Intracorporeal and extracorporeal anastomosis for robotic-assisted and laparoscopic right colectomy: Short-term outcomes of a multi-center prospective trial

BACKGROUND: Studies to date show contrasting conclusions when comparing intracorporeal and extracorporeal anastomoses for minimally invasive right colectomy. Large multi-center prospective studies comparing perioperative outcomes between these two techniques are needed. The purpose of this study was to compare intracorporeal and extracorporeal anastomoses outcomes for robotic assisted and laparoscopic right colectomy. METHODS: Multi-center, prospective, observational study of patients with malignant or benign disease scheduled for laparoscopic or robotic-assisted right colectomy. Outcomes included conversion rate, gastrointestinal recovery, and complication rates. RESULTS: There were 280 patients: 156 in the robotic assisted and laparoscopic intracorporeal anastomosis (IA) group and 124 in the robotic assisted and laparoscopic extracorporeal anastomosis (EA) group. The EA group was older (mean age 67 vs. 65 years, p = 0.05) and had fewer white (81% vs. 90%, p = 0.05) and Hispanic (2% vs. 12%, p = 0.003) patients. The EA group had more patients with comorbidities (82% vs. 72%, p = 0.04) while there was no significant difference in individual comorbidities between groups. IA was associated with fewer conversions to open and hand-assisted laparoscopic approaches (p = 0.007), shorter extraction site incision length (4.9 vs. 6.2 cm; p ≤ 0.0001), and longer operative time (156.9 vs. 118.2 min). Postoperatively, patients with IA had shorter time to first flatus, (1.5 vs. 1.8 days; p ≤ 0.0001), time to first bowel movement (1.6 vs. 2.0 days; p = 0.0005), time to resume soft/regular diet (29.0 vs. 37.5 h; p = 0.0014), and shorter length of hospital stay (median, 3 vs. 4 days; p ≤ 0.0001). Postoperative complication rates were comparable between groups. CONCLUSION: In this prospective, multi-center study of minimally invasive right colectomy across 20 institutions, IA was associated with significant improvements in conversion rates, return of bowel function, and shorter hospital stay, as well as significantly longer operative times compared to EA. These data validate current efforts to increase training and adoption of the IA technique for minimally invasive right colectomy

Total Neoadjuvant Therapy With Short-Course Radiation: US Experience of a Neoadjuvant Rectal Cancer Therapy

BACKGROUND: Short-course radiation followed by chemotherapy as total neoadjuvant therapy has been investigated primarily in Europe and Australia with increasing global acceptance. There are limited data on this regimen\u27s use in the United States, however, potentially delaying implementation. OBJECTIVE: This study aimed to compare clinical performance and oncologic outcomes of 2 rectal cancer neoadjuvant treatment modalities: short-course total neoadjuvant therapy versus standard chemoradiation. DESIGN: This is a retrospective cohort study. SETTING: This study was performed at a National Cancer Institute-designated cancer center. PATIENTS: A total of 413 patients had locally advanced rectal cancers diagnosed from June 2009 to May 2018 and received either short-course total neoadjuvant therapy or standard chemoradiation. INTERVENTIONS: There were 187 patients treated with short-course total neoadjuvant therapy (5 × 5 Gy radiation followed by consolidation oxaliplatin-based chemotherapy) compared with 226 chemoradiation recipients (approximately 50.4 Gy radiation in 28 fractions with concurrent fluorouracil equivalent). MAIN OUTCOME MEASURES: Primary end points were tumor downstaging, measured by complete response and low neoadjuvant rectal score rates, and progression-free survival. Secondary analyses included treatment characteristics and completion, sphincter preservation, and recurrence rates. RESULTS: Short-course total neoadjuvant therapy was associated with higher rates of complete response (26.2% vs 17.3%; p = 0.03) and low neoadjuvant rectal scores (40.1% vs 25.7%; p \u3c 0.01) despite a higher burden of node-positive disease (78.6% vs 68.9%; p = 0.03). Short-course recipients also completed trimodal treatment more frequently (88.4% vs 50.4%; p \u3c 0.01) and had fewer months with temporary stomas (4.8 vs 7.0; p \u3c 0.01). Both regimens achieved comparable local control (local recurrence: 2.7% short-course total neoadjuvant therapy vs 2.2% chemoradiation, p = 0.76) and 2-year progression-free survival (88.2% short-course total neoadjuvant therapy (95% CI, 82.9-93.5) vs 85.6% chemoradiation (95% CI, 80.5-90.7)). LIMITATIONS: Retrospective design, unbalanced disease severity, and variable dosing of neoadjuvant consolidation chemotherapy were limitations of this study. CONCLUSIONS: Short-course total neoadjuvant therapy was associated with improved downstaging and similar progression-free survival compared with chemoradiation. These results were achieved with shortened radiation courses, improved treatment completion, and less time with diverting ostomies. Short-course total neoadjuvant therapy is an optimal regimen for locally advanced rectal cancer

