The "double-fired" gastro-jejunostomy as a form of improved efficiency during Whipple procedure.

BACKGROUND: Gastro-jejunostomy (GJ) after pylorus-resecting pancreatoduodenectomy (PD) is most commonly performed in a hand-sewn fashion. Intestinal stapled anastomosis are reported to be as effective as hand-sewn in terms of patency and risk of leakage in other indications. However, the use of a stapled gastro-jejunostomy hasn't been fully assessed in PD. The aim of the present technical report is to evaluate functional outcomes of stapled GJ during PD, its associated effect on operative time and related complications. METHODS: The institutional database for pancreatic duct adenocarcinoma (PDAC) was retrospectically reviewed. Pylorus resecting open PD without vascular or multivisceral resections were considered for the analysis. The incidence of clinically significant delayed gastric emptying (DGE from the International Stufy Group of Pancreatic Surgery (ISGPS) grade B and C), other complications, operative time and overall hospitalization were evaluated. RESULTS: Over a 10-years study period, 1182 PD for adenocarcinoma were performed and recorded in the database. 243 open Whipple procedures with no vascular and with no associated multivisceral resections were available and constituted the study population. Hand-sewn (HS) anastomosis was performed in 175 (72 %), stapled anastomosis (St) in 68 (28 %). No significant differences in baseline characteristics were observed between the two groups, with the exception of a higher rate of neoadjuvant chemotherapy in the HS group (74 % St vs. 86 % HS, p = 0.025). Intraoperatively, a significantly reduced median operative time in the St group was observed (248 min St vs. 370 mins HS, p < 0.001). Post-operatively, rates of clinically relevant delayed gastric emptying (7 % St vs. 14 % HS, p = 0.140), clinically relevant pancreatic fistula (10 % St, 15 % HS, p = 0.300), median length of stay (7 days for each group, p = 0.289), post-pancreatectomy hemorrhage (4.4 % St vs. 6.3 % HS, p = 0.415) and complication rate (22 % St vs. 34 % HS, p = 0.064) were similar between groups. However, readmission rates were significantly lower after St GJ (13.2 % St vs 29.7 % HS, p = 0.008). CONCLUSION: Our results indicate that a stapled GJ anastomosis during a standard Whipple procedure is non-inferior to a hand-sewn GJ, with a comparable rate of DGE and no increase of gastrointestinal related long term complications. Further, a stapled GJ anastomosis might be associated with reduced operative times.

Implementation of 26 Gy in five fractions over 1 week adjuvant radiotherapy for breast cancer: Prospective report of acute skin toxicity and consideration of resource implications.

PURPOSE: In March 2020, a 1-week adjuvant breast radiotherapy schedule, 26 Gy in 5 fractions, was adopted to reduce the risk of COVID19 for staff and patients. This study quantifies acute toxicity rates and the effect on linac capacity. MATERIALS AND METHODS: This is a report of consecutive patients receiving ultrafractionated breast radiotherapy ( ± sequential boost) Mar-Aug 2020. Virtual consultations assessed acute skin toxicity during treatment and weeks 1, 2, 3 and 4 post treatment using CTCAE V5 scoring criteria. The number of linac minutes saved was estimated accounting for boost and DIBH use. RESULTS: In total, 128/135 (95%) patients, including 31/33 boost patients, completed at least 3/5 assessments. 0/128 (0%) reported moist desquamation not confined to skin folds or minor bleeding (Grade 3), 41/128 (32%) reported brisk erythema, moist desquamation confined to skin folds or breast swelling (Grade 2), 62/128 (48%) reported faint erythema or dry desquamation (Grade 1) as their worst skin toxicity, with the remaining 20% reporting no skin toxicity. The highest prevalence of grade 2 toxicity occurred week 1 following treatment (20%), reducing to 3% by week 4. There was no difference in toxicity between those who received a boost versus not (p = 1.00). Delivering this schedule to 135 patients over six months saved 21,300 linac minutes and 1485 hospital visits compared to a 3-week schedule. CONCLUSION: Rapidly implementing ultrahypofractionated breast radiotherapy is feasible and acute toxicity rates are acceptable even when followed by boost.

A retrospective, observational study of medicolegal cases against obstetricians and gynaecologists in South Africa's private sector.

