BACKGROUND: Transthoracic minimally invasive esophagectomy (MIE) is increasingly performed as part of curative multimodality treatment. There appears to be no robust evidence on the preferred ...location of the anastomosis after transthoracic MIE. OBJECTIVE: To compare an intrathoracic with a cervical anastomosis in a randomized clinical trial. DESIGN, SETTING, AND PARTICIPANTS: This open, multicenter randomized clinical superiority trial was performed at 9 Dutch high-volume hospitals. Patients with midesophageal to distal esophageal or gastroesophageal junction cancer planned for curative resection were included. Data collection occurred from April 2016 through February 2020. INTERVENTION: Patients were randomly assigned (1:1) to transthoracic MIE with intrathoracic or cervical anastomosis. MAIN OUTCOMES AND MEASURES: The primary end point was anastomotic leakage requiring endoscopic, radiologic, or surgical intervention. Secondary outcomes were overall anastomotic leak rate, other postoperative complications, length of stay, mortality, and quality of life. RESULTS: Two hundred sixty-two patients were randomized, and 245 were eligible for analysis. Anastomotic leakage necessitating reintervention occurred in 15 of 122 patients with intrathoracic anastomosis (12.3%) and in 39 of 123 patients with cervical anastomosis (31.7%; risk difference, −19.4% 95% CI, −29.5% to −9.3%). Overall anastomotic leak rate was 12.3% in the intrathoracic anastomosis group and 34.1% in the cervical anastomosis group (risk difference, −21.9% 95% CI, −32.1% to −11.6%). Intensive care unit length of stay, mortality rates, and overall quality of life were comparable between groups, but intrathoracic anastomosis was associated with fewer severe complications (risk difference, −11.3% −20.4% to −2.2%), lower incidence of recurrent laryngeal nerve palsy (risk difference, −7.3% 95% CI, −12.1% to −2.5%), and better quality of life in 3 subdomains (mean differences: dysphagia, −12.2 95% CI, −19.6 to −4.7; problems of choking when swallowing, −10.3 95% CI, −16.4 to 4.2; trouble with talking, −15.3 95% CI, −22.9 to −7.7). CONCLUSIONS AND RELEVANCE: In this randomized clinical trial, intrathoracic anastomosis resulted in better outcome for patients treated with transthoracic MIE for midesophageal to distal esophageal or gastroesophageal junction cancer. TRIAL REGISTRATION: Trialregister.nl Identifier: NL4183 (NTR4333)
Summary Background Early enteral feeding following surgery can be given orally, via a jejunostomy or via a nasojejunal tube. However, the best feeding route following esophagectomy is unclear. ...Objectives To determine the best route for enteral nutrition following esophagectomy regarding anastomotic leakage, pneumonia, percentage meeting the nutritional requirements, weight loss, complications of tube feeding, mortality, patient satisfaction and length of hospital stay. Design A systematic literature review following PRISMA and MOOSE guidelines. Results There were 17 eligible studies on early oral intake, jejunostomy or nasojejunal tube feeding. Only one nonrandomized study ( N = 133) investigated early oral feeding specifically following esophagectomy. Early oral feeding was associated with a reduced length of stay with delayed oral feeding, without increased complication rates. Postoperative nasojejunal tube feeding was not significantly different from jejunostomy tube feeding regarding complications or catheter efficacy in the only randomised trial on this subject ( N = 150). Jejunostomy tube feeding outcome was reported in 12 non-comparative studies ( N = 3293). It was effective in meeting short-term nutritional requirements, but major tube-related complications necessitated relaparotomy in 0–2.9% of patients. In three non-comparative studies ( N = 135) on nasojejunal tube feeding only minor complications were reported, data on nutritional outcome was lacking. Data on patient satisfaction and long-term nutritional outcome were not found for any of the feeding routes investigated. Conclusion It is unclear what the best route for early enteral nutrition is after esophagectomy. Especially data regarding early oral intake are scarce, and phase 2 trials are needed for further investigation. Registration International prospective register of systematic reviews, CRD42013004032.
OBJECTIVE:To investigate the morbidity that is associated with the learning curve of minimally invasive esophagectomy.
