Tumour-specific mesorectal excision (TSME) practice for rectal cancer only relies on small retrospective studies. This study aimed to perform a systematic review and meta-analysis to assess the ...oncological and functional outcomes of TSME practice.
A systematic review protocol was drawn to include all the studies that compared partial versus total mesorectal excision (PME vs TME) practised for rectal adenocarcinoma up to 16 cm from the anal verge. A systematic literature search was conducted on EMBASE-Medline, Pubmed and Cochrane Library. Reports were screened for the study's outcomes: oncological radicality, postoperative anastomotic leak risk and functional outcomes. Included studies were appraised for risk-of-bias and meta-analysed. Evidence was rated with the GRADE approach.
Twenty-seven studies were included, consisting of 12325 patients (PME n = 4460, 36.2%; TME n = 7865, 63.8%). PME was performed for tumours higher than 10 cm from the anal verge in 54.5% of patients. There was no difference between PME and TME in circumferential resection margin positivity (OR 1.31, 95%CI 0.43–3.95, p = 0.64; I2 = 38%), and local recurrence risk (HR 1.05, 95%CI 0.52–2.10, p = 0.90; I2 = 40%). The postoperative leak risk (OR 0.42, 95%CI 0.27–0.67, p < 0.001; I2 = 60%) and the major low anterior resection syndrome risk (OR 0.34, 95%CI 0.28–0.40, p < 0.001; I2 = 0%) were lower after PME surgery. No difference was found in urinary incontinence (OR 0.68, 95%CI 0.13–3.67, p = 0.66) and urinary retention after early catheter removal (OR 2.00, 95%CI 0.24–16.51, p = 0.52).
Evidence from this meta-analysis shows that TSME for rectal cancer has good oncological results and leads to the best-fitted functional results possible for the patient's condition.
Background
The association between compliance to an enhanced recovery protocol (ERAS) and outcome after surgery for gastric cancer has been poorly investigated, particularly in Western patients. The ...aim of the study was to evaluate whether the rate of adherence to the ERAS program was correlated with outcome and time of discharge.
Methods
A prospective, observational, multicenter study was designed to be performed at Italian referral centers for gastric surgery. The protocol was discussed and approved by the Italian Research Group on Gastric Cancer. Twenty-three ERAS domains were applied. A multivariate logistic regression was used to assess the association between ERAS compliance and overall and major complication rates. The Poisson regression model (measured as mean ratios) was used to assess the association of ERAS compliance rate and length of stay (LOS).
Results
Eight centers participated and 290 subjects with a median age of 73 years were enrolled. The overall rates of adherence to pre-, intra-, and postoperative ERAS items were 69.8%, 60.3%, and 82.5%, respectively. At the multivariate model, there was an association between overall rate of morbidity and an overall ERAS compliance rate greater than 70% (OR 0.413; 95% CI 0.235–0.7240; P 0.002). A similar association was found for major complications (OR 0.328; 95% CI 0.151–0.709; P 0.005). The Poisson regression showed that in patients with ERAS compliance rate >70%, LOS was reduced of approximately 20% (mean ratio 0.812; 95% CI 0.694–0.950; P 0.009).
Conclusions
These results suggest a moderate compliance to an ERAS program and a significant association between adherence and outcomes.
Background
Gastric cancer (GC) is the third leading cause of cancer-related death worldwide, with a poor prognosis for patients with advanced disease. Since the oncogenic role of
KRAS
mutants has ...been poorly investigated in GC, this study aims to biochemically and biologically characterize different
KRAS-mutated
models and unravel differences among
KRAS
mutants in response to therapy.
Methods
Taking advantage of a proprietary, molecularly annotated platform of more than 200 GC PDXs (patient-derived xenografts), we identified KRAS-mutated PDXs, from which primary cell lines were established. The different mutants were challenged with KRAS downstream inhibitors in in vitro and in vivo experiments.
Results
Cells expressing the rare
KRAS A146T
mutant showed lower RAS-GTP levels compared to those bearing the canonical
G12/13D
mutations. Nevertheless, all the KRAS-mutated cells displayed
KRAS
addiction. Surprisingly, even if the GEF SOS1 is considered critical for the activation of
KRAS A146T
mutants, its abrogation did not significantly affect cell viability. From the pharmacologic point of view, Trametinib monotherapy was more effective in
A146T
than in
G12D
-mutated models, suggesting a vulnerability to MEK inhibition. However, in the presence of mutations in the PI3K pathway, more frequently co-occurrent in A146T models, the association of Trametinib and the AKT inhibitor MK-2206 was required to optimize the response.
Conclusion
A deeper genomic and biological characterization of
KRAS
mutants might sustain the development of more efficient and long-lasting therapeutic options for patients harbouring
KRAS
-driven GC.
Background and Objectives
Several inflammation markers were found to have a prognostic value in cancer. We investigated the significance of preoperative white cell ratios in determining ...gastrointestinal stromal tumors (GISTs) outcome.
