Routine nasogastric suction may be unnecessary after a pancreatic resection

AbstractBackgroundMost surgeons routinely place a nasogastric tube at the time of a pancreatic resection. The goal of the present study was to evaluate the outcome when a pancreatic resection is performed without routine post-operative nasogastric suction.MethodsOne hundred consecutive patients underwent a pancreatic resection (64a pancreaticoduodenectomy, 98% pylorus sparing and 36a distal pancreatectomy). In the first cohort (50 patients), a nasogastric tube was routinely placed at the time of surgery and in the second cohort (50 patients) the nasogastric was removed in the operating room. Outcomes for these two cohorts were recorded in a prospective database and compared using the χ2 or Fisher's exact test and Wilcoxon's rank-sum test.ResultsDemographical, surgical and pathological details were similar between the two cohorts. A post-operative complication occurred in 22 (44%) in each group (P= 1.000). There were no statistically significant differences in the frequency or severity of complications, or length of stay between groups. The spectrum of complications experienced by the two cohorts was similar including complications that could potentially be related to the use of nasogastric suction such as delayed gastric emptying, anastomotic leak, wound dehiscence and pneumonia. There was no difference between the two groups in the number of patients who required post-operative nasogastric tube placement (or replacement) [2 (4%) vs. 4 (8%), P= 0.678].ConclusionIt may be safe to place a nasogastric tube post-operatively in a minority of patients after a pancreatic resection and spare the majority the discomfort associated with routine post-operative nasogastric suction

Ampullary cancers harbor ELF3 tumor suppressor gene mutations and exhibit frequent WNT dysregulation

The ampulla of Vater is a complex cellular environment from which adenocarcinomas arise to form a group of histopathologically heterogenous tumors. To evaluate the molecular features of these tumors, 98 ampullary adenocarcinomas were evaluated and compared to 44 distal bile duct and 18 duodenal adenocarcinomas. Genomic analyses revealed mutations in the WNT signaling pathway among half of the patients and in all three adenocarcinomas irrespective of their origin and histological morphology. These tumors were characterized by a high frequency of inactivating mutations of ELF3, a high rate of microsatellite instability, and common focal deletions and amplifications, suggesting common attributes in the molecular pathogenesis are at play in these tumors. The high frequency of WNT pathway activating mutation, coupled with small-molecule inhibitors of β-catenin in clinical trials, suggests future treatment decisions for these patients may be guided by genomic analysis

Ampullary Cancers Harbor ELF3 Tumor Suppressor Gene Mutations and Exhibit Frequent WNT Dysregulation

The ampulla of Vater is a complex cellular environment from which adenocarcinomas arise to form a group of histopathologically heterogenous tumors. To evaluate the molecular features of these tumors, 98 ampullary adenocarcinomas were evaluated and compared to 44 distal bile duct and 18 duodenal adenocarcinomas. Genomic analyses revealed mutations in the WNT signaling pathway among half of the patients and in all three adenocarcinomas irrespective of their origin and histological morphology. These tumors were characterized by a high frequency of inactivating mutations of ELF3, a high rate of microsatellite instability, and common focal deletions and amplifications, suggesting common attributes in the molecular pathogenesis are at play in these tumors. The high frequency of WNT pathway activating mutation, coupled with small-molecule inhibitors of beta-catenin in clinical trials, suggests future treatment decisions for these patients may be guided by genomic analysis

Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK.

