Background
Failure to rescue (FTR) patients with postoperative complications contribute to a significant proportion of postoperative mortality. Our main objective was to determine the risk factors ...for FTR among patients undergoing pancreaticoduodenectomy who suffered a life-threatening complication requiring intensive care unit (ICU) management.
Materials and Methods
Consecutive patients undergoing pancreaticoduodenectomy from 2011 to 2020 were reviewed retrospectively. Causes of organ failure were described as the one that most commonly contributed to patient’s transfer to ICU or death. Two groups were created based on whether patients had FTR and risk factors for FTR were compared. The impact of baseline characteristics, operative characteristics, and risk scoring on FTR was analyzed using multiple logistic regression.
Results
There were 19/58 (33%) FTR patients. Baseline, operative characteristics, postoperative complications, and length of hospital and ICU stay were similar between groups. However, a higher proportion of FTR patients experienced a postoperative pancreatic fistula (POPF) (16% vs 2.6%, P = .062). Among patients who experienced a POPF, the FTR group had a trend in delayed time from diagnosis to treatment (7 vs 23 hours, P=.131). Renal complications (OR 6.12, 95% CI, 1.23 to 38.43, P = .035) and time from POPF diagnosis to treatment (OR 1.05, 95% CI, 1.00 to 1.11, P = .036) were independent predictors of FTR by multivariable analysis.
Conclusion
The occurrence of certain postoperative complications such as renal complications as well as delayed timing of the management of POPF is predictive of FTR following pancreaticoduodenectomy, especially as delayed timing to treatment is a risk factor for FTR.
Frailty is a clinically recognizable state of decreased reserve and function across physiologic systems, characterized by an inability to cope with acute stressors. A validated modified frailty index ...(mFI) was used to evaluate the impact of frailty on postoperative complications following pancreaticoduodenectomy.
Data from consecutive patients undergoing pancreaticoduodenectomy from 2011 to 2020 were collected retrospectively at a high-volume tertiary care hepatopancreatobiliary hospital. Based on an 11-item mFI, patients were grouped by high (≥0.27) and low mFI. The main outcome was postoperative complications (Clavien-Dindo classification). The impact of frailty on complications was analyzed by evaluating baseline and operative characteristics using multivariable logistic regression. Secondary outcomes included postoperative mortality, length of hospital stay, and intensive care unit (ICU) admission, which were analyzed using univariable logistic regression.
There were 64/554 patients (12%) with high mFI. Low and high mFI had similar characteristics, including proportion of pancreatic adenocarcinoma (low mFI = 247/490 50% vs. high mFI = 31/64 48%, p = 0.767), intermediate or hard pancreatic texture (low mFI = 75/191 39% vs. high mFI = 6/19 32%, p = 0.512), operative room time (low mFI = 370 min vs. high mFI = 368 min, p = 0.630), and drain placement (low mFI = 355/490 72% vs. high mFI = 48/64 75%, p = 0.642). The mFI score was an independent predictor for the development of any type of postoperative complications (OR 1.44, 95% CI 1.02-2.10) and major postoperative complications (OR 1.44, 95% CI 1.05-1.98) by multivariable analysis. High mFI patients had a higher 90-day mortality rate (high mFI = 7/64 11% vs. low mFI = 20/490 4.1%, p = 0.017), a longer median length of hospital stay (high mFI = 11 days vs. low mFI = 8 days, p = 0.016), and a higher rate of ICU admission (high mFI = 47/64 73% vs. low mFI = 211/490 43%, p < 0.001).
Among patients who are considered surgical candidates, the mFI can identify those at high risk of developing postoperative complications. This tool can be used to accurately discuss postoperative risk with patients undergoing pancreaticoduodenectomy.
Background
Liver resection is commonly performed among patients at risk of being frail. Frailty can be used to assess perioperative risk. Thus, we evaluated frailty as a predictor of postoperative ...complications following liver resection using a validated modified frailty index (mFI).
