Evolution of Esophagectomy for Cancer Over 30 Years: Changes in Presentation, Management and Outcomes.

BACKGROUND: Esophageal cancer has seen a considerable change in management and outcomes over the last 30 years. Historically, the overall prognosis has been regarded as poor; however, the use of multimodal treatment and the integration of enhanced recovery pathways have improved short- and long-term outcomes. OBJECTIVE: The aim of this study was to evaluate the changing trends in presentation, management, and outcomes for patients undergoing surgical treatment for esophageal cancer over 30 years from a single-center, high-volume unit in the UK. PATIENTS AND METHODS: Data from consecutive patients undergoing esophagectomy for cancer (adenocarcinoma or squamous cell carcinoma) between 1989 and 2018 from a single-center, high-volume unit were reviewed. Presentation method, management strategies, and outcomes were evaluated. Patients were grouped into successive 5-year cohorts for comparison and evaluation of changing trends. RESULTS: Between 1989 and 2018, 1486 patients underwent esophagectomy for cancer. Median age was 65 years (interquartile range [IQR] 59-71) and 1105 (75%) patients were male. Adenocarcinoma constituted 1105 (75%) patients, and overall median survival was 29 months (IQR 15-68). Patient presentation changed, with epigastric discomfort now the most common presentation (70%). An improvement in mortality from 5 to 2% (p < 0.001) was seen over the time period, and overall survival improved from 22 to 56 months (p < 0.001); however, morbidity increased from 54 to 68% (p = 0.004). CONCLUSIONS: Long-term outcomes have significantly improved over the 30-year study period. In addition, mortality and length of stay have improved despite an increase in complications. The reasons for this are multifactorial and include the use of perioperative chemo(radio)therapy, the introduction of an enhanced recovery pathway, and improved patient selection.

Impact of Smoking Status on Perioperative Morbidity, Mortality, and Long-Term Survival Following Transthoracic Esophagectomy for Esophageal Cancer.

INTRODUCTION: Esophagectomy is a key component in the curative treatment of esophageal cancer. Little is understood about the impact of smoking status on perioperative morbidity and mortality and the long-term outcome of patients following esophagectomy. OBJECTIVE: This study aimed to evaluate morbidity and mortality according to smoking status in patients undergoing esophagectomy for esophageal cancer. METHODS: Consecutive patients undergoing two-stage transthoracic esophagectomy (TTE) for esophageal cancers (adenocarcinoma or squamous cell carcinoma) between January 1997 and December 2016 at the Northern Oesophagogastric Unit were included from a prospectively maintained database. The main explanatory variable was smoking status, defined as current smoker, ex-smoker, and non-smoker. The primary outcome was overall survival (OS), while secondary outcomes included perioperative complications (overall, anastomotic leaks, and pulmonary complications) and survival (cancer-specific survival [CSS], recurrence-free survival [RFS]). RESULTS: During the study period, 1168 patients underwent esophagectomy for cancer. Of these, 24% (n = 282) were current smokers and only 30% (n = 356) had never smoked. The median OS of current smokers was significantly shorter than ex-smokers and non-smokers (median 36 vs. 42 vs. 48 months; p = 0.015). However, on adjusted analysis, there was no significant difference in long-term OS between smoking status in the entire cohort. The overall complication rates were significantly higher with current smokers compared with ex-smokers or non-smokers (73% vs. 66% vs. 62%; p = 0.018), and there were no significant differences in anastomotic leaks and pulmonary complications between the groups. On subgroup analysis by receipt of neoadjuvant therapy and tumor histology, smoking status did not impact long-term survival in adjusted multivariable analyses. CONCLUSION: Although smoking is associated with higher rates of short-term perioperative morbidity, it does not affect long-term OS, CSS, and RFS following esophagectomy for esophageal cancer. Therefore, implementation of perioperative pathways to optimize patients may help reduce the risk of complications.

Chyle Leak Following Radical En Bloc Esophagectomy with Two-Field Nodal Dissection: Predisposing Factors, Management, and Outcomes.