BACKGROUND:  The viability of obstetric practice in the private sector has been threatened as a result of steep increases in professional indemnity fees over the past 10 years. Despite this, empirical research investigating key aetiological factors to target risk management interventions has been lacking. OBJECTIVES: To explore private practice medicolegal data linked to obstetricians and gynaecologists (O&Gs) to identify factors in clinical practice associated with claims, for the purposes of guiding future research and risk management solutions. METHODS:  This was a retrospective, observational study of private sector O&Gs' medicolegal case histories. All incidents declared to a prominent local professional indemnity insurer were categorised in terms of medicolegal case type, as well as clinical parameters. To allow for risk-adjusted calculations of case incidence, year of entry into private practice was estimated for all practitioners. RESULTS:  Steep increases in medicolegal investigations and demands were demonstrated for both obstetrics- and gynaecology-related cases from about 2003 to 2012. Whereas the total numbers of claims, regulatory complaints and requests for records were similar for obstetrics and gynaecology in recent years (accounting for 52% v. 48% of known cases, respectively), a significantly greater percentage of demands and paid settlements related to gynaecology rather than obstetrics (58% and 76% v. 42% and 24% of cases, respectively). In obstetrics, about half of all cases on record with a paid settlement were in the context of severe neonatal birth-related neurological injury (n=9). For gynaecology, procedure-related complications accounted for 92% of settlements, of which at least 41% were for intraoperative injuries to internal organs and vessels. Laparoscopic procedures were most frequently associated with such intraoperative injuries, followed by vaginal and abdominal hysterectomies/oophorectomies and caesarean sections. For O&Gs in private practice for >2 years, 50/458 (11%) accounted for 138/228 (61%) of demands over a 10-year period. CONCLUSIONS:  The higher number of gynaecological demands and settlements in comparison with obstetric cases was unexpected and is contrary to international experiences and public sector findings, calling for more research to identify reasons for this finding. Other than further exploring surgical outcomes in private sector gynaecological patients, aspects of surgical training and accreditation standards in gynaecology may need review. Regarding birth-related injuries, the contribution of system failures needs quantification and further interrogation. The high contribution towards the medicolegal burden by a small group of practitioners suggests a need for doctor-focused interventions, including strengthening of peer review and regulatory oversight.

A Risk Score Model for Locoregional Recurrence Following Upfront Surgery for Pancreatic Adenocarcinoma: Implications for Adjuvant Therapy.

AIMS: The aims of the study were to identify predictors of locoregional failure (LRF) following surgery for pancreatic adenocarcinoma, develop a prediction risk score model of LRF and evaluate the impact of postoperative radiation therapy (PORT) on LRF. MATERIALS AND METHODS: A retrospective review was conducted on patients with stages I-III pancreatic adenocarcinoma who underwent surgery at our institution (2005-2016). Univariable and then multivariable analyses were used to evaluate clinicopathological factors associated with LRF for patients who did not receive PORT. The risk score of LRF was calculated based on the sum of coefficients of the predictors of LRF. The model was applied to the entire cohort to evaluate the impact of PORT on the high- and low-risk groups for LRF. RESULTS: In total, 467 patients were identified (median follow-up 22 months). Among patients who did not receive PORT (n = 440), predictors of LRF were pN+, involved or close ≤1 mm margin(s), moderately and poorly differentiated tumour grade and lymphovascular invasion. After adding patients who received PORT, the 2-year LRF in the high-risk group was 57% for patients who did not receive PORT (n = 242) and 32% among patients who received PORT (n = 22), with an absolute benefit to LRF of 25% (95% confidence interval 5-52%, P = 0.07). The 2-year overall survival for the high-versus the low-risk group was 36% versus 67% (P < 0.001). CONCLUSION: This risk group classification could be used to identify pancreatic adenocarcinoma patients with higher risk of LRF who may benefit from PORT. However, validation and prospective evaluation are warranted.

Combined APRI/ALBI score to predict mortality after hepatic resection.

