A senior surgical resident can safely perform complex esophageal cancer surgery after surgical mentoring program-experience of a European high-volume center.

Previous studies have shown that surgical residents can safely perform a variation of complex abdominal surgeries when provided with adequate training, proper case selection, and appropriate supervision. Their outcomes are equivalent when compared to experienced board-certified surgeons. Our previously published training curriculum for robotic assisted minimally invasive esophagectomy already demonstrated a possible reduction in time to reach proficiency. However, esophagectomy is a technically challenging procedure and comes with high morbidity rates of up to 60%, making it difficult to provide opportunities to train surgical residents. We aimed to investigate if a surgical resident could safely perform complex esophageal surgery when a structured modular teaching curriculum is applied. A structured teaching program based on our previously published modular step-up approach was applied by two experienced board-certified esophageal surgeons. Our IRB-approved (Institutional Review Board) database was searched to identify all Ivor-Lewis esophagectomies performed by the selected surgical resident from August 2019 to July 2021. The cumulative sum method was used to analyze the learning curve of the surgical resident. Outcomes of patients operated by the resident were then compared to our overall cohort of open, hybrid, and robotic Ivor-Lewis esophagectomies from May 2016 to May 2020. The total cohort included 567 patients, of which 65 were operated by the surgical resident and 502 patients were operated by experienced esophageal cancer surgeons as the control group. For baseline characteristics, a significant difference for BMI (Body mass index) was observed, which was lower in the resident's group (25.5 kg/m2 vs. 26.8 kg/m2 (P = 0.046). A significant difference of American Society of Anesthesiologists- and Eastern Cooperative Oncology Group-scores was seen, and a subgroup analysis including all patients with American Society of Anesthesiologists I and Eastern Cooperative Oncology Group 0 was performed revealing no significant differences. Postoperative complications did not differ between groups. The anastomotic leak rate was 13.8% in the resident's cohort and 12% in the control cohort (P = 0.660). Major complications (Clavien-Dindo ≥ IIIb) occurred in 16.9% of patients in both groups. Oncological outcome, defined by harvested lymph nodes (35 vs. 32.33, P = 0.096), proportion of lymph node compliant performed operations (86.2% vs. 88.4%, P = 0.590), and R0-resection rate (96.9% vs. 96%, P = 0.766), was not compromised when esophagectomies were performed by the resident. The resident completed the learning curves after 39 cases for the total operating time, 38 cases for the thoracic operating time, 26 cases for the number of harvested lymph nodes, 29 cases for anastomotic leak rate, and finally 58 cases for the comprehensive complication index. For postoperative complications, no significant difference was seen between patients operated in the resident group versus the control group, with a third of patients being discharged with a textbook outcome in both cohorts. Furthermore, no difference in oncological quality of the resection was found, emphasizing safety and feasibility of our training program. A structured modular step-up for training a surgical resident to perform complex esophageal cancer surgery can successfully maintain patient safety and outcomes.

There is no correlation between a delayed gastric conduit emptying and the occurrence of an anastomotic leakage after Ivor-Lewis esophagectomy.

INTRODUCTION: Esophagectomy is the gold standard in the surgical therapy of esophageal cancer. It is either performed thoracoabdominal with a intrathoracic anastomosis or in proximal cancers with a three-incision esophagectomy and cervical reconstruction. Delayed gastric conduit emptying (DGCE) is the most common functional postoperative disorder after Ivor-Lewis esophagectomy (IL). Pneumonia is significantly more often in patients with DGCE. It remains unclear if DGCE anastomotic leakage (AL) is associated. Aim of our study is to analyze, if AL is more likely to happen in patients with a DGCE. PATIENTS AND METHODS: 816 patients were included. All patients have had an IL due to esophageal/esophagogastric-junction cancer between 2013 and 2018 in our center. Intrathoracic esophagogastric end-to-side anastomosis was performed with a circular stapling device. The collective has been divided in two groups depending on the occurrence of DGCE. The diagnosis DGCE was determined by clinical and radiologic criteria in accordance with current international expert consensus. RESULTS: 27.7% of all patients suffered from DGCE postoperatively. Female patients had a significantly higher chance to suffer from DGCE than male patients (34.4% vs. 26.2% vs., p = 0.040). Pneumonia was more common in patients with DGCE (13.7% vs. 8.5%, p = 0.025), furthermore hospitalization was longer in DGCE patients (median 17 days vs. 14d, p < 0.001). There was no difference in the rate of type II anastomotic leakage, (5.8% in both groups DGCE). All patients with ECCG type II AL (n = 47; 5.8%) were treated successfully by endoluminal/endoscopic therapy. The subgroup analysis showed that ASA ≥ III (7.6% vs. 4.4%, p = 0.05) and the histology squamous cell carcinoma (9.8% vs. 4.7%, p = 0.01) were independent risk factors for the occurrence of an AL. CONCLUSION: Our study confirms that DGCE after IL is a common finding in a standardized collective of patients in a high-volume center. This functional disorder is associated with a higher rate of pneumonia and a prolonged hospital stay. Still, there is no association between DGCE and the occurrence of an AL after esophagectomy. The hypothesis, that an DGCE results in a higher pressure on the anastomosis and therefore to an AL in consequence, can be refuted. DGCE is not a pathogenetic factor for an AL.

