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2.
Ann Surg Oncol ; 2024 Mar 13.
Article in English | MEDLINE | ID: mdl-38480565

ABSTRACT

BACKGROUND: Radical esophagectomy for resectable esophageal cancer is a major surgical intervention, associated with considerable postoperative morbidity. The introduction of robotic surgical platforms in esophagectomy may enhance advantages of minimally invasive surgery enabled by laparoscopy and thoracoscopy, including reduced postoperative pain and pulmonary complications. This systematic review aims to assess the clinical and oncological benefits of robot-assisted esophagectomy. METHODS: A systematic literature search of the MEDLINE (PubMed), Embase and Cochrane databases was performed for studies published up to 1 August 2023. This review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) protocols and was registered in the PROSPERO database (CRD42022370983). Clinical and oncological outcomes data were extracted following full-text review of eligible studies. RESULTS: A total of 113 studies (n = 14,701 patients, n = 2455 female) were included. The majority of the studies were retrospective in nature (n = 89, 79%), and cohort studies were the most common type of study design (n = 88, 79%). The median number of patients per study was 54. Sixty-three studies reported using a robotic surgical platform for both the abdominal and thoracic phases of the procedure. The weighted mean incidence of postoperative pneumonia was 11%, anastomotic leak 10%, total length of hospitalisation 15.2 days, and a resection margin clear of the tumour was achieved in 95% of cases. CONCLUSIONS: There are numerous reported advantages of robot-assisted surgery for resectable esophageal cancer. A correlation between procedural volume and improvements in outcomes with robotic esophagectomy has also been identified. Multicentre comparative clinical studies are essential to identify the true objective benefit on outcomes compared with conventional surgical approaches before robotic surgery is accepted as standard of practice.

3.
Int J Surg ; 2024 Mar 25.
Article in English | MEDLINE | ID: mdl-38526511

ABSTRACT

BACKGROUND: Radical surgery for esophageal cancer requires macroscopic and microscopic clearance of all malignant tissue. A critical element of the procedure is achieving a negative circumferential margin (CRM) to minimize local recurrence. The utility of minimally invasive surgery poses challenges in replicating techniques developed in open surgery, particularly for hiatal dissection in esophago-gastrectomy. In this study, the technical approach and clinical and oncological outcomes for open and laparoscopic esophago-gastrectomy are described with particular reference to CRM involvement. MATERIALS AND METHODS: This cohort study included all patients undergoing either open or laparoscopic esophago-gastrectomy between January 2004 to June 2022 in a single tertiary center. A standard surgical technique for hiatal dissection of the esophago-gastric junction developed in open surgery was adapted for a laparoscopic approach. Clinical parameters, length of stay (LOS), post-operative complications and mortality data were collected and analyzed by a Mann-Whitney U or Fisher's exact method. RESULTS: Overall 447 patients underwent an esophago-gastrectomy in the study with 219 open and 228 laparoscopic procedures. The CRM involvement was 18.8% in open surgery and 13.6% in laparoscopic surgery. The 90-day-mortality for open surgery was 4.1% compared with 2.2% for laparoscopic procedures. Median Intensive care unit (ITU), inpatient LOS and 30-day readmission rates were shorter for laparoscopic compared with open esophago-gastrectomy (ITU: 5 versus 8 days, P=0.0004; LOS: 14 versus 20 days, P=0.022; 30-day re-admission 7.46% versus 10.50%). Post-operative complication rates were comparable across both cohorts. The rates of starting adjuvant chemotherapy were 51.8% after open and 74.4% in laparoscopic esophago-gastrectomy. CONCLUSION: This study presents a standardized surgical approach to hiatal dissection for esophageal cancer. We present equivalence between open and laparoscopic esophago-gastrectomy in clinical, oncological and survival outcomes with similar rates of CRM involvement. We also observe a significantly shorter hospital length of stay with the minimally invasive approach.

