and 77 (24.9%) after CPB. PPF50 was associated with longer duration of TPOD (median [inter-quartile range]; before CPB: 27 h [11-72] vs 19 h [8.5-42], P=0.02; after CPB: 27 h [11-61] vs 20 h [8-42], P=0.006). After adjusting for confounders, PPF50 before CPB showed significant association with TPOD. PPF50 after CPB was associated with a higher rate of major postoperative complications (36.4% vs 20.3%, P=0.006). CONCLUSIONS: Abnormal portal vein flow pulsatility before cardiopulmonary bypass was associated with longer duration of life support therapy after cardiac surgery in high-risk patients. Abnormal portal vein flow pulsatility after cardiopulmonary bypass separation was associated with a higher risk of major postoperative complications although this association was not independent of other factors. CLINICAL TRIAL REGISTRATION: NCT03656263.