Early recognition and management of postoperative complications, before they become clinically relevant, can improve postoperative outcomes for patients, especially for high-risk procedures such as ...pancreatic resection.
We did an open-label, nationwide, stepped-wedge cluster-randomised trial that included all patients having pancreatic resection during a 22-month period in the Netherlands. In this trial design, all 17 centres that did pancreatic surgery were randomly allocated for the timing of the crossover from usual care (the control group) to treatment given in accordance with a multimodal, multidisciplinary algorithm for the early recognition and minimally invasive management of postoperative complications (the intervention group). Randomisation was done by an independent statistician using a computer-generated scheme, stratified to ensure that low–medium-volume centres alternated with high-volume centres. Patients and investigators were not masked to treatment. A smartphone app was designed that incorporated the algorithm and included the daily evaluation of clinical and biochemical markers. The algorithm determined when to do abdominal CT, radiological drainage, start antibiotic treatment, and remove abdominal drains. After crossover, clinicians were trained in how to use the algorithm during a 4-week wash-in period; analyses comparing outcomes between the control group and the intervention group included all patients other than those having pancreatic resection during this wash-in period. The primary outcome was a composite of bleeding that required invasive intervention, organ failure, and 90-day mortality, and was assessed by a masked adjudication committee. This trial was registered in the Netherlands Trial Register, NL6671.
From Jan 8, 2018, to Nov 9, 2019, all 1805 patients who had pancreatic resection in the Netherlands were eligible for and included in this study. 57 patients who underwent resection during the wash-in phase were excluded from the primary analysis. 1748 patients (885 receiving usual care and 863 receiving algorithm-centred care) were included. The primary outcome occurred in fewer patients in the algorithm-centred care group than in the usual care group (73 8% of 863 patients vs 124 14% of 885 patients; adjusted risk ratio RR 0·48, 95% CI 0·38–0·61; p<0·0001). Among patients treated according to the algorithm, compared with patients who received usual care there was a decrease in bleeding that required intervention (47 5% patients vs 51 6% patients; RR 0·65, 0·42–0·99; p=0·046), organ failure (39 5% patients vs 92 10% patients; 0·35, 0·20–0·60; p=0·0001), and 90-day mortality (23 3% patients vs 44 5% patients; 0·42, 0·19–0·92; p=0·029).
The algorithm for the early recognition and minimally invasive management of complications after pancreatic resection considerably improved clinical outcomes compared with usual care. This difference included an approximate 50% reduction in mortality at 90 days.
The Dutch Cancer Society and UMC Utrecht.
A majority of the human tumor-associated Ags characterized to date are derived from nonmutated "self"-proteins. Little is currently understood about the nature of the self-reactive lymphocytes that ...recognize these Ags. We recently characterized two nonmutated tumor-associated Ags for the B16 murine melanoma: tyrosinase-related protein-2 (TRP-2) and the endogenous retroviral envelope protein, p15E. We previously reported that both TRP-2 and p15E reactive CTL could be detected in the spleens of naive animals after a single in vitro stimulation using 10(-5)-10(-6) M of the appropriate Kb-binding 9-amino acid epitope. In this report we show that the CTL found in naive animals are low avidity lymphocytes, that respond only to high concentrations of peptide in vitro. We demonstrate that titration of in vitro-stimulating peptide to limiting concentrations distinguishes qualitative differences in the lymphocyte reactivity to these two Ags between vaccinated and unvaccinated animals. We further demonstrate that in vitro expansion of CTL in either high or low concentrations of stimulating peptide generated CTL cultures with different avidities for the relevant epitopes. CTL expanded in low concentrations demonstrated higher avidity for peptide-pulsed targets and better tumor recognition, when compared to CTL generated in the presence of high concentrations of Ag. More importantly, high avidity CTL demonstrated superior in vivo antitumor activity. These results demonstrate that qualitative differences in the CTL that recognize these two self-Ags are critically important to their in vitro and in vivo anti-tumor efficacy.
Purpose
In 2003, randomized trials demonstrated potentially improved outcomes when local instead of general anesthesia is used for inguinal hernia repair. Our study aimed to evaluate how the use of ...local anesthesia for this procedure changed over time following the publication of the trials’ level 1 evidence.
Methods
We used the 1998–2018 Veterans Affairs Surgical Quality Improvement Program database to identify adults who underwent open, unilateral inguinal hernia repair under local or general anesthesia. Our primary outcome was the percentage of cases performed under local anesthesia. We used a time-series design to examine the trend and rate of change of the use of local anesthesia.
Results
We included 97,437 veterans, of which 22,333 (22.9%) had hernia surgery under local anesthesia. The median age of veterans receiving local anesthesia remained stable at 64–67 years over time. The use of local anesthesia decreased steadily, from 38.2% at the beginning year to 15.1% in the final year (
P
< 0.0001). The publication of results from randomized trials (in 2003) did not appear to increase the overall use or change the rate of decline in the use of local anesthesia. Overall, we found that the use of local anesthesia decreased by about 1.5% per year.
Conclusion
The utilization of local anesthesia for inguinal hernia repair in the VA has steadily declined over the last 20 + years, despite data showing equivalence or superiority to general anesthesia. Future studies should explore barriers to the use of local anesthesia for hernia repair.
A historically important but little known debate regarding the necessity and meaning of macroscopic superpositions, in particular those containing different gravitational fields, is reviewed and ...discussed from a modern perspective.
In this study, we assessed the ability of a highly tumor-selective oncolytic vaccinia virus armed with a yeast cytosine deaminase gene to infect and lyse human and murine ovarian tumors both in vitro ...and in vivo. The virus vvDD-CD could infect, replicate in and effectively lyse both human and mouse ovarian cancer cells in vitro. In two different treatment schedules involving either murine MOSEC or human A2780 ovarian carcinomatosis models, regional delivery of vvDD-CD selectively targeted tumor cells and ovarian tissue, effectively delaying the development of either tumor or ascites and leading to significant survival advantages. Oncolytic virotherapy using vvDD-CD in combination with the prodrug 5-fluorocytosine conferred an additional long-term survival advantage upon tumor-bearing immunocompetent mice. These findings demonstrate that a tumor-selective oncolytic vaccinia combined with gene-directed enzyme prodrug therapy is a highly effective strategy for treating advanced ovarian cancers in both syngeneic mouse and human xenograft models. Given the biological safety, tumor selectivity and oncolytic potency of this armed oncolytic virus, this dual therapy merits further investigation as a promising new treatment for metastatic ovarian cancer.
Robotic-Assisted Major Pancreatic Resection Zeh, H.J., MD; Bartlett, David L., MD; Moser, A. James, MD
Advances in surgery (Chicago),
2011, Letnik:
45, Številka:
1
Journal Article
Recenzirano
Robotic-assisted major pancreatic resections allow recreation of time-tested open surgical procedures on a minimally invasive platform. Early outcomes from robotic-assisted major pancreatic ...resections are comparable with those of laparoscopic and open approaches. Robotic assistance has the potential to bring the well-recognized advantages of minimally invasive surgery to major pancreatic resections. Technological innovations and increased surgeon familiarity with this approach will improve, likely leading to greater adoption and acceptance.
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