4.
Dis Esophagus ; 37(2)2024 Jan 31.
Article in English | MEDLINE | ID: mdl-38300628

ABSTRACT

The optimal treatment for esophageal cancer in elderly patients is still debated and data on postoperative results are limited. This retrospective international study aims to clarify the impact of age on clinical and oncological outcomes after esophagectomy. All patients that underwent esophagectomy for cancer between 2007 and 2016 at two European high-volume Centers have been included in the study. Patients were divided into three groups according to their age: young-age group (YAG) (18-69), middle-age group (70-74) and old-age group (>74). Primary outcome was 5-year overall survival (OS), while secondary outcomes considered were 5-year disease free survival and disease related survival, 90-day morbidity and mortality, readmission rate and radicality. A total of 575 patients were included. No differences emerged in terms of morbidity and length of stay, while mortality increased with aging from 2% in YAG to 4.8% in old-aged (P = 0.003). Old-age patients had less neoadjuvant treatment (P < 0.001), a less aggressive mediastinal lymphadenectomy and presented a more advanced pathological stage. As expected, OS decreased significantly for older patients compared with the other two age groups (P = 0.044) but, on the other hand, disease free and disease related survival were comparable between the groups. Age itself should not be considered a contraindication to esophagectomy. Although in patients older than 75 years postoperative mortality is significantly increased, esophagectomy could be still an option in selected patients, favoring the use of minimally invasive techniques and enhanced recovery protocols.


Subject(s)
Esophageal Neoplasms , Esophagectomy , Aged , Middle Aged , Humans , Retrospective Studies , Aging , Disease-Free Survival , Esophageal Neoplasms/surgery
5.
Br J Cancer ; 130(3): 457-466, 2024 02.
Article in English | MEDLINE | ID: mdl-38123705

ABSTRACT

BACKGROUND: Tumour-associated fat cells without desmoplastic stroma reaction at the invasion front (Stroma AReactive Invasion Front Areas (SARIFA)) is a prognostic biomarker in gastric and colon cancer. The clinical utility of the SARIFA status in oesophagogastric cancer patients treated with perioperative chemotherapy is currently unknown. METHODS: The SARIFA status was determined in tissue sections from patients recruited into the MAGIC (n = 292) or ST03 (n = 693) trials treated with surgery alone (S, MAGIC) or perioperative chemotherapy (MAGIC, ST03). The relationship between SARIFA status, clinicopathological factors, overall survival (OS) and treatment was analysed. RESULTS: The SARIFA status was positive in 42% MAGIC trial S patients, 28% MAGIC and 48% ST03 patients after pre-operative chemotherapy. SARIFA status was related to OS in MAGIC trial S patients and was an independent prognostic biomarker in ST03 trial patients (HR 1.974, 95% CI 1.555-2.507, p < 0.001). ST03 patients with lymph node metastasis (ypN + ) and SARIFA-positive tumours had poorer OS than patients with ypN+ and SARIFA-negative tumours (plogrank < 0.001). CONCLUSIONS: The SARIFA status has clinical utility as prognostic biomarker in oesophagogastric cancer patients irrespective of treatment modality. Whilst underlying biological mechanisms warrant further investigation, the SARIFA status might be used to identify new drug targets, potentially enabling repurposing of existing drugs targeting lipid metabolism.


Subject(s)
Adenocarcinoma , Stomach Neoplasms , Humans , Prognosis , Stomach Neoplasms/drug therapy , Stomach Neoplasms/surgery , Stomach Neoplasms/pathology , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Adenocarcinoma/pathology , Risk Assessment , Biomarkers
6.
Ann Surg ; 278(5): 823-831, 2023 11 01.
Article in English | MEDLINE | ID: mdl-37555342

