Preoperative chemoradiotherapy may improve the radical resection rate for resectable or borderline resectable pancreatic cancer, but the overall benefit is unproven.
In this randomized phase III ...trial in 16 centers, patients with resectable or borderline resectable pancreatic cancer were randomly assigned to receive preoperative chemoradiotherapy, which consisted of 3 courses of gemcitabine, the second combined with 15 × 2.4 Gy radiotherapy, followed by surgery and 4 courses of adjuvant gemcitabine or to immediate surgery and 6 courses of adjuvant gemcitabine. The primary end point was overall survival by intention to treat.
Between April 2013 and July 2017, 246 eligible patients were randomly assigned; 119 were assigned to preoperative chemoradiotherapy and 127 to immediate surgery. Median overall survival by intention to treat was 16.0 months with preoperative chemoradiotherapy and 14.3 months with immediate surgery (hazard ratio, 0.78; 95% CI, 0.58 to 1.05;
= .096). The resection rate was 61% and 72% (
= .058). The R0 resection rate was 71% (51 of 72) in patients who received preoperative chemoradiotherapy and 40% (37 of 92) in patients assigned to immediate surgery (
< .001). Preoperative chemoradiotherapy was associated with significantly better disease-free survival and locoregional failure-free interval as well as with significantly lower rates of pathologic lymph nodes, perineural invasion, and venous invasion. Survival analysis of patients who underwent tumor resection and started adjuvant chemotherapy showed improved survival with preoperative chemoradiotherapy (35.2
19.8 months;
029). The proportion of patients who suffered serious adverse events was 52% versus 41% (
096).
Preoperative chemoradiotherapy for resectable or borderline resectable pancreatic cancer did not show a significant overall survival benefit. Although the outcomes of the secondary end points and predefined subgroup analyses suggest an advantage of the neoadjuvant approach, additional evidence is required.
Wireless continuous vital sign monitoring by wearable devices have recently become available for patients on general wards to promote timely detection of clinical deterioration. Many continuous ...monitoring systems use conventional threshold alarm settings to alert nurses in case of deviating vital signs. However, frequent false alarms often lead to alarm fatigue and inefficiencies in the workplace. The aim of this study was to determine the feasibility of continuous vital sign monitoring without the use of alarms, thereby exclusively relying on interval trend monitoring.
This explanatory sequential mixed methods study was conducted at an abdominal surgical ward of a tertiary teaching hospital. Heart rate and respiratory rate of patients were measured every minute by a wearable sensor. Trends were visualized and assessed six times per day by nurses and once a day by doctors during morning rounds. Instead of using alarms we focused exclusively on regular vital sign trend analysis by nurses and doctors. Primary outcome was feasibility in terms of acceptability by professionals, assessed by the Usefulness, Satisfaction and Ease of Use questionnaire and further explored in two focus groups, as well as fidelity.
A total of 56 patients were monitored and in 80.5% (n = 536) of nurses' work shifts the trends assessments were documented. All deviating trends (n = 17) were recognized in time. Professionals (N = 46) considered continuous monitoring satisfying (4.8±1.0 on a 1-7 Likert-scale) and were willing to use the technology. Although insight into vital sign trends allowed faster anticipation and action upon changed patient status, professionals were neutral about usefulness (4.4±1.0). They found continuous monitoring easy to use (4.7±0.8) and easy to learn (5.3±1.0) but indicated the need for gaining practical experience. Nurses considered the use of alarms for deviating vital signs unnecessary, when trends were regularly assessed and reported.
We demonstrated that continuous vital signs trend monitoring without using alarms was feasible in the general ward setting, thereby avoiding unnecessary alarms and preventing alarm fatigue. When monitoring in a general ward setting, the standard use of alarms may therefore be reconsidered.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The benefit of neoadjuvant chemoradiotherapy in resectable and borderline resectable pancreatic cancer remains controversial. Initial results of the PREOPANC trial failed to demonstrate a ...statistically significant overall survival (OS) benefit. The long-term results are reported.