BACKGROUND:Although learning curves have been described, it is currently unknown ...how much extra morbidity is associated with the learning curve of technically challenging surgical procedures.
METHODS:Prospectively collected data were retrospectively analyzed of all consecutive patients undergoing minimally invasive Ivor Lewis esophagectomy in 4 European expert centers. The primary outcome parameter was anastomotic leakage. Secondary outcome parameters were operative time and textbook outcome (“optimal outcome”). Learning curves were plotted using weighted moving average and CUSUM analysis was used to determine after how many cases the plateau was reached. Learning associated morbidity was calculated with area under the curve analysis.
RESULTS:This study included 646 patients. Three of the 4 hospitals reached the plateau of 8% anastomotic leakage. The length of the learning curve was 119 cases. The mean incidence of anastomotic leakage decreased from 18.8% during the learning phase to 4.5% after the plateau had been reached (P < 0.001). Thirty-six extra patients (10.1% of all patients operated on during the learning curve) experienced learning associated anastomotic leakage, that could have been avoided if patients were operated by surgeons who had completed the learning curve. The incidence of textbook outcome increased from 28% to 53% and the mean operative time decreased from 344 minutes to 270 minutes.
CONCLUSIONS:A considerable number of 36 extra patients (10.1%) experienced learning associated anastomotic leakage. More research is urgently needed to investigate how learning associated morbidity can be reduced to increase patient safety during learning curves.
Background
The preferred surgical approach for esophageal cancer is a minimally invasive transthoracic esophagectomy with a two-field lymph node dissection. The thoracoscopic phase may be performed ...either in prone- or in left lateral decubitus (LLD) position. Prone positioning has been associated with better pulmonary outcomes compared to LLD positioning; however, conversion to a classic thoracotomy is more difficult. The semiprone position has been proposed as an alternative approach.
Methods
A retrospective review of a prospectively maintained database (2008–2014) was performed to compare postoperative complications, surgical radicality, and lymph node yield between patients who underwent three-stage minimally invasive transthoracic esophagectomy in either the prone or semiprone position. Comparative analyses were conducted before and after propensity score matching.
Results
One hundred and twenty-one patients were included. In total, 82 patients underwent minimally invasive esophagectomy (MIE) in semiprone position and 39 patients in prone position. After propensity score matching, both groups consisted of 39 patients. The operative time in the semiprone group was longer (368 vs. 225 min,
P
< 0.001) and in this group the lymph node yield was significantly higher (16 (range 6–80) vs. 13 (range 3–33),
P
= 0.019). There were no statistically significant differences regarding radical resections, postoperative complications, and hospital stay.
Conclusion
The use of semiprone positioning in MIE is safe, feasible, and at least comparable to MIE in prone position in terms of oncological clearance and postoperative complications.
Observational studies on long-term endocrine treatment among breast cancer patients have presented discontinuation rates on tamoxifen, but lack information on the continuance of any endocrine ...treatment both tamoxifen and aromatase inhibitors (AIs) within the same cohort. In this study we determined switching rates from tamoxifen to AIs, discontinuation rates of tamoxifen only, discontinuation rates of any endocrine treatment and determinants of first treatment switch and treatment discontinuation. Patients with early stage breast cancer (stage I-IIIa) starting on tamoxifen were selected from the linked Eindhoven Cancer Registry-PHARMO RLS cohort in the period 1998-2006. Continuous use (allowing a 60 days gap between refills) of tamoxifen only and any endocrine treatment were determined after various follow-up periods: 1, 2, 3, 4, and 5 years. Time to first switch from tamoxifen to an AI was assessed. Cox regression was used to identify determinants of first treatment switch, discontinuation of tamoxifen, and discontinuation of any endocrine treatment. A total of 1,451 new early stage breast cancer patients started on tamoxifen. Of those, 380 had a treatment switch to an AI during follow-up. Of the patients followed for 5 years, 40% continuously used tamoxifen, which was 49% for any endocrine treatment. Older age (older than 70 versus 50-69 years) was independently associated with increased discontinuation of tamoxifen and any endocrine therapy. Patients with two or more concomitant diseases (versus no comorbidity) showed an increased likelihood to stop any endocrine treatment or switch treatment from tamoxifen to an AI. In conclusion, up to half of the breast cancer patients starting tamoxifen continued 5 years of endocrine treatment. Identification of patients at risk of discontinuation will assist in the development of interventions to improve treatment continuation comparable to that of patients included in clinical trials.