Methods
A retrospective cohort of consecutive patients undergoing liver resection (2011-2018) were stratified according to the mFI and classified as the following: high (≥.27) and low mFI (<.27). The effect of mFI on postoperative complications (Clavien-Dindo) was evaluated using multiple logistic regression, expressed as odds ratios (OR) and 95% CI.
Results
Of 409 patients, 58 (14%) had high mFI. There were no differences in type of liver resection (laparoscopic: 57% vs 55%, P = .766), number of segments resected (3 vs 4, P = .417), or operative time (257 vs 293 minutes, P = .097) between the high and low mFI groups, respectively. High mFI patients had a longer median length of hospital stay (9.5 vs 5 days, P < .001) and higher proportion of postoperative complications (79% vs 46%, P < .001), including minor complications (69% vs 42%, P < .001), major complications (50% vs 13%, P < .001), and 90-day postoperative mortality (12% vs 3.4%, P = .04). On multivariable analysis, longer operating time (OR 1.15, 95% CI, 1.03 to 1.27), higher number of segments resected (OR 1.43, 95% CI, 1.12 to 1.82), and high mFI (OR 6.74, 95% CI, 2.76 to 16.51) were independent predictors of major postoperative complications.
Discussion
mFI predicts postoperative outcomes following liver resection and can be used as a risk stratification tool for patients being considered for surgery.
Background
Perioperative carbohydrate loading, increased protein intake, and immunonutrition may decrease postoperative complications. Studies on the topic have led to controversial results.
Methods
...We searched Medline, EMBASE, and CENTRAL up to August 2018 for randomized trials comparing the effect of perioperative nutritional supplements (intervention) versus control on postoperative complications in patients undergoing gastrointestinal cancer surgery. Secondary outcomes included infectious complications and length of hospital stay (LOS). Random effects model was used to estimate the pooled risk ratio (RR) of treatment effects. Pooled mean difference (MD) was used to compare LOS. Heterogeneity was assessed using
I
2
. Sources of heterogeneity were explored through subgroup analysis by nutritional supplementation protocol, type of surgery, and type of nutritional supplement. Risk of bias and quality of the evidence were assessed.
Results
Of 3951 articles, we identified 56 trials (
n
= 6370). Perioperative nutrition was associated with a lower risk of postoperative complications (RR 0.74, 95% confidence interval (CI) 0.69–0.80); postoperative infections (RR 0.71, 95% CI 0.64–0.79,
n
= 4582); and postoperative non-infectious complications (RR 0.79, 95% CI 0.71–0.87,
n
= 4883). There were no significant heterogeneity outcomes analyzed (
I
2
= 14%, 1%, and 7%, respectively). LOS was shorter for the intervention group, MD − 1.58 days; 95% CI − 1.83 to − 1.32;
I
2
= 89%). Subgroup analysis did not identify sources of heterogeneity. The quality of evidence for postoperative complications was high and for LOS was moderate.
Conclusion
Perioperative nutritional optimization decreases the risk of postoperative infectious and non-infectious complications. It also decreases LOS in patients undergoing gastrointestinal cancer surgery, but these findings should be taken with caution given the high heterogeneity.
Extended venous thromboembolism prophylaxis after abdominopelvic cancer surgery has not been widely adopted. We compared outcomes of patients pre- and postimplementation of extended venous ...thromboembolism prophylaxis with low molecular weight heparin.
Prospectively collected data from a quality initiative project aimed at prescribing extended venous thromboembolism prophylaxis after abdominopelvic cancer surgery was compared with previously published data from a prospective cohort without extended venous thromboembolism prophylaxis. The primary outcome was 6-month postoperative symptomatic venous thromboembolism incidence. Secondary outcomes: differences in 1- and 3-month venous thromboembolism incidence and factors associated with venous thromboembolism using Cox-proportional hazard models. Cumulative incidence of venous thromboembolism was estimated using Kaplan-Meier methods and expressed as proportions with 95% confidence interval.
