Background: The potential for exhaled breath to be a valuable diagnostic tool is often overlooked as it can be difficult to imagine how a barely visible sample of breath could hold such a rich source of information about the state of our health. However, technological advances over the last 50 years have enabled us to detect volatile organic compounds (VOCs) present in exhaled breath, and this provides the key to understanding the wealth of information contained within these readily available samples.
Summary: VOCs are produced as a by-product of metabolism; hence, changes in the underlying physiological processes will be reflected in the exact composition of VOCs in exhaled breath. It has been shown that characteristic changes occur in the breath VOC profile associated with certain diseases including cancer, which may enable the non-invasive detection of cancer at primary care level for patients with vague symptoms. The use of breath testing as a diagnostic tool has many advantages. It is non-invasive and quick, and the test is widely accepted by patients and clinicians. However, breath samples provide a snapshot of the VOCs present in a particular patient at a given point in time, so this can be heavily influenced by external factors such as diet, smoking, and the environment. These must all be accounted for when attempting to draw conclusions about disease status. This review focuses on the current applications for breath testing in the field of surgery, as well as discussing the challenges encountered with developing a breath test in a clinical environment. The future of breath testing in the surgical setting is also discussed, including the translation of breath research into clinical practice.
Key messages: Analysis of VOCs in exhaled breath can identify the presence of underlying disease including cancer as well as other infectious or inflammatory conditions. Despite the patient factors, environmental factors, storage, and transport considerations that must be accounted for, breath testing demonstrates ideal characteristics for a triage test, being non-invasive, simple, and universally acceptable to patients and clinicians. Many novel biomarkers and diagnostic tests fail to translate into clinical practice because their potential clinical application does not align with the requirements and unmet needs of the healthcare sector. Non-invasive breath testing, however, has the great potential to revolutionise the early detection of diseases, such as cancer, in the surgical setting for patients with vague symptoms.
Introduction: Evidence-based grading of the impact of intracranial surgery on rat's well-being is important for ethical and legal reasons. We assessed the severity of complex and repeated intracranial surgery in a 6-hydroxydopamine (6-OHDA) Parkinson's rat model with subsequent intracranial electrode implantation and in an intracranial tumor model with subsequent resection.
Methods: Stereotactic surgery was performed in adult male rats with the same general anesthesia and perioperative pain management. In Parkinson's model, Sprague Dawley rats received unilateral injection of 6-OHDA (n = 11) or vehicle (n = 7) into the medial forebrain bundle as first operation (1st OP). After four weeks, neural electrodes were implanted in all rats as second operation (2nd OP). For tumor formation, BDIX/UlmHanZtm rats (n = 8) received frontocortical injection of BT4Ca cells as 1st OP, followed by tumor resection as 2nd OP after one week. Multiple measures severity assessment was done two days before and four days after surgery in all rats, comprising clinical scoring, body weight, and detailed behavioral screening. To include a condition with a known burden, rats with intracranial tumors were additionally assessed up to a predefined humane endpoint that has previously been classified as "moderate".
Results: After the 1st OP, only 6-OHDA injection resulted in transient elevated clinical scores, a mild long-lasting weight reduction, and motor disturbances. After the second surgery, body weight was transiently reduced in all groups. All other parameters showed variable results. Principal component analysis showed a separation from the preoperative state driven by motor-related parameters after 6-OHDA injection, while separation after electrode implantation and more clearly after tumor resection was driven by pain-related parameters, although not reaching the level of the humane endpoint of our tumor model.
Conclusion: Overall, cranial surgery of different complexity only transiently and rather mildly affects rat's well-being. Multiple measures assessment allows the differentiation of model-related motor disturbances in Parkinson's model from potentially pain-related conditions after tumor resection and electrode implantation.
We have recently incorporated simple modifications of the konjac flour noodle model to enable DIY home microsurgical training by (i) placing a smartphone on a mug to act as a microscope with at least ×3.5-5 magnification, and (ii) rather than cannulating with a 22G needle as described by others, we have found that cannulation with a 23G needle followed by a second pass with an 18G needle will create a lumen (approximately 0.83 mm) without an overly thick and unrealistic "vessel" wall. The current setup, however, did not allow realistic evaluation of anastomotic patency as the noodles became macerated after application of standard microvascular clamps, which also did not facilitate practice of back-wall anastomoses. In order to simulate the actual operative environment as much as possible, we introduced the use of 3D-printed microvascular clamps. These were modified from its previous iteration (suitable for use in silastic and chicken thigh vessels), and video recordings were submitted for internal validation by senior surgeons. A "wet" operative field where the konjac noodle lumen can be distended or collapsed, unlike other nonliving models, was noted by senior surgeons. With the 3D clamps, the noodle could now be flipped over for back-wall anastomosis and allowed patency testing upon completion as it did not become macerated, unlike that from clinical microvascular clamps. The perceived advantages of this model are numerous. Not only does it comply with the 3Rs of simulation-based training, but it can also reduce the associated costs of training by up to a hundred-fold or more when compared to a traditional rat course and potentially be extended to low-middle income countries without routine access to microsurgical training for capacity development. That it can be utilized remotely also bodes well with the current limitations on face-to-face training due to COVID restrictions and lockdowns.
