Adjuvant chemotherapy in stage 1 colon cancer: Patient characteristics and survival analysis from the national cancer database.

BACKGROUND: A subset of patients in ACS-NCDB with stage-1 colon cancer received adjuvant chemotherapy (AC), in contrast to national guidelines. This study aimed to define this population and evaluate associations between AC and survival. METHODS: Patients with T1-2N0 colon cancer from 2004 to 2016 were separated into AC and non-AC groups. Adverse pathological features (APF) included T2, poor differentiation, lymphovascular invasion, positive margin, and inadequate lymph nodes (<12). Cox proportional hazard models were used to estimate prognostic factors for overall survival (OS). RESULTS: A total of 1745 of 139,857 patients (1.2 %) received AC. Receiving AC was associated with male sex (p = 0.02), uninsured (p < 0.01), low income (p = 0.02), or having ≥2 APFs (p < 0.001). In the total cohort, AC was associated with increased mortality (HR 1.14 [1.04-1.24] P < 0.01). On subset analysis, AC was associated with improved OS for patients with ≥2 APFs (log-rank P=<0.001), and decreased mortality when adjusted for covariates (HR 0.81 [0.69-0.95] P=<0.01). The most significant predictor of mortality was old age (HR 3.78 [3.67, 3.89] p ≤ 0.01), followed by higher Charlson Comorbidity Index (HR 1.73 [1.69, 1.76] (p ≤ 0.01), and higher APF score (HR 1.46 [1.42, 15.2] p ≤ 0.01). CONCLUSION: AC was associated with decreased survival in the total cohort of stage 1 colon cancer patients, but was associated with improved survival for patients with multiple APFs.

A retrospective comparison of 90-day outcomes, length of stay, and readmissions between robotic-assisted and laparoscopic colectomy.

Investigations generally assess 30 days of perioperative outcomes with robotic-assisted and laparoscopic colectomy. Outcomes beyond 30 days serve as a quality metric of surgical services and an assessment of 90 days of outcomes may have greater clinical utility. The purpose of this study was to assess 90 days of outcomes, length of stay (LOS), and readmissions among patients who underwent a robotic-assisted versus laparoscopic colectomy using a national database. Patients undergoing either robotic-assisted or laparoscopic colectomy were identified using Current Procedural Terminology (CPT) codes within PearlDiver, a national, inpatient records database from 2010 to 2019. Outcomes were defined using the National Surgical Quality Improvement Program (NSQIP) risk calculator and identified using International Classification of Disease (ICD) diagnosis codes. Categorical variables were compared using chi-square tests, and continuous variables were compared using paired t tests. Covariate-adjusted regression models were also constructed to evaluate these associations while accounting for potential confounders. A total of 82,495 patients were assessed in this study. At 90 days, patients of the laparoscopic colectomy cohort experienced a higher rate of complications than patients who underwent robotic-assisted colectomy (9.5 vs. 6.6%, p < 0.001). There were no significant differences in LOS (6 vs. 6.5 days, p = 0.08) and readmissions (6.1 vs. 6.7%, p = 0.851) at 90 days. Patients undergoing robotic-assisted colectomy have a lower risk for morbidity at 90 days. Neither approach is superior for LOS nor 90 days of readmissions. Both techniques are effective minimally invasive procedures, yet patients may gain a greater risk benefit from robotic colectomy.

Evaluation of a commonly used tool: Does the 5-item frailty index predict phenotypic frailty?

BACKGROUND: The simplified frailty index (sFI) is a commonly used instrument to estimate postoperative risk, but its correlation with phenotypic frailty has been questioned. This study evaluates the relationship between sFI and phenotypic frailty, as measured by the Sinai Abbreviated Geriatric Evaluation (SAGE). METHODS: Charts were retrospectively reviewed from patients ≥75 years old who underwent surgery between 2012-2022. The sFI score was calculated by adding 1 point for hypertension, COPD, congestive heart failure, functional dependence, and diabetes (score 0-5). SAGE was calculated by adding 1 point for normal gait speed, normal Mini-Cog©, and independent activities of daily living (ADL) (0-3). Spearman rank correlation was used to test the relationship between sFI and SAGE. SAGE components were used as binary-dependent outcomes in covariate-adjusted logistic regression modeling to evaluate associations with sFI scores while adjusting for potential confounders. RESULTS: 334 patients were assessed, with a mean age of 84.0. SAGE and sFI scores were significantly associated, with a modest inverse relationship (r=-0.24, p<0.0001). Each 1-point increase in sFI score was associated with increased odds of ADL deficit (OR 2.3, 95%CI [1.5-3.8], p<0.0001) and abnormal gait speed (OR 1.9, 95%CI 1.2-3.0, p<0.01). The sFI score was not associated with deficits in the Mini-Cog (OR 1.5, 95%CI [0.96-2.3], p=0.07). CONCLUSION: Higher sFI was significantly associated with increased phenotypic frailty, particularly with the loss of physical condition and function but not associated with cognitive deficit. Therefore, sFI may not be an appropriate tool to estimate postoperative complications related to cognition, such as delirium risk.