BACKGROUND: A safe and efficacious vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), if deployed with high coverage, could contribute to the control of the COVID-19 pandemic. We evaluated the safety and efficacy of the ChAdOx1 nCoV-19 vaccine in a pooled interim analysis of four trials. METHODS: This analysis includes data from four ongoing blinded, randomised, controlled trials done across the UK, Brazil, and South Africa. Participants aged 18 years and older were randomly assigned (1:1) to ChAdOx1 nCoV-19 vaccine or control (meningococcal group A, C, W, and Y conjugate vaccine or saline). Participants in the ChAdOx1 nCoV-19 group received two doses containing 5 × 1010 viral particles (standard dose; SD/SD cohort); a subset in the UK trial received a half dose as their first dose (low dose) and a standard dose as their second dose (LD/SD cohort). The primary efficacy analysis included symptomatic COVID-19 in seronegative participants with a nucleic acid amplification test-positive swab more than 14 days after a second dose of vaccine. Participants were analysed according to treatment received, with data cutoff on Nov 4, 2020. Vaccine efficacy was calculated as 1 - relative risk derived from a robust Poisson regression model adjusted for age. Studies are registered at ISRCTN89951424 and ClinicalTrials.gov, NCT04324606, NCT04400838, and NCT04444674. FINDINGS: Between April 23 and Nov 4, 2020, 23 848 participants were enrolled and 11 636 participants (7548 in the UK, 4088 in Brazil) were included in the interim primary efficacy analysis. In participants who received two standard doses, vaccine efficacy was 62·1% (95% CI 41·0-75·7; 27 [0·6%] of 4440 in the ChAdOx1 nCoV-19 group vs71 [1·6%] of 4455 in the control group) and in participants who received a low dose followed by a standard dose, efficacy was 90·0% (67·4-97·0; three [0·2%] of 1367 vs 30 [2·2%] of 1374; pinteraction=0·010). Overall vaccine efficacy across both groups was 70·4% (95·8% CI 54·8-80·6; 30 [0·5%] of 5807 vs 101 [1·7%] of 5829). From 21 days after the first dose, there were ten cases hospitalised for COVID-19, all in the control arm; two were classified as severe COVID-19, including one death. There were 74 341 person-months of safety follow-up (median 3·4 months, IQR 1·3-4·8): 175 severe adverse events occurred in 168 participants, 84 events in the ChAdOx1 nCoV-19 group and 91 in the control group. Three events were classified as possibly related to a vaccine: one in the ChAdOx1 nCoV-19 group, one in the control group, and one in a participant who remains masked to group allocation. INTERPRETATION: ChAdOx1 nCoV-19 has an acceptable safety profile and has been found to be efficacious against symptomatic COVID-19 in this interim analysis of ongoing clinical trials. FUNDING: UK Research and Innovation, National Institutes for Health Research (NIHR), Coalition for Epidemic Preparedness Innovations, Bill & Melinda Gates Foundation, Lemann Foundation, Rede D'Or, Brava and Telles Foundation, NIHR Oxford Biomedical Research Centre, Thames Valley and South Midland's NIHR Clinical Research Network, and AstraZeneca

Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK

Background A safe and efficacious vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), if deployed with high coverage, could contribute to the control of the COVID-19 pandemic. We evaluated the safety and efficacy of the ChAdOx1 nCoV-19 vaccine in a pooled interim analysis of four trials. Methods This analysis includes data from four ongoing blinded, randomised, controlled trials done across the UK, Brazil, and South Africa. Participants aged 18 years and older were randomly assigned (1:1) to ChAdOx1 nCoV-19 vaccine or control (meningococcal group A, C, W, and Y conjugate vaccine or saline). Participants in the ChAdOx1 nCoV-19 group received two doses containing 5 × 1010 viral particles (standard dose; SD/SD cohort); a subset in the UK trial received a half dose as their first dose (low dose) and a standard dose as their second dose (LD/SD cohort). The primary efficacy analysis included symptomatic COVID-19 in seronegative participants with a nucleic acid amplification test-positive swab more than 14 days after a second dose of vaccine. Participants were analysed according to treatment received, with data cutoff on Nov 4, 2020. Vaccine efficacy was calculated as 1 - relative risk derived from a robust Poisson regression model adjusted for age. Studies are registered at ISRCTN89951424 and ClinicalTrials.gov, NCT04324606, NCT04400838, and NCT04444674. Findings Between April 23 and Nov 4, 2020, 23 848 participants were enrolled and 11 636 participants (7548 in the UK, 4088 in Brazil) were included in the interim primary efficacy analysis. In participants who received two standard doses, vaccine efficacy was 62·1% (95% CI 41·0–75·7; 27 [0·6%] of 4440 in the ChAdOx1 nCoV-19 group vs71 [1·6%] of 4455 in the control group) and in participants who received a low dose followed by a standard dose, efficacy was 90·0% (67·4–97·0; three [0·2%] of 1367 vs 30 [2·2%] of 1374; pinteraction=0·010). Overall vaccine efficacy across both groups was 70·4% (95·8% CI 54·8–80·6; 30 [0·5%] of 5807 vs 101 [1·7%] of 5829). From 21 days after the first dose, there were ten cases hospitalised for COVID-19, all in the control arm; two were classified as severe COVID-19, including one death. There were 74 341 person-months of safety follow-up (median 3·4 months, IQR 1·3–4·8): 175 severe adverse events occurred in 168 participants, 84 events in the ChAdOx1 nCoV-19 group and 91 in the control group. Three events were classified as possibly related to a vaccine: one in the ChAdOx1 nCoV-19 group, one in the control group, and one in a participant who remains masked to group allocation. Interpretation ChAdOx1 nCoV-19 has an acceptable safety profile and has been found to be efficacious against symptomatic COVID-19 in this interim analysis of ongoing clinical trials

