OBJECTIVE:The aim of this study was to assess long-term health-related quality of life (HRQL) in patients after thoracoscopic and open esophagectomy.
SUMMARY OF BACKGROUND DATA:Trials comparing ...minimally invasive with open transthoracic esophagectomy have shown improved short-term outcomes; however, long-term HRQL data are lacking. This prospective nonrandomized study compared HRQL and survival after thoracoscopically assisted McKeown esophagectomy (TAMK) and open transthoracic Ivor Lewis esophagectomy (TTIL) for esophageal or gastroesophageal junction (GEJ) cancer.
METHODS:Patients with esophageal or GEJ cancer selected for TAMK or TTIL completed baseline and follow-up HRQL assessments for up to 24 months using the EORTC generic and disease-specific measures, QLQ-C30 and QLQ-OES18. Baseline clinical variables were examined between the treatment groups and changes in mean HRQL scores over time estimated and tested using generalised estimating equations with propensity score (generated by boosted regression) adjustment.
RESULTS:Of the 487 patients, 377 underwent TAMK and 110 underwent TTIL. Most clinical variables were similar in the 2 groups; however, there were significantly more patients with AJCC stage 3 disease who underwent TTIL than TAMK (54% vs 32%, P < 0.01) and this was reflected in the survival data.Mean symptom scores for pain were significantly higher in the TTIL group than in TAMK for 2 years postoperatively (P = 0.036). In addition, mean constipation scores were significantly higher for the TTIL group, with a 15-point difference in mean score at 3 months postoperatively (P = 0.037).
CONCLUSIONS:This large comprehensive nonrandomized analysis of longitudinal HRQL shows that TTIL is associated with more pain and constipation than TAMK.
The perioperative intravenous fluid administration in each group was measured from the onset of anaesthesia within two time periods: 0–24 h and 24–48 h. Secondary outcomes were postoperative ...vasopressor requirements, 30-day mortality, morbidity (including acute kidney injury (AKI), PPC, arrhythmia, anastomotic leak), length of hospital stay and hospital readmission rates. ...intraoperative fluid restriction was not associated with harm and should be considered as the standard for esophagectomy.CRediT authorship contribution statement Rachel L. Ng: Conceptualization, Methodology, Investigation, Writing - original draft, Validation. ERAS N = 61 Traditional care N = 57 P value Intraoperative blood loss; ml 220 (110–400) 350 (200–530) 0.009 Intraoperative fluid administration; ml Crystalloid 1847 (1400–2150) 4000 (3100–5000) <0.001 Colloid 500 (0–784) 1000 (500–1500) <0.001 Total 2300 (1842–2736) 5000 (4000–6000) <0.001 Intraoperative fluid infusion rate; ml·kg−1·h−1 4.1 (3.1–5.3) 9.5 (7.4–11.9) <0.001 Postoperative ICU fluid administration in first 24 h; ml Crystalloid 1355 (1142–1566) 1547 (1355–1745) 0.003 Colloid 250 (0–500) 250 (0–750) 0.60 Total 1675 (1355–2107) 1928 (1534–2484) 0.04 Total fluid administration between 0 and 24 h; ml 3995 (3470–4843) 7214 (5855–8078) <0.001 Total fluid administration between 24 and 48 h; ml 2000 (1520–2408) 1920 (1660–2277) 1.0 Post-operative vasopressor use 19 (31) 18 (32) 0.96 30-day mortality 0 0 Perioperative morbidity Overall 40 (66) 47 (82) 0.04 Major 16 (27) 15 (27) 1.0 Postoperative pulmonary complications Overall 30 (49) 31 (54) 0.59 Major 16 (26) 13 (23) 0.71 Arrhythmia/AF 17 (28) 13 (23) 0.54 Anastomotic leak Overall 14 (23) 9 (16) 0.34 Major (required active intervention) 4 (7) 3 (5) 0.65 Acute kidney injury 8 (13) 13 (23) 0.17 Length of hospital stay; days 11 (8–19) 15 (11–20) 0.008 Readmission to hospital (30 day) 6 (10) 4 (7) 0.56 Table 1 Periopoerative fluid volumes and outcomes.
Background
The optimal treatment strategy for patients with esophageal adenocarcinoma (EAC) remains undetermined. This study compared outcomes in patients undergoing neoadjuvant chemotherapy (nCT) ...and neoadjuvant chemoradiotherapy (nCRT) for EAC.
Methods
Patients who underwent nCT or nCRT followed by surgery for EAC were identified from a prospective database (2000‐2017) and included. After propensity score matching, the impact of the treatments on postoperative complications, in‐hospital mortality, pathological outcomes, and survival rates were compared.