FDG-PET/MRI for nonoperative management of rectal cancer: A prospective pilot study

Nonoperative management (NOM) is increasingly utilized for rectal cancer patients with a clinical complete response (cCR) following total neoadjuvant therapy (TNT). The objective of this pilot study was to determine whether FDG-PET/MRI alters clinical response assessments among stage I-III rectal cancer patients undergoing TNT followed by NOM, relative to MRI alone. This prospective study included 14 subjects with new rectal cancer diagnoses. Imaging consisted of FDG-PET/MRI for initial staging, post-TNT restaging, and surveillance during NOM. Two independent readers assessed treatment response on MRI followed by FDG-PET/MRI. Inter-reader differences were resolved by consensus review. The reference standard for post-TNT restaging consisted of surgical pathology or clinical follow-up. 7/14 subjects completed post-TNT restaging FDG-PET/MRIs. 5/7 subjects had evidence of residual disease and underwent total mesorectal excision; 2/7 subjects had initial cCR with no evidence of disease after 12 months of NOM. FDG-PET/MRI assessments of cCR status at post-TNT restaging had an accuracy of 100%, compared with 71% for MRI alone, as FDG-PET detected residual tumor in 2 more subjects. Inter-reader agreement for cCR status on FDG-PET/MRI was moderate (kappa, 0.56). FDG-PET provided added value in 82% (9/11) of restaging/surveillance scans. Our preliminary data indicate that FDG-PET/MRI can detect more residual disease after TNT than MRI alone, with the FDG-PET component providing added value in most restaging/surveillance scans

Intracorporeal and Extracorporeal Anastomosis for Robotic-Assisted and Laparoscopic Right Colectomy: Short-Term Outcomes of a Multi-Center Prospective Trial

Background: Studies to date show contrasting conclusions when comparing intracorporeal and extracorporeal anastomoses for minimally invasive right colectomy. Large multi-center prospective studies comparing perioperative outcomes between these two techniques are needed. The purpose of this study was to compare intracorporeal and extracorporeal anastomoses outcomes for robotic assisted and laparoscopic right colectomy. Methods: Multi-center, prospective, observational study of patients with malignant or benign disease scheduled for laparoscopic or robotic-assisted right colectomy. Outcomes included conversion rate, gastrointestinal recovery, and complication rates. Results: There were 280 patients: 156 in the robotic assisted and laparoscopic intracorporeal anastomosis (IA) group and 124 in the robotic assisted and laparoscopic extracorporeal anastomosis (EA) group. The EA group was older (mean age 67 vs. 65 years, p = 0.05) and had fewer white (81% vs. 90%, p = 0.05) and Hispanic (2% vs. 12%, p = 0.003) patients. The EA group had more patients with comorbidities (82% vs. 72%, p = 0.04) while there was no significant difference in individual comorbidities between groups. IA was associated with fewer conversions to open and hand-assisted laparoscopic approaches (p = 0.007), shorter extraction site incision length (4.9 vs. 6.2 cm; p ≤ 0.0001), and longer operative time (156.9 vs. 118.2 min). Postoperatively, patients with IA had shorter time to first flatus, (1.5 vs. 1.8 days; p ≤ 0.0001), time to first bowel movement (1.6 vs. 2.0 days; p = 0.0005), time to resume soft/regular diet (29.0 vs. 37.5 h; p = 0.0014), and shorter length of hospital stay (median, 3 vs. 4 days; p ≤ 0.0001). Postoperative complication rates were comparable between groups. Conclusion: In this prospective, multi-center study of minimally invasive right colectomy across 20 institutions, IA was associated with significant improvements in conversion rates, return of bowel function, and shorter hospital stay, as well as significantly longer operative times compared to EA. These data validate current efforts to increase training and adoption of the IA technique for minimally invasive right colectomy

