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-hydr...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.
OBJECTIVES: The disruption to surgical training and medical education caused by the global COVID-19 pandemic highlighted the need for realistic, reliable, and engaging educational opportunities available outside of the o...OBJECTIVES: The disruption to surgical training and medical education caused by the global COVID-19 pandemic highlighted the need for realistic, reliable, and engaging educational opportunities available outside of the operating theatre and accessible for trainees of all levels. This article presents the design and development of a virtual reality curriculum which simulates the surgical mentorship experience outside of the operating theatre, with a focus on surgical anatomy and surgical decision-making. METHOD: This was a multi-institutional study between London's King's College and Imperial College. The index procedure selected for the module was robotic radical prostatectomy. For each stage of the surgical procedure, subject-matter experts (N = 3) at King's College London, identified (1) the critical surgical-decision making points, (2) critical anatomical landmarks, and (3) tips and techniques for overcoming intraoperative challenges. Content validity was determined by an independent panel of subject-matter experts (N = 8) at Imperial College, London, using Fleiss' kappa statistic. The experts' teaching points were combined with operative footage and illustrative animations, and projected onto a virtual reality headset. The module was piloted to surgical science students (N = 15). Quantitative analysis compared participants' confidence regarding their anatomical knowledge before and after taking the module. Qualitative data were gathered from students regarding their views on using the virtual reality model. RESULTS: Multi-rater agreement between experts was above the 70.0% threshold for all steps of the procedure. Seventy-three percentage of pilot study participants "agreed" or "strongly agreed" that they achieved a better understanding of surgical anatomy and the rationale behind each procedural step. This was reflected in an increase in the median knowledge score after trialing the curriculum (p < 0.001). 100% of subject-matter experts and 93.3% of participants "agreed" or "strongly agreed" that virtual mentorship would be useful for future surgical training. CONCLUSIONS: This study demonstrated that virtual surgical mentorship could be a feasible and cost-effective alternative to traditional training methods with the potential to improve technical skills, such as operative proficiency and nontechnical skills such as decision-making and situational judgement.
BACKGROUND: Systematic reviews and meta-analyses are generally regarded as sitting atop the hierarchy of clinical evidence. The unbiased summary of current evidence that a systematic review provides, along with the incre...BACKGROUND: Systematic reviews and meta-analyses are generally regarded as sitting atop the hierarchy of clinical evidence. The unbiased summary of current evidence that a systematic review provides, along with the increased statistical power from larger numbers of patients, is invaluable in guiding clinical decision-making and development of practice guidelines. Surgical specialties have historically lagged behind other areas of medicine in the application of evidence-based medicine, perhaps due to the unique challenges faced in the conduct of surgical clinical trials. These challenges extend to the conduct of systematic reviews, due to issues with the quality and heterogeneity of the underlying literature. SUMMARY: Recent years have seen an improvement in the quality of randomized controlled trials in surgical topics and an explosion in the publication of systematic reviews. This review explores recent trends in systematic reviews in surgery and discussed some of the aspects in conducting and interpreting reviews that are unique to surgical topics, including blinding, surgical heterogeneity and learning curves, patient and clinician preference, and industry involvement. Key Messages: Clinical trials, and therefore systematic reviews, of surgical interventions pose unique challenges which are important to consider when conducting them or applying the findings to clinical practice. Despite the challenges, systematic reviews still represent the best level of evidence for development of surgical practice guidelines.