There were 241 patients in the venous thromboembolism-prophylaxis cohort and 284 patients in the no venous thromboembolism prophylaxis cohort. Patients in the venous thromboembolism-prophylaxis cohort were more likely to be female (69% vs 60%, P = .018), have metastatic disease (49% vs 29%, P < .001), have longer operative times (236 min vs 197 min, P < .001), and to receive neoadjuvant chemotherapy (27% vs 23%, P = .006). Respectively, the 1- (0.5% 95% confidence interval, 0.1–2.5 vs 0.4% 95% confidence interval, 0.1–2.5), 3- (2.6% 95% confidence interval, 1.2–5.6 vs 2.5% 95% confidence interval, 1.2–5.2), and 6-month (7.5% 95% confidence interval, 4.8–11.5 vs 7.2% 95% confidence interval, 4.7–11.0) venous thromboembolism incidence were similar. By multivariable analysis, history of venous thromboembolism (hazard ratio 3.52; 95% confidence interval, 1.03–12.05; P = .045) and longer duration of hospital stay (hazard ratio 1.07; 95% confidence interval, 1.01–1.12; P = .016) demonstrated increased risk of venous thromboembolism.
This study failed to demonstrate a decreased 1-, 3-, and 6-month postoperative venous thromboembolism incidence after the implementation of extended venous thromboembolism prophylaxis.
Despite initial responses to first-line treatment with platinum and taxane-based combination chemotherapy, most high-grade serous ovarian carcinoma (HGSOC) patients will relapse and eventually ...develop a cisplatin-resistant fatal disease. Due to the lethality of this disease, there is an urgent need to develop improved targeted therapies against HGSOC. Herein, we identified CASC10, a long noncoding RNA upregulated in cisplatin-resistant ovarian cancer cells and ovarian cancer patients. We performed RNA sequencing (RNA-seq) in total RNA isolated from the HGSOC cell lines OVCAR3 and OV-90 and their cisplatin-resistant counterparts. Thousands of RNA transcripts were differentially abundant in cisplatin-sensitive vs. cisplatin-resistant HGSOC cells. Further data filtering unveiled CASC10 as one of the top RNA transcripts significantly increased in cisplatin-resistant compared with cisplatin-sensitive cells. Thus, we focused our studies on CASC10, a gene not previously studied in ovarian cancer. SiRNA-mediated CASC10 knockdown significantly reduced cell proliferation and invasion; and sensitized cells to cisplatin treatment. SiRNA-mediated CASC10 knockdown also induced apoptosis, cell cycle arrest, and altered the expression of several CASC10 downstream effectors. Multiple injections of liposomal CASC10-siRNA reduced tumor growth and metastasis in an ovarian cancer mouse model. Our results demonstrated that CASC10 levels mediate the susceptibility of HGSOC cells to cisplatin treatment. Thus, combining siRNA-mediated CASC10 knockdown with cisplatin may represent a plausible therapeutic strategy against HGSOC.
Perioperative nutritional supplementation may improve outcomes. Trials have not investigated the role of combination strategy using different types of nutritional supplements.
We conducted a ...single-site randomized pilot trial, among gastrointestinal cancer patients undergoing surgery, comparing perioperative nutritional supplements versus placebo (1 placebo to each supplement), to determine feasibility of a larger trial. Intervention, administered in sequence, included: protein supplementation (preoperative day 30–6), protein supplementation rich in arginine and omega-6 (preoperative day 5–1, and postoperative day 1–5), and carbohydrate loading (surgery day). Primary outcome was enrollment. Secondary outcomes included participant compliance with study supplements (target ≥70% of total packets). We planned protocol modifications to improve enrollment and compliance. Postoperative complications were described.