In this multicenter, phase III trial, patients with resectable and borderline resectable pancreatic cancer were randomly assigned (1:1) to neoadjuvant chemoradiotherapy or upfront surgery in 16 Dutch centers. Neoadjuvant chemoradiotherapy consisted of three cycles of gemcitabine combined with 36 Gy radiotherapy in 15 fractions during the second cycle. After restaging, patients underwent surgery followed by four cycles of adjuvant gemcitabine. Patients in the upfront surgery group underwent surgery followed by six cycles of adjuvant gemcitabine. The primary outcome was OS by intention-to-treat. No safety data were collected beyond the initial report of the trial.
Between April 24, 2013, and July 25, 2017, 246 eligible patients were randomly assigned to neoadjuvant chemoradiotherapy (n = 119) and upfront surgery (n = 127). At a median follow-up of 59 months, the OS was better in the neoadjuvant chemoradiotherapy group than in the upfront surgery group (hazard ratio, 0.73; 95% CI, 0.56 to 0.96;
= .025). Although the difference in median survival was only 1.4 months (15.7 months
14.3 months), the 5-year OS rate was 20.5% (95% CI, 14.2 to 29.8) with neoadjuvant chemoradiotherapy and 6.5% (95% CI, 3.1 to 13.7) with upfront surgery. The effect of neoadjuvant chemoradiotherapy was consistent across the prespecified subgroups, including resectable and borderline resectable pancreatic cancer.
Neoadjuvant gemcitabine-based chemoradiotherapy followed by surgery and adjuvant gemcitabine improves OS compared with upfront surgery and adjuvant gemcitabine in resectable and borderline resectable pancreatic cancer.
Wearable wireless sensors for continuous vital signs monitoring (CVSM) offer the potential for early identification of patient deterioration, especially in low-intensity care settings like general ...wards. This study aims to review advances in wearable CVSM - with a focus on the general ward - highlighting the technological characteristics of CVSM systems, user perspectives and impact on patient outcomes by exploring recent evidence.
The accuracy of wearable sensors measuring vital signs exhibits variability, especially notable in ambulatory patients within hospital settings, and standard validation protocols are lacking. Usability of CMVS systems is critical for nurses and patients, highlighting the need for easy-to-use wearable sensors, and expansion of the number of measured vital signs. Current software systems lack integration with hospital IT infrastructures and workflow automation. Imperative enhancements involve nurse-friendly, less intrusive alarm strategies, and advanced decision support systems. Despite observed reductions in ICU admissions and Rapid Response Team calls, the impact on patient outcomes lacks robust statistical significance.
Widespread implementation of CVSM systems on the general ward and potentially outside the hospital seems inevitable. Despite the theoretical benefits of CVSM systems in improving clinical outcomes, and supporting nursing care by optimizing clinical workflow efficiency, the demonstrated effects in clinical practice are mixed. This review highlights the existing challenges related to data quality, usability, implementation, integration, interpretation, and user perspectives, as well as the need for robust evidence to support their impact on patient outcomes, workflow and cost-effectiveness.
The functional roles of SNPs within the 8q24 gene desert in the cancer phenotype are not yet well understood. Here, we report that CCAT2, a novel long noncoding RNA transcript (lncRNA) encompassing ...the rs6983267 SNP, is highly overexpressed in microsatellite-stable colorectal cancer and promotes tumor growth, metastasis, and chromosomal instability. We demonstrate that MYC, miR-17-5p, and miR-20a are up-regulated by CCAT2 through TCF7L2-mediated transcriptional regulation. We further identify the physical interaction between CCAT2 and TCF7L2 resulting in an enhancement of WNT signaling activity. We show that CCAT2 is itself a WNT downstream target, which suggests the existence of a feedback loop. Finally, we demonstrate that the SNP status affects CCAT2 expression and the risk allele G produces more CCAT2 transcript. Our results support a new mechanism of MYC and WNT regulation by the novel lncRNA CCAT2 in colorectal cancer pathogenesis, and provide an alternative explanation of the SNP-conferred cancer risk.
To describe outcome after pancreatic surgery in the first 6 years of a mandatory nationwide audit.
Within the Dutch Pancreatic Cancer Group, efforts have been made to improve outcome after pancreatic ...surgery. These include collaborative projects, clinical auditing, and implementation of an algorithm for early recognition and management of postoperative complications. However, nationwide changes in outcome over time have not yet been described.