Introduction: The open field test (OFT) is a common tool to assess anxiety and behavioural changes in rodents. It has been adapted to pigs with no systematic investigation of how environmental changes may alter the performance of pigs. Currently, the number of published studies including the OFT in domestic pig models is increasing without standardization.
Methods: Our review aimed to investigate the open field (OF) set-ups in published studies and the similarities between performance and published parameters.
Results: Following the PRISMA guidelines for reviews, we selected 69 studies for inclusion in this systematic review. We determined the specific set-up conditions such as dimensions, duration, and time of day for most of the included studies; we found high variability across studies with respect to these test specifics.
Discussion: Our results indicate the inconsistent implementation of the set-up, including dimensions, timing, parameters, and additional combined tests (e.g., new object tests). Based on our findings, we have made recommendations for the performance of the OFT, according to the current literature.
Introduction: The impact of ustekinumab (UST) therapy on surgical complications in patients with Crohn's disease (CD) remains controversial. The aim of this meta-analysis is to explore the link between these two.
Methods: Databases (PubMed, Web of Science, Cochrane, and Springer Link) were searched until April 2022. Studies of CD patients who received UST and no UST prior to surgery (including no biological therapy, anti-tumor necrosis factor-α [anti-TNF-α] agent, and vedolizumab [VDZ]) were included. Primary outcomes included overall complications, infectious complications, and noninfectious complications.
Results: Nine studies totaling 3,225 CD patients were enrolled; 332 patients received UST treatment. There was no evidence of difference in the overall complications (odds ratio [OR] = 0.84, p = 0.37, 95% confidence interval [CI] = [0.57-1.23], I2 = 40%) between CD patients who had UST treatment preoperatively and those who had no UST treatment. There was no evidence of a difference in infectious complications (OR = 1.15, p = 0.35, 95% CI = [0.86-1.53], I2 = 2%). Additionally, there was no significant evidence of difference between these groups in terms of noninfectious complications and death. Specifically, there was no evidence of difference in overall complications, infection complications (including wound complications, sepsis, abscess, and anastomotic leakage), and noninfection complications (ileus, readmission, and return to operation), compared with no biological therapy and anti-TNF-α agents. At the same time, no significant evidence of difference was discovered in the comparison of preoperative UST and VDZ therapy in terms of overall complications, infectious complications (sepsis and abscess), and noninfectious complications (intestinal obstruction, readmission, and recovery surgery).
Conclusion: In general, compared with other biological agents, preoperative use of UST in the treatment of CD patients is usually safe and does not increase surgical complications.
Introduction: Laparoscopic liver resections (LLRs) constitute an area of surgery that has been kept away from residents in their hands-on training. The aim of our study is to assess the feasibility and the value of a didactic "step-by-step" program for LLR performed by residents using the swine training model.
Methods: From May 2018 to November 2019, three hands-on workshops were held. The protocol involved the performance of cholecystectomy, liver mobilization, minor and major hepatectomies. The participants' performance results in terms of operative time, blood loss, conversion, trainers' intervention, and intraoperative mortality, were recorded. The first workshop was comprised of 30 residents who previously participated in laparoscopic surgery workshops. In the second workshop, after six residents dropped out due to residency completion, the findings for the remaining 24 residents were compared to those for 24 junior-attending surgeons who did not follow the protocol and had not performed LLR previously, and to another 24 residents in a third workshop, who had not taken the training program before but followed the protocol.
Results: All residents fully completed the surgical procedures. Trained residents achieved better operative times and less blood loss compared to junior-attending surgeons (p < 0.017), however, the remaining parameters were comparable. When compared to non-trained residents, those who underwent training achieved significantly better results only in operative times (p < 0.001).
Conclusion: A continuous LLR "step-by-step" training program on swine for residents is feasible and the "step-by-step" protocol is a valuable tool for a proper surgical education.
Introduction: For patients with advanced hepatocellular carcinoma (HCC), hepatic artery infusion chemotherapy (HAIC) is a common and mature treatment, but the safety and efficacy of HAIC combined with lenvatinib for advanced HCC patient treatment remains unclear. Therefore, this study compared the safety and efficacy of HAIC with or without lenvatinib in unresectable HCC patients.
Methods: We retrospectively analyzed 13 unresectable advanced HCC patients who received HAIC monotherapy or combination therapy of HAIC and lenvatinib. Overall survival (OS), disease control rate (DCR), objective response rate (ORR), progression-free survival (PFS), incidence of adverse events (AEs), and changes in liver function were compared between the two groups. We applied a Cox regression analysis to evaluate the independent risk factors affecting survival outcomes.
Results: The ORR in the HAIC+lenvatinib group was markedly increased compared to the HAIC group (p < 0.05), while the DCR in the HAIC group was higher (p > 0.05). No notable difference was found between the two groups in median OS and PFS (p > 0.05). Compared to the HAIC+lenvatinib group, more patients had improved liver function in the HAIC group after treatment, but the difference was not dramatical (p > 0.05). The AEs incidence was 100.00% in both groups, which was relieved with corresponding treatment. Besides, Cox regression analysis did not identify independent risk factors related to OS and PFS.
Conclusion: Combination therapy of HAIC and lenvatinib notably performed better than the HAIC monotherapy in patients with unresectable HCC in terms of ORR and was well tolerated, which deserves further investigation with large-scale clinical trials.