ABSTRACT

OBJECTIVE: To assess the rate of textbook outcome (TO) and textbook oncological outcome (TOO) in the European population based on the GASTRODATA registry. BACKGROUND: TO is a composite parameter assessing surgical quality and strongly correlates with improved overall survival. Following the standard of treatment for locally advanced gastric cancer, TOO was proposed as a quality and optimal multimodal treatment parameter. METHODS: TO was achieved when all the following criteria were met: no intraoperative complications, radical resection according to the surgeon, pR0 resection, retrieval of at least 15 lymph nodes, no severe postoperative complications, no reintervention, no admission to the intensive care unit, no prolonged length of stay, no postoperative mortality and no hospital readmission. TOO was defined as TO with the addition of perioperative chemotherapy compliance. RESULTS: Of the 2558 patients, 1700 were included in the analysis. TO was achieved in 1164 (68.5%) patients. The use of neoadjuvant chemotherapy [odds ratio (OR) = 1.33, 95% CI: 1.04-1.70] and D2 or D2+ lymphadenectomy (OR = 1.55, 95% CI: 1.15-2.10) had a positive impact on TO achievement. Older age (OR = 0.73, 95% CI: 0.54-0.94), pT3/4 (OR = 0.79, 95% CI: 0.63-0.99), ASA 3/4 (OR = 0.68, 95% CI: 0.54-0.86) and total gastrectomy (OR = 0.56, 95% CI: 0.45-0.70), had a negative impact on TO achievement. TOO was achieved in 388 (22.8%) patients. Older age (OR = 0.37, 95% CI: 0.27-0.53), pT3 or pT4 (OR = 0.52, 95% CI: 0.39-0.69), and ASA 3 or 4 (OR = 0.58, 95% CI: 0.43-0.79) had a negative impact on TOO achievement. CONCLUSIONS: Despite successively improved surgical outcomes, stage-appropriate chemotherapy in adherence to the current guidelines for multimodal treatment of gastric cancer remains poor. Further implementation of oncologic quality metrics should include greater emphasis on perioperative chemotherapy and adequate lymphadenectomy.


Subject(s)
Stomach Neoplasms , Humans , Stomach Neoplasms/surgery , Lymph Node Excision/adverse effects , Lymph Nodes/pathology , Gastrectomy/adverse effects , Postoperative Complications/etiology , Retrospective Studies , Treatment Outcome
7.
J Clin Oncol ; 41(28): 4522-4534, 2023 10 01.
Article in English | MEDLINE | ID: mdl-37499209

ABSTRACT

PURPOSE: There is limited evidence regarding the prognostic effects of pathologic lymph node (LN) regression after neoadjuvant chemotherapy for esophageal adenocarcinoma, and a definition of LN response is lacking. This study aimed to evaluate how LN regression influences survival after surgery for esophageal adenocarcinoma. METHODS: Multicenter cohort study of patients with esophageal adenocarcinoma treated with neoadjuvant chemotherapy followed by surgical resection at five high-volume centers in the United Kingdom. LNs retrieved at esophagectomy were examined for chemotherapy response and given a LN regression score (LNRS)-LNRS 1, complete response; 2, <10% residual tumor; 3, 10%-50% residual tumor; 4, >50% residual tumor; and 5, no response. Survival analysis was performed using Cox regression adjusting for confounders including primary tumor regression. The discriminatory ability of different LN response classifications to predict survival was evaluated using Akaike information criterion and Harrell C-index. RESULTS: In total, 17,930 LNs from 763 patients were examined. LN response classified as complete LN response (LNRS 1 ≥1 LN, no residual tumor in any LN; n = 62, 8.1%), partial LN response (LNRS 1-3 ≥1 LN, residual tumor ≥1 LN; n = 155, 20.3%), poor/no LN response (LNRS 4-5; n = 303, 39.7%), or LN negative (no tumor/regression; n = 243, 31.8%) demonstrated superior discriminatory ability. Mortality was reduced in patients with complete LN response (hazard ratio [HR], 0.35; 95% CI, 0.22 to 0.56), partial LN response (HR, 0.72; 95% CI, 0.57 to 0.93) or negative LNs (HR, 0.32; 95% CI, 0.25 to 0.42) compared with those with poor/no LN response. Primary tumor regression and LN regression were discordant in 165 patients (21.9%). CONCLUSION: Pathologic LN regression after neoadjuvant chemotherapy was a strong prognostic factor and provides important information beyond pathologic TNM staging and primary tumor regression grading. LN regression should be included as standard in the pathologic reporting of esophagectomy specimens.