Accuracy of CT in predicting malignant potential of cystic pancreatic neoplasms

Background. Cystic lesions of the pancreas are being identified more frequently. Deciding which asymptomatic lesions can be safely followed with serial imaging and which require resection due to malignant potential is an increasingly common question. Current clinical practice is to rely on characteristics of the lesions on CT scan, and additional information from endoscopic ultrasound with fine-needle aspiration (EUS-FNA) and cyst fluid analysis or endoscopic retrograde pancreatography (ERCP) to assess malignant potential. Hypothesis. The malignant potential of pancreatic cystic lesions cannot be accurately predicted by CT scan. Methods. CT scans from 48 patients with cystic lesions of the pancreas were stripped of patient identifiers and retrospectively presented to two expert radiologists. The radiologists recorded specific characteristics of the lesions thought to be important in the differential diagnosis and their opinion of the likely diagnosis. Diagnostic accuracy was assessed by comparing the radiologists’ diagnoses to the final pathologic diagnosis after resection. To determine if clinical history, EUS-FNA or ERCP findings improved diagnostic accuracy, medical records were retrospectively reviewed and scored as either supporting or not supporting malignant potential of the lesion. Results. Specific diagnoses based on CT findings alone were correct in an average of 39% of the cases. Even when diagnoses were dichotomized as benign (43%) or potentially malignant (57%, papillary mucinous neoplasms, mucinous cystic neoplasms, cancer), determinations based on CT alone were accurate in an average of 61% of cases. Accuracy rates were 60.4 and 62.5% for the two radiologists, although there was only fair agreement between them (Kappa=0.28, 95% CI=(0.01–0.55), p=0.05). When all clinical information available was considered together as a single dichotomous indicator of malignant potential, the indicator was accurate in 90% of the cases (Kappa=0.73, 95% CI=(0.51–0.95, p<0.0001)). Conclusion. Specific preoperative diagnosis of pancreatic cystic neoplasms by CT alone is substantially inaccurate. Complementary tests such as EUS-FNA with fluid analysis and ERCP should be recommended to improve diagnosis especially if nonoperative treatment is planned

Treatment of bacteriobilia decreases wound infection rates after pancreaticoduodenectomy

AbstractBackgroundAlthough mortality following pancreaticoduodenectomy is decreasing, postoperative morbidity remains high. It was hypothesized that culture-directed treatment of bacteriobilia would decrease the incidence of infectious complications following pancreaticoduodenectomy.MethodsIn a retrospective study of 197 pancreaticoduodenectomy patients, those in the control group (n = 128, 2005–2009) were given perioperative prophylactic antibiotics, whereas those in the treatment group (n = 69, 2009–2011) were continued on antibiotics until intraoperative bile culture results became available. Patients with bacteriobilia received 10 days of antibiotic treatment, which was otherwise discontinued in patients without bacteriobilia. Various complication rates were compared using Fisher's exact test for categorical variables, Wilcoxon rank sum test for ordinal variables, and a two-sample t-test for continuous variables.ResultsDemographics, comorbidities, baseline clinical characteristics, and intraoperative and postoperative variables were similar between the two groups. There were higher incidences of elevated creatinine (19% versus 4%; P = 0.004) and preoperative hyperglycaemia (18% versus 7%; P = 0.053) in the control group. Fewer patients in the control group underwent preoperative biliary stenting (48% versus 67%; P = 0.017) and intraperitoneal drains were placed at the time of resection more frequently in the control group (85% versus 38%; P < 0.001). Bacteriobilia was found in 59% of patients. Treatment of bacteriobilia was associated with a decrease in the rate of postoperative wound infections (12% in the control group versus 3% in the treatment group; P = 0.036) and overall complication severity score (1 in the control group versus 0 in the treatment group; P = 0.027).ConclusionsProlonged antibiotic therapy for bacteriobilia may decrease postoperative wound infection rates after pancreaticoduodenectomy. A randomized prospective trial is warranted to provide evidence to further support this practice