BACKGROUND: In Dupuytren's surgery, limited fasciectomy is still the gold-standard treatment. A relatively high risk of iatrogenic nerve injury has been observed especially when the spiral cords of the Dupuytren's tissue...BACKGROUND: In Dupuytren's surgery, limited fasciectomy is still the gold-standard treatment. A relatively high risk of iatrogenic nerve injury has been observed especially when the spiral cords of the Dupuytren's tissue pull digital nerves away from their normal anatomical location. Intraoperative neural marking could facilitate locating the potentially displaced nerves. Hence, surgery could be undertaken more quickly with a lower risk of iatrogenic nerve injury. OBJECTIVES: We hypothesize that digital nerves may be stained with methylene blue (MB) in vivo providing a visual aid to distinguish them from Dupuytren's tissue. We aim to (a) test an in vivo nerve staining technique using MB in a rat sciatic nerve model and to (b) assess the safety of epineural MB injection. METHODS: Three experiments were performed: first, the effects of (a) sham surgery, (b) epineural needle insertion, and (c) 40 μL epineural saline injection were tested in the rat sciatic nerve. Second, we determined the (a) histoanatomical localization of the epineurally injected 40 µL 1 m/m% MB stock solution and (b) we tested which saline dilution (i.e., 1:40, 1:80, and 1:160) of the stock solution does provide optimal blue color upon 40 µL epineural injection. Third, the functional and morphological effect of 40 µL 1:80 diluted MB injection was compared with that of saline, injected into the contralateral sciatic nerve. The functional effects were tested by assessing the pain threshold by using a dynamic plantar esthesiometer (DPA) and by examination of the animal's gate and paw posture. Sciatic nerves were subjected to histological examination and morphometry to test structural damage. RESULTS: Neither epineural needle insertion nor saline injection caused any functional or morphological changes. Histological examination revealed that the MB stained the epineural compartment. Epineural injection of 40 μL 1:80 diluted MB into the sciatic nerve stained an 18.18-mm segment of the nerve distal to the puncture point. DPA revealed unchanged pain threshold values on the plantar surface of the limbs. Normal gait and foot posture suggested normal motor functions in all groups. No histological changes were seen in the stained nerves, and the nerve fiber density remained unchanged. CONCLUSION: We demonstrated that in vivo nerve staining with MB is a suitable method to mark nerves without causing detectable negative effect to the stained nerve. Human trials are required to prove the efficacy of the technique in Dupuytren's disease.
INTRODUCTION: Aorto-iliac vascular disease (AVD) is frequently found during the workup for kidney transplantation. However, recommendations on screening and management are lacking. We aimed to assess differences in scree...INTRODUCTION: Aorto-iliac vascular disease (AVD) is frequently found during the workup for kidney transplantation. However, recommendations on screening and management are lacking. We aimed to assess differences in screening, management, and acceptance of these patients for transplantation by performing a survey among transplant surgeons. Second, we aimed to identify center- and surgeon-related factors associated with decline or acceptance of kidney transplant candidates with AVD. METHODS: A survey was sent to transplant surgeons and urologists. The survey contained general questions (part I) and 2 patient-based cases (part II) with Trans-Atlantic Inter-Society Consensus (TASC) D and B AVD supported with videos of their CT scans. RESULTS: One hundred ninety-one (20.3%) participants responded; 171 were currently involved in kidney transplantation: 161 (94.2%) completed part I and 145 (84.8%) part II. Screening for AVD was often (38.5%) restricted to high-risk patients. The majority of respondents (67.7%) rated "technical problems" as the most important concern in case of AVD, followed by "increased mortality risk because of cardiovascular comorbidity" (29.8%). Pretransplant vascular interventions to facilitate transplantation were infrequently performed (71.4% mentioned <10 per year). Ninety (64.3%) respondents answered that an open vascular procedure should preferably be performed prior to kidney transplantation while 42 (30.0%) respondents preferred a simultaneous open vascular procedure. The decline rate was higher in the TASC D case compared to the TASC B case (26.9% and 9.7%, respectively). Respondents from centers with expertise in pretransplant vascular interventions were more likely to accept both patients with TASC D and B for transplantation. CONCLUSION: There is no uniformity in the screening, management, and acceptance of patients with AVD for transplantation. If a center declines a patient with AVD because of technical concerns, the patient should be referred for a second opinion to a tertiary center with expertise in pretransplant vascular interventions. Multidisciplinary meetings including a vascular surgeon and a cardiologist could help optimize these patients for transplantation.