Use of fluorescence imaging and indocyanine green during colorectal surgery: Results of an intercontinental Delphi survey.

BACKGROUND: Fluorescence imaging with indocyanine green is increasingly being used in colorectal surgery to assess anastomotic perfusion, and to detect sentinel lymph nodes. METHODS: In this 2-round, online, Delphi survey, 35 international experts were asked to vote on 69 statements pertaining to patient preparation and contraindications to fluorescence imaging during colorectal surgery, indications, technical aspects, potential advantages/disadvantages, and effectiveness versus limitations, and training and research. Methodological steps were adopted during survey design to minimize risk of bias. RESULTS: More than 70% consensus was reached on 60 of 69 statements, including moderate-strong consensus regarding fluorescence imaging's value assessing anastomotic perfusion and leak risk, but not on its value mapping sentinel nodes. Similarly, although consensus was reached regarding most technical aspects of its use assessing anastomoses, little consensus was achieved for lymph-node assessments. Evaluating anastomoses, experts agreed that the optimum total indocyanine green dose and timing are 5 to 10 mg and 30 to 60 seconds pre-evaluation, indocyanine green should be dosed milligram/kilogram, lines should be flushed with saline, and indocyanine green can be readministered if bright perfusion is not achieved, although how long surgeons should wait remains unknown. The only consensus achieved for lymph-node assessments was that 2 to 4 injection points are needed. Ninety-six percent and 100% consensus were reached that fluorescence imaging will increase in practice and research over the next decade, respectively. CONCLUSION: Although further research remains necessary, fluorescence imaging appears to have value assessing anastomotic perfusion, but its value for lymph-node mapping remains questionable.

Post-Operative Day Zero Discharge after Laparoscopic Appendectomy Does Not Worsen High-Yield Outcomes: A NSQIP Database Observational Study.

Background: Post-operative day zero (POD-0) discharge after laparoscopic appendectomy for uncomplicated appendicitis has been studied primarily in single-center or pediatric studies. A larger study from a national sample addressing high-yield outcomes can update and supplement current literature and evaluate early discharge rates.Methods: This is a retrospective, observational National Surgical Quality Improvement (NSQIP) database study of laparoscopic appendectomies for uncomplicated appendicitis performed 2016-2019, with discharge POD-0 or post-operative day one (POD-1). Study outcomes included any or serious complication, unplanned readmission, and unplanned return to operating room (OR). Unadjusted outcomes comparisons were estimated via chi-square tests. Multivariate logistic regression models were constructed to adjust for potential confounders (sex, ethnicity, frailty, ASA score, tobacco use and diabetes).Results: A total of 25,629 patients were included in this analysis. More patients were discharged POD-1 (n = 15,229) than POD-0 (n = 10,440). Rate of any or serious complication was lower in patients discharged POD-0 than POD-1 (any complication: 2.0 vs. 2.8, p = 0.0002, serious complication: 1.4 vs. 2.1, p < 0.0001). Unplanned return to OR and unplanned readmission rates were not different between POD-0 and POD-1 discharged groups (p = 0.9 and p = 0.6, respectively). These findings were robust to adjustment for covariates in logistic regression modeling.Conclusions: This study found that unplanned readmission and other outcomes do not appear to be adversely affected by early discharge after laparoscopic appendectomy for uncomplicated appendicitis, confirming prior evidence on the topic in a large, national sample. It also found that early discharge does not appear to be used in most of these patients.

Post-operative day 0 discharge after laparoscopic appendectomy for uncomplicated appendicitis does not increase readmission or return to OR ­ but is it happening in practice?