Methods
Clinicopathological features of patients who underwent surgery for GIST were reviewed. The following peripheral blood inflammation markers were calculated: neutrophil‐lymphocyte ratio (NLR), monocyte‐lymphocyte ratio (MLR), platelet‐lymphocyte ratio (PLR), neutrophil‐white blood cell ratio (NWR), lymphocyte‐white cell ratio (LWR), monocyte‐white cell ratio (MWR), and platelet‐white cell ratio (PWR).
Results
We analyzed 127 patients. Three‐ and five‐year disease‐free survival (DFS) were 89.7% and 86.9%, respectively. The univariate analysis selected tumor diameter (P = 0.003), gastric location (
P = 0.024), cell type (
P = 0.024), mitosis (
P < 0.001), MLR (
P = 0.014), NLR (
P = 0.016), and PLR (
P = 0.001) as the factors associated to DFS. The independent prognostic factors for DFS were mitosis (
P = 0.001), NLR (
P = 0.015), MLR (
P = 0.015), and PLR (
P = 0.031), with MLR showing the highest statistical significance and hazard ratio (HR) value. MLR, NLR, and PLR were the only prognostic factors in the subgroup of patients with moderate to high Miettinen's risk class. A high value of MLR was associated with reduced DFS.
Conclusion
MLR, NLR, and PLR are independent prognostic factors for DFS in GISTs. We first demonstrated the role of MLR as a predictor of recurrence in GIST. Its inclusion into clinical management may improve the recurrence estimation.
Management of mediastinal anastomotic leaks (MALs) after Ivor Lewis esophagectomy includes conservative, endoscopic, or surgical management. Endoscopic vacuum therapy (EVAC) is becoming a routine ...approach for MALs, although the outcomes have not been defined. This study aimed to describe the incidence, treatment, and outcomes of MALs in patients who underwent esophagectomy in 3 Italian high-volume centers that routinely use EVAC for MAL.
Patients who underwent Ivor Lewis esophagectomy between September 2018 and March 2023 were included.
A total of 681 patients underwent Ivor Lewis esophagectomy, of whom 88 had MAL. The MAL rates for open, minimally invasive, and robotic esophagectomies were 11.5%, 13.4%, and 14.8%, respectively. Global and specific 30- and 90-day mortality rates for MAL were 0.9% and 2.1% and 6.8% and 15.9%, respectively. Nonoperative management (NOM) as the primary treatment was chosen for 62 patients. EVAC was the most common NOM (62.9%), and the most common operative management (OM) was anastomotic redo (53.8%). Diversion was the OM for 7 patients, of whom 3 patients died. Primary treatment proved successful in 40 patients. Among them, EVAC alone was successful in 35.9% of patients. Globally, endoscopic treatment, including EVAC, was successful in 79.0% of NOM and 55.7% of MALs. NOM and OM were chosen as secondary treatments for 27 and 10 patients, respectively. Secondary treatment proved successful in 21 patients.
The incidence of MALs after Ivor Lewis esophagectomy is approximately 13%. Endoscopic techniques have a success rate of almost 80%, with EVAC representing a significant part of this treatment process.
Background
Radio-guided surgery (RGS) holds promise for improving surgical outcomes in neuroendocrine tumors (NETs). Previous studies showed low specificity (SP) using γ-probes to detect radiation ...emitted by radio-labeled somatostatin analogs.
Objective
We aimed to assess the sensitivity (SE) and SP of the intraoperative RGS approach using a β-probe with a per-lesion analysis, while assessing safety and feasibility as secondary objectives.
Methods
This prospective, single-arm, single-center, phase II trial (NCT05448157) enrolled 20 patients diagnosed with small intestine NETs (SI-NETs) with positive lesions detected at
68
Ga-DOTA-TOC positron emission tomography/computed tomography (PET/CT). Patients received an intravenous injection of 1.1 MBq/Kg of 68Ga-DOTA-TOC 10 min prior to surgery. In vivo measurements were conducted using a β-probe. Receiver operating characteristic (ROC) analysis was performed, with the tumor-to-background ratio (TBR) as the independent variable and pathology result (cancer vs. non-cancer) as the dependent variable. The area under the curve (AUC), optimal TBR, and absorbed dose for the surgery staff were reported.
Results
The intraoperative RGS approach was feasible in all cases without adverse effects. Of 134 specimens, the AUC was 0.928, with a TBR cut-off of 1.35 yielding 89.3% SE and 86.4% SP. The median absorbed dose for the surgery staff was 30 µSv (range 12–41 µSv).
Conclusion
This study reports optimal accuracy in detecting lesions of SI-NETs using the intraoperative RGS approach with a novel β-probe. The method was found to be safe, feasible, and easily reproducible in daily clinical practice, with minimal radiation exposure for the staff. RGS might potentially improve radical resection rates in SI-NETs.