BACKGROUND: Aspartate aminotransferase/platelet ratio index (APRI) and albumin-bilirubin grade (ALBI) are validated prognostic indices implicated as predictors of postoperative liver dysfunction after hepatic resection. The aim of this study was to evaluate the relevance of the combined APRI/ALBI score for postoperative clinically meaningful outcomes. METHODS: Patients undergoing hepatectomy were included from the American College of Surgeons National Surgical Quality Improvement Program database. The association between APRI/ALBI score and postoperative grade C liver dysfunction, liver dysfunction-associated and overall 30-day mortality was assessed. RESULTS: A total of 12 055 patients undergoing hepatic resection from 2014 to 2017 with preoperative blood values and detailed 30-day postoperative outcomes were included (exploration cohort: January 2014 to December 2016; validation cohort: 2017). In the exploration cohort (8538 patients), the combination of both scores (APRI/ALBI) was significantly associated with postoperative grade C liver dysfunction, 30-day mortality, and liver dysfunction-associated 30-day mortality, and was superior to either score alone. The association with postoperative 30-day mortality was confirmed in multivariable analysis. A predictive model was generated using the exploration cohort. The predicted incidence of events closely followed the observed incidence in the validation cohort (3517 patients). Subgroup analyses of tumour types were used to generate disease-specific risk models to assess risk in different clinical scenarios. These findings informed development of a smartphone application (https://tellaprialbi.37binary.com). CONCLUSION: The predictive potential of the combined APRI/ALBI score for clinically relevant outcomes such as mortality was demonstrated. An evidence-based smartphone application will allow clinical translation and facilitation of risk assessment before hepatic resection using routine laboratory parameters.

Cost-effectiveness of intensive care for hospitalized COVID-19 patients: experience from South Africa.

BACKGROUND: Given projected shortages of critical care capacity in public hospitals during the COVID-19 pandemic, the South African government embarked on an initiative to purchase this capacity from private hospitals. In order to inform purchasing decisions, we assessed the cost-effectiveness of intensive care management for admitted COVID-19 patients across the public and private health systems in South Africa. METHODS: Using a modelling framework and health system perspective, costs and health outcomes of inpatient management of severe and critical COVID-19 patients in (1) general ward and intensive care (GW + ICU) versus (2) general ward only (GW) were assessed. Disability adjusted life years (DALYs) were evaluated and the cost per admission in public and private sectors was determined. The model made use of four variables: mortality rates, utilisation of inpatient days for each management approach, disability weights associated with severity of disease, and the unit cost per general ward day and per ICU day in public and private hospitals. Unit costs were multiplied by utilisation estimates to determine the cost per admission. DALYs were calculated as the sum of years of life lost (YLL) and years lived with disability (YLD). An incremental cost-effectiveness ratio (ICER) - representing difference in costs and health outcomes of the two management strategies - was compared to a cost-effectiveness threshold to determine the value for money of expansion in ICU services during COVID-19 surges. RESULTS: A cost per admission of ZAR 75,127 was estimated for inpatient management of severe and critical COVID-19 patients in GW as opposed to ZAR 103,030 in GW + ICU. DALYs were 1.48 and 1.10 in GW versus GW + ICU, respectively. The ratio of difference in costs and health outcomes between the two management strategies produced an ICER of ZAR 73,091 per DALY averted, a value above the cost-effectiveness threshold of ZAR 38,465. CONCLUSIONS: Results indicated that purchasing ICU capacity from the private sector during COVID-19 surges may not be a cost-effective investment. The 'real time', rapid, pragmatic, and transparent nature of this analysis demonstrates an approach for evidence generation for decision making relating to the COVID-19 pandemic response and South Africa's wider priority setting agenda.

Managing the healthcare demand-supply gap during and after COVID-19: The need to review the approach to healthcare priority-setting in South Africa.

Healthcare demands are rising globally, and regardless of the approach to financing and delivering healthcare services, no country can meet all the healthcare demands of its population. The demand-supply gap for healthcare services in South Africa (SA) is large, particularly for the public sector. The objectives of this article are to examine some of the underlying factors contributing to this gap, and how the COVID- 19 pandemic is likely to impact on them, and to describe why SA needs to adopt an explicit and equity-informed approach to healthcare priority-setting to assist in managing the gap.

Radiolabelling and immunohistochemistry reveal platelet recruitment into lungs and platelet migration into airspaces following LPS inhalation in mice.