This nationwide cohort study included consecutive patients after pancreatoduodenectomy (PD) and distal pancreatectomy from the mandatory Dutch Pancreatic Cancer Audit (January 2014-December 2019). Patient, tumor, and treatment characteristics were compared between 3 time periods (2014-2015, 2016-2017, and 2018-2019). Short-term surgical outcome was investigated using multilevel multivariable logistic regression analyses. Primary endpoints were failure to rescue (FTR) and in-hospital mortality.
Overall, 5345 patients were included, of whom 4227 after PD and 1118 after distal pancreatectomy. After PD, FTR improved from 13% to 7.4% odds ratio (OR) 0.64, 95% confidence interval (CI) 0.50-0.80, P <0.001 and in-hospital mortality decreased from 4.1% to 2.4% (OR 0.68, 95% CI 0.54-0.86, P =0.001), despite operating on more patients with age >75 years (18%-22%, P =0.006), American Society of Anesthesiologists score ≥3 (19%-31%, P <0.001) and Charlson comorbidity score ≥2 (24%-34%, P <0.001). The rates of textbook outcome (57%-55%, P =0.283) and major complications remained stable (31%-33%, P =0.207), whereas complication-related intensive care admission decreased (13%-9%, P =0.002). After distal pancreatectomy, improvements in FTR from 8.8% to 5.9% (OR 0.65, 95% CI 0.30-1.37, P =0.253) and in-hospital mortality from 1.6% to 1.3% (OR 0.88, 95% CI 0.45-1.72, P =0.711) were not statistically significant.
During the first 6 years of a nationwide audit, in-hospital mortality and FTR after PD improved despite operating on more high-risk patients. Several collaborative efforts may have contributed to these improvements.
OBJECTIVES:To investigate the effect of preoperative chemoradiotherapy on surgical complications in patients after pancreatic resection for (borderline-)resectable pancreatic cancer.
SUMMARY OF ...BACKGROUND DATA:Preoperative chemoradiotherapy is increasingly used in patients with (borderline-)resectable pancreatic cancer. Concerns have been raised about the potential harmful effect of any preoperative therapy on the surgical complication rate after pancreatic resection.
METHODS:An observational analysis was performed within the multicenter randomized controlled PREOPANC trial (April 2013–July 2017). The trial randomly assigned (1:1) patients to preoperative chemoradiotherapy followed by surgery and the remaining adjuvant chemotherapy or to immediate surgery, followed by adjuvant chemotherapy. The main analysis consisted of a per-protocol approach. The endpoints of the present analyses were the rate of postoperative complications.
RESULTS:This study included 246 patients from 16 centers, of whom 66 patients underwent resection after preoperative therapy and 98 patients after immediate surgery. No differences were found regarding major complications (37.9% vs 30.6%, P = 0.400), postpancreatectomy hemorrhage (9.1% vs 5.1%, P = 0.352), delayed gastric emptying (21.2% vs 22.4%, P = 0.930), bile leakage (4.5% vs 3.1%, P = 0.686), intra-abdominal infections (12.1% vs 10.2%, P = 0.800), and mortality (3.0% vs 4.1%, P = 1.000). There was a significant lower incidence of postoperative pancreatic fistula in patients who received preoperative chemoradiotherapy (0% vs 9.2%, P = 0.011).
CONCLUSIONS:Preoperative chemoradiotherapy did not increase the incidence of surgical complications or mortality and reduced the rate of postoperative pancreatic fistula after resection in patients with (borderline-)resectable pancreatic cancer.
To develop a fistula risk score for auditing, to be able to compare postoperative pancreatic fistula (POPF) after pancreatoduodenectomy among hospitals.
For proper comparisons of outcomes in surgical ...audits, case-mix variation should be accounted for.
This study included consecutive patients after pancreatoduodenectomy from the mandatory nationwide Dutch Pancreatic Cancer Audit. Derivation of the score was performed with the data from 2014 to 2018 and validation with 2019 to 2020 data. The primary endpoint of the study was POPF (grade B or C). Multivariable logistic regression analysis was performed for case-mix adjustment of known risk factors.
