Reduction in Delayed Gastric Emptying Following Non-Pylorus Preserving Pancreaticoduodenectomy by Addition of a Braun Enteroenterostomy

Context Delayed gastric emptying is a major cause of morbidity following pancreaticoduodenectomy. Objective The impact of a Braun enteroenterostomy on delayed gastric emptying, used in reconstruction following classic pancreaticoduodenectomy, was assessed. Patients Forty-four consecutive patients undergoing non-pylorus preserving pancreaticoduodenectomy from 2009 to 2011 by a single surgeon were included in this study. Interventions The first 20 patients had a standard antecolic gastroenterostomy and the subsequent 24 had the addition of a Braun enteroenterostomy. Results Patient characteristics, the extent of surgery, surgical findings and tumor characteristics were similar between the two groups. The delayed gastric emptying rate in the Braun enteroenterostomy (1/24, 4.2%) was significantly lower (P=0.008) than the standard reconstruction group (7/20, 35.0%). In the standard group, 6 of 7 cases (85.7%) of delayed gastric emptying were class C in nature. After exclusion of 8 total pancreatectomy patients, the pancreatic fistula rate in the Braun enteroenterostomy group (4/19, 21.1%) was similar (0.706) to the standard reconstruction group (5/17, 29.4%) as was the median length of hospital stay (10 days vs. 15 days; P=0.291). Braun enteroenterostomy technique was the only significant independent factor associated with reduced delayed gastric emptying with an odds ratio of 0.08 (95% confidence interval: 0.01-0.73; P=0.025). Conclusion The use of Braun enteroenterostomy following non-pylorus preserving pancreaticoduodenectomy appears to result in a significant reduction in delayed gastric emptying.Image: Reconstruction with the addition of Braun enteroenterostomy

Induction of Th1Immune responses following laser ablation in a murine model of colorectal liver metastases

<p>Abstract</p> <p>Background</p> <p>Preliminary experimental studies have suggested that the in situ destruction of tumor tissue by local laser ablation (LA) may also stimulate host immunity against cancer. We investigated local and systemic induction of immune responses after laser ablation in the setting of residual tumor.</p> <p>Methods</p> <p>A murine colorectal cancer (CRC) liver metastasis model was used. Selected tumors of liver CRC bearing mice and livers of mice without tumor induction were treated with LA. Liver and tumor tissues from the ablation sites and from distant sites were collected at various time points following LA and changes in CD3+ T cells and Kupffer cells (F4/80 marker) infiltration and the expression of interferon gamma (IFNγ) were investigated by immunohistochemistry and ELISpot. Base line levels of CD3+ T cells and Kupffer cells were established in untreated mice.</p> <p>Results</p> <p>The presence of tumor induced significant accumulation of CD3+ T cells and Kupffer cells at the tumor-host interface, within the tumor vascular lakes and increased their baseline concentration within the liver parenchyma. LA of the <it>liver </it>induced accumulation of CD3+ T-cells and Kupffer cells at the site of injury and systemic induction of immune responses as discerned by the presence of IFNγ secreting splenocytes. LA of liver <it>tumors </it>induced significant increase of CD3+ T-cells at site of injury, within normal liver parenchyma, and the tumor-host interface of both ablated and distant tumors. In contrast Kupffer cells only accumulated in ablated tumors and the liver parenchyma but not in distant tumors. IFNγ expression increased significantly in ablated tumors and showed an increasing trend in distant tumors.</p> <p>Conclusion</p> <p>Laser ablation in addition to local tumor destruction induces local and systemic Th1 type immune responses which may play a significant role in inhibiting tumor recurrence from residual micrometastases or circulating tumor cells.</p

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 &lt; 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

The effect of hyperbaric oxygen on apoptosis and proliferation in severe acute pancreatitis