Results
Of the 396 eligible patients, 262 patients were analysed following matching with 131 patients in both groups. There were no significant differences between the nCT and nCRT groups for overall complications (59% vs 57%, P = 0.802) or in‐hospital mortality (2% vs 0%, P = 0.156). Patients who had nCRT had more R0 resections (93% vs 83%, P = 0.013), and higher pathological complete response rates (15% vs 5%, P < 0.001). No differences in 5‐year overall survival rates (nCT vs nCRT; 44% vs 33%, P = 0.645) were found.
Conclusion
In this study no differences between nCT and nCRT were seen in postoperative complications and in‐hospital mortality in patients treated for EAC. Inspite of improved complete resection and pathological response there was no difference in the overall survival between the treatment modalities.
Background
Little is known about the association between signet ring cell (SRC) differentiation and response to neoadjuvant chemotherapy (nCT) or neoadjuvant chemoradiotherapy (nCRT) in patients with ...esophageal and junctional adenocarcinoma (EAC). We aimed to assess if SRC differentiation is associated with survival and response to nCT or nCRT in patients with EAC.
Methods
Patients who underwent nCT and nCRT followed by surgery for EAC from 2000 until 2016 were identified from two institutional prospectively maintained databases. The pretreatment biopsy report or surgical resection specimen was used to differentiate patients into an SRC or non-SRC group.
Results
Overall, 129 (19%) of 689 patients included had SRCs (nCT:
n
= 64; nCRT:
n
= 65). The SRC group had a more advanced ypT stage (
p
= 0.003), a higher number of positive lymph nodes in the resection specimen {median (interquartile range IQR) 2 0–5 vs. 1 0–3;
p
= 0.002} and a higher rate of R1/R2 resections (19.4% vs. 12%;
p
= 0.026). SRC differentiation was not an independent prognostic factor for overall survival (OS) or disease-free survival (DFS). Following nCT, the SRC group had significantly shorter DFS (median IQR 12 5–50 vs. 23 8–164;
p
= 0.013), but not OS, compared with the non-SRC group. In contrast, no differences according to SRC status for OS or DFS were found in patients who underwent nCRT.
Conclusions
SRC differentiation was not independently associated with worse OS in patients with EAC who underwent neoadjuvant therapy and surgery. However, nCRT was associated with greater tumor downstaging and better DFS.
Neoadjuvant therapy (NAT) for oesophageal cancer may reduce cardiopulmonary function, assessed by cardiopulmonary exercise testing (CPEX). Impaired cardiopulmonary function is associated with ...mortality following esophagectomy. We sought to assess the impact of NAT on cardiopulmonary function using CPEX and assessing the clinical relevance of any change in particular if changes were associated with post-operative morbidity.
This was a prospective, cohort study of 40 patients in whom CPEX was performed before and after NAT. Thirty-eight patients underwent surgery and follow-up with perioperative outcomes measured. The primary variables derived from CPEX were the anaerobic threshold (AT) and peak oxygen uptake (V˙O2peak).
There were significant reductions in the AT (pre-NAT: 12.4 ± 3.0 vs. post-NAT 10.6 ± 2.0 mL kg−1.min−1; p = 0.001). This reduction was also evident for V˙O2peak (pre-NAT: 16.6 ± 3.6 vs. post-NAT 14.9 ± 3.7 mL kg−1.min−1; p = 0.004). The relative reduction in V˙O2peak was greater in chemotherapy patients who developed any peri-operative morbidity (p = 0.04). For patients who underwent chemoradiotherapy, there was a significantly greater relative reduction in AT (p = 0.03) for those who encountered a respiratory complication.
Cardiopulmonary function significantly declined as a result of NAT prior to oesophagectomy. The reduction in AT and V˙O2peak was similar in both the chemotherapy and chemoradiotherapy groups.
•Neoadjuvant therapy reduces a patient's anaerobic threshold (AT) by 14.5%.•Neoadjuvant therapy reduces a patient's peak oxygen uptake (V˙O2peak) by 10.2%.•The reduction in cardiopulmonary function is similar with neoadjuvant chemotherapy and neoadjuvant chemoradiotherapy.
The authors report the recurrence pattern of esophageal cancer after thoracoscopic-assisted esophagectomy (TAE), comparing it to the recurrence pattern after open surgery and identify prognostic ...factors for recurrence.
To improve long-term survival for esophageal cancer radical surgery has been proposed increasingly, however, recurrent disease remains a problem. Opinion is divided as to the adequacy of resection possible using minimally invasive techniques with concerns that there may be an increased incidence in locoregional recurrence.
A total of 221 patients who underwent esophagectomy at the Princess Alexandra Hospital without any neoadjuvant or adjuvant therapy were identified from a prospective database. Patients were followed up for the detection of symptomatic recurrence for a median of 59 months.