INTRODUCTION: Platelets are under investigation for their role in host defence and inflammatory lung diseases and have been demonstrated to be recruited to the lung. However, the mechanisms and consequences of platelet recruitment into lungs are poorly understood. We have utilised a murine model to investigate the mechanisms of platelet involvement in lung inflammation induced by intranasal administration of LPS. OBJECTIVES: Our aim was to characterise lung platelet recruitment following LPS inhalation in mice using immunohistochemistry, and non-invasive and invasive radiolabelled platelet tracking techniques. RESULTS: Intranasal administration of LPS caused an increase in lung platelet staining in lung tissue and elicited the recruitment of radiolabelled platelets into the lung. Prior to these responses in the lung, we observed an earlier decrease in blood platelet counts, temporally associated with platelet recruitment to the liver and spleen. Non-invasive measurements of thoracic radioactivity reflected changes in blood counts rather than extravascular lung platelet recruitment. However, both in situ counting of radiolabelled platelets and immunostaining for platelet surface markers showed LPS-induced increases in extravascular platelets into lung airspaces suggesting that some of the platelets recruited to the lung enter air spaces. CONCLUSIONS: Intranasal administration of LPS activates the innate immune response which includes a fall in peripheral blood platelet counts with subsequent platelet recruitment to the lung, spleen and liver, measured by immunohistochemistry and radiolabelling techniques.

Predictors of Post-operative Pain and Opioid Consumption in Patients Undergoing Liver Surgery.

BACKGROUND: Post-operative pain management is a critical component of perioperative care. Patients at risk of poorly controlled post-operative pain may benefit from early measures to optimize pain management. We sought to identify risk factors for post-operative pain and opioid consumption in patients undergoing liver resection. METHODS: This is a multi-institutional prospective nested cohort study of patients undergoing open liver resection. Opioid consumption and pain scores were collected following surgery. To estimate the effects of patient factors on opioid consumption (oral morphine equivalents-OME) and on pain scores (NRS-11), we used generalized linear models and multivariable linear regression model, respectively. RESULTS: One hundred and fifty-three patients who underwent open liver resection between 2013 and 2016 were included in the study. The mean patient age was 62.2 years, and 43.3% were female. Younger patients were significantly more likely to use more opioids in the early post-operative period (16.7 OME/10 years, p < 0.001). Patient factors that were significantly associated with increased NRS-11 pain scores also included younger patient age (difference in pain score of 0.3/10 years with cough and 0.2/10 years at rest, p < 0.01 for both) as well as a history of analgesic use (difference in pain score of 0.9 with cough and 0.6 at rest, p < 0.01 and p = 0.07, respectively). CONCLUSION: Younger patients and those with a history of analgesic use are more likely to report higher post-operative pain and require higher doses of opioids. Early identification of these patients, and measures to better manage their pain, may contribute to optimal perioperative care.

Development of the place-based Adelante social marketing campaign for prevention of substance use, sexual risk and violence among Latino immigrant youth.

Immigrant Latino youth represent a high-risk subgroup that should be targeted with health promotion efforts. However, there are considerable barriers to engagement in health-related programming. Little is known about the engagement possibilities of social marketing campaigns and digital strategies for traditionally 'hard-to-reach' immigrants, underscoring the importance of testing these techniques with immigrant Latino adolescents. We developed and piloted a place-based social marketing campaign in coordination with the branded, Positive Youth Development-based (PYD) Adelante intervention targeting risk factors for co-occurring youth substance abuse, sexual risk and violence. Building on prior research, we conducted a four-phase formative research process, and planned the Adelante social marketing campaign based on findings from one group interview and ongoing consultation with Adelante staff (n=8) and four focus groups with youth (n=35). Participants identified four overarching campaign themes, and suggested portrayal of resilient, proud youth who achieved goals despite adversity. Youth guided selection of campaign features and engagement strategies, including message/visual content, stylistic elements, and a mixed language approach. We developed a 12-month campaign to be delivered via print ads, multi-platform social media promotion, contests, youth-generated videos, blog posts, and text messaging. We describe the process and outcome of campaign development and make recommendations for future campaigns.

Lipopolysaccharide (LPS) induced pulmonary neutrophil recruitment and platelet activation is mediated via the P2Y1 and P2Y14 receptors in mice.

