Changes in circulating exosome molecular profiles following surgery/(chemo)radiotherapy: early detection of response in head and neck cancer patients

Background Head and neck cancers (HNSCC) are highly immunosuppressive. Plasma-derived exosomes of HNSCC patients carry immunomodulatory molecules, and their cargo correlates with clinical parameters. Here, we evaluated the exosomal molecular profile for early detection of treatment failure in locally advanced HNSCC patients treated with conventional therapy.Methods Plasma from 17 HNSCC patients was collected before, during, and after treatment by surgery with adjuvant (chemo)radiation and at recurrence. Exosomes were isolated by size-exclusion chromatography. Total exosomal protein (TEP) was used to estimate exosome load and on-bead flow cytometry to evaluate relative fluorescence intensity (RFI) of tumour-associated and immunoregulatory proteins on exosomes. Exosomal effects on the activity of and adenosine production by T cells was assessed by flow cytometry and mass spectrometry.Results TEP and the ratio of tumour-/immune-cell-derived exosomes varied during and after therapy with an overall decrease in the tumour-free follow-up but an increase at recurrence. RFI values of immunoregulatory proteins on exosomes, their ability for T cell inhibition and adenosine production changed during and after therapy. PD-L1 was the earliest discriminator for treatment failure and disease-free survival.Conclusions Monitoring of plasma exosomes during therapy represents a promising opportunity for early detection of treatment failure and risk stratification to delay/avoid recurrence.Subject terms: Head and neck cancer, Tumour immunology     

Extrahepatic portal vein ligation in major hepatectomies performed under selective vascular exclusion: a case-control study

The aim of our study is to assess the effect of extrahepatic ipsilateral portal vein branch ligation in hepatectomies conducted under selective hepatic vascular exclusion with sharp transection of the liver parenchyma. Twenty-six patients (Group A) underwent major hepatectomy from January 2007 to December 2009, and hemostasis was achieved by ligation of the ipsilateral portal vein branch in addition to suture ligation of the cut surface vessels. A control group (Group B) was composed of 26 matched patients picked from our hospital's database, in which hemostasis was achieved by suture ligation of the cut surface vessels only. Warm ischemia time, intraoperative blood loss, blood transfusions, and liver function were compared. Reduced blood loss (450 vs 680 mL, P = 0.03), less transfusions (8 vs 20% of the patients, P = 0.04), and decreased warm ischemia time (34 vs 42 minutes, P = 0.04) were observed in Group A. Extrahepatic ligation of the ipsilateral portal vein branch is simple, safe, and effective in reducing blood loss and warm ischemia time in major hepatectomies performed under selective vascular exclusion.     

Promoting Undergraduate Surgical Education: Current Evidence and Students’ Views on ESMSC International Wet Lab Course

Background: Undergraduate Surgical Education is becoming an essential element in the training of the future generation of safe and efficient surgeons. Essential Skills in the Management of Surgical Cases (ESMSC), is an international, joint applied surgical science and simulation-based learning wet lab course. Methods: We performed a review of the existing literature on the topic of undergraduate surgical education. Following that, we analyzed the feedback questionnaire received 480 from 2 recent series of ESMSC courses (May 2015, n = 49 and November 2015, n = 40), in order to evaluate European Union students' (UK, Germany, Greece) views on the ESMSC course, as well as on the undergraduate surgical education. Results Using a 10 point graded scale, the overall ESMSC concept was positively evaluated, with a mean score of 9.41 ± 0.72 (range: 8–10) and 8.94 ± 1.1 (range: 7–10). The majority of delegates from both series [9.86 ± 0.43 (range: 8–10) and 9.58 ± 0.91 (range: 6–10), respectively] believed that ESMSC should be incorporated in the undergraduate surgical curriculum. Comparison of responses from the UK to the Greek Medical Student, as well as the findings from the third and fourth year versus the fifth and sixth year Medical Students, revealed no statistically significant differences pertaining to any of the questions (p > 0.05). Conclusions: Current evidence in the literature supports the enhancement of surgical education through the systematic use of various modalities that provide Simulation-Based Training (SBT) hands-on experience, starting from the early undergraduate level. The findings of the present study are in agreement with these previous reports.     

Secondary tracheal distortion in an adult patient after therapy for diphtheria at childhood

We report a rare case of difficult intubation because of trachea deformation after therapy for diphtheria and subsequent tracheostomy at childhood. The patient was admitted to be subjected to a Bentall procedure, because of ascending aorta dilatation. With a detailed preanesthetic assessment and simulation for intubation by using three-dimensional technology, he was successfully intubated and the operation was accomplished uneventfully. 3D-printed models of the difficult airway enhance imaging of difficult anatomy, assist in simulation and management of potentially problematic intubation, and can be a valuable tool when dealing with airways with potential anatomical malformations.     

Introducing In Vivo Dissection Modules for Undergraduate Level Trainees: What Is the Actual Benefit and How Could We Make It More Efficient?