OBJECTIVES: The present study aimed to identify significant causes of readmission within 30 days following coronary artery bypass graft (CABG) surgery and compare readmission incidence related to surgical site infections...OBJECTIVES: The present study aimed to identify significant causes of readmission within 30 days following coronary artery bypass graft (CABG) surgery and compare readmission incidence related to surgical site infections (SSIs) before and after implementing international recommendations for antibiotic prophylaxis. METHODS: We analyzed 2,225 CABG patients who received either guideline-directed antibiotic prophylaxis (GDAP = 568) or institutional antibiotic prophylaxis (non-GDAP = 1,657) between January 2017 and December 2019. The primary outcome was a composite of sternal wound infection (SWI) or harvest SWI. Secondary outcomes consisted of the individual components of composite end point, the incidence of in-hospital SSIs, and prolonged postoperative length of hospital stay (LOS) (>7 days). Propensity matching was used to select pairs for final comparison. RESULTS: Before implementing GDAP, the most frequent reason for readmission were SSIs, causing 58.2% of all readmissions within 30 days. Of 429 matched pairs, 48 patients in the GDAP group and 67 patients in the non-GDAP group were readmitted to a hospital within 30 days for any cause (11.2 vs. 15.6%, p = 0.048). We found a decreased readmission incidence for reasons related to SSIs, although these differences did not reach statistical significance (7.4 vs. 10.0%, p = 0.069). Adherence to GDAP was associated with reduced in-hospital risks of SSIs and prolonged postoperative LOS (19.6 vs. 26.6%, p = 0.015). CONCLUSIONS: In this contemporary clinical practice study, the adherence to GDAP was an insufficient measure to decrease rehospitalization due to SSIs. The present findings warrant further investigation on factors that may contribute to SSIs development after hospital discharge.
INTRODUCTION: Extracorporeal shock waves (ESWs) have been shown to have a positive effect on skin wound healing; however, little is known on the regeneration of the microcirculation and angiogenesis as well as the differ...INTRODUCTION: Extracorporeal shock waves (ESWs) have been shown to have a positive effect on skin wound healing; however, little is known on the regeneration of the microcirculation and angiogenesis as well as the different application modes. METHODS: A total of 40 BALB/c mice were provided with dorsal skin fold chambers and were divided into 3 therapy groups (n = 30) and one control group (n = 10). The 3 therapy groups were treated with shock waves at different pulse rates (500-1,000 pulses/min) and application frequencies (day 0 and day 6 or day 0 only). Photographic documentation and intravital microscopy were carried out on day 1, 2, 4, and 6 after wounding. RESULTS: Using the newly developed Diver Box, shock waves could be applied in vivo without mechanical tissue damage. Shock wave therapy to skin wounds demonstrated to induce faster wound closure rates in the beginning than controls in groups with higher pulse rates and frequencies of the shock waves. Furthermore, the regeneration of microcirculation and perfusion in the healing skin was significantly improved after the application of, in particular, higher pulse rates as given by increased numbers of perfused capillaries and functional vessel density. The study of inflammation showed, especially in high-pulse ESW groups, higher leukocyte counts, and rolling leukocytes over time until day 6 as a response to the induction of inflammatory reaction after ESW application. Angiogenesis showed a marked increase in positive areas as given by sprouts, coils, and recruitments in all ESW groups, especially between days 4 and 6. CONCLUSION: The major findings of this trial demonstrate that ESW therapy to skin wounds is effective and safe. This is demonstrated by the initially faster wound closure rate, but later the same wound closure rate in the treatment groups than in controls. Furthermore, during the regeneration of microcirculation and perfusion in the healing skin, a significant improvement was observed after the application of, in particular, higher ESW pulse rates, suggesting an ESW-related increase in nutrient and oxygen supply in the wound tissue.