BACKGROUND: Chyle leak is an uncommon complication following esophagectomy, accounting for significant morbidity and mortality; however, the optimal treatment for the chylothorax is still controversial. OBJECTIVE: The aim of this study was to evaluate the incidence, management, and outcomes of chyle leaks within a specialist esophagogastric cancer center. METHODS: Consecutive patients undergoing esophagectomy for esophageal cancers (adenocarcinoma or squamous cell carcinoma) between 1997 and 2017 at the Northern Oesophagogastric Unit were included from a contemporaneously maintained database. Primary outcome was overall survival, while secondary outcomes were overall complications, anastomotic leaks, and pulmonary complications. RESULTS: During the study period, 992 patients underwent esophagectomy for esophageal cancers, and 5% (n = 50) of them developed chyle leaks. There was no significant difference in survival in patients who developed a chyle leak compared with those who did not (median: 40 vs. 45 months; p = 0.60). Patients developing chyle leaks had a significantly longer length of stay in critical care (median: 4 vs. 2 days; p = 0.002), but no difference in total length of hospital stay. CONCLUSION: Chyle leak remains a complication following esophagectomy, with limited understanding on its pathophysiology in postoperative recovery. However, these data indicate chyle leak does not have a long-term impact on patients and does not affect long-term survival.

Trimodality therapy versus perioperative chemotherapy in the management of locally advanced adenocarcinoma of the oesophagus and oesophagogastric junction (Neo-AEGIS): an open-label, randomised, phase 3 trial.

BACKGROUND: The optimum curative approach to adenocarcinoma of the oesophagus and oesophagogastric junction is unknown. We aimed to compare trimodality therapy (preoperative radiotherapy with carboplatin plus paclitaxel [CROSS regimen]) with optimum contemporaneous perioperative chemotherapy regimens (epirubicin plus cisplatin or oxaliplatin plus fluorouracil or capecitabine [a modified MAGIC regimen] before 2018 and fluorouracil, leucovorin, oxaliplatin, and docetaxel [FLOT] subsequently). METHODS: Neo-AEGIS (CTRIAL-IE 10-14) was an open-label, randomised, phase 3 trial done at 24 centres in Europe. Patients aged 18 years or older with clinical tumour stage T2-3, nodal stage N0-3, and M0 adenocarcinoma of the oesophagus and oesophagogastric junction were randomly assigned to perioperative chemotherapy (three preoperative and three postoperative 3-week cycles of intravenous 50 mg/m2 epirubicin on day 1 plus intravenous 60 mg/m2 cisplatin or intravenous 130 mg/m2 oxaliplatin on day 1 plus continuous infusion of 200 mg/m2 fluorouracil daily or oral 625 mg/m2 capecitabine twice daily up to 2018, with four preoperative and four postoperative 2-week cycles of 2600 mg/m2 fluorouracil, 85 mg/m2 oxaliplatin, 200 mg/m2 leucovorin, and 50 mg/m2 docetaxel intravenously on day 1 as an option from 2018) or trimodality therapy (41·4 Gy in 23 fractions on days 1-5, 8-12, 15-19, 22-26, and 29-31 with intravenous area under the curve 2 mg/mL per min carboplatin plus intravenous 50 mg/m2 paclitaxel on days 1, 8, 15, 22, and 29). The primary endpoint was overall survival, assessed in all randomly assigned patients who received at least one dose of study drug, regardless of which study drug they received, by intention to treat. Secondary endpoints were disease-free survival, site of treatment failure, operative complications, toxicity, pathological response (complete [ypT0N0] and major [tumour regression grade 1 and 2]), margin-free resection (R0), and health-related quality of life. Toxicity and safety data were analysed in the safety population, defined as patients who took at least one dose of study drug, according to treatment actually received. The initial power calculation was based on superiority of trimodality therapy (n=366 patients); it was adjusted after FLOT became an option to a non-inferiority design with a margin of 5% for perioperative chemotherapy (n=540). This study is registered with ClinicalTrials.gov, NCT01726452. FINDINGS: Between Jan 24, 2013, and Dec 23, 2020, 377 patients were randomly assigned, of whom 362 were included in the intention-to treat population (327 [90%] male and 360 [99%] White): 184 in the perioperative chemotherapy group and 178 in the trimodality therapy group. The trial closed prematurely in December, 2020, after the second interim futility analysis (143 deaths), on the basis of similar survival metrics and the impact of the COVID-19 pandemic. At a median follow-up of 38·8 months (IQR 16·3-55·1), median overall survival was 48·0 months (95% CI 33·6-64·8) in the perioperative chemotherapy group and 49·2 months (34·8-74·4) in the trimodality therapy group (3-year overall survival 55% [95% CI 47-62] vs 57% [49-64]; hazard ratio 1·03 [95% CI 0·77-1·38]; log-rank p=0·82). Median disease-free survival was 32·4 months (95% CI 22·8-64·8) in the perioperative chemotherapy group and 24·0 months (18·0-40·8) in the trimodality therapy group [hazard ratio 0·89 [95% CI 0·68-1·17]; log-rank p=0·41). The pattern of recurrence, locoregional or systemic, was not significantly different (odds ratio 1·35 [95% CI 0·63-2·91], p=0·44). Pathological complete response (odds ratio 0·33 [95% CI 0·14-0·81], p=0·012), major pathological response (0·21 [0·12-0·38], p<0·0001), and R0 rates (0·21 [0·08-0·53], p=0·0003) favoured trimodality therapy. The most common grade 3-4 adverse event was neutropenia (49 [27%] of 183 patients in the perioperative chemotherapy group vs 11 [6%] of 178 patients in the trimodality therapy group), followed by diarrhoea (20 [11%] vs none), and pulmonary embolism (ten [5%] vs nine [5%]). One (1%) patient in the perioperative chemotherapy group and three (2%) patients in the trimodality therapy group died from serious adverse events, two (one in each group) of which were possibly related to treatment. No differences were seen in operative mortality (five [3%] deaths in the perioperative chemotherapy group vs four [2%] in the trimodality therapy group), major morbidity, or in global health status at 1 and 3 years. INTERPRETATION: Although underpowered and incomplete, Neo-AEGIS provides the largest comprehensive randomised dataset for patients with adenocarcinoma of the oesophagus and oesophagogastric junction treated with perioperative chemotherapy (predominantly the modified MAGIC regimen), and CROSS trimodality therapy, and reports similar 3-year survival and no major differences in operative and health-related quality of life outcomes. We suggest that these data support continued clinical equipoise. FUNDING: Health Research Board, Cancer Research UK, Irish Cancer Society, Oesophageal Cancer Fund, and French National Cancer Institute.

