The aim of this study was to develop an alternative fistula risk score (a-FRS) for postoperative pancreatic fistula (POPF) after pancreatoduodenectomy, without blood loss as a predictor.
Blood loss, ...one of the predictors of the original-FRS, was not a significant factor during 2 recent external validations.
The a-FRS was developed in 2 databases: the Dutch Pancreatic Cancer Audit (18 centers) and the University Hospital Southampton NHS. Primary outcome was grade B/C POPF according to the 2005 International Study Group on Pancreatic Surgery (ISGPS) definition. The score was externally validated in 2 independent databases (University Hospital of Verona and University Hospital of Pennsylvania), using both 2005 and 2016 ISGPS definitions. The a-FRS was also compared with the original-FRS.
For model design, 1924 patients were included of whom 12% developed POPF. Three predictors were strongly associated with POPF: soft pancreatic texture odds ratio (OR) 2.58, 95% confidence interval (95% CI) 1.80-3.69, small pancreatic duct diameter (per mm increase, OR: 0.68, 95% CI: 0.61-0.76), and high body mass index (BMI) (per kg/m increase, OR: 1.07, 95% CI: 1.04-1.11). Discrimination was adequate with an area under curve (AUC) of 0.75 (95% CI: 0.71-0.78) after internal validation, and 0.78 (0.74-0.82) after external validation. The predictive capacity of a-FRS was comparable with the original-FRS, both for the 2005 definition (AUC 0.78 vs 0.75, P = 0.03), and 2016 definition (AUC 0.72 vs 0.70, P = 0.05).
The a-FRS predicts POPF after pancreatoduodenectomy based on 3 easily available variables (pancreatic texture, duct diameter, BMI) without blood loss and pathology, and was successfully validated for both the 2005 and 2016 POPF definition. The online calculator is available at www.pancreascalculator.com.
Pancreatic ductal adenocarcinoma (PDAC) has the worst prognosis of all common cancers. However, divergent outcomes exist between patients, suggesting distinct underlying tumor biology. Here, we ...delineated this heterogeneity, compared interconnectivity between classification systems, and experimentally addressed the tumor biology that drives poor outcome. RNA-sequencing of 90 resected specimens and unsupervised classification revealed four subgroups associated with distinct outcomes. The worst-prognosis subtype was characterized by mesenchymal gene signatures. Comparative (network) analysis showed high interconnectivity with previously identified classification schemes and high robustness of the mesenchymal subtype. From species-specific transcript analysis of matching patient-derived xenografts we constructed dedicated classifiers for experimental models. Detailed assessments of tumor growth in subtyped experimental models revealed that a highly invasive growth pattern of mesenchymal subtype tumor cells is responsible for its poor outcome. Concluding, by developing a classification system tailored to experimental models, we have uncovered subtype-specific biology that should be further explored to improve treatment of a group of PDAC patients that currently has little therapeutic benefit from surgical treatment.
Background
FOLFIRINOX prolongs survival in patients with metastatic pancreatic cancer and may also benefit patients with locally advanced pancreatic cancer (LAPC). Furthermore, it may downstage a ...proportion of LAPC into (borderline) resectable disease, however data are lacking. This review assessed outcomes after FOLFIRINOX-based therapy in LAPC.
Methods
The PubMed, EMBASE and Cochrane library databases were systematically searched for studies published to 31 August 2015. Primary outcome was the (R0) resection rate.
Results
Fourteen studies involving 365 patients with LAPC were included; three studies administered a modified FOLFIRINOX regimen. Of all patients, 57 % (
n
= 208) received radiotherapy. The pooled resection rate was 28 % (
n
= 103, 77 % R0), with a perioperative mortality of 3 % (
n
= 2), and median overall survival ranged from 8.9 to 25.0 months. Survival data after resection were scarce, with only one study reporting a median overall survival of 24.9 months in 28 patients. A complete pathologic response was found in 6 of 85 (7 %) resected specimens. Dose reductions were described in up to 65 % of patients, grade 3–4 toxicity occurred in 23 % (
n
= 51) of patients, and 2 % (
n
= 5) had to discontinue treatment. Data of patients treated solely with FOLFIRINOX, without additional radiotherapy, were available from 292 patients: resection rate was 12 % (
n
= 29, 70 % R0), with 15.7 months median overall survival and 19 % (
n
= 34) grade 3–4 toxicity.
Conclusions
Outcomes after FOLFIRINOX-based therapy in patients with LAPC seem very promising but further prospective studies are needed, especially with regard to survival after resection.