INTRODUCTION: The International Study Group of Liver Surgery (ISGLS) definition of bile leakage is an elevated total bilirubin concentration in the drainage fluid after post-operative day (POD) 3, which has been widely a...INTRODUCTION: The International Study Group of Liver Surgery (ISGLS) definition of bile leakage is an elevated total bilirubin concentration in the drainage fluid after post-operative day (POD) 3, which has been widely accepted. However, there were no reports about direct bilirubin in drainage fluid to predict bile leakage. METHODS: Data from 257 patients who underwent hepatectomy were retrospectively reviewed. The optimal cut-off value was investigated using receiver-operating characteristic curves. The predictive power of drainage fluid total bilirubin (dTB) and drainage fluid direct bilirubin (dDB) to predict bile leakage, which was defined using ISGLS grade B or grade C, were compared. RESULTS: ISGLS grade B bile leakage occurred in 16 patients (6.2%). Area under the curve (AUC) of dDB was always higher than that of dTB on each POD. The AUC of dDB was >0.75 on PODs 2, 3, and 5, and then it increased with the increasing POD. The dDB on POD 5 showed the highest accuracy (0.91) and positive predictive value (PPV) (0.67), which was followed by dTB/serum total bilirubin (sTB) on POD 3 (accuracy, 0.91; PPV, 0.33). Because the PPV of dDB increased as the POD increased, dDB was better than dTB for predicting clinically significant bile leakage. dDB on POD 3 showed the highest negative predictive value (0.97). The positive likelihood of dDB increased and the negative likelihood of dDB decreased on the basis of the POD. Among patients with dTB/sTB ≤3 on POD 3, 19.1% of these patients had bile leakage when dDB was >0.44 on POD 3. CONCLUSIONS: Measurement of both dDB and dTB, which are easy to perform, can be used to effectively predict clinically significant bile leakage.
PURPOSE: The aim was to examine the predictive value of the hypovolemic shock classification currently accepted by the Advanced Trauma Life Support (ATLS) program over the previous one, which used only vital signs (VS) f...PURPOSE: The aim was to examine the predictive value of the hypovolemic shock classification currently accepted by the Advanced Trauma Life Support (ATLS) program over the previous one, which used only vital signs (VS) for patient allocation. The primary outcome was 30-day mortality; as secondary outcome, heart rate (HR), systolic blood pressure (SBP), Glasgow Coma Scale (GCS) and base deficit (BD) data were compared and investigated in terms of mortality prediction. METHODS: Retrospective analysis at a level I trauma center between 2014 and 2019. Adult patients treated by trauma teams were allocated into severity classes (I-IV) based on the criteria of the current and previous ATLS classifications, respectively. The prognostic values for the classifications were determined with Fisher's exact test and χ2 test for independence, and compared with the 2-proportion Z test. The individual variables were analyzed with receiver-operating characteristic (ROC) analyses. RESULTS: A total of 156 patients met the inclusion criteria. Mortality was effectively predicted by both classifications, and there was no statistically significant difference between the predictive performances. According to ROC analyses, GCS, BD and SBP had significant prognostic values while HR change was ineffective in this regard. CONCLUSIONS: The currently used ATLS shock classification does not appear to be superior to the VS-based previous classification. GCS, BD and SBP are useful parameters to predict the prognosis. Changes in HR do not reflect the clinical course accurately; thus, further studies will be needed to determine the value of this parameter in trauma-associated hypovolemic-hemorrhagic shock conditions.
OBJECTIVE: The role of antibiotic prophylaxis (AP) in the prevention of surgical site infection (SSI) after hernia repair is debated. We conducted this systematic review and meta-analysis to assess the evidence on the va...OBJECTIVE: The role of antibiotic prophylaxis (AP) in the prevention of surgical site infection (SSI) after hernia repair is debated. We conducted this systematic review and meta-analysis to assess the evidence on the value of prophylactic antibiotics in reducing the risks of SSI after open hernia surgery. METHODS: We ran an online and manual search to identify relevant randomized controlled trials that compared prophylactic antibiotics to nonantibiotic controls in patients undergoing open surgical hernia repair. Data on SSI risk were extracted and pooled as risk ratios (RRs) with 95% confidence intervals (95% CIs), using RevMan software. We further used the Cochrane risk of bias tool and GRADE assessment to evaluate the quality of generated evidence. RESULTS: Twenty-nine studies (N = 8,616 patients) were included in the current analysis. Antibiotic prophylaxis reduced the risk of SSI in open hernia repair patients (RR = 0.65, 95% CI = 0.53, 0.79). Subgroup analysis showed a significant benefit for antibiotics in mesh repair patients (RR = 0.60, 95% CI = 0.48, 0.76) yet no significant difference in SSI risk after herniorrhaphy (RR = 0.86, 95% CI = 0.54, 1.36). In addition, AP was associated with a significant reduction in superficial SSI risk (RR = 0.56, 95% CI = 0.43, 0.72) but not deep SSI (RR = 0.70, 95% CI = 0.30, 1.62). Further analysis showed a significant reduction in SSI risk with amoxicillin/clavulanic acid and cefazolin but not with cefuroxime. CONCLUSION: The present meta-analysis suggests that AP is beneficial prior to open mesh hernia repair. However, the quality of evidence was low, and further well-designed trials are needed.