Short-Term Outcomes for Restorative and Non-Restorative Proctocolectomy in Older Adults.

BACKGROUND: Curative surgery for ulcerative colitis can be subdivided into restorative (with pouch and anastomosis) and non-restorative operations. Restorative surgery in older adults is controversial, due to concerns about surgical risk and long-term functional outcome. The goal of this study is to compare 30-day outcomes for restorative and non-restorative surgery in older adults with ulcerative colitis. METHODS: Data were obtained from the American College of Surgeons National Surgical Quality Initiative Program from 2012-2018. Patients were included if they were >65 years old and had ulcerative colitis. Restorative and non-restorative surgeries were defined with procedure codes. Patient characteristics and adverse surgical outcomes were compared between restorative and non-restorative surgeries utilizing chi-square tests and Fisher's exact tests. Multivariate logistic regression models were constructed to evaluate the association of restorative versus non-restorative surgery with adverse surgical outcomes while adjusting for potential confounders. RESULTS: Of 392 total patients, 95 had restorative and 297 had non-restorative surgery. Patients undergoing restorative surgery, compared to non-restorative surgery, were significantly younger (P<0.01), had lower incidences of steroid usage (P<0.001) and higher rates of readmission (P = 0.02). There were no differences in post-operative complications between the groups in both unadjusted analyses and covariate-adjusted regression analysis (P > 0.05). CONCLUSION: In carefully selected older patients with ulcerative colitis, restorative surgery is associated with increased readmission, but otherwise similar rates of morbidity or mortality compared to non-restorative surgery. Data regarding postoperative functional outcome and quality of life are also needed to help select the most appropriate curative option for older adults.

Telehealth Adaptation for Multidisciplinary Colorectal Cancer Clinic During the COVID-19 Pandemic.

Background The study objectives were to transition in-person colorectal cancer multidisciplinary clinic (MDC) to a telehealth MDC (tele-MDC) format and to assess early outcomes.  Methods A colorectal tele-MDC was devised, in which patients used remote-access technology while supervised by a clinician. The team consisted of surgeons, medical oncologists, radiation oncologists, radiologists, and pathologists. Outcomes were assessed with patient and provider surveys, using a 5-point Likert scale (higher = more favorable). Results A total of 18 patients participated in the tele-MDC. Surveyed patients (n=18) and physicians (n=19) were satisfied with the quality of care (mean Likert = 4.93, 4.53, respectively), and low standard deviations (range 0-1.03) across all questions reflected homogeneity in satisfaction with the metrics surveyed. Conclusions This pilot study demonstrates that a functional colorectal cancer tele-MDC is a feasible alternative to in-person MDC during the coronavirus disease 2019 (COVID-19) pandemic, with the potential for a high degree of patient and physician satisfaction.

Metformin use and the risk of anal intraepithelial neoplasia in type II diabetic patients.

AIM: Emerging evidence has suggested that metformin may be protective against the development of human-papillomavirus-related cancers. Anal intraepithelial neoplasia (AIN) is highly associated with human papillomavirus infection and a precancerous status of anal cancer. The aim of this study was to investigate the relationship between metformin usage and the development of AIN in a large national sample. METHODOLOGY: The IBM MarketScan dataset was used to design a nested case-control study from 2010 to 2017. Patients aged 18-65 years with type 2 diabetes mellitus (DM) were evaluated, and cases of AIN were identified. Four controls were randomly selected in the risk set of each case by using incidence density sampling. The association between metformin usage and AIN was assessed using multivariate logistic regression modelling. RESULTS: A total of 258 patients with type 2 DM were diagnosed with AIN during the study interval, and these were matched to 1032 control patients without a diagnosis of AIN. Patients who developed AIN had 38% lower odds of prior metformin use compared to those without a history of AIN (P < 0.01) and this finding remained robust after adjusting for age, sex, human immunodeficiency virus infection and DM complications (P = 0.02). Patients with AIN had 56% lower odds of long-term metformin use compared to control patients (P = 0.01). CONCLUSIONS: An AIN diagnosis in patients with DM is associated with 56% lower likelihood of prior metformin use. This relationship suggests that metformin could potentially play a protective role against AIN. Prospective studies in non-diabetic patients are warranted to examine these findings further.

Frailty is a stronger predictor than age for postoperative morbidity in Crohn's disease.

