Liver regeneration after portal and hepatic vein embolization improves overall survival compared with portal vein embolization alone: mid-term survival analysis of the multicentre DRAGON 0 cohort.

BACKGROUND: The purpose of this study was to compare 3-year overall survival after simultaneous portal (PVE) and hepatic vein (HVE) embolization versus PVE alone in patients undergoing liver resection for primary and secondary cancers of the liver. METHODS: In this multicentre retrospective study, all DRAGON 0 centres provided 3-year follow-up data for all patients who had PVE/HVE or PVE, and were included in DRAGON 0 between 2016 and 2019. Kaplan-Meier analysis was undertaken to assess 3-year overall and recurrence/progression-free survival. Factors affecting survival were evaluated using univariable and multivariable Cox regression analyses. RESULTS: In total, 199 patients were included from 7 centres, of whom 39 underwent PVE/HVE and 160 PVE alone. Groups differed in median age (P = 0.008). As reported previously, PVE/HVE resulted in a significantly higher resection rate than PVE alone (92 versus 68%; P = 0.007). Three-year overall survival was significantly higher in the PVE/HVE group (median survival not reached after 36 months versus 20 months after PVE; P = 0.004). Univariable and multivariable analyses identified PVE/HVE as an independent predictor of survival (univariable HR 0.46, 95% c.i. 0.27 to 0.76; P = 0.003). CONCLUSION: Overall survival after PVE/HVE is substantially longer than that after PVE alone in patients with primary and secondary liver tumours.

Hospital text paging communication as a surgical quality improvement initiative.

BACKGROUND: Studies on medicine wards have shown that numeric pages can be disruptive of workflow and patient care. We created a quality improvement program among surgical ward nurses and residents and hypothesized that a text-based, urgency-stratified initiative would improve communication at no detriment to patient care. METHODS: Surgery residents recorded preintervention data for 1 mo including number of total pages, text pages, and numeric pages received from surgical floors. Nurses and residents completed surveys to assess preintervention satisfaction with communication, responsiveness, and workflow. Nurses were then instructed to use text paging for nonurgent issues. Paging data were again recorded for 1 mo, surveys repeated, and patient safety and satisfaction data collected. Primary endpoints evaluated included patient safety and satisfaction data. Secondary endpoints included communication satisfaction of nurses and residents. RESULTS: After text paging implementation, 40.1% of nonurgent pages sent from nurses to resident physicians were alphanumeric texts versus only 17.9% before implementation (P < 0.0001). There was a 19.5% reduction in the number of nonurgent numeric pages sent (P < 0.0001). Overall, 70% of nurses responded postintervention that text paging was the preferred method of contacting a physician and that the text paging initiative improved efficiency. After implementation, 62% of nurses thought that overall communication with clinicians improved. In addition, there was no change in patient safety issues or patient satisfaction. CONCLUSIONS: Our text paging initiative for all nonurgent pages from nurses to residents improved physician-nurse workflow and communication on the surgical ward with no decrease in patient satisfaction or safety.

Navigating Complex Challenges: Preoperative Assessment and Surgical Strategies for Liver Resection in Patients with Fibrosis or Cirrhosis.

This review explores the intricacies of evaluating cirrhotic patients for liver resection while exploring how to extend surgical intervention to those typically excluded by the Barcelona Clinic Liver Cancer (BCLC) criteria guidelines by focusing on the need for robust preoperative assessment and innovative surgical strategies. Cirrhosis presents unique challenges and complicates liver resection due to the altered physiology of the liver, portal hypertension, and liver decompensation. The primary objective of this review is to discuss the current approaches in assessing the suitability of cirrhotic patients for liver resection and aims to identify which patients outside of the BCLC criteria can safely undergo liver resection by highlighting emerging strategies that can improve surgical safety and outcomes.

Debulking Hepatectomy for Colorectal Liver Metastasis Conveys Survival Benefit.