Bisphenol a exposure causes meiotic aneuploidy in the female mouse

There is increasing concern that exposure to man-made substances that mimic endogenous hormones may adversely affect mammalian reproduction. Although a variety of reproductive complications have been ascribed to compounds with androgenic or estrogenic properties, little attention has been directed at the potential consequences of such exposures to the genetic quality of the gamete. A sudden, spontaneous increase in meiotic disturbances, including aneuploidy, in studies of oocytes from control female mice in our laboratory coincided with the accidental exposure of our animals to an environmental source of bisphenol A (BPA). BPA is an estrogenic compound widely used in the production of polycarbonate plastics and epoxy resins. We identified damaged caging material as the source of the exposure, as we were able to recapitulate the meiotic abnormalities by intentionally damaging cages and water bottles. In subsequent studies of female mice, we administered daily oral doses of BPA to directly test the hypothesis that low levels of BPA disrupt female meiosis. Our results demonstrated that the meiotic effects were dose dependent and could be induced by environmentally relevant doses of BPA. Both the initial inadvertent exposure and subsequent experimental studies suggest that BPA is a potent meiotic aneugen. Specifically, in the female mouse, short-term, low-dose exposure during the final stages of oocyte growth is sufficient to elicit detectable meiotic effects. These results provide the first unequivocal link between mammalian meiotic aneuploidy and an accidental environmental exposure and suggest that the oocyte and its meiotic spindle will provide a sensitive assay system for the study of reproductive toxins

TDP-43 pathology in the population: prevalence and associations with dementia and age

Background: The significance of TDP-43 pathology in relation to aging and dementia in the population is unclear. Objective: We aimed to determine the prevalence of transactive response DNA-binding protein of 43 kDA (TDP-43) neuronal inclusions in a population-based sample, and associations with age group at death (≤90 and >90 years) and clinical dementia status prior to death. Further, we investigate associations between TDP-43 inclusions and other key dementia-related neuropathologies (plaques, tangles, and neuronal loss) within the hippocampus and entorhinal and temporal cortices. Methods: All brain donors within the Cambridge City over-75 s Cohort (CC75C), which is population-based and longitudinally tracked (n = 228), were included. Age at death ranged from 78 to 106 years. TDP-43 neuronal inclusions were assessed in the hippocampus, entorhinal cortex, and temporal cortex. These data were combined with existing clinical and neuropathological data. Results: TDP-43 neuronal inclusions were present in 27% of the sample, 36% of those with clinical dementia and 18% without dementia. Individuals who died later (>90 years) or with clinical dementia were more likely to show TDP-43 inclusions. Hippocampal and entorhinal TDP-43 inclusions were significantly associated with dementia severity and increasing age, taking into account other neuropathologies. TDP-43 neuronal inclusions appeared to be co-localize with severe neuronal loss. Conclusion: Findings indicate that hippocampal and entorhinal TDP-43 inclusions are important substrates of late onset dementia which appear to co-localize with severe neuronal loss, but not with Alzheimer's disease markers of amyloid and tau. This broadens the accepted view of TDP-43 pathology in dementias.Hannah A.D. Keage, Sally Hunter, Fiona E. Matthews, Paul G. Ince, John Hodges, Suvi R.K. Hokkanen, J. Robin Highley, Tom Dening, Carol Brayne (and on behalf of the Cambridge City over 75s Cohort