Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P < 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

Transarterial Chemoembolization Complicated by Deteriorating Hepatic Function

Worsening hepatic function is a well-known potential complication of chemoembolization and occurs in up to 58% of patients undergoing chemoembolization. Although liver function returns to baseline levels within 3–4 weeks in the majority of patients, fulminant liver failure and death occur with a reported frequency of ~2–10%. Poor performance status, portal vein obstruction, biliary obstruction, extensive tumor burden, and Child-Pugh status B or C are among factors predisposing to an increased risk of transient or fulminant hepatic failure, with Child-Pugh status being the most accurate. Unless the patient is a candidate for liver transplantation, treatment for hepatic failure is limited to supportive measures

Rapid dramatic alterations to the tumor microstructure in pancreatic cancer following irreversible electroporation ablation.

AimNanoKnife(®) (Angiodynamics, Inc., NY, USA) or irreversible electroporation (IRE) is a newly available ablation technique to induce the formation of nanoscale pores within the cell membrane in targeted tissues. The purpose of this study was to elucidate morphological alterations following 30 min of IRE ablation in a mouse model of pancreatic cancer.Materials & methodsImmunohistochemistry markers were compared with diffusion-weighted MRI apparent diffusion coefficient measurements before and after IRE ablation.ResultsImmunohistochemistry apoptosis index measurements were significantly higher in IRE-treated tumors than in controls. Rapid tissue alterations after 30 min of IRE ablation procedures (structural and morphological alterations along with significantly elevated apoptosis markers) were consistently observed and well correlated to apparent diffusion coefficient measurements.DiscussionThis imaging assay offers the potential to serve as an in vivo biomarker for noninvasive detection of tumor response following IRE ablation

Assessment and optimization of electroporation-assisted tumoral nanoparticle uptake in a nude mouse model of pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is a particularly lethal form of cancer. In 2012, the incidence of PDAC was 43,920. Five-year survival for patients with PDAC is around 6%, regardless of staging, making PDAC one of the deadliest forms of cancer. One reason for this dismal prognosis is chemoresistance to the current first-line therapy, gemcitabine. There are multiple factors that contribute to the chemoresistance observed in pancreatic cancer. Among them, desmoplasia has been increasingly seen as a significant contributor to chemoresistance. To overcome desmoplastic chemoresistance, several novel methods of treatment have been developed. Electroporation is one such novel treatment. High electrical fields are applied to cells to create pores that increase cell permeability. It has been previously demonstrated that electroporation enhances the therapeutic efficacy of anticancer drugs in pancreatic tumor models. Nanoparticle-based drug delivery systems constitute a second novel method to overcome desmoplastic chemoresistance. Due to their intrinsic design advantages, nanoparticles have been shown to increase the effectiveness of chemotherapeutic agents, while further reducing or even eliminating side effects. To date, there have been no studies evaluating the cumulative effect of combining both nanoparticle and electroporation strategies to overcome chemoresistance in PDAC. Our preliminary studies assessed the in vitro and in vivo uptake of doxorubicin-loaded iron oxide nanoparticles as a function of electroporation voltage and timing of administration in pancreatic adenocarcinoma cells. Our studies demonstrated that addition of electroporation to administration of nanoparticles significantly increased the amount of intracellular iron oxide nanoparticle uptake by a PANC-1 cell line in an athymic nude mouse model of PDAC. Further, electroporation-assisted nanoparticle uptake could be significantly altered by changing the timing of application of electroporation

Quantitative magnetization transfer MRI of desmoplasia in pancreatic ductal adenocarcinoma xenografts.

Quantitative assessment of desmoplasia in pancreatic ductal adenocarcinoma (PDAC) may be critical for staging or prediction of response to therapy. We performed quantitative magnetization transfer (qMT) MRI measurements in 18 mouse xenograft tumors generated from three PDAC cell lines. The qMT parameter bound proton fraction (BPF) was found to be significantly higher in tumors grown using the BxPC-3 cell line (5.31 ± 0.87, mean ± standard deviation) compared with the BPF measured for tumors grown from Panc-1 (3.65 ± 0.60) and Capan-1 (1.50 ± 0.58) cell lines (P < 0.05 for each comparison). Histologic measurements demonstrated a similar trend; BxPC-3 tumors had significantly higher fibrosis levels (percentage of fibrotic tissue area, 6.21 ± 2.10) compared with Panc-1 (2.88 ± 1.13) and Capan-1 (1.69 ± 1.01) tumors. BPF was well correlated with quantitative fibrosis levels (r = 0.77, P < 0.01). Our results indicate that qMT measurements offer the potential to noninvasively quantify fibrosis levels in PDAC mouse xenograft models and thus serve as a valuable in vivo biomarker of desmoplasia in PDAC

Localized Hyperthermia with Iron Oxide-Doped Yttrium Microparticles: Steps toward Image-Guided Thermoradiotherapy in Liver Cancer

Purpose To test whether iron oxide (IO)-containing yttrium aluminosilicate (YAS) microparticles (MPs) can generate localized therapeutic hyperthermia (≥ 43 C) when injected intratumorally in an animal model of liver cancer and whether MP distributions could be visualized with magnetic resonance (MR) imaging. Materials and Methods Twenty-one Sprague-Dawley rats implanted with N1-S1 liver tumors were assigned to alternating magnetic field (AMF) exposure following intratumoral injection with IO-YAS MPs (n = 7), sham surgery (n = 7), or baseline iron quantification (n = 7). Three fiberoptic probes allowed spatial and temporal monitoring of temperatures during 24 minutes of AMF exposure. T2-weighted turbo spin-echo MR imaging was performed within 1 hour after the procedure to detect signal voids caused by IO-YAS deposition. Hematoxylin and eosin-stained pathologic slides were also obtained, and the presence of IO-YAS was evaluated with inductively coupled plasma optical emission spectroscopy. Results Following AMF exposure, intratumoral temperatures after IO-YAS MP injection achieved therapeutic hyperthermia whereas those after sham surgery did not (46.6 C ± 1.3 vs 36.8 C ± 0.4; P \u3c .0001). Within the treated group, the normal hepatic parenchyma (NHP) and rectal temperatures were 37.4 C ± 0.9 and 36.5 C ± 1.0 (P =.0809) at the conclusion of AMF exposure, respectively. A T2-weighted signal void at the tumor site was observed in all seven treated animals, and intratumoral IO-YAS was visualized on subsequent histopathologic examination in each case. The mean ratio of tumor:NHP Fe concentrations attributable to IO-YAS MPs was 108:1. Conclusions AMF exposure of intratumoral IO-YAS MPs generates localized therapeutic hyperthermia in an animal model of liver cancer. MR detectability and potential for combination brachytherapy warrants further investigation for thermoradiotherapy in liver cancer