INTRODUCTION: This study aimed to determine the preoperative clinicophysiological and postoperative clinicopathological predictors of malignancy in patients with intraductal papillary mucinous neoplasm (IPMN). METHODS: T...INTRODUCTION: This study aimed to determine the preoperative clinicophysiological and postoperative clinicopathological predictors of malignancy in patients with intraductal papillary mucinous neoplasm (IPMN). METHODS: This was a retrospective observational study. We included 121 patients (73 men and 48 women; mean age: 68.7 years) who had undergone pancreatic resection for IPMN between 2007 and 2018. These patients were grouped into invasive carcinoma (IPMN-INV, N = 21) and low/high-grade IPMN (IPMN-LG/HG, N = 100) groups. Univariate and multivariate analyses of clinicophysiological parameters were carried out. These parameters were also compared between the IPMN-INV/HG (N = 53) and IPMN-LG (N = 68) groups. Survival analyses according to macroscopic type and IPMN subtypes were performed. RESULTS: On univariate analysis, age (p = 0.038), carbohydrate antigen (CA) 19-9 (p < 0.001), IPMN macroscopic type (p = 0.001), IPMN subtype (p < 0.001), pancreatic duct diameter (p < 0.001), and mural nodule (p = 0.042), between IPMN-INV and IPMN-LG/HG were found to be significant prognostic factors of malignancy. CA 19-9 was found to be an independent prognostic factor of IPMN malignancy on multivariate analysis (p = 0.035). The 1-, 3-, and 5-year overall survival (OS) rates of the IPMN-INV and IPMN-LG/HG groups were 94.4/100%, 94.4/100%, and 67.2/100%, respectively. The OS rate in the IPMN-LG/HG group was significantly higher than that in the IPMN-INV group (p < 0.001). On univariate analysis, platelet (p = 0.043), CA 19-9 (p = 0.039), prognostic nutritional index (p = 0.034), platelet/lymphocyte ratio (p = 0.01), IPMN macroscopic type (p < 0.001), IPMN subtype (p < 0.001), pancreatic duct diameter (p = 0.036), and mural nodule (p = 0.032) between IPMN-INV/HG and IPMN-LG were found to be significant prognostic factors of malignancy. On multivariate analysis, CA 19-9 was found to be an independent prognostic factor (p = 0.042) between IPMN-INV/HG and IPMN-LG of malignancy. The 1-, 3-, and 5-year OS rates of the IPMN-INV/HG and IPMN-LG groups were 97.9/100%, 97.9/100%, and 82.6/100%, respectively. The OS rate was significantly higher in the IPMN-LG group than in the IPMN-INV/HG group (p = 0.03). No significant differences in survival were observed in patients with macroscopic tumors (p= 0.544). CONCLUSION: CA 19-9 is an independent invasive malignancy predictor of IPMN.
BACKGROUND: The present study examined whether patient characteristics, management, and outcome of kidney transplant recipients (KTx) with COVID-19 changed in the second versus the first pandemic wave. METHODS: We review...BACKGROUND: The present study examined whether patient characteristics, management, and outcome of kidney transplant recipients (KTx) with COVID-19 changed in the second versus the first pandemic wave. METHODS: We reviewed all available data (demographics, medical history, comorbidities, therapeutic interventions, and outcome) on our KTx with COVID-19 during the first wave (March-September 2020, n = 33) and the second wave (October 2020-February 2021, n = 149) of the COVID-19 pandemic. RESULTS: One hundred eighty-two out of our 1,503 KTx in active follow-up got COVID-19 during 12-month period, corresponding to a prevalence of 12.1%. No difference was found in age, gender distribution, comorbidities, body mass index, or baseline immunosuppression between the 2 COVID-19 waves. Bilateral COVID pneumonia was more frequent during the first wave. More KTx were managed as outpatients during the second wave (15 vs. 39%, p < 0.01). Calcineurin inhibitors were more sparingly reduced during the second wave, whereas antimetabolites were similarly reduced (91 vs. 86, p = ns). Admission to intensive care units was comparable between the first (27%) and second waves (23%). During the first wave, 8 out of 9 patients (89%) requiring intensive care died, whereas the mortality of the ICU patients in the second wave was 68% (23 deaths) (p = 0.2). The overall mortality was 24% during the first wave and 16% during the second wave (p = 0.21), while in-hospital mortality was identical between the CO-VID-19 waves (27%). Increasing age and poor allograft function were significant predictors of mortality. CONCLUSIONS: Most patient characteristics and outcome were comparable between the first 2 COVID-19 waves. More KTx were managed as outpatients without an overall negative impact on outcome.