During esophagectomy, the vagus nerve is transected, which may add to the development of postoperative complications. The vagus nerve has been shown to attenuate inflammation and can be activated by ...a high-fat nutrition via the release of acetylcholine. This binds to α7 nicotinic acetylcholine receptors (α7nAChR) and inhibits α7nAChR-expressing inflammatory cells. This study investigates the role of the vagus nerve and the effect of high-fat nutrition on lipopolysaccharide (LPS)-induced lung injury in rats. Firstly, 48 rats were randomized in 4 groups as follows: sham (sparing vagus nerve), abdominal (selective) vagotomy, cervical vagotomy and cervical vagotomy with an α7nAChR-agonist. Secondly, 24 rats were randomized in 3 groups as follows: sham, sham with an α7nAChR-antagonist and cervical vagotomy with an α7nAChR-antagonist. Finally, 24 rats were randomized in 3 groups as follows: fasting, high-fat nutrition before sham and high-fat nutrition before selective vagotomy. Abdominal (selective) vagotomy did not impact histopathological lung injury (LIS) compared with the control (sham) group (
> 0.999). There was a trend in aggravation of LIS after cervical vagotomy (
= 0.051), even after an α7nAChR-agonist (
= 0.090). Cervical vagotomy with an α7nAChR-antagonist aggravated lung injury (
= 0.004). Furthermore, cervical vagotomy increased macrophages in bronchoalveolar lavage (BAL) fluid and negatively impacted pulmonary function. Other inflammatory cells, TNF-α and IL-6, in the BALF and serum were unaffected. High-fat nutrition reduced LIS after sham (
= 0.012) and selective vagotomy (
= 0.002) compared to fasting. vagotomy. This study underlines the role of the vagus nerve in lung injury and shows that vagus nerve stimulation using high-fat nutrition is effective in reducing lung injury, even after selective vagotomy.
OBJECTIVE:Patients undergoing an esophagectomy are often kept nil-by-mouth postoperatively out of fear for increasing anastomotic leakage and pulmonary complications. This study investigates the ...effect of direct start of oral feeding following minimally invasive esophagectomy (MIE) compared with standard of care.
BACKGROUND:Elements of enhanced recovery after surgery (ERAS) protocols have been successfully introduced in patients undergoing an esophagectomy. However, start of oral intake, which is an essential part of the ERAS protocols, remains a matter of debate.
METHODS:Patients in this multicenter, international randomized controlled trial were randomized to directly start oral feeding (intervention) after a MIE with intrathoracic anastomosis or to receive nil-by-mouth and tube feeding for 5 days postoperative (control group). Primary outcome was time to functional recovery. Secondary outcome parameters included anastomotic leakage, pneumonia rate, and other surgical complications scored by predefined definitions.
RESULTS:Baseline characteristics were similar in the intervention (n = 65) and control (n = 67) group. Functional recovery was 7 days for patients receiving direct oral feeding compared with 8 days in the control group (P = 0.436). Anastomotic leakage rate did not differ in the intervention (18.5%) and control group (16.4%, P = 0.757). Pneumonia rates were comparable between the intervention (24.6%) and control group (34.3%, P = 0.221). Other morbidity rates were similar, except for chyle leakage, which was more prevalent in the standard of care group (P = 0.032).
CONCLUSION:Direct oral feeding after an esophagectomy does not affect functional recovery and did not increase incidence or severity of postoperative complications.
Bariatric surgery results in sustained weight loss, improvement of metabolic and hormonal changes, and reduction of comorbidities in obese patients. However, beneficial effects of bariatric surgery ...are not solely explained by restriction and malabsorption induced by surgery itself. Changes in the microbiome might play a role in this mechanism. A systematic review was performed in which 21 studies were included. The microbiome was affected by surgery and profound changes occurred in the first year of follow-up. An increase in
Bacteroides
and
Proteobacteria
and a decrease in Firmicutes were observed postoperatively in most studies. These changes were associated with weight loss. Bariatric surgery induces profound changes in the microbiome. This may be related to the beneficial effect of bariatric surgery on comorbidities associated with obesity.