The interest for telemedicine has increased since the COVID-19 pandemic because of the risk of infection. Recently, commercial companies started selling digital USB-otoscopes (DUO) that can be ...connected to a mobile phone. These DUOs are inexpensive (costing approximately $6–35 each) and make it possible to visualize the whole tympanic membrane. Here, we illustrate the case of a patient who had operative correction of a tympanic membrane retraction, and who self-monitored the tympanic membrane in the course of time. Additionally, we discuss the use of DUOs in otolaryngology telemedicine practice. The use of simple digital USB otoscopes provides a promising method to assess and monitor the tympanic membrane remotely. However, more research is needed to establish the role of DUOs in telemedicine.
Pancreatic ductal adenocarcinoma (PDAC) is characterized by abundant stroma that harbors tumor-promoting properties. No good biomarkers exist to monitor the effect of stromal targeting therapies or ...to predict response. We set out to identify such non-invasive markers for PDAC stroma and predict response to therapy. Gene expression datasets, co-culture experiments, xenografts, and patient samples were analyzed. Serum samples were measured from a cohort of 58 resected patients, and 87 metastatic or locally advanced PDAC patients. Baseline and follow-up levels were assessed in 372 additional metastatic PDAC patients who received nab-paclitaxel with gemcitabine (n = 184) or gemcitabine monotherapy (n = 188) in the phase III MPACT trial. Increased levels of ADAM12 were found in PDAC patients compared to healthy controls (p < 0.0001, n = 157 and n = 38). High levels of ADAM12 significantly associated with poor outcome in resected PDAC (HR 2.07, p = 0.04). In the MPACT trial survival was significantly longer for patients who received nab-paclitaxel and had undetectable ADAM12 levels before treatment (OS 12.3 m vs 7.9 m p = 0.0046). Consistently undetectable or decreased ADAM12 levels during treatment significantly associated with longer survival as well (OS 14.4 m and 11.2 m, respectively vs 8.3, p = 0.0054). We conclude that ADAM12 is a blood-borne proxy for stromal activation, the levels of which have prognostic significance and correlate with treatment benefit.
•High instrumented sedentary behaviour (i-SB) and low instrumented physical activity (i-PA) are associated with a higher mortality risk.•Adjustments for relatively higher or lower levels of i-PA for ...i-SB or i-PA, respectively, attenuated these associations.•The highest mortality risk for i-PA was found for total i-PA, suggesting all physical activity levels contribute to lowering mortality risk.
Sedentary behaviour (SB) and physical activity (PA) can be objectively assessed with inertial sensors to describe bodily movement. Higher SB and lower PA is associated with higher chronological age and negative health outcomes. This study aimed to quantify the association between instrumented measures of SB (i-SB) and PA (i-PA) and mortality in community-dwelling older adults, to subsequently compare the quantitative effect sizes and to determine the dose-response relationships.
An electronic search in six databases from inception to 27th of June 2019 was conducted. All articles reporting on i-SB or i-PA and mortality in community-dwelling older adults aged 60 years or older were considered eligible. A meta-analysis was conducted for the association between i-SB and i-PA and mortality expressed in Hazard Ratios (HR) and 95% Confidence Intervals (95% CI). A meta-regression analysis was performed to determine the dose-response relationship between i-SB and steps per day and mortality.
Twelve prospective articles representing eleven cohorts, reporting data of 38,141 participants were included. In total 2502 (6.4%) participants died during follow-up (2.0 to 9.8 years). Comparing the most sedentary with the least sedentary groups of participants resulted in a pooled HR of 2.44 (95% CI 1.82–3.25). Comparing the least active with the most active groups of participants resulted in a pooled HR of 1.93 (95% CI 1.39-2.69); 2.66 (95% CI 2.11–3.35); 3.43 (95% CI 2.61–4.52), and 3.09 (95% CI 2.33–4.11) for light, moderate-to-vigorous-, total PA and steps per day, respectively. Meta-regression analyses showed clear dose-response relationships between i-SB and steps per day and mortality risk.
Both i-SB and i-PA are significantly associated with mortality in community-dwelling older adults, showing the largest effect size for total physical activity. Dose-response relationships could be observed for i-SB and steps per day.
Background
Restaging of locally advanced pancreatic cancer (LAPC) after induction chemotherapy using contrast-enhanced computed tomography (CE-CT) imaging is imprecise in evaluating local tumor ...response. This study explored the value of 3 Tesla (3 T) contrast-enhanced (CE) and diffusion-weighted (DWI) magnetic resonance imaging (MRI) for local tumor restaging.
Methods
This is a prospective pilot study including 20 consecutive patients with LAPC with RECIST non-progressive disease on CE-CT after induction chemotherapy. Restaging CE-CT, CE-MRI, and DWI-MRI were retrospectively evaluated by two abdominal radiologists in consensus, scoring tumor size and vascular involvement. A halo sign was defined as replacement of solid perivascular (arterial and venous) tumor tissue by a zone of fatty-like signal intensity.