AbstractObjectivesThis paper investigates the significance of apoptosis in severe acute pancreatitis (SAP) and the possible modulating effects of hyperbaric oxygen (HBO).MethodsWistar rats (250–350g) were induced with SAP by biliopancreatic infusion of 4% sodium taurocholate. Rats were randomized for HBO treatment. Pancreatic tissue was stained for apoptosis with immunohistochemistry (anti-CASPASE-3 antibody and TUNEL), and histopathology haematoxylin and eosin (H&E). Acini were stained for proliferation with an anti-KI67 antibody. ImageProPlus was used to quantify apoptosis and proliferation in acinar cells. Statistical analysis was performed with two-independent-sample t-test or non-parametric Mann–Whitney test.ResultsIn normal acini there is a low rate of apoptosis (0.165 ± 0.157%, 0.181 ± 0.168%, 0.130 ± 0.298% in CASPASE-3, H&E and TUNEL, respectively) and proliferation (0.951 ± 0.926%) (mean ± standard deviation [SD]). When compared with normal, apoptosis (CASPASE-3: 1.28 ± 1.12%, P= 0.008; 2.40 ± 3.04%, P= 0.101; 1.23 ± 0.87%, P= 0.091; H&E: 0.47 ± 0.36%, P= 0.051; 0.69 ± 0.63%, P= 0.001; 0.68 ± 0.28%, P= 0; TUNEL: 1.08 ± 1.42%, P= 0; 1.96 ± 1.87%, P= 0; 2.36 ± 2.26%, P= 0) and proliferation (1.96 ± 1.89%, P= 0.187; 1.73 ± 1.76%, P= 0.165; 1.36 ± 1.40%, P= 0.571) were increased on days 1, 2 and 3 post-induction, respectively. In comparison with the untreated controls, HBO increased apoptosis on day 1 (CASPASE-3: 3.11 ± 1.97%, P= 0.04; H&E: 0.97 ± 0.76%, P= 0.005) and day 2 (TUNEL: 3.61 ± 3.05%, P= 0.034). Treatment with HBO increased proliferation (3.04 ± 3.14%, P= 0.519; 7.33 ± 7.55%, P= 0.153) on days 2 and 3, respectively, compared with the untreated controls.ConclusionsDuring SAP, acini apoptosis and proliferation were increased. Hyperbaric oxygen therapy may improve the condition of SAP by promoting apoptosis and proliferation

Public health patient experience of elective surgery waiting lists

The objective of this scoping review is to explore and understand the patient experience of waiting for elective surgery in public hospitals and identify any existing frameworks or interventions that have been implemented to support patients while they are waiting for elective surgery

Treatment with the vascular disruptive agent OXi4503 induces an immediate and widespread epithelial to mesenchymal transition in the surviving tumor

Epithelial to mesenchymal transition (EMT) is considered an important mechanism in tumor resistance to drug treatments; however, in vivo observation of this process has been limited. In this study we demonstrated an immediate and widespread EMT involving all surviving tumor cells following treatment of a mouse model of colorectal liver metastases with the vascular disruptive agent OXi4503. EMT was characterized by significant downregulation of E-cadherin, relocation and nuclear accumulation of b-catenin as well as significant upregulation of ZEB1 and vimentin. Concomitantly, significant temporal upregulation in hypoxia and the pro-angiogenic growth factors hypoxia-inducible factor 1-alpha, hepatocyte growth factor, vascular endothelial growth factor and transforming growth factor-beta were seen within the surviving tumor. The process of EMT was transient and by 5 days after treatment tumor cell reversion to epithelial morphology was evident. This reversal, termed mesenchymal to epithelial transition (MET) is a process implicated in the development of new metastases but has not been observed in vivo histologically. Similar EMT changes were observed in response to other antitumor treatments including chemotherapy, thermal ablation, and antiangiogenic treatments in our mouse colorectal metastasis model and in a murine orthotopic breast cancer model after OXi4503 treatment. These results suggest that EMT may be an early mechanism adopted by tumors in response to injury and hypoxic stress, such that inhibition of EMT in combination with other therapies could play a significant role in future cancer therapy

Renin–Angiotensin Inhibitor, Captopril, Attenuates Growth of Patient-Derived Colorectal Liver Metastasis Organoids

The recurrence of colorectal liver metastasis (CRLM) following liver resection is common; approximately 40% of patients will experience tumor recurrence post-surgery. Renin–angiotensin inhibitors (RASis) have been shown to attenuate the growth and progression of CRLM in pre-clinical models following liver resection. This study examined the efficacy of the RASi captopril on patient-derived colorectal liver metastasis organoids. Patient-derived organoids (PDOs) were established using fresh samples of colorectal liver metastasis from appropriately consented patients undergoing liver resection. To mimic the regenerating liver post-CRLM liver resection, PDOs were cultured under hepatocyte regeneration conditions in vitro. CRLM PDOs were established from three patients’ parent tissue. CRLM PDOs and parent tissue expressed markers of colorectal cancer, CDX2 and CK20, consistently. Furthermore, CRLM PDOs treated with captopril showed a dose dependent reduction in their expansion in vitro. In conclusion, CRLM PDOs recapitulate in vivo disease and displayed a dose-dependent response to treatment with captopril. RASis may be an additional viable treatment for patients with CRLM