INTRODUCTION: Indeterminate renal cysts may require several imaging modalities before clinical decision. The aim of this study was to investigate the effect of the imaging modality used to characterize indeterminate rena...INTRODUCTION: Indeterminate renal cysts may require several imaging modalities before clinical decision. The aim of this study was to investigate the effect of the imaging modality used to characterize indeterminate renal cysts on the pathological findings after surgical resection. METHODS: From our institutional database, we identified all patients surgically treated for Bosniak III renal masses between January 2008 and January 2018. All complex renal cysts were characterized with a combination of computed tomography (CT) and/or magnetic resonance imaging (MRI), and/or contrast-enhanced ultrasound (CEUS) and discussed during a multidisciplinary tumor board. Potential association between clinical/radiological characteristics and the pathological findings were investigated, using univariate and multivariate analyses. RESULTS: Of the 52 renal cystic lesions surgically removed, with a preoperative diagnosis of Bosniak III renal cyst, 19 (37%) were malignant and 33 (63%) were benign. The proportion of malignant lesions decreased from 47% when the renal cyst was characterized with cross-sectional imaging (CT and/or MRI) to 17% when the diagnosis required CEUS in addition to cross-sectional imaging. In multivariate analysis, prior history of renal cell carcinoma was associated with a higher risk of malignancy (p = 0.016) and diagnosis made with CEUS was associated with a lower risk of malignancy (p = 0.040). CONCLUSION: We found that using CEUS in addition to cross-sectional imaging to characterize indeterminate renal cysts tends to redefine Bosniak III as lesions with a lower risk of malignancy and can lead to overclassification.
INTRODUCTION: During thoracic resection procedures, complete hemostasis and aerostasis are priorities. A persistent alveolar air leak is associated with increased morbidity and mortality rates. This study aimed to evalua...INTRODUCTION: During thoracic resection procedures, complete hemostasis and aerostasis are priorities. A persistent alveolar air leak is associated with increased morbidity and mortality rates. This study aimed to evaluate whether the novel medical adhesive VIVO (Adhesys Medical GmbH Aachen, Germany) is a reliable alternative sealing technique to routine surgical procedures. METHODS: We conducted an in vitro animal study by analyzing 21 lungs of New Zealand (n = 19) and Chinchilla Bastard (n = 2) rabbits (age, 11-18 weeks; weight, 2,400-3,600 g). Three groups, each comprising 7 animals, were evaluated. VIVO (VIVO-group) was compared with standard surgical lung parenchymal lesion closure with a polypropylene suture (Suture-group) and TachoSil® (TachoSil-group). We adopted a stable, pressure-controlled ventilation protocol. After explantation, a surgical incision 0.5-cm deep and 1.5-cm wide was made in the lungs using a customized template. Air leak was measured quantitatively (mL/min) using a respirator and visualized qualitatively by 2 observers who made independent judgments. Next, the leak was closed using VIVO, suture, or TachoSil® as specified by the manufacturer. Subsequently, positive end-expiratory pressure (PEEP) and inspiratory pressure were gradually increased until a maximum of 15 and 30 mbar were attained, respectively. RESULTS: At PEEPs of 8, 10, and 15 mbar, VIVO achieved complete sealing of the profound parenchymal defect in all (n = 7) lungs. After closure of the incision, we observed an air leak variation of 127 ± 114 mL/min (Suture-group), 31 ± 49 mL/min (VIVO-group), and 114 ± 134 mL/min (TachoSil-group). VIVO showed a significantly lower air leak than surgical sutures (p = 0.031) and TachoSil® (p = 0.046). CONCLUSION: VIVO offers sufficient closure of the lung parenchymal lesions. The novel adhesive enabled significantly better sealing with lower persistent air leakage than TachoSil® or surgical sutures. Further investigation using in vivo models is strongly encouraged to confirm our findings.