(1) Background: Despite advances in surgical technique and systemic chemotherapy, some patients with multifocal, bilobar colorectal liver metastases (CRLM) remain unresectable. These patients may benefit from surgical debulking of liver tumors in combination with chemotherapy compared to chemotherapy alone. (2) Methods: A retrospective study including patients evaluated for curative intent resection of CRLM was performed. Patients were divided into three groups: those who underwent liver resection with recurrence within 6 months (subtotal debulked, SD), those who had the first stage only of a two-stage hepatectomy (partially debulked, PD), and those never debulked (ND). Kaplan-Meier survival curves and log-rank test were performed to assess the median survival of each group. (3) Results: 174 patients underwent liver resection, and 34 patients recurred within 6 months. Of the patients planned for two-stage hepatectomy, 35 underwent the first stage only. Thirty-two patients were never resected. Median survival of the SD, PD, and ND groups was 31 months, 31 months, and 19.5 months, respectively (p = 0.012); (4) Conclusions: Patients who underwent a debulking of CRLM demonstrated a survival benefit compared to patients who did not undergo any surgical resection. This study provides support for the evaluation of intentional debulking versus palliative chemotherapy alone in a randomized trial.

Targeting Liver Metastases to Potentiate Immunotherapy in MS-Stable Colorectal Cancer-A Review of the Literature.

Immunotherapy has revolutionized the treatment of several cancers, including melanoma and lung cancer. However, for colorectal cancer, it is ineffective for 95% of patients with microsatellite-stable disease. Recent evidence suggests that the liver's immune microenvironment plays a pivotal role in limiting the effectiveness of immunotherapy. There is also evidence to show that targeting liver metastases with locoregional therapies, such as surgery or irradiation, could potentiate immunotherapy for these patients. This review presents evidence from preclinical studies regarding the underlying mechanisms and from clinical studies that support this approach. Furthermore, we outline potential directions for future clinical trials. This innovative strategy could potentially establish immunotherapy as an effective treatment for MS-stable colorectal cancer patients, which are currently considered resistant.

Postoperative Mortality in Patients With Cirrhosis: Reconsidering Expectations.

BACKGROUND: A diagnosis of cirrhosis increases a patient's risk of postoperative mortality. Surgeons are reticent to operate when cirrhosis is known unless no option is available. This study aimed to identify the modern perioperative risk in cirrhotic patients undergoing intervention under general anesthesia for non-transplant operations. METHODS: A retrospective chart review was conducted utilizing the Rush Medical Center electronic medical record. All patients over 18 years of age with a diagnosis of cirrhosis undergoing intervention between 2009 and 2019 were reviewed. 90-day mortality rates in patients grouped by Child's score, Model for End-Stage Liver Disease (MELD), and Model for End-Stage Liver Disease with sodium incorporated (MELDNa) were compared to previously accepted rates. RESULTS: 93 patients (46% women) aged 22-72 years of all Child-Turcot-Pugh (CTP) (40% A, 36% B, and 25% C) classifications and MELD/MELDNa ranging 6-40 were analyzed. 90-day mortality of the entire population was 16%, significantly lower than expected based on CTP score (16% vs. 32%; P = .0005), MELD (16% vs. 41%; P < .0001), and MELDNa (16% vs. 46.8%; P < .0001). This was also true for CTP-B patients (12% vs. 30%; P = .025), CTP-C patients (35% vs. 70%; P = .0002), patients with MELD >14 (27% vs. 70%; P < .001), and patients with MELDNa >14 (23% vs. 70%; P < .0001). CONCLUSION: Data indicate that perioperative mortality is lower than widely accepted. This suggests the need for a national database study using a representative population to determine the risk of mortality for patients with cirrhosis having surgery in recent times. Accurate estimation of this risk allows for meaningful discussion between physicians and patients when deciding to proceed with elective, necessary operations.

Pediatric Inpatient Antimicrobial Stewardship Program Safely Reduces Antibiotic Use in Patients with Bronchiolitis Caused by Respiratory Syncytial Virus: A Retrospective Chart Review.