Clinical Trials Registration
68
Ga-DOTATOC Radio-Guided Surgery with β-Probe in GEP-NET (RGS GEP-NET) NCT0544815;
https://classic.clinicaltrials.gov/ct2/show/NCT05448157
Purpose
Pre-operative diagnosis and staging of small intestine neuroendocrine tumors (SI-NETs) remain sub-optimal, with open palpation during surgery still considered the gold standard. This limits a ...standardized implementation of minimally invasive surgery (MIS). The aim of this single-center retrospective study was to assess a tailored diagnostic work-up to identify candidates at low risk of undetected disease who may benefit from MIS.
Methods
Patients diagnosed with SI-NETs between 2013 and 2022 who underwent contrast-enhanced computed tomography enterography (CTE) and Ga68-DOTATOC-positron emission tomography-CT (68 Ga DOTATATE PET/CT) preoperatively and subsequently underwent open surgical resection were included. Imaging studies were reassessed by two radiologists. Combined use of CTE and 68 Ga DOTATATE PET/CT in determining primary lesion disease burden (number of lesions) and LN disease stage (distal and proximal relative to superior mesenteric vessels) was assessed, using surgical reports and pathology as gold standard.
Results
Overall, 56 patients were included. Sensitivity of CTE and 68 Ga DOTATATE PET/CT for at least one primary SI-NET was 100% and 94%, respectively. In the presence of concordance between studies, combined use of CTE and 68 Ga DOTATATE PET/CT for detection of single primary tumors improved specificity to 89% (
n
= 25/28) with a positive predictive value of 87.5% (
n
= 21/24). Distal LN disease was identified in 89.2% of cases (
n
= 33/37). The association of single lesion and distal LN disease was found pre-operatively in 32% of patients (
n
= 18).
Conclusion
Combined use of CTE and 68 Ga DOTATATE PET/CT enables identifying low-risk surgical candidates (single SI-NET lesions with distal LN disease).
Introduction
The COVID-19 pandemic has resulted in unparalleled changes to patient care, including the suspension of cancer surgery. Concerns regarding COVID-19-related risks to patients and ...healthcare workers with the re-introduction of major complex minimally invasive and open surgery have been raised. This study examines the COVID-19 related risks to patients and healthcare workers following the re-introduction of major oesophago-gastric (EG) surgery.
Patients and Methods
This was an international, multi-centre, observational study of consecutive patients treated by open and minimally invasive oesophagectomy and gastrectomy for malignant or benign disease. Patients were recruited from nine European centres serving regions with a high population incidence of COVID-19 between 1 May and 1 July 2020. The primary endpoint was 30-day COVID-19-related mortality. All staff involved in the operative care of patients were invited to complete a health-related survey to assess the incidence of COVID-19 in this group.
Results
In total, 158 patients were included in the study (71 oesophagectomy, 82 gastrectomy). Overall, 87 patients (57%) underwent MIS (59 oesophagectomy, 28 gastrectomy). A total of 403 staff were eligible for inclusion, of whom 313 (78%) completed the health survey. Approaches to mitigate against the risks of COVID-19 for patients and staff varied amongst centres. No patients developed COVID-19 in the post-operative period. Two healthcare workers developed self-limiting COVID-19.
Conclusions
Precautions to minimise the risk of COVID-19 infection have enabled the safe re-introduction of minimally invasive and open EG surgery for both patients and staff. Further studies are necessary to determine the minimum requirements for mitigations against COVID-19.
Utilizing a standardized dataset based on a newly developed list of 27 univocally defined complications, this study analyzed data to assess the incidence and grading of complications and evaluate ...outcomes associated with gastrectomy for cancer in Europe.
The absence of a standardized system for recording gastrectomy-associated complications makes it difficult to compare results from different hospitals and countries.
Using a secure online platform (www.gastrodata.org), referral centers for gastric cancer in 11 European countries belonging to the Gastrectomy Complications Consensus Group recorded clinical, oncological, and surgical data, and outcome measures at hospital discharge and at 30 and 90 days postoperatively. This retrospective observational study included all consecutive resections over a 2-year period.
A total of 1349 gastrectomies performed between January 2017 and December 2018 were entered into the database. Neoadjuvant chemotherapy was administered to 577 patients (42.8%). Total (46.1%) and subtotal (46.4%) gastrectomy were the predominant resections. D2 or D2+ lymphadenectomy was performed in almost 80% of operations. The overall complications' incidence was 29.8%; 402 patients developed 625 complications, with the most frequent being nonsurgical infections (23%), anastomotic leak (9.8%), other postoperative abnormal fluid from drainage and/or abdominal collections (9.3%), pleural effusion (8.3%), postoperative bleeding (5.6%), and other major complications requiring invasive treatment (5.6%). The median Clavien-Dindo score and Comprehensive Complications Index were IIIa and 26.2, respectively. In-hospital, 30-day, and 90-day mortality were 3.2%, 3.6%, and 4.5%, respectively.
The use of a standardized platform to collect European data on perioperative complications revealed that gastrectomy for gastric cancer is still associated with heavy morbidity and mortality. Actions are needed to limit the incidence of, and to effectively treat, the most frequent and most lethal complications.
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