INTRODUCTION: The microvascular events following portal vein embolization (PVE) are poorly understood despite the pivotal role of the microcirculation in liver regeneration and tumor progression. We aimed to assess the c...INTRODUCTION: The microvascular events following portal vein embolization (PVE) are poorly understood despite the pivotal role of the microcirculation in liver regeneration and tumor progression. We aimed to assess the changes in hepatic microvascular perfusion and neo-angiogenesis after experimental PVE. METHODS: PVE of the cranial liver lobes was performed in 12 New Zealand White rabbits divided into 2 groups of permanent (P-PVE) and reversible PVE (R-PVE), respectively. Hepatobiliary scintigraphy and CT were used to evaluate hepatic function and volume. Hepatic microcirculation was assessed using a handheld vital microscope (Cytocam) to measure microvascular density (total vessel density; TVD) before PVE, right after PVE, and 20 min after PVE, as well as at 14 days (D14 post-PVE) and 35 days (D35 post-PVE). Additionally, on D35, microvascular PO2 and liver parenchymal VEGF were assessed. RESULTS: Eleven rabbits were included after PVE (R-PVE, n = 5; P-PVE, n = 6). TVD in the nonembo-lized (hypertrophic) lobes was higher than in the embolized (atrophic) lobes of the P-PVE group at D35 post-PVE (36.7 ± 7.2 vs. 23.4 ± 4.9 mm/mm2; p < 0.05). In the R-PVE group, TVD in the nonembolized lobes was not increased at D35. Function and volume were increased in the nonembolized lobes of the P-PVE group compared to the embolized lobes, but not in the R-PVE group. Likewise, the mmicrovascular PO2 and VEGF staining rate were higher in the nonembolized lobes of the P-PVE group at D35 post-PVE. DISCUSSION/CONCLUSION: Successful volumetric and functional hypertrophy of the nonembolized lobe was accompanied by microvascular alterations featuring increased neo-angiogenesis, microvascular density, and microvascular oxygen pressure following P-PVE.
INTRODUCTION: Microbiomes play a vital role in the development and progression of cancer. The clinical status, including prognosis, genetic mutations, and sensitivity to chemotherapy, differs depending on the location of...INTRODUCTION: Microbiomes play a vital role in the development and progression of cancer. The clinical status, including prognosis, genetic mutations, and sensitivity to chemotherapy, differs depending on the location of colorectal cancer (CRC); however, the association between gut microbiota and the location of CRC is not entirely understood. This study was conducted to evaluate the differences in the gut microbiota in patients with CRC according to the location of the tumor. METHODS: Fifty-six patients who underwent surgery for CRC between August 2018 and November 2019 were included in the study. Three patients who had received neoadjuvant therapy or antibiotic treatment within 1 month before surgery were excluded. The metagenomes of microbiota in preoperative feces were assessed using the V3-V4 region of 16s rRNA amplicon sequences. RESULTS: The beta diversity of the Bray-Curtis distance was significantly higher in left-sided than in right-sided CRC. Fusobacterium predominated in left-sided CRC according to the linear discriminant analysis effect size method. Blautia, Eryspelotrichales, Holdemanella, Faecalibacterium, Subdoligranulum, and Dorea constituted the dominant intestinal flora in right-sided CRC. Pathway analysis revealed that L-lysine fermentation and cob(II)yrinate a,c-diamide biosynthesis I were predominant in left-sided CRC. DISCUSSION: This study demonstrated that fecal microbiota in left-sided CRC constitutionally and functionally differ from those in right-side CRC. These results will help to elucidate the biological differences according to tumor location and develop treatments for human CRC.