Subject(s)
Adenocarcinoma , Esophageal Neoplasms , Lymph Nodes , Humans , Adenocarcinoma/drug therapy , Adenocarcinoma/surgery , Adenocarcinoma/pathology , Cohort Studies , Esophageal Neoplasms/drug therapy , Esophageal Neoplasms/surgery , Esophagectomy , Lymph Nodes/surgery , Lymph Nodes/pathology , Neoadjuvant Therapy , Neoplasm Staging , Neoplasm, Residual/pathology , Prognosis , United Kingdom
8.
J Pathol Inform ; 14: 100192, 2023.
Article in English | MEDLINE | ID: mdl-36818020

ABSTRACT

Treatment of patients with oesophageal and gastric cancer (OeGC) is guided by disease stage, patient performance status and preferences. Lymph node (LN) status is one of the strongest prognostic factors for OeGC patients. However, survival varies between patients with the same disease stage and LN status. We recently showed that LN size from patients with OeGC might also have prognostic value, thus making delineations of LNs essential for size estimation and the extraction of other imaging biomarkers. We hypothesized that a machine learning workflow is able to: (1) find digital H&E stained slides containing LNs, (2) create a scoring system providing degrees of certainty for the results, and (3) delineate LNs in those images. To train and validate the pipeline, we used 1695 H&E slides from the OE02 trial. The dataset was divided into training (80%) and validation (20%). The model was tested on an external dataset of 826 H&E slides from the OE05 trial. U-Net architecture was used to generate prediction maps from which predefined features were extracted. These features were subsequently used to train an XGBoost model to determine if a region truly contained a LN. With our innovative method, the balanced accuracies of the LN detection were 0.93 on the validation dataset (0.83 on the test dataset) compared to 0.81 (0.81) on the validation (test) datasets when using the standard method of thresholding U-Net predictions to arrive at a binary mask. Our method allowed for the creation of an "uncertain" category, and partly limited false-positive predictions on the external dataset. The mean Dice score was 0.73 (0.60) per-image and 0.66 (0.48) per-LN for the validation (test) datasets. Our pipeline detects images with LNs more accurately than conventional methods, and high-throughput delineation of LNs can facilitate future LN content analyses of large datasets.

10.
Ann Surg Oncol ; 30(4): 2266-2275, 2023 Apr.
Article in English | MEDLINE | ID: mdl-36258058

ABSTRACT

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic caused unprecedented disruption to global healthcare delivery. In England, the majority of elective surgery was postponed or cancelled to increase intensive care capacity. Our unit instituted the 'RM Partners Cancer Hub' at the Royal Marsden Hospital in London, to deliver ongoing cancer surgery in a 'COVID-lite' setting. This article describes the operational set-up and outcomes for upper gastrointestinal (UGI) cancer resections performed during this period. METHODS: From April 2020 to April 2021, the Royal Marsden Hospital formed the RM Partners Cancer Hub. This approach was designed to coordinate resources and provide as much oncological treatment as feasible for patients across the RM Partners West London Cancer Alliance. A UGI surgical case prioritisation strategy, along with strict infection control pathways and pre-operative screening protocols, was adopted. RESULTS: A total of 231 patients underwent surgery for confirmed or suspected UGI cancer during the RM Partners Cancer Hub, with 213 completed resections and combined 90-day mortality rate of 3.5%. Good short-term survival outcomes were demonstrated with 2-year disease free survival (DFS) and overall survival (OS) for oesophageal (70.8% and 72.9%), gastric (66.7% and 83.3%) and pancreatic cancer resections (68.0% and 88.0%). One patient who developed perioperative COVID-19 during the RM Partners Cancer Hub operation made a full recovery with no lasting clinical sequelae. CONCLUSION: Our experience demonstrates that the RM Partners Cancer Hub approach is a safe strategy for continuing upper gastrointestinal (GI) resectional surgery during future periods of healthcare service disruption.