Evolution of gastrectomy for cancer over 30-years: Changes in presentation, management, and outcomes.

BACKGROUND: Gastric cancer has seen a considerable change in management, and outcomes for the past 30 years. Historically, the overall prognosis has been regarded as poor. However, the use of multimodal treatment, and integration of enhanced recovery pathways have improved short and long-term outcomes. The aim of this study was to evaluate the changing trends in presentation, management, and outcomes for patients undergoing surgical treatment for gastric cancers over 30 years. METHODS: Data from consecutive patients undergoing gastrectomy with curative intent for gastric adenocarcinoma between 1989 and 2018 from a single-center, high-volume unit were reviewed. Presentation method, management strategies and outcomes were reviewed. Patients were grouped into successive 5-year cohorts for comparison and evaluation of changing trends. RESULTS: Between 1989 and 2018, 1,162 patients underwent gastrectomy with curative intent for cancer. Median age was 71 years (interquartile range, 63-76 years) and 763 (66%) were male. Patient presentation changed with epigastric discomfort now the most common presentation (67%). An improvement in overall complications from 54% to 35% (P = .006) and mortality from 8% to 1% (P < .001) was seen over the time period and overall survival improved from 28 months to 53 months (P < .001). CONCLUSION: Both short-term and long-term outcomes have significantly improved over the 30 years studied. The reasons for this are multifactorial and include the use of perioperative chemotherapy, the introduction of an enhanced recovery pathway, and improved preoperative assessment of patients through a multidisciplinary input.

A case series of myectomy: a review of its current application as an adjunct procedure.

In this article, we review the role played by myectomy in cardiac surgery. For this purpose, we looked at three cases of different etiology where myectomy in conjunction with treatment of the primary condition proved invaluable in the outcome of these patients. The primary conditions requiring treatment were subaortic membrane, hypertrophic obstructive cardiomyopathy with mitral valve regurgitation, and aortic stenosis.

Successful graft patency after factor VIIa use for bleeding in coronary artery surgery: an unusual complication of a coronary artery bypass surgery.

There is a growing literature regarding the use of recombinant activated factor VII (rFVIIa) (NovoSeven, NovoNordisk, Copenhagen, Denmark) to control refractory hemorrhage after cardiopulmonary bypass in cardiac surgery. This supporting evidence is mostly documented as case reports on patients, of which only six involve coronary artery grafting. We present our experience of a patient undergoing coronary artery bypass grafting, who suffered an anaphylactic reaction to protamine preventing safe reversal of systemic heparinization. Subsequent management of postoperative bleeding was successfully achieved only after rFVIIa administration.