Encapsulation of anthocyanins from bilberries - Effects on bioavailability and intestinal accessibility in humans.

Anthocyanins are flavonoids that have been suggested to provide beneficial health effects. The biological activity of anthocyanins is influenced by their pharmacokinetic properties, but anthocyanins are associated with limited bioavailability in humans. In the presented study, we investigated how the encapsulation of bilberry extract (BE), a source of anthocyanins, with either whey protein or citrus pectin influences the bioavailability and intestinal accessibility of anthocyanins in humans. We performed an intervention study that analyzed anthocyanins and their degradation products in the urine, plasma, and ileal effluent of healthy volunteers and ileostomists (subjects without an intact colon). We were able to show, that whey protein encapsulation modulated short-term bioavailability and that citrus pectin encapsulation increased intestinal accessibility during passage through the small intestine and modulated the formation of the degradation product phloroglucinol aldehyde (PGAL) in human plasma.

Human intervention study to investigate the intestinal accessibility and bioavailability of anthocyanins from bilberries.

We investigated the importance of the large intestine on the bioavailability of anthocyanins from bilberries in humans with/without a colon. Low bioavailability of anthocyanins in plasma and urine was observed in the frame of this study. Anthocyanins reached the circulation mainly as glucuronides. Analysis of ileal effluents (at end of small intestine) demonstrated that 30% of ingested anthocyanins were stable during 8h passage through the upper intestine. Only 20% degradants were formed and mostly intact anthocyanins were absorbed from the small intestine. Higher amounts of degradants than anthocyanins reached the circulation after bilberry extract consumption in both groups of subjects. Comparison of the bioavailability of anthocyanins in healthy subjects versus ileostomists revealed substantially higher amounts of anthocyanins and degradants in the plasma/urine of subjects with an intact gut. The results suggested that the colon is a significant site for absorption of bioactive components such as anthocyanins and their degradation products.

Influence of triterpenoids present in apple peel on inflammatory gene expression associated with inflammatory bowel disease (IBD).

Various ursanic, oleanic and lupanic pentacyclic triterpenoids found in apple peel were studied for anti-inflammatory effects in vitro using T84 colon carcinoma cells. After pretreatment with single triterpenoids, cells were stimulated with pro-inflammatory cytokines (TNF-α, INF-γ, IL-1ß). Regulation of mRNA expression was analysed for three specific inflammation-associated marker genes (TNF-α, IL-8, IP-10) using qRT-PCR. Furthermore, the effects of ursolic acid (UA) and oleanolic acid (OA) on the synthesis of certain pro-inflammatory proteins were examined. IP-10 expression was inhibited in a dose-dependent manner by all the tested compounds at concentrations ≥25 µM. The mRNA expression of TNF-α was slightly affected and the IL-8 level was increased. At the protein level, UA and OA (25 µM) reduced the synthesis of IP-10; sICAM-1, IL-23 and GROα were slightly repressed. The TNF-α level was not modulated, whereas induction of IL-8 was increased. UA also enhanced the synthesis of IL-1ra, while OA suppressed the level of I-TAC. The present study confirms that triterpenoids present in apple peel and ß-damascone may be implicated in the anti-inflammatory properties of apple constituents, suggesting that these substances might be helpful in the treatment of IBD as nutrient supplements.

Modulation of Nrf2-dependent gene transcription by bilberry anthocyanins in vivo.

In a human pilot intervention study (healthy + ileostomy probands), the questions were addressed whether in vivo consumption of an anthocyanin-rich bilberry (Vaccinium myrtillius L.) pomace extract (BE) affects (i) the transcription of Nrf2-dependent genes in peripheral blood mononuclear cells (PBMC), indicative for systemic effects, and (ii) the level of oxidative DNA damage in these cells. In healthy test subjects transcripts of NAD(P)H quinone oxidoreductase 1 (NQO1) were significantly elevated throughout the observation period (1-8 h), whereas transcription of heme oxygenase 1 (HO-1) and Nrf2 was significantly decreased. NQO1 and HO-1 transcription remained unchanged in the ileostomy probands, whereas Nrf2-transcription was suppressed in both groups. Decrease in oxidative DNA damage was observed 2 h after BE consumption again only in healthy subjects. In vitro studies using a reporter gene approach (CHO) and qPCR (HT29) indicate that not the intact anthocyanins/anthocyanidins are the activating constituents but the intestinal degradation product phloroglucinol aldehyde (PGA). Taken together, consumption of anthocyanin-rich BE was found to modulate Nrf2-dependent gene expression in PBMCs indicative for systemic activity. Limitation of the effect to healthy test subjects suggests a role of colonic processes for bioactivity, supported by the results on Nrf2-activating properties of the intestinal anthocyanin degradation product PGA.