In the derivation cohort, 3271 patients were included, of whom 479 (14.6%) developed POPF. Male sex odds ratio (OR)=1.34; 95% confidence interval (CI): 1.09-1.66, higher body mass index (OR=1.07; 95% CI: 1.05-1.10), a final diagnosis other than pancreatic ductal adenocarcinoma/pancreatitis (OR=2.41; 95% CI: 1.90-3.06), and a smaller duct diameter (OR=1.43/mm decrease; 95% CI: 1.32-1.55) were independently associated with POPF. Diabetes mellitus (OR=0.73; 95% CI: 0.55-0.98) was independently associated with a decreased risk of POPF. Model discrimination was good with a C -statistic of 0.73 in the derivation cohort and 0.75 in the validation cohort (n=913). Hospitals differed in particular in the proportion of pancreatic ductal adenocarcinoma/pancreatitis patients, ranging from 36.0% to 58.1%. The observed POPF risk per center ranged from 2.9% to 25.4%. The expected POPF rate based on the 5 risk factors ranged from 11.6% to 18.0% among hospitals.
The auditing fistula risk score was successful in case-mix adjustment and enables fair comparisons of POPF rates among hospitals.
Abstract
Background
Emerging evidence indicates that an elevated C-reactive protein-to-albumin ratio (CAR) may be associated with a poor prognosis in pancreatic ductal adenocarcinoma (PDAC). Further ...evidence showing that this ratio has significant prognostic value could contribute to current prediction models and clinical decision-making.
Methods
Data were analysed of consecutive patients who underwent curative pancreatic resection between 2013 and 2018 and were histologically diagnosed with PDAC. We investigated the relation between the ultimate preoperative CAR and overall survival.
Results
A total of 163 patients were analysed. Median overall survival was 18 months (IQR 9–36). Multivariate analysis demonstrated that a higher CAR (HR 1.745,
P
= 0.004), a higher age (HR 1.062,
P
< 0.001), male sex (HR 1.977,
P
= 0.001), poor differentiation grade (HR 2.812,
P
< 0.001), and positive para-aortic lymph node(s) (HR 4.489,
P
< 0.001) were associated with a lower overall survival. Furthermore, a CAR ≥ 0.2 was associated with decreased overall survival (16 vs. 26 months,
P
= 0.003).
Conclusion
We demonstrated that an ultimate preoperative elevated CAR is an independent indicator of decreased overall survival after resection for PDAC. The preoperative CAR may be of additional value to the current prediction models.
To study the feasibility and impact of a nationwide training program in minimally invasive distal pancreatectomy (MIDP).
Superior outcomes of MIDP compared with open distal pancreatectomy have been ...reported. In the Netherlands (2005 to 2013) only 10% of distal pancreatectomies were in a minimally invasive fashion and 85% of surgeons welcomed MIDP training. The feasibility and impact of a nationwide training program is unknown.
From 2014 to 2015, 32 pancreatic surgeons from 17 centers participated in a nationwide training program in MIDP, including detailed technique description, video training, and proctoring on-site. Outcomes of MIDP before training (2005-2013) were compared with outcomes after training (2014-2015).
In total, 201 patients were included; 71 underwent MIDP in 9 years before training versus 130 in 22 months after training (7-fold increase, P < 0.001). The conversion rate (38% n = 27 vs 8% n = 11, P < 0.001) and blood loss were lower after training and more pancreatic adenocarcinomas were resected (7 10% vs 28 22%, P = 0.03), with comparable R0-resection rates (4/7 57% vs 19/28 68%, P = 0.67). Clavien-Dindo score ≥III complications (15 21% vs 19 15%, P = 0.24) and pancreatic fistulas (20 28% vs 41 32%, P = 0.62) were not significantly different. Length of hospital stay was shorter after training (9 7-12 vs 7 5-8 days, P < 0.001). Thirty-day mortality was 3% vs 0% (P = 0.12).
A nationwide MIDP training program was feasible and followed by a steep increase in the use of MIDP, also in patients with pancreatic cancer, and decreased conversion rates. Future studies should determine whether such a training program is applicable in other settings.
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