Subject(s)
COVID-19 , Digestive System Surgical Procedures , Neoplasms , Humans , Pandemics/prevention & control , Neoplasms/surgery , United Kingdom
11.
Ann Surg ; 277(2): e320-e331, 2023 02 01.
Article in English | MEDLINE | ID: mdl-34520429

ABSTRACT

OBJECTIVE: To analyze the relationship between negative lymph node (LNneg) size as a possible surrogate marker of the host antitumor immune response and overall survival (OS) in esophageal cancer (EC) patients. BACKGROUND: Lymph node (LN) status is a well-established prognostic factor in EC patients. An increased number of LNnegs is related to better survival in EC. Follicular hyperplasia in LNneg is associated with better survival in cancer-bearing mice and might explain increased LN size. METHODS: The long axis of 304 LNnegs was measured in hematoxylin-eosin stained sections from resection specimens of 367 OE02 trial patients (188 treated with surgery alone (S), 179 with neoadjuvant chemotherapy plus surgery (C+S)) as a surrogate of LN size. The relationship between LNneg size, LNneg microarchitecture, clinicopathological variables, and OS was analyzed. RESULTS: Large LNneg size was related to lower pN category ( P = 0.01) and lower frequency of lymphatic invasion ( P = 0.02) in S patients only. Irrespective of treatment, (y)pN0 patients with large LNneg had the best OS. (y)pN1 patients had the poorest OS irrespective of LNneg size ( P < 0.001). Large LNneg contained less lymphocytes ( P = 0.02) and had a higher germinal centers/lymphocyte ratio ( P = 0.05). CONCLUSIONS: This is the first study to investigate LNneg size in EC patients randomized to neoadjuvant chemotherapy followed by surgery or surgery alone. Our pilot study suggests that LNneg size is a surrogate marker of the host antitumor immune response and a potentially clinically useful new prognostic biomarker for (y)pN0 EC patients. Future studies need to confirm our results and explore underlying biological mechanisms.


Subject(s)
Esophageal Neoplasms , Lymph Nodes , Esophageal Neoplasms/surgery , Lymph Nodes/pathology , Pilot Projects , Prognosis , United Kingdom , Humans
15.
Eur J Cancer ; 170: 140-148, 2022 07.
Article in English | MEDLINE | ID: mdl-35635935

ABSTRACT

BACKGROUND: Adenocarcinoma with more than 50% extracellular mucin is a relatively rare histological subtype of gastrointestinal adenocarcinomas. The clinical impact of extracellular mucin in oesophageal adenocarcinoma (OeAC) has not been investigated in detail. We hypothesised that patients with mucinous OeAC (OeACmucin) do not benefit from neoadjuvant chemotherapy. METHODS: OeAC patients either treated by surgery alone in the OE02 trial (S-patients) or by neoadjuvant chemotherapy followed by surgery (CS-patients) in OE02 or OE05 trials were included. Cancers from 1055 resection specimens (OE02 [test cohort]: 187 CS, 185 S; OE05 [validation cohort]: 683 CS) were classified as either mucinous (more than 50% of the tumour area consists of extracellular mucin, OeACmucin) or non-mucinous adenocarcinoma (OeACnon-mucin). The relationship between histological phenotype, clinicopathological characteristics, survival and treatment was analysed. RESULTS: Overall, 7.3% and 9.6% OeAC were classified as OeACmucin in OE02 and OE05, respectively. In OE02, the frequency of OeACmucin was similar in S and CS-patients. Patients with OeACmucin treated with surgery alone had a poorer overall survival compared with OeACnon-mucin patients (hazard ratio: 2.222, 95% confidence interval: 1.08-4.56, P = 0.025). Patients with OeACmucin treated with neoadjuvant chemotherapy and surgery had similar survival as OeACnon-mucin patients in test and validation cohort. CONCLUSIONS: This is the first study to suggest in a post-hoc analysis of material from two independent phase III clinical trials that the poor survival of patients with mucinous OeAC can be improved by neoadjuvant chemotherapy. Future studies are warranted to identify potential underlying biological, biochemical or pharmacokinetic interactions between extracellular mucin and chemotherapy.