Investigation of hospital discharge cases and SARS-CoV-2 introduction into Lothian care homes

Background The first epidemic wave of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in Scotland resulted in high case numbers and mortality in care homes. In Lothian, over one-third of care homes reported an outbreak, while there was limited testing of hospital patients discharged to care homes. Aim To investigate patients discharged from hospitals as a source of SARS-CoV-2 introduction into care homes during the first epidemic wave. Methods A clinical review was performed for all patients discharges from hospitals to care homes from 1st March 2020 to 31st May 2020. Episodes were ruled out based on coronavirus disease 2019 (COVID-19) test history, clinical assessment at discharge, whole-genome sequencing (WGS) data and an infectious period of 14 days. Clinical samples were processed for WGS, and consensus genomes generated were used for analysis using Cluster Investigation and Virus Epidemiological Tool software. Patient timelines were obtained using electronic hospital records. Findings In total, 787 patients discharged from hospitals to care homes were identified. Of these, 776 (99%) were ruled out for subsequent introduction of SARS-CoV-2 into care homes. However, for 10 episodes, the results were inconclusive as there was low genomic diversity in consensus genomes or no sequencing data were available. Only one discharge episode had a genomic, time and location link to positive cases during hospital admission, leading to 10 positive cases in their care home. Conclusion The majority of patients discharged from hospitals were ruled out for introduction of SARS-CoV-2 into care homes, highlighting the importance of screening all new admissions when faced with a novel emerging virus and no available vaccine

SARS-CoV-2 Omicron is an immune escape variant with an altered cell entry pathway

Vaccines based on the spike protein of SARS-CoV-2 are a cornerstone of the public health response to COVID-19. The emergence of hypermutated, increasingly transmissible variants of concern (VOCs) threaten this strategy. Omicron (B.1.1.529), the fifth VOC to be described, harbours multiple amino acid mutations in spike, half of which lie within the receptor-binding domain. Here we demonstrate substantial evasion of neutralization by Omicron BA.1 and BA.2 variants in vitro using sera from individuals vaccinated with ChAdOx1, BNT162b2 and mRNA-1273. These data were mirrored by a substantial reduction in real-world vaccine effectiveness that was partially restored by booster vaccination. The Omicron variants BA.1 and BA.2 did not induce cell syncytia in vitro and favoured a TMPRSS2-independent endosomal entry pathway, these phenotypes mapping to distinct regions of the spike protein. Impaired cell fusion was determined by the receptor-binding domain, while endosomal entry mapped to the S2 domain. Such marked changes in antigenicity and replicative biology may underlie the rapid global spread and altered pathogenicity of the Omicron variant

Acute Tissue Injury Caused by Subcutaneous Fat Biopsies Produces Endoplasmic Reticulum Stress

Background: It is not known whether acute tissue injury is associated with endoplasmic reticulum (ER) stress

Association of omental pedicled flap with anastomotic leak following low anterior resection for rectal cancer

Background and objectives: Anastomotic leak following colorectal anastomosis adversely impacts short-term, oncologic, and quality-of-life outcomes. This study aimed to assess the impact of omental pedicled flap (OPF) on anastomotic leak among patients undergoing low anastomotic resection (LAR) for rectal cancer using a multi-institutional database.Methods: Adult rectal cancer patients in the US Rectal Cancer Consortium, who underwent a LAR for stage I-III rectal cancer with or without an OPF were included. Patients with missing data for surgery type and OPF use were excluded from the analysis. The primary outcome was the development of anastomotic leaks. Multivariable logistic regression was used to determine the association.Results: A total of 853 patients met the inclusion criteria and OPF was used in 106 (12.4%) patients. There was no difference in age, sex, or tumor stage of patients who underwent OPF versus those who did not. OPF use was not associated with an anastomotic leak (p = 0.82), or operative blood loss (p = 0.54) but was associated with an increase in the operative duration [β = 21.42 (95% confidence interval = 1.16, 41.67) p = 0.04].Conclusions: Among patients undergoing LAR for rectal cancer, OPF use was associated with an increase in operative duration without any impact on the rate of anastomotic leak