BACKGROUND: Patients with Crohn's disease are particularly susceptible to preoperative frailty owing to the chronic nature of the illness and immunosuppressive therapy. The hypothesis in this study was that frailty would have a greater impact on postoperative outcome than age in older individuals with Crohn's disease. METHODS: Data were obtained from the National Surgical Quality Improvement Program (NSQIP) from the years 2012 to 2018. Patients with Crohn's disease who underwent a bowel resection were identified from diagnostic and procedure codes. Frailty was assessed using the 5-point Simplified Frailty Index (0-not frail, 5-most frail). Age was defined as an ordinal variable with 3 age ranges (18-64, 65-79, >80 years). Aggregate morbidity was classified according to the standard NSQIP definitions. Simplified Frailty Index was evaluated as a potential predictor of morbidity and mortality using covariate-adjusted logistic regression modeling. RESULTS: A total of 9,023 patients underwent bowel resection for Crohn's disease during the study period. Patient Simplified Frailty Index ranged from 0 to 3 (Simplified Frailty Index = 0, 82%; 1, 15%; 2, 2.5%; 3, 0.1%), and higher Simplified Frailty Index was associated with increased age (P < .01). In multivariate regression, a Simplified Frailty Index was significantly associated with postoperative morbidity (Simplified Frailty Index ≥ 2: odds ratio = 2.59, 95% confidence interval [1.84-3.63], P < .0001). In contrast, age was not found to be a significant predictor of morbidity when adjusted for Simplified Frailty Index and other covariates (P > .05). CONCLUSION: Frailty is a stronger predictor than age for morbidity in Crohn's-related bowel resection. Functional assessments and vulnerability screening should be used to determine surgical candidacy rather than age alone.

Preoperative functional status is associated with discharge to nonhome in geriatric individuals.

INTRODUCTION: Discharging older individuals to rehabilitation facilities is associated with adverse outcomes, including readmission or increased mortality rate. As preoperative functional status is an important factor impacting patient outcome, we hypothesized that this would be associated with patient disposition to nonhome locations. MATERIALS AND METHODS: A retrospective analysis was performed using data from the 2013-2018 American College of Surgeons National Surgical Quality Improvement Program, including targeted variables from the Geriatric Pilot Project. Patients aged 65 and older in 33 institutions across the nation were included (n = 44,219). Preoperative functional status was categorized as independent, partially dependent, and dependent. The primary outcome was home versus nonhome disposition. Nonhome was defined as rehabilitation facility and nursing home. Descriptive analyses were performed. Variables associated with postoperative discharge to nonhome were identified using logistic regression. RESULTS: The largest percentage of operations was orthopedics (40.8%), followed by general surgery (29.2%) and vascular operations (10.0%). The majority of the patients were independent before operations (93.1% independent, 6% partially dependent, and 0.9% totally dependent). In regression analyses, patients who were partially dependent preoperatively had five times higher odds of discharging to nonhome, compared to patients who were independent (odds ratio [OR] 5.04, p < 0.01). Similarly, patients who were totally dependent had 3.2 higher odds of discharging to nonhome than patients who were independent (OR 3.22, p < 0.01). CONCLUSION: Better preoperative functional status is associated with patient discharge to home in older adults. Preoperative interventions aimed at improving functional status, such as prehabilitation, may be beneficial in improving patient outcomes.

Predictors of underlying carcinoma in patients with suspected acute diverticulitis.

BACKGROUND: A subset of patients who undergo colon resection for suspected diverticulitis will unexpectedly be found to have cancer. We hypothesized that a subset of variables could be used to help predict a diagnosis of cancer preoperatively. METHODS: National Surgical Quality Improvement Program data (2012-2018) were used to identify all patients with a preoperative diagnosis of diverticulitis who had unexpected cancer using postoperative staging data. Key characteristics of the study groups were compared with χ2 tests and multivariate logistic regression modeling. RESULTS: A total of 17,368 patients were identified with an operative indication of acute diverticulitis. Of these, 164 (0.94%) had an unexpected postoperative diagnosis of cancer. Most cancer patients had locally advanced tumors (T1-2: 15%; T3: 39%; T4: 45%), and 37.1% had positive lymph nodes. Rates of margin positivity and inadequate lymph node harvest were 1.2% and 15.9%, respectively. In bivariate analyses, cancer patients had increased age (P < .01), decreased albumin (P < .001), and increased rates of preoperative anemia (P = .01), sepsis (P < .01), and weight loss (>10% in 6 months) (P < .001). The only variables significantly associated with cancer in multivariate regression analysis were sepsis (odds ratio 2.14, 95% confidence interval [1.3-3.6]; P < .01), weight loss (odds ratio 2.31, 95% confidence interval [1.1-4.4]; P = .01), and preoperative albumin level (odds ratio 0.64, 95% confidence [0.45-0.92]; P < .01). CONCLUSION: An unexpected postoperative diagnosis of cancer occurs in a small percentage of patients with suspected diverticulitis. Surgeons should have a high index of suspicion for cancer in patients with sepsis or malnutrition.