Subject(s)
Adenocarcinoma, Mucinous , Adenocarcinoma , Esophageal Neoplasms , Adenocarcinoma/pathology , Adenocarcinoma, Mucinous/pathology , Esophageal Neoplasms/pathology , Humans , Mucins/therapeutic use , Neoadjuvant Therapy , Prognosis , United Kingdom
16.
BJS Open ; 6(1)2022 01 06.
Article in English | MEDLINE | ID: mdl-35195263

ABSTRACT

BACKGROUND: Perioperative FLOT (fluorouracil plus leucovorin, oxaliplatin, and docetaxel) chemotherapy is a recent regimen used to treat resectable oesophagogastric (OG) adenocarcinoma, associated with improved overall survival versus earlier chemotherapy strategies. This study compared short-term perioperative morbidity in a large tertiary centre series of FLOT to a matched cohort receiving ECX/ECF (epirubicin, cisplatin, capecitabine (X) or 5-fluorouracil (F)). METHODS: Consecutive patients completing four perioperative cycles of FLOT and proceeding to surgery with resectable OG adenocarcinoma were included. This was matched to patients from a historic ECX/ECF cohort from the same institution. A propensity score was calculated, and a secondary analysis using a propensity-matched group performed. RESULTS: Cohorts were matched by tumour location and operations performed. In total there were 129 (64.5 per cent) oesophageal and 71 (35.5 per cent) gastric resections (FLOT 57 oesophageal, 43 gastric; ECF/ECX 64 oesophageal, 36 gastric). The median length of stay after surgery was 12 days in the FLOT group versus 15 in ECF/ECX (P = 0.035). There were no significant differences in overall perioperative complications and, specifically, no difference in OG anastomotic leaks, analysed by site (gastric (FLOT 0/79 (0 per cent) versus ECX 2/79 (2.5 per cent); P = 0.123), oesophageal (FLOT 4/121 (3.3 per cent) versus ECX 5/121 (4.1 per cent); P = 0.868) or type of surgery (open FLOT 1/121 (0.8 per cent) versus ECX 3/121 (2.5 per cent); P = 0.368; minimally invasive (FLOT 3/121 (2.5 per cent) versus ECX 2/121 (1.7 per cent); P = 0.555)). There was no statistical difference in leak-related return to theatre, 30-day (FLOT 0 (0 per cent) versus ECX 3/100 (3.0 per cent); P = 0.081), or 90-day (FLOT 0 (0 per cent) versus ECX 2/100 (2.0 per cent); P = 0.155) mortality. CONCLUSION: In terms of surgical complications, FLOT and ECX/ECF were equally safe in patients undergoing resection for OG adenocarcinoma.


Subject(s)
Adenocarcinoma , Antineoplastic Combined Chemotherapy Protocols , Esophageal Neoplasms , Stomach Neoplasms , Adenocarcinoma/drug therapy , Adenocarcinoma/surgery , Antineoplastic Agents/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Capecitabine/administration & dosage , Cisplatin/administration & dosage , Cohort Studies , Docetaxel/administration & dosage , Epirubicin/administration & dosage , Esophageal Neoplasms/drug therapy , Esophageal Neoplasms/surgery , Fluorouracil/administration & dosage , Humans , Leucovorin/administration & dosage , Oxaliplatin/administration & dosage , Perioperative Care , Propensity Score , Stomach Neoplasms/drug therapy , Stomach Neoplasms/surgery , Treatment Outcome
17.
Br J Surg ; 109(3): 291-297, 2022 02 24.
Article in English | MEDLINE | ID: mdl-35179206