Over 18 months, 495 patients were screened, 144 were deemed eligible, and 71 consented to participate, resulting in an enrollment fraction of 71/144 (49%, 95% confidence interval: 41%–57%). ‘Too much burden’ was the most common reason for refusal to participate (34%). Participants’ median overall compliance with study packets was 80%. Protocol modifications (decreasing the interval from enrollment to surgery from 4 to 2 weeks and decreasing length of baseline assessment) did not impact enrollment or compliance. Postoperative complications were similar between control (18/31 58%, 95% confidence interval: 4–74), and intervention (22/34 65%, 95% confidence interval: 48–79) arms, with a higher proportion of infectious complications in the control arm (16/31, 52% vs 12/34, 35%).
Results from this pilot suggest a larger phase III trial is feasible. Postoperative infectious complications were common, making this a suitable outcome of interest.
Background
Up to two thirds of patients presenting for abdominal cancer surgery are malnourished pre‐operatively. Perioperative nutritional supplementation has been proposed to improve surgical ...outcomes, though its effect on quality of life (QoL) is not yet understood.
Methods
A randomized controlled feasibility trial for perioperative nutrition among patients undergoing major abdominal cancer surgery was conducted. Participants in the intervention group received supplements for 30 days before surgery. Participants completed two QoL questionnaires (EORTC‐QLQ‐C‐30 and FACT‐G) at baseline, then 4 and 12 weeks postoperatively. Participants were compared between and within groups at baseline, Weeks 4, and 12 using t tests. Minimal clinically important differences (MCIDs) were considered as a 10‐point worsening from baseline.
Results
Sixty‐six participants were available for analysis in this study, including 33 in the intervention and 30 in the control arms. Baseline demographics were balanced between groups except for different rates of pancreas cancer (36% intervention vs. 9% control) and colorectal cancer (19% intervention vs. 34% control). At baseline, participants in the intervention group had lower overall QoL (59% vs. 77%, p = 0.01), role functioning (72% vs 88%, p = 0.045), and cognitive functioning (79% vs 90%, p = 0.047). Following surgery, role and physical functioning worsened in the control group, without significant differences between groups. Role functioning was persistently worsened at 12 weeks in the control group. The rates of MCIDs were similar between both intervention and control groups.
Discussion
Perioperative nutrition was associated with preservation of QoL in the postoperative period following major abdominal cancer surgery compared to placebo.
Summary
Among patients undergoing surgery for cancer, the majority present at high risk for malnutrition. In this placebo‐controlled randomized trial among patients undergoing major abdominal surgery for cancer, preoperative nutrition supplementation was associated with the preservation of QoL in the postoperative period.
Metastasis and drug resistance are major contributors to cancer-related fatalities worldwide. In ovarian cancer (OC), a staggering 70% develop resistance to the front-line therapy, cisplatin. Despite ...proposed mechanisms, the molecular events driving cisplatin resistance remain unclear. Dysregulated microRNAs (miRNAs) play a role in OC initiation, progression, and chemoresistance, yet few studies have compared miRNA expression in OC samples and cell lines. This study aimed to identify key miRNAs involved in the cisplatin resistance of high-grade-serous-ovarian-cancer (HGSOC), the most common gynecological malignancy. MiRNA expression profiles were conducted on RNA isolated from formalin-fixed-paraffin-embedded human ovarian tumor samples and HGSOC cell lines. Nine miRNAs were identified in both sample types. Targeting these with oligonucleotide miRNA inhibitors (OMIs) reduced proliferation by more than 50% for miR-203a, miR-96-5p, miR-10a-5p, miR-141-3p, miR-200c-3p, miR-182-5p, miR-183-5p, and miR-1206. OMIs significantly reduced migration for miR-183-5p, miR-203a, miR-296-5p, and miR-1206. Molecular pathway analysis revealed that the nine miRNAs regulate pathways associated with proliferation, invasion, and chemoresistance through PTEN, ZEB1, FOXO1, and SNAI2. High expression of miR-1206, miR-10a-5p, miR-141-3p, and miR-96-5p correlated with poor prognosis in OC patients according to the KM plotter database. These nine miRNAs could be used as targets for therapy and as markers of cisplatin response.
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