Platelet activation occurs during host defence and in various inflammatory disorders. In animal models of infection and inflammation, experimental depletion of platelets leads to significantly reduced leukocyte recruitment and impaired clearance of pathogens from the lung. It is now appreciated that purinergic receptor activation is required for leukocyte activation, motility and adhesion, and platelet interactions with leukocytes can be modulated by purinergic stimulation of platelets. Here, we have investigated the role of platelet P2Y1, P2Y12, P2Y14, and P2X1 receptors on leukocyte recruitment and chemotaxis. Mice were administered either vehicle controls or selective P2Y1, P2Y12, P2Y14, or P2X1 antagonists intravenously before intranasal administration of lipopolysaccharide (LPS) to investigate the effect of these drugs on pulmonary leukocyte recruitment, peripheral platelet counts, bleeding times, and ex vivo platelet aggregation. Separately, platelets were incubated with P2Y1, P2Y12, P2X1 antagonists, or P2Y14 agonists to assess effects on platelet-induced neutrophil chemotaxis in vitro. Pulmonary neutrophil recruitment induced by intranasal LPS administration was inhibited in mice administered either with P2Y1 or P2Y14 antagonists, but not with P2Y12 or P2X1 antagonists. Furthermore, the administration of either a P2Y1 or a P2Y14 antagonist reversed the incidence of peripheral thrombocytopaenia associated with LPS exposure. Bleeding times were significantly increased in mice administered P2Y1, P2Y12, or P2X1 antagonists, whilst ex vivo platelet aggregation to ADP was significantly reduced. These haemostatic responses remained unaltered following antagonism of P2Y14. In vitro chemotaxis assays revealed direct antagonism of platelet P2Y1, but not P2Y12 or P2X1 receptors suppressed platelet-dependent neutrophil motility towards Macrophage derived chemokine (MDC, CCL22). Furthermore, the stimulation of platelets with selective P2Y14 agonists (UDP-glucose, MRS2690) resulted in significant platelet-dependent neutrophil chemotaxis. These results reveal a role for P2Y1 and P2Y14 activation of platelets following exposure to LPS, whilst haemostatic indices were unaffected by inhibition of platelet function with the P2Y14 antagonist in response to LPS.

Continuous subcutaneous insulin infusion (CSII) therapy at Derby Teaching Hospitals: sustained benefits in glucose control.

AIM: In the short term, continuous subcutaneous insulin infusion (CSII) has been associated with improved glycaemic control, reduced hypoglycaemia and improved quality of life (QOL). However, limited data are available on its long-term benefits, particularly in the UK. We aimed to assess the impact of CSII on longer term outcomes. METHOD: Patient-level data were obtained for CSII users at Derby Teaching Hospitals, UK. Patient confidence and satisfaction questionnaires using the Likert scale were used to assess confidence in self-management. Comparative statistics were conducted using Pearson's chi-square and Student's t-tests. RESULTS: Some 258 CSII users were identified (60.1% female, mean age 43.9 ± 13.4 years). Overall, there was significant decrease in HbA1c from 78 mmol/mol (9.3 ± 2.0%) at baseline, to 69 mmol/mol (8.5 ± 1.3%) at 6 months [mean difference (md): -0.64; 95% confidence interval (95% CI): -0.91 to -0.37; P < 0.0001]; which was sustained at 6 years of follow-up (HbA1c : 66 mmol/mol, 8.2 ± 1.3%; md: -1.07%; 95% CI: -1.45 to -0.69; P < 0.0001). One hundred and twenty-one patients (47%) responded to the survey, of whom 95 (78.5%) reported a reduction in the frequency of hypoglycaemia; 102 (84.3%) were satisfied with the quality of care received in the insulin pump service. CONCLUSION: CSII therapy led to a sustained long-term improvement in glycaemic control in addition to a reduction in self-reported hypoglycaemia.

Can contrast-enhanced MRI with gadoxetic acid predict liver failure and other complications after major hepatic resection?

AIM: To determine whether a combination of clinical factors, the future liver remnant (FLR) ratio, and hepatic uptake of gadoxetic acid can be used to predict post-hepatectomy liver failure (PHLF) and other major complications (OMC). MATERIALS AND METHODS: Sixty-five consecutive patients who underwent pre-hepatectomy gadoxetic acid-enhanced magnetic resonance imaging (MRI) between October 2010 and December 2013 were included. The relative liver enhancement (RLE) of gadoxetic acid was calculated from regions of interest on MRI, and FLR ratios were obtained from computed tomography (CT). PHLF and OMC were defined by the International Study Group of Liver Surgery criteria and Clavien-Dindo grade of ≥3, respectively. Multivariate logistic regression modelling was performed to identify predictors of PHLF and OMC, including RLE, FLR ratio, age, sex, chemotherapy history, intra-operative blood loss, and intra-operative transfusion. RESULTS: Nine patients experienced PHLF and another nine patients experienced OMC. RLE was comparable to the FLR ratio in predicting PHLF (areas under the receiver operating characteristic [AUROC] curves, 0.665 and 0.705), but performed poorly in predicting OMCs (AUROCs, 0.556 and 0.702). Combining all clinical and imaging parameters as predictors yielded the best performing predictive models (AUROCs, 0.875 and 0.742 for PHLF and OMC, respectively). CONCLUSION: A model based on clinical parameters, the FLR ratio, and RLE of gadoxetic acid may improve pre-hepatectomy risk assessment.