ABSTRACT

BACKGROUND: Patients with Epstein-Barr virus-positive gastric cancers or those with microsatellite instability appear to have a favourable prognosis. However, the prognostic value of the chromosomal status (chromosome-stable (CS) versus chromosomal instable (CIN)) remains unclear in gastric cancer. METHODS: Gene copy number aberrations (CNAs) were determined in 16 CIN-associated genes in a retrospective study including test and validation cohorts of patients with gastric cancer. Patients were stratified into CS (no CNA), CINlow (1-2 CNAs) or CINhigh (3 or more CNAs). The relationship between chromosomal status, clinicopathological variables, and overall survival (OS) was analysed. The relationship between chromosomal status, p53 expression, and tumour infiltrating immune cells was also assessed and validated externally. RESULTS: The test and validation cohorts included 206 and 748 patients, respectively. CINlow and CINhigh were seen in 35.0 and 15.0 per cent of patients, respectively, in the test cohort, and 48.5 and 20.7 per cent in the validation cohort. Patients with CINhigh gastric cancer had the poorest OS in the test and validation cohorts. In multivariable analysis, CINlow, CINhigh and pTNM stage III-IV (P < 0.001) were independently associated with poor OS. CIN was associated with high p53 expression and low immune cell infiltration. CONCLUSION: CIN may be a potential new prognostic biomarker independent of pTNM stage in gastric cancer. Patients with gastric cancer demonstrating CIN appear to be immunosuppressed, which might represent one of the underlying mechanisms explaining the poor survival and may help guide future therapeutic decisions.


Subject(s)
Adenocarcinoma/genetics , Adenocarcinoma/immunology , Chromosomal Instability , Gene Dosage , Immunocompromised Host , Stomach Neoplasms/genetics , Stomach Neoplasms/immunology , Adenocarcinoma/pathology , Adenocarcinoma/virology , Aged , Biomarkers, Tumor/genetics , Female , Genes, p53/genetics , Herpesvirus 4, Human/isolation & purification , Humans , Male , Middle Aged , Mutation , Neoplasm Staging , Prognosis , Retrospective Studies , Stomach Neoplasms/pathology , Stomach Neoplasms/virology
18.
Dis Esophagus ; 35(11)2022 Nov 15.
Article in English | MEDLINE | ID: mdl-35138383

ABSTRACT

Preoperative cardiopulmonary exercise testing (CPET) provides an objective assessment of aerobic fitness in patients undergoing surgery. While peak oxygen uptake during exercise (VO2peak) and anaerobic threshold have demonstrated a moderate correlation with the development of complications following esophagectomy, no clinically useful threshold values have been defined. By pooling patient level data from existing studies, we aimed to define optimal thresholds for preoperative CPET parameters to predict patients at high risk of postoperative complications. Studies reporting on the relationship between preoperative CPET variables and post-esophagectomy complications were determined from a comprehensive literature search. Patient-level data were obtained from six contributing centers for pooled-analyses. Outcomes of interest included cardiopulmonary and non-cardiopulmonary complications, unplanned intensive care unit readmission, and 90-day and 12-month all-cause mortality. Receiver operating characteristic curves and logistic regression models estimated the predictive value of CPET parameters for each individual outcome of interest. This analysis comprised of 621 patients who underwent CPET prior to esophagectomy during the period from January 2004 to March 2017. For both anaerobic threshold and VO2peak, none of the receiver operating characteristic curves achieved an area under the curve value > 0.66 for the outcomes of interest. The discriminatory ability of CPET for determining high-risk patients was found to be poor in patients undergoing an esophagectomy. CPET may only carry an adjunct role to clinical decision-making.


Subject(s)
Esophagectomy , Exercise Test , Humans , Esophagectomy/adverse effects , Exercise Test/adverse effects , Anaerobic Threshold , ROC Curve , Postoperative Complications/diagnosis , Postoperative Complications/etiology , Oxygen Consumption
19.
Eur J Cancer ; 163: 180-188, 2022 03.
Article in English | MEDLINE | ID: mdl-35085931