Results
Adequate MRI was obtained in 19 patients with LAPC after induction chemotherapy. Tumor diameter was non-significantly smaller on CE-MRI compared to CE-CT (26 mm vs. 30 mm;
p
= 0.073). An MRI-halo sign was seen on CE-MRI in 52.6% (
n
= 10/19), whereas a CT-halo sign was seen in 10.5% (
n
= 2/19) of patients (
p
= 0.016). An MRI-halo sign was not associated with resection rate (60.0% vs. 62.5%;
p
= 1.000). In the resection cohort, patients with an MRI-halo sign had a non-significant increased R0 resection rate as compared to patients without an MRI-halo sign (66.7% vs. 20.0%;
p
= 0.242). Positive and negative predictive values of the CE-MRI-halo sign for R0 resection were 66.7% and 66.7%, respectively.
Conclusions
3 T CE-MRI and the MRI-halo sign might be helpful to assess the effect of induction chemotherapy in patients with LAPC, but its diagnostic accuracy has to be evaluated in larger series.
Background
There is an increasing demand for structured objective ex vivo training and assessment of laparoscopic psychomotor skills prior to implementation of these skills in practice. The aim of ...this study was to establish the internal validity of the TrEndo, a motion-tracking device, for implementation on a laparoscopic box trainer.
Methods
Face validity and content validity were addressed through a structured questionnaire. To assess construct validity, participants were divided into an expert group and a novice group and performed two basic laparoscopic tasks. The TrEndo recorded five motion analysis parameters (MAPs) and time.
Results
Participants demonstrated a high regard for face and content validity. All recorded MAPs differed significantly between experts and novices after performing a square knot. Overall, the TrEndo correctly assigned group membership in 84.7 and 95.7% of cases based on two laparoscopic tasks.
Conclusion
Face, content, and construct validities of the TrEndo were established. The TrEndo holds real potential as a (home) training device.
Abstract
Objective.
Subfertility has been reported as a long-term complication of unrecognized and/or untreated coeliac disease (CD); however, the results from studies on this topic are ambiguous. We ...aimed to determine the prevalence of unrecognized CD in subfertile male-female couples visiting a fertility clinic compared with the general population.
Methods.
Subjects included 1038 male-female couples (n = 2076) who visited the fertility clinic of the Leiden University Medical Center in the Netherlands between 2003 and 2009. All consecutive patients were routinely, serologically screened, and those with positive test results for antibodies against IgA anti-tissue transglutaminase type 2 and IgA endomysial antibodies were considered to have unrecognized CD. Clinical data on gender, age, height, weight, diagnosis of subfertility, and previously diagnosed CD were collected from the clinical files. Subsequently, after serological screening, all patients were anonymized. The prevalence of unrecognized CD was compared with the one in the general adult population in the Netherlands (0.35%).
Results.
The prevalence of unrecognized CD in subfertile male-female couples was 0.48% (10/2076; 6 females and 4 males) and was not significantly more frequent compared with the general population. Compared with the control group, similar CD prevalences were found within the different subfertility categories separately: unexplained subfertility, anovulation, tubal pathology, and male factor (p = NS).
Conclusion.
In our large study cohort of subfertile male-female couples, the prevalence of unrecognized CD is comparable to the general population in the Netherlands. No association was observed between CD and subfertility in the different subfertility categories and genders.
Determining the resectability of locally advanced pancreatic cancer (LAPC) after FOLFIRINOX chemotherapy is challenging because CT-scans cannot reliably assess vascular involvement. This study ...evaluates the added value of intra-operative ultrasound (IOUS) in LAPC following FOLFIRINOX induction chemotherapy.
Prospective multicenter study in patients with LAPC who underwent explorative laparotomy with IOUS after FOLFIRINOX chemotherapy. Resectability was defined according to the National Comprehensive Cancer Network guidelines. IOUS findings were compared with preoperative CT-scans and pathology results.
CT-staging in 38 patients with LAPC after FOLFIRINOX chemotherapy defined 22 patients LAPC, 15 borderline resectable and one resectable. IOUS defined 19 patients LAPC, 13 borderline resectable and six resectable. In 12/38 patients, IOUS changed the resectability status including five patients from borderline resectable to resectable and five patients from LAPC to borderline resectable. Two patients were upstaged from borderline resectable to LAPC. Tumor diameters were significantly smaller upon IOUS (31.7 ± 9.5 mm versus 37.1 ± 10.0 mm, p = 0.001) and resectability varied significantly (p = 0.043). Ultimately, 20 patients underwent resection of whom 14 were evaluated as (borderline) resectable on CT-scan, and 17 on IOUS.
This prospective study demonstrates that IOUS may change the resectability status up to a third of patients with LAPC following FOLFIRINOX chemotherapy.
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