Abstract Background Neoadjuvant hormonal therapy (NHT) is playing an increasing role in the clinical management of breast cancer (BC) and may improve surgical outcomes for postmenopausal, oestrogen ...receptor (ER)-positive BC patients. However, there is currently no consensus on the optimal duration of NHT before surgery. Here, we present the outcomes of the TEAM IIA trial, a multicentre, phase II trial investigating the efficacy of six months of neoadjuvant exemestane in postmenopausal, strong ER-positive (ER+, ⩾50%) BC patients. Methods 102 patients (stage T2-T4ac) were included in the study after exclusion of ineligible patients. Primary end-point was clinical response at 3 and 6 months as measured by palpation. Secondary end-point was radiological response as measured by magnetic resonance imaging (MRI), mammography and/or ultrasound. Linear mixed models (95% confidence interval (CI)) were used to compare changes in mean tumour size (in mm) between baseline, 3 and 6 months after the start of endocrine therapy. Conversion rates from mastectomy to breast conserving surgery (BCS) were evaluated. Results Median age of all patients was 72 years (range 53–88). Overall response rate by clinical palpation was 64.5% in all patients with a final palpation measurement. Four patients had clinically progressive disease. 63 patients had both 3-month and >3-month palpation measurements. Overall response was 58.7% at 3 months and 68.3% at final palpation (>3 months). Mean tumour size by clinical palpation at T = 0 was 39.1 mm (95% CI 34.8–43.4 mm), and decreased to 23.0 mm (95% CI 18.7–27.2 mm) and 16.7 mm (95% CI 12.6–20.8) at T = 3 and T > 3 months, respectively ( p = 0.001). Final radiological response rates at the end of treatment for MRI ( n = 37), ultrasound ( n = 77) and mammography ( n = 56) were 70.3%, 41.6% and 48.2%, respectively. Feasibility of BCS improved from 61.8% to 70.6% (McNemar p = 0.012). Conclusion 6 months of neoadjuvant exemestane therapy helps reduce mean tumour size further in strongly ER-positive BC patients without significant side-effects compared to 3 months. Nevertheless, some patients still experience disease progression under exemestane. Feasibility of breast conservation rates improved by almost 10%.
The European Organisation for Research and Treatment of Cancer 10981-22023 AMAROS trial evaluated axillary lymph node dissection (ALND) versus axillary radiotherapy (ART) in patients with cT1-2, ...node-negative breast cancer and a positive sentinel node (SN) biopsy. At 5 years, both modalities showed excellent and comparable axillary control, with significantly less morbidity after ART. We now report the preplanned 10-year analysis of the axillary recurrence rate (ARR), overall survival (OS), and disease-free survival (DFS), and an updated 5-year analysis of morbidity and quality of life.
In this open-label multicenter phase III noninferiority trial, 4,806 patients underwent SN biopsy; 1,425 were node-positive and randomly assigned to either ALND (n = 744) or ART (n = 681).
Per intention-to-treat analysis, 10-year ARR cumulative incidence was 0.93% (95% CI, 0.18 to 1.68; seven events) after ALND and 1.82% (95% CI, 0.74 to 2.94; 11 events) after ART (hazard ratio HR, 1.71; 95% CI, 0.67 to 4.39). There were no differences in OS (HR, 1.17; 95% CI, 0.89 to 1.52) or DFS (HR, 1.19; 95% CI, 0.97 to 1.46). ALND was associated with a higher lymphedema rate in updated 5-year analyses (24.5%
11.9%;
< .001). Quality-of-life scales did not differ by treatment through 5 years. Exploratory analysis showed a 10-year cumulative incidence of second primary cancers of 12.1% (95% CI, 9.6 to 14.9) after ART and 8.3% (95% CI, 6.3 to 10.7) after ALND.
This 10-year analysis confirms a low ARR after both ART and ALND with no difference in OS, DFS, and locoregional control. Considering less arm morbidity, ART is preferred over ALND for patients with SN-positive cT1-2 breast cancer.
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