Within this group 165 patients underwent TAE and 56 an open transthoracic esophagectomy (TTE). The 5-year overall recurrence rate was 133/221 (60%). The 5-year rates of symptomatic first recurrence following TAE was 4%, 9%, and 47% for local, regional, and distant recurrence, respectively. The 5-year rates of symptomatic first recurrence following TTE was 5%, 18%, and 55% for local, regional, and distant recurrence, respectively. Operative approach was not a prognostic factor for any type of recurrence. Independent prognostic factors associated with locoregional recurrence were positive margins and number of positive nodes. Distant recurrence was associated with T stage, differentiation, tumor length >6 cm, and number of positive nodes.
Distant recurrence remains a significant problem in esophageal cancer. TAE achieved adequate locoregional control and compared favorably with open TTE.
Background
The incidence of gastric cancer is decreasing in Australia, yet it remains a common cause of cancer-related mortality. Surgical resection remains the cornerstone of curative treatment. ...High-volume specialized units have reported superior perioperative and oncological outcomes. The role of D2 lymphadenectomy has been controversial as a result of concerns over increased morbidity. Our aim is to report the perioperative and oncological outcomes of curative gastric resection from a specialist Australian upper GI unit.
Methods
Data from a prospectively maintained database were reviewed for all patients undergoing curative resection for gastric adenocarcinoma from a single unit during a 12-year period. Perioperative and long-term outcomes were compiled.
Results
There were 255 curative gastric resections during 12 years. An R0 resection was performed in 96 % with a perioperative mortality rate of 1.6 %. A D2 dissection was performed in 85 % of cases in the past 6 years, with no increase in perioperative morbidity or mortality detected. The 5-year overall survival was 53 %.
Conclusion
Our results demonstrate that both short- and long-term outcomes of surgical resection in gastric cancer patients, comparable to international high-volume centers, can be achieved in an Australian upper GI unit. A D2 lymph node dissection can be performed safely without any increase in perioperative risk in a specialist unit that has the necessary training but also the perioperative support structures to manage these complex patients.
Casitas B-lymphoma proto-oncogene-b (Cbl-b), a member of the Cbl family of RING finger E3 ubiquitin ligases, has been demonstrated to play a central role in regulating effector T-cell function. ...Multiple studies using gene-targeting approaches have provided direct evidence that Cbl-b negatively regulates T, B, and NK cell activation via a ubiquitin-mediated protein modulation. Thus, inhibition of Cbl-b ligase activity can lead to immune activation and has therapeutic potential in immuno-oncology. Herein, we describe the discovery and optimization of an arylpyridone series as Cbl-b inhibitors by structure-based drug discovery to afford compound 31. This compound binds to Cbl-b with an IC50 value of 30 nM and induces IL-2 production in T-cells with an EC50 value of 230 nM. Compound 31 also shows robust intracellular target engagement demonstrated through inhibition of Cbl-b autoubiquitination, inhibition of ubiquitin transfer to ZAP70, and the cellular modulation of phosphorylation of a downstream signal within the TCR axis.
ObjectivesFor patients with a reduced left ventricular ejection fraction (LVEF) heart failure with reduced ejection fraction (HFrEF) and iron deficiency, administration of intravenous iron improves ...symptoms, exercise capacity and may in the following 12 months, reduce hospitalisations for heart failure. The Effectiveness of Intravenous iron treatment versus standard care in patients with heart failure and iron deficiency (IRONMAN) trial evaluated whether the benefits of intravenous iron persist in the longer term and impact on morbidity and mortality.MethodsIRONMAN is a prospective, randomised, open-label, blinded endpoint (PROBE) event-driven trial. Patients aged ≥18 years with HFrEF (LVEF ≤45%) and evidence of iron deficiency (ferritin <100 µg/L and/or TSAT <20%) were enrolled if they had either a current or recent hospitalisation for heart failure or elevated plasma concentrations of a natriuretic peptide. Participants were randomised to receive, or not to receive, intravenous ferric derisomaltose in addition to guideline-recommended therapy for HFrEF. Every 4 months, intravenous iron was administered if either ferritin was <100 µg/L or, provided ferritin was ≤400 µg/L, TSAT was <25%. The primary endpoint is a composite of total hospitalisations for heart failure and cardiovascular death. Hospitalisation and deaths due to infection are safety endpoints.ResultsTrial recruitment was completed across 70 UK hospital sites in October 2021. Participants were followed until the end of March 2022. We plan to report the results by November 2022.ConclusionsIRONMAN will determine whether repeated doses of intravenous ferric derisomaltose are beneficial and safe for the long-term treatment of a broad range of patients with HFrEF and iron deficiency.Trial registration number NCT02642562.
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