ABSTRACT

BACKGROUND: Peri-operative chemotherapy improves survival in patients with locally advanced oesophago-gastric adenocarcinoma. Two regimens with proven survival benefits are epirubicin, cisplatin plus capecitabine or fluorouracil (Medical Research Council Adjuvant Gastric Infusional Chemotherapy, MAGIC) and fluorouracil plus leucovorin, oxaliplatin, and docetaxel (FLOT). This study aimed to compare the effect of these regimens on survival (primary aim) and pathological response, surgical complications, adverse events and chemotherapy completion rates. METHODS: Cohort study including 946 patients treated with FLOT (n = 257) or MAGIC (n = 689) who underwent surgical resection for oesophageal (n = 743) or gastric (n = 203) adenocarcinoma between 2002 and 2021 at St Thomas' Hospital or The Royal Marsden Hospital, London, UK. Survival analysis was performed using multivariable Cox regression, providing hazard ratios (HRs) with 95% confidence intervals (CIs) adjusted for age, sex, clinical T-stage, clinical N-stage, tumour grade and presence of signet ring cells. RESULTS: Patients treated with FLOT had better overall survival (HR = 0.69, 95% CI 0.50-0.94) and disease-free survival (HR = 0.75, 95% CI 0.58-0.98) than MAGIC. Patients treated with FLOT were more likely to have a complete pathological response (9.5% FLOT versus 5.5% MAGIC, p = 0.027) and were less likely to have a positive resection margin (19.1% FLOT versus 32.2% MAGIC, p < 0.001). The stratified analysis revealed similar results for oesophageal and gastric tumours. Rates of surgical complications, chemotherapy-associated adverse events and completion were similarly distributed between treatment groups. CONCLUSIONS: Patients with oesophageal or gastric adenocarcinoma treated with peri-operative FLOT had better survival and pathological response than those treated with peri-operative MAGIC. Rates of surgical complications, adverse events and chemotherapy completion were comparable.


Subject(s)
Adenocarcinoma , Esophageal Neoplasms , Stomach Neoplasms , Adenocarcinoma/drug therapy , Adenocarcinoma/pathology , Adenocarcinoma/surgery , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Cohort Studies , Esophageal Neoplasms/drug therapy , Esophageal Neoplasms/pathology , Esophageal Neoplasms/surgery , Esophagogastric Junction/pathology , Esophagogastric Junction/surgery , Fluorouracil , Humans , Stomach Neoplasms/drug therapy , Stomach Neoplasms/pathology , Stomach Neoplasms/surgery
20.
Ann Surg ; 275(2): e392-e400, 2022 02 01.
Article in English | MEDLINE | ID: mdl-32404661

ABSTRACT

OBJECTIVE: To identify the most prevalent symptoms and those with greatest impact upon health-related quality of life (HRQOL) among esophageal cancer survivors. BACKGROUND: Long-term symptom burden after esophagectomy, and associations with HRQOL, are poorly understood. PATIENTS AND METHODS: Between 2010 and 2016, patients from 20 European Centers who underwent esophageal cancer surgery, and were disease-free at least 1 year postoperatively were asked to complete LASER, EORTC-QLQ-C30, and QLQ-OG25 questionnaires. Specific symptom questionnaire items that were associated with poor HRQOL as identified by EORTC QLQ-C30 and QLQ-OG25 were identified by multivariable regression analysis and combined to form a tool. RESULTS: A total of 876 of 1081 invited patients responded to the questionnaire, giving a response rate of 81%. Of these, 66.9% stated in the last 6 months they had symptoms associated with their esophagectomy. Ongoing weight loss was reported by 10.4% of patients, and only 13.8% returned to work with the same activities.Three LASER symptoms were correlated with poor HRQOL on multivariable analysis; pain on scars on chest (odds ratio (OR) 1.27; 95% CI 0.97-1.65), low mood (OR 1.42; 95% CI 1.15-1.77) and reduced energy or activity tolerance (OR 1.37; 95% CI 1.18-1.59). The areas under the curves for the development and validation datasets were 0.81 ±â€Š0.02 and 0.82 ±â€Š0.09 respectively. CONCLUSION: Two-thirds of patients experience significant symptoms more than 1 year after surgery. The 3 key symptoms associated with poor HRQOL identified in this study should be further validated, and could be used in clinical practice to identify patients who require increased support.


Subject(s)
Esophageal Neoplasms/surgery , Esophagectomy , Postoperative Complications/epidemiology , Quality of Life , Aged , Cross-Sectional Studies , Europe , Female , Humans , Male , Middle Aged , Self Report , Symptom Assessment
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