Essential Skills in the Management of Surgical Cases (ESMSC) is an international wet lab simulation course aimed at undergraduate students. It combines basic science workshops, case-based lectures and ex vivo skills modules, as well as in vivo dissections using a swine model. This study aims to evaluate the effectiveness of high-fidelity In Vivo Simulation-Based Learning for undergraduate level trainees. Also our goal was to compare the skill-based performance of final year students vs. more junior-level ones. Forty undergraduate delegates at clinical rotation level (male = 28, female = 12, mean age = 23.12, 22–24, SD = 0.69) attended this 2-day course in Athens. N = 1 (2.5 %) was year 3, N = 4 (10 %) were year 4, N = 23 (57.5 %) were year 5 and N = 12 (30 %) were year 6. N = 30 (75 %) came from Hellenic universities, N = 8 (20 %) from the UK and N = 2 (5 %) from Germany. N = 20 (50 %) attended the in vivo dissections module first, and then the ex vivo one (type A rotation), whereas N = 20 followed the reverse training sequence with the ex vivo dissection first, followed by the in vivo one (type B rotation). The mean global rating scores for type A rotation were better in both the in vivo by 0.10 (2.40 vs. 2.30) and ex vivo modules by 0.15 (2.85 vs. 2.70), though it did not reach statistical significance (p > 0.05). Furthermore, the mean improvement of performance, in the laparoscopic skills station for the type A rotation, was better compared to type B by 0.351 (2.00 vs. 1.65, p = 0.003). Year 6 students performed better in the laparoscopic station (2.00 vs. 1.75, p = 0.059), whereas years 3, 4 and 5 performed better in the in vivo (2.42 vs. 2.16, p = 0.157) as well as the ex vivo dissections (2.78 vs. 2.75, p = 0.832), though none of those comparisons reached statistical significance. Delegates seemed to appreciate and enjoy the in vivo dissections as reflected in the feedback (8.67/10, min = 6 and max = 10, SD = 1.79). Although medical students seem to appreciate in vivo dissections modules, currently, further evidence is needed to support their recommendation in the undergraduate level. Surgical skills should be part of the undergraduate curriculum to improve final year students’ performance in the theatre.     

Transhepatic lactate gradient in relation to liver ischemia/reperfusion injury during major hepatectomies.

Hepatectomies performed under selective hepatic vascular exclusion are associated with a series of events culminating in ischemia/reperfusion injury, a state that shares common characteristics with situations known to result in global or regional hyperlactatemia. Accordingly, we sought to determine whether lactate is released by the liver during hepatic resections performed under blood flow deprivation and what relation this has to a possible systemic hyperlactatemic state. After ethical approval, 14 consecutive patients with resectable liver tumors subjected to hepatectomy under inflow and outflow occlusion of the liver were studied. Lactate concentrations were assessed in simultaneously drawn arterial, portal venous, and hepatic venous blood before liver dissection and 50 minutes postreperfusion. Moreover, the transhepatic lactate gradient (hepatic vein - portal vein) was calculated to see if there was net production or consumption of lactate. Before hepatic dissection, the transhepatic lactate gradient was negative, suggesting consumption by the liver. Fifty minutes after reperfusion, this gradient became significantly positive, demonstrating release of lactate by the liver (0.12 +/- 0.31 vs. -0.38 +/- 0.30 mmol/L, P < 0.05). The magnitude of lactate release correlated with systemic arterial lactate levels at the same time point (r(2) = 0.63, P < 0.001). A weaker but significant correlation was demonstrated between the transhepatic lactate gradient postreperfusion and systemic arterial lactate levels 24 hours postoperatively (r(2) = 0.41, P = 0.013). A strong correlation between the transhepatic lactate gradient postreperfusion and peak postoperative aspartate aminotransferase values was also demonstrated (r(2) = 0.73, P < 0.001). The liver becomes a net producer of lactate in hepatectomies performed under blood flow deprivation. This lactate release can explain some of the systemic hyperlactatemia seen in this context and relates to the extent of ischemia/reperfusion injury.     

Performance of a third‐generation TSH‐receptor antibody in a UK clinic

Background UK national guidelines recommend the measurement of TSH receptor antibodies (TRAb) in certain clinical scenarios. A commercial third‐generation TRAb autoantibody M22‐biotin ELISA assay was introduced in May 2008 in our centre. Objective To evaluate the diagnostic performance of a TRAb assay in a retrospective and subsequently a prospective cohort in a UK centre. Design A retrospective review of patients with thyroid disease followed by a prospective observational study in consecutive patients with newly found suppressed serum thyrotrophin (TSH). Patients and Measurements Medical records of 200 consecutive patients with thyroid disorders who had TRAb measured since the introduction of the assay. In a prospective study 44 patients with newly identified hyperthyroidism (TSH < 0·02 mIU/l) had sera assayed for TRAb prior to their clinic appointment at which a final diagnosis was sought. Results In the retrospective cohort, the manufacturer’s cut‐off point of TRAb ≥0·4 U/l resulted in a positive predictive value (PPV) of 95%, sensitivity 85%, specificity 94% and negative predictive value (NVP) 79% to diagnose Graves’ disease using defined criteria. Receiver operating characteristic (ROC) analysis determined an optimal cut‐off point of TRAb ≥3·5 U/l with a 100% specificity to exclude patients without Graves’ disease at the cost though of a lower sensitivity (43%). In the prospective study, the sensitivity, PPV, specificity and NPV were all 96% using the ≥0·4 U/l cut‐off. When combining hyperthyroid patients from both cohorts the assay sensitivity and specificity at ≥0·4 U/l cut‐off were 95% and 92% respectively. A positive TRAb result increased the probability of Graves’ disease for a particular patient by 25–35% and only six (2·5%) patients had a diagnosis of hyperthyroidism of uncertain aetiology after TRAb testing. Conclusions The assay studied specifically identifies patients with Graves’ disease. It is a reliable tool in the initial clinical assessment to determine the aetiology of hyperthyroidism and has the potential for cost‐savings.