Bronchiolitis is a common lower respiratory tract illness in young children often caused by the respiratory syncytial virus (RSV). Antimicrobials are not recommended in infants with bronchiolitis unless there is strong evidence that a bacterial coinfection exists. METHODS: We conducted a retrospective chart review comparing antimicrobial use and outcomes in previously healthy infants ≤24 months of age with RSV bronchiolitis at a single Canadian tertiary pediatric hospital during RSV seasons (December-April) from 2011 to 2016. An audit and feedback antimicrobial stewardship program was introduced in this hospital in August 2014. RESULTS: Compared with the 2011-2012 cohort, the 2015-2016 cohort showed a decrease of 46% in mean days of therapy per 1,000 patient-days in the >28 days old age group of patients. There was also a 15.1% absolute reduction in the proportion of patients who received any antimicrobials in the hospital between the 2 cohorts (neonates included). The proportion of patients receiving antimicrobial prescriptions at discharge also decreased from 33.5% to 19%. The use of second-generation cephalosporins was eliminated in the 2016 cohort. There was a significant decrease in length of stay between the 2011-2012 and 2015-2016 cohorts, and no readmissions were documented. CONCLUSIONS: This study adds to the accumulating literature that antimicrobial stewardship program interventions along with guidelines and order sets can safely contribute to a reduction in antimicrobial use both in hospital and at discharge in children <2 years of age hospitalized due to RSV. Further research in identifying those who would or would not benefit from antibiotics should be promoted.

Laparoscopic Parenchymal-Sparing Hepatectomy: the New Maximally Minimal Invasive Surgery of the Liver-a Systematic Review and Meta-Analysis.

BACKGROUND: Parenchymal-sparing hepatectomies (PSH) are liver resections with preservation of as much liver parenchyma as possible. PSH can be performed laparoscopically (LPSH), but access to the posterosuperior segments is difficult and they are challenging when there are multiple bilobar lesions; the procedure may require repositioning and may be long and cumbersome. The objective of this systematic review is to analyze the feasibility and limitations of laparoscopic PSH in the literature. METHODS: A systematic review of the literature was performed by searching Medline/PubMed, Scopus, and Cochrane databases. Resections were categorized by segment(s), and data regarding operative time, blood loss, length of hospital stay, complications, and R0 resection were analyzed. RESULTS: Of 351 studies screened for relevance, 48 studies were reviewed. Ten publications fulfilled inclusion criteria, reporting data from 579 patients undergoing LPSH. The most common indication was CRLM (58%) followed by hepatocellular carcinoma (16%). Only 92 patients were reported to have resections of more than one tumor; the maximum number of lesions resected was seven. Of resected lesions, 21.5% were located in the cranial segments. Mean operating time was 335.2 min, estimated blood loss was 462 cc, and hospital stay was 7.6 days. Conversion rate was 9.7%, and complications occurred in 19.4% of cases. No perioperative mortality was reported. R0 resections were achieved in 87.7% of cases. CONCLUSION: Laparoscopic PSH is performed and reported, but the data quality is low so far. The main limitation of LPSH is the low number of lesions resected, especially for bilobar, metastatic disease. Prospective reports with tumor-specific oncological data are desirable.

Simultaneous hepatic and portal vein ligation induces rapid liver hypertrophy: A study in pigs.

BACKGROUND: Liver hypertrophy induced by partial portal vein occlusion (PVL) is accelerated by adding simultaneous parenchymal transection ("ALPPS procedure"). This preclinical experimental study in pigs tests the hypothesis that simultaneous ligation of portal and hepatic veins of the liver also accelerates regeneration by abrogation of porto-portal collaterals without need for operative transection. METHODS: A pig model of portal vein occlusion was compared with the novel model of simultaneous portal and hepatic vein occlusion, where major hepatic veins draining the portal vein-deprived lobe were identified with intraoperative ultrasonography and ligated using pledgeted transparenchymal sutures. Kinetic growth was compared, and the portal vein system was then studied after 7 days using epoxy casts of the portal circulation. Portal vein flow and portal pressure were measured, and Ki-67 staining was used to evaluate the proliferative response. RESULTS: Pigs were randomly assigned to portal vein occlusion (n = 8) or simultaneous portal and hepatic vein occlusion (n = 6). Simultaneous portal and hepatic vein occlusion was well tolerated and led to mild cytolysis, with no necrosis in the outflow vein-deprived liver sectors. The portal vein-supplied sector increased by 90 ± 22% (mean ± standard deviation) after simultaneous portal and hepatic vein occlusion compared with 29 ± 18% after PVL (P < .001). Collaterals to the deportalized liver developed after 7 days in both procedures but were markedly reduced in simultaneous portal and hepatic vein occlusion. Ki-67 staining at 7 days was comparable. CONCLUSION: This study in pigs found that simultaneous portal and hepatic vein occlusion led to rapid hypertrophy without necrosis of the deportalized liver. The findings suggest that the use of simultaneous portal and hepatic vein occlusion accelerates liver hypertrophy for extended liver resections and should be evaluated further.