Pathologic complete response is associated with decreased morbidity following rectal cancer resection.

BACKGROUND: There are conflicting data regarding the relationship between pathologic complete response (pCR) and post-operative complications following rectal cancer resection. The objective of this study was to compare the rates of morbidity among pCR patients and non-pCR patients and to identify factors that predict pCR morbidity in a large national database. METHODS: This is a retrospective study using American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) targeted proctectomy data (2016-18). Patients with neoadjuvant chemoradiation therapy followed by proctectomy were included, and divided into pCR and non-pCR groups according to final stage. The groups were compared with Student's t-test, Chi-squared or Fisher's exact test. Multivariate logistic regression models were constructed to estimate the association between pCR status and post-operative morbidity while adjusting for key covariates. RESULTS: 244 pCR and 1656 non-pCR patients were included. pCR patients had higher body mass index (28.1 ± 6.2 vs. 29.1 ± 5.9 kg/m2; p = 0.01) and lower pre-operative stage (T stage, p = 0.03; N stage, p < 0.001). The groups were equivalent with respect to surgical approach, type of surgery, and operative time (p > 0.05). Post-operative complications in pCR patients were less frequent than in non-pCR patients (23.0% vs. 29.3%; p = 0.04). This association was robust to adjustment for confounders in logistic regression, as patients with pCR had decreased odds of post-operative morbidity (OR 0.66, CI [0.43, 0.96], p = 0.04). CONCLUSION: pCR is associated with fewer post-operative complications compared to non-pCR, suggesting that pCR is not a marker of severe pelvic fibrosis. This difference may be due to underlying tumor biology, and associated increased technical challenges resecting larger, non-responsive tumors.

Preoperative Nutritional Status Predicts Major Morbidity After Primary Rectal Cancer Resection.

BACKGROUND: Malnutrition has been associated with adverse surgical outcomes, but data regarding its impact specifically in rectal cancer are sparse. The goal of this study was to use national data to determine the effects of malnutrition on surgical outcomes in rectal cancer resection. METHODS: Data were obtained from the American College of Surgeons National Surgical Quality Initiative Program from the years 2012-2015. Patients were included on the basis of International Classification of Disease 9/10 and Current Procedural Terminology codes for rectal cancer and proctectomy. Malnutrition was defined as body mass index <18.5 kg/m2, weight loss >10% in 6 mo, or preoperative albumin <3.5 mg/dL. Associations between malnutrition and postoperative outcomes were assessed by the Student t-test and chi-square test. Multivariate regression models were constructed to adjust for potential confounders of the association between malnutrition and surgical outcomes. RESULTS: Of the 9289 patients with primary rectal cancer who underwent resection, 1425 (15%) were in a state of malnutrition at the time of surgery. Patients with malnutrition had longer mean length of stay (LOS), and higher rates of 30-d mortality, wound infection, organ-space infection, sepsis, reoperation, prolonged LOS (>30 d), failure to wean off ventilator, renal failure, and cardiac arrest. With the exception of LOS, renal failure, and organ-space infection, malnutrition was still significantly associated with higher rates of these adverse outcomes after adjustment for confounders in multivariate regression models. CONCLUSIONS: Malnutrition is a practical marker associated with a variety of adverse outcomes after rectal cancer surgery, and it represents a potential target for nutritional therapies to improve surgical outcomes.

Post-Streptococcal Glomerulonephritis in Two Patients Following Deceased Donor Kidney Transplant.