Multidisciplinary managed care networks-Life-saving interventions for hepatitis C patients.

Successful hepatitis C virus (HCV) therapy depends on effective pathways of care. Over two decades, we have developed four sequential models of care latterly using a multidisciplinary managed care network to improve HCV testing, care and treatment. This was a cohort study to evaluate the effectiveness of care pathways, carried out using all HCV antibody-positive individuals tested in a geographical region between 1994 and 2014. The study involved 3122 HCV-positive patients. They were divided into four subgroups representing different care pathways defined by their date of HCV antibody diagnosis. The number who accessed treatment services within 1 year of diagnosis increased from 77 of 292 (26.3%) to 521 of 821 (72.9%). The rate of treatment starts within 1 year of diagnosis increased from 6 of 292 (2.0%) to 133 of 821 (16.2%), and the sustained viral response rate improved from 61.6% to 77.4%. All-cause mortality decreased from 232 of 688 (33.7%) in subgroup A to 55 of 1207 (4.5%) in subgroup D, and multivariate analysis showed that pathway type was an independent predictor of mortality irrespective of age, sex, SVR status or HIV co-infection with pathway in D having an odds ratio of 0.53(0.40-0.77; P<.001) compared to pathway in A. At study end, 78% (3122) of an estimated 4000 HCV positive had been diagnosed. In total, 97.5% of HCV caseload was referred to specialist services and 89% attended for assessment. The introduction of a managed care network increased access to care and reduced all-cause mortality.

A missense TGFB2 variant p.(Arg320Cys) causes a paradoxical and striking increase in aortic TGFB1/2 expression.

Loeys-Dietz syndrome (LDS) is an autosomal dominant connective tissue disorder with a range of cardiovascular, skeletal, craniofacial and cutaneous manifestations. LDS type 4 is caused by mutations in TGFß ligand 2 (TGFB2) and based on the family pedigrees described to date, appears to have a milder clinical phenotype, often presenting with isolated aortic disease. We sought to investigate its molecular basis in a new pedigree. We identified a missense variant p.(Arg320Cys) (NM_003238.3) in a highly evolutionary conserved region of TGFB2 in a new LDS type 4 pedigree with multiple cases of aortic aneurysms and dissections. There was striking upregulation of TGFB1 and TGFB2 expression on immunofluorescent staining, and western blotting of the aortic tissue from the index case confirming the functional importance of the variant. This case highlights the striking paradox of predicted loss-of-function mutations in TGFB2 causing enhanced TGFß signaling in this emerging familial aortopathy.

The application of local hypobaric pressure - A novel means to enhance macromolecule entry into the skin.

The local application of controlled hypobaric stress represents a novel means to facilitate drug delivery into the skin. The aims of this work were to understand how hypobaric stress modified the properties of the skin and assess if this penetration enhancement strategy could improve the percutaneous penetration of a macromolecule. Measurements of skin thickness demonstrated that the topical application of hypobaric stress thinned the tissue (p<0.05), atomic force microscopy showed that it shrunk the corneocytes in the stratum corneum (p<0.001) and the imaging of the skin hair follicles using multiphoton microscopy showed that it opened the follicular infundibula (p<0.001). Together, these changes contributed to a 19.6-fold increase in in vitro percutaneous penetration of a 10,000 molecular weight dextran molecule, which was shown using fluorescence microscopy to be localized around the hair follicles, when applied to the skin using hypobaric stress. In vivo, in the rat, a local hemodynamic response (i.e. a significant increase in blood flow, p<0.001) was shown to contribute to the increase in follicular transport of the dextran to produce a systemic absorption of 7.2±2.81fg·mL(-1). When hypobaric stress was not applied to the rat there was no detectable absorption of dextran and this provided evidence that this novel penetration enhancement technique can improve the percutaneous penetration of macromolecules after topical application to the skin.