Maintaining the momentum: key factors influencing acceptance of influenza vaccination among pregnant women following the H1N1 pandemic.

This survey study compared pre- and post-pandemic knowledge, attitudes, beliefs, and intended behaviors of pregnant women regarding influenza vaccination (seasonal and/or pandemic) during pregnancy in order to determine key factors influencing their decision to adhere to influenza vaccine recommendations. Only 36% of 662 pre-pandemic respondents knew that influenza was more severe in pregnant women, compared to 62% of the 159 post-pandemic respondents. Of the pre-pandemic respondents, 41% agreed or strongly agreed that that it was safer to wait until after the first 3 months to receive the seasonal influenza vaccine, whereas 23% of the post-pandemic cohort agreed or strongly agreed; 32% of pre-pandemic participants compared to 11% of post-pandemic respondents felt it was best to avoid all vaccines while pregnant. Despite 61% of the pre-pandemic cohort stating that they would have the vaccine while pregnant if their doctor recommended it and 54% citing their doctor/nurse as their primary source of vaccine information, only 20% said their doctor discussed influenza vaccination during their pregnancy, compared to 77% of the post-pandemic respondents who reported having this conversation. Women whose doctors discussed influenza vaccine during pregnancy had higher overall knowledge scores (P<0.0001; P=0.005) and were more likely to believe the vaccine is safe in all stages of pregnancy (P<0.0001; P=0.001) than those whose doctors did not discuss influenza vaccination. The 2009 H1N1 pandemic experience appeared to change attitudes and behaviours of health care providers and their pregnant patients toward influenza vaccination.

Calcium current homeostasis and synaptic deficits in hippocampal neurons from Kelch-like 1 knockout mice.

Kelch-like 1 (KLHL1) is a neuronal actin-binding protein that modulates voltage-gated CaV2.1 (P/Q-type) and CaV3.2 (α1H T-type) calcium channels; KLHL1 knockdown experiments (KD) cause down-regulation of both channel types and altered synaptic properties in cultured rat hippocampal neurons (Perissinotti et al., 2014). Here, we studied the effect of ablation of KLHL1 on calcium channel function and synaptic properties in cultured hippocampal neurons from KLHL1 knockout (KO) mice. Western blot data showed the P/Q-type channel α1A subunit was less abundant in KO hippocampus compared to wildtype (WT); and P/Q-type calcium currents were smaller in KO neurons than WT during early days in vitro, although this decrease was compensated for at late stages by increases in L-type calcium current. In contrast, T-type currents did not change in culture. However, biophysical properties and western blot analysis revealed a differential contribution of T-type channel isoforms in the KO, with CaV3.2 α1H subunit being down-regulated and CaV3.1 α1G up-regulated. Synapsin I levels were also reduced in the KO hippocampus and cultured neurons displayed a concomitant reduction in synapsin I puncta and decreased miniature excitatory postsynaptic current (mEPSC) frequency. In summary, genetic ablation of the calcium channel modulator resulted in compensatory mechanisms to maintain calcium current homeostasis in hippocampal KO neurons; however, synaptic alterations resulted in a reduction of excitatory synapse number, causing an imbalance of the excitatory-inhibitory synaptic input ratio favoring inhibition.

Human challenge studies: a review of adequacy of reporting methods and results.

Since the 1940s, researchers have purposefully infected healthy adult humans with pathogenic organisms to study how these pathogens cause disease and can be treated and prevented. 'Challenge studies' can be safe, ethical, extremely informative and an efficient use of resources during the clinical development of vaccines, but knowledge of this form of clinical research trial is not widespread. A review of the human challenge literature was performed to determine whether common elements of challenge studies can be identified in the articles published to date. The review demonstrated incomplete reporting of study characteristics deemed necessary for the correct interpretation and application of human challenge study results and for the accurate replication of study methodology. An unofficial extension of the Consolidated Standards of Reporting Trials (CONSORT) statement is proposed.