BACKGROUND Post-streptococcal glomerulonephritis (PSGN) is a well-known cause of renal injury. This disease is caused by a prior infection with specific nephritogenic strains of group A beta-hemolytic streptococcus resulting in formation of immune complexes in the glomeruli. Clinical presentation can range from asymptomatic, microscopic hematuria to the nephritic syndrome which is defined by red to brown urine, nephrotic range proteinuria, edema, hypertension, and acute kidney injury. A few reports have described PSGN in kidney transplant recipients in the post-transplantation period. However, biopsy-proven, donor-derived, PSGN in kidney transplant recipients has not been described. CASE REPORT Kidneys were donated from a 25-year-old Caucasian female with no history of hypertension or diabetes who had anoxic brain death in the setting of sepsis due to group A Streptococcus pyogenes bacteremia. The recipients were a 55-year-old male and a 68-year-old female, both of whom had end stage renal disease (ESRD) secondary to hypertensive nephrosclerosis. The recipients had kidney biopsies, one at the time of implantation and the other on post-operative day (POD) 2. Both biopsies showed streptococcal-associated glomerulonephritis. The prompt recognition and treatment of this disease in the immediate post-operative period resulted in histological resolution of the disease as well as good graft outcomes. CONCLUSIONS Utilizing kidneys from donors with streptococcal bacteremia is possible while maintaining a high degree of suspicion for possible streptococcal-associated glomerulonephritis.

Serum lipid expression correlates with function and regeneration following living donor liver transplantation.

Following living donor liver transplantation (LDLT; and unlike deceased donor liver transplantation [DDLT]), the liver must rapidly regenerate, and sometimes segmental graft dysfunction (SGD) is observed. Hepatic regeneration requires substantial de novo lipid synthesis, and we previously reported that expression of lipid-related genes is dysregulated in LDLT. Here, we compare serum lipid measurements in 41 LDLT recipients and 43 DDLT recipients at baseline and at serial posttransplant time points. In addition, we examined whether serum lipid/apolipoprotein (apo) levels correlate with the degree of liver regeneration (measured using percent volume increase [%VI] at 3 months) or SGD in LDLT recipients. In contrast to DDLT, lipid levels declined early after LDLT but returned to baseline by 30 days. The odds ratio (OR) for achieving robust regeneration (>90 %VI) was 2.53 (95% confidence interval [CI], 1.15-5.52) for every 1 mg/dL increase in serum apoE at 30 days. The OR of SGD for every year increase in donor age was 1.19 (95% CI, 1.02-1.39), and 0.61 for every 1 mg/dL increase in serum high-density lipoprotein cholesterol at 7 days (95% CI, 0.34-1.11). No associations were detected between preoperative serum lipids/apos in LDLT donors and SGD or %VI in recipients. In conclusion, we suggest that initiation of regeneration prevents the liver from participating fully in lipid transport and metabolism. Inability to meet systemic metabolic needs may result in compromised liver function and SGD. Certain serum lipid concentrations correlate with extent of liver regeneration and function.

Mesenchymal Stromal Cell-Derived Factors Promote Tissue Repair in a Small-for-Size Ischemic Liver Model but Do Not Protect against Early Effects of Ischemia and Reperfusion Injury.

UNLABELLED: Loss of liver mass and ischemia/reperfusion injury (IRI) are major contributors to postresectional liver failure and small-for-size syndrome. Mesenchymal stromal cell- (MSC-) secreted factors are described to stimulate regeneration after partial hepatectomy. This study investigates if liver-derived MSC-secreted factors also promote liver regeneration after resection in the presence of IRI. C57BL/6 mice underwent IRI of 70% of their liver mass, alone or combined with 50% partial hepatectomy (PH). Mice were treated with MSC-conditioned medium (MSC-CM) or unconditioned medium (UM) and sacrificed after 6 or 24 hours (IRI group) or after 48 hours (IRI + PH group). Blood and liver tissue were analyzed for tissue injury, hepatocyte proliferation, and gene expression. In the IRI alone model, serum ALT and AST levels, hepatic tissue damage, and inflammatory cytokine gene expression showed no significant differences between both treatment groups. In the IRI + PH model, significant reduction in hepatic tissue damage as well as a significant increase in hepatocyte proliferation was observed after MSC-CM treatment. CONCLUSION: Mesenchymal stromal cell-derived factors promote tissue regeneration of small-for-size livers exposed to ischemic conditions but do not protect against early ischemia and reperfusion injury itself. MSC-derived factors therefore represent a promising treatment strategy for small-for-size syndrome and postresectional liver failure.