Eastern Canadian Gastrointestinal Cancer Consensus Conference 2016.

The annual Eastern Canadian Gastrointestinal Cancer Consensus Conference 2016 was held in Montreal, Quebec, 5-7 February. Experts in radiation oncology, medical oncology, surgical oncology, and infectious diseases involved in the management of patients with gastrointestinal malignancies participated in presentations and discussion sessions for the purpose of developing the recommendations presented here. This consensus statement addresses multiple topics: ■ Follow-up and survivorship of patients with resected colorectal cancer■ Indications for liver metastasectomy■ Treatment of oligometastases by stereotactic body radiation therapy■ Treatment of borderline resectable and unresectable pancreatic cancer■ Transarterial chemoembolization in hepatocellular carcinoma■ Infectious complications of antineoplastic agents.

Vitamin D and pancreatic cancer: a pooled analysis from the Pancreatic Cancer Case-Control Consortium.

BACKGROUND: The potential role of vitamin D in the aetiology of pancreatic cancer is unclear, with recent studies suggesting both positive and negative associations. PATIENTS AND METHODS: We used data from nine case-control studies from the International Pancreatic Cancer Case-Control Consortium (PanC4) to examine associations between pancreatic cancer risk and dietary vitamin D intake. Study-specific odds ratios (ORs) were estimated using multivariable logistic regression, and ORs were then pooled using a random-effects model. From a subset of four studies, we also calculated pooled estimates of association for supplementary and total vitamin D intake. RESULTS: Risk of pancreatic cancer increased with dietary intake of vitamin D [per 100 international units (IU)/day: OR = 1.13, 95% confidence interval (CI) 1.07-1.19, P = 7.4 × 10(-6), P-heterogeneity = 0.52; ≥230 versus <110 IU/day: OR = 1.31, 95% CI 1.10-1.55, P = 2.4 × 10(-3), P-heterogeneity = 0.81], with the association possibly stronger in people with low retinol/vitamin A intake. CONCLUSION: Increased risk of pancreatic cancer was observed with higher levels of dietary vitamin D intake. Additional studies are required to determine whether or not our finding has a causal basis.

Diabetes, antidiabetic medications, and pancreatic cancer risk: an analysis from the International Pancreatic Cancer Case-Control Consortium.

BACKGROUND: Type 2 diabetes mellitus has been associated with an excess risk of pancreatic cancer, but the magnitude of the risk and the time-risk relationship are unclear, and there is limited information on the role of antidiabetic medications. PATIENTS AND METHODS: We analyzed individual-level data from 15 case-control studies within the Pancreatic Cancer Case-Control Consortium, including 8305 cases and 13 987 controls. Pooled odds ratios (ORs) were estimated from multiple logistic regression models, adjusted for relevant covariates. RESULTS: Overall, 1155 (15%) cases and 1087 (8%) controls reported a diagnosis of diabetes 2 or more years before cancer diagnosis (or interview, for controls), corresponding to an OR of 1.90 (95% confidence interval, CI, 1.72-2.09). Consistent risk estimates were observed across strata of selected covariates, including body mass index and tobacco smoking. Pancreatic cancer risk decreased with duration of diabetes, but a significant excess risk was still evident 20 or more years after diabetes diagnosis (OR 1.30, 95% CI 1.03-1.63). Among diabetics, long duration of oral antidiabetic use was associated with a decreased pancreatic cancer risk (OR 0.31, 95% CI 0.14-0.69, for ≥15 years). Conversely, insulin use was associated with a pancreatic cancer risk in the short term (OR 5.60, 95% CI 3.75-8.35, for <5 years), but not for longer duration of use (OR 0.95, 95% CI 0.53-1.70, for ≥15 years). CONCLUSION: This study provides the most definitive quantification to date of an excess risk of pancreatic cancer among diabetics. It also shows that a 30% excess risk persists for more than two decades after diabetes diagnosis, thus supporting a causal role of diabetes in pancreatic cancer. Oral antidiabetics may decrease the risk of pancreatic cancer, whereas insulin showed an inconsistent duration-risk relationship.