INTRODUCTION: In animal research, obtaining efficient and constant pain control is regulatory but challenging. The gold standard pain management consists of opioid analgesic administration, such as buprenorphine or fenta...INTRODUCTION: In animal research, obtaining efficient and constant pain control is regulatory but challenging. The gold standard pain management consists of opioid analgesic administration, such as buprenorphine or fentanyl extended-release patches. However, as in all drugs with a short half-life time, repeated buprenorphine administrations are needed, leading to multiple injections that affect the research protocol. On the other hand, fentanyl patch efficacy is discussed in some species. These elements highlight the need of an optimal formulation of analgesic drugs for laboratory animals. In this study, we investigated how Recuvyra®, a fentanyl transdermal solution (FTS), validated in dog perioperative pain management, could provide sustained analgesia after a single topical administration in pigs in a surgical context. METHODS: A total of 11 minipigs were used in this study. As a preliminary experiment, two different doses were tested as a single application on five pigs: two pigs at full dose (2.6 mg/kg) and three pigs at half dose (1.3 mg/kg). Plasma fentanyl dosages were performed during 4 consecutive days, using liquid chromatography with tandem mass spectrometry detection. The efficacy of FTS was then evaluated in a perioperative period. Six minipigs benefited from a surgical intervention comprising a laparotomy. The FTS was blotted on the skin in a single application 20 min before the surgical incision and plasma fentanyl dosages, clinical examination (body weight, food intake, heart rate, and body temperature) and pain assessment were performed for 7 consecutive days. RESULTS: During the preliminary experiment, all fentanyl concentrations reached the minimum effective concentration (MEC) extrapolated in pigs (fentanylemia ≥0.2 ng/mL) throughout the 4 days. The half dose was chosen for the next step of the study. After the surgical intervention, all plasma fentanyl concentrations remained above the MEC up to 7 days post administration. Pig clinical examinations and pain evaluations showed efficient and constant pain control at the half dose, and few adverse events were observed. DISCUSSION AND CONCLUSION: This study confirms the pharmacological and clinical efficacy of FTS at 1.3 mg/kg in pigs throughout at least 7 postoperative days following laparotomy. The clinical analgesic effect of FTS appears more efficient and well-tolerated than the one observed with repeated injections of buprenorphine. This analgesic drug formulation could be universally used in animal research to provide optimal perioperative pain management and long-term analgesia.
OBJECTIVE: During the last decades, surgeons of several specialties presenting different levels of expertise in colon handling have been involved in laparoscopic procedures. The aim of the present experimental study was...OBJECTIVE: During the last decades, surgeons of several specialties presenting different levels of expertise in colon handling have been involved in laparoscopic procedures. The aim of the present experimental study was to investigate the feasibility of TISSEELTM versus the conventional suture placement technique on confined bowel lesions in rats. METHODS: Twenty-four Sprague-Dawley rats underwent confined bowel perforation and were divided into three groups: the SUTURE group (sutures were used), the SUTURE + TISSEELTM group (sutures and TISSEELTM were utilized), and the TISSEELTM group (only TISSEELTM was used). Blinded histopathologic analysis followed animal sacrifice. RESULTS: The median weight of the rats was 526 ± 50 g. A single animal had hematochezia on the first postoperative day. Cessation of bleeding at the perforation margin was indicated intraoperatively after TISSEELTM application. Animals in the TISSEELTM group presented less intraperitoneal adhesions and lower hemorrhagic infiltration compared to animals of the two other groups. In addition, animals in the TISSEELTM group showed thrombus formation at the bowel perforation site compared to animals of the two other groups (p = 0.042). Histopathologic analysis demonstrated reduced inflammatory reaction (p = 0.003), diminished fibrosis (p = 0.001), and better tissue regeneration (p = 0.000) in the TISSEELTM group compared to the other two groups. CONCLUSION: Application of TISSEELTM at the perforation site was associated with increased regeneration of the intestinal wall and less inflammatory and fibrotic reaction compared to suture placement. However, more experimental and clinical studies should be conducted before implementation in humans.
Silicone implant-based augmentation rhinoplasty or mammoplasty induces capsular contracture, which has been acknowledged as a process that develops an abnormal fibrotic capsule associated with the immune response to allo...Silicone implant-based augmentation rhinoplasty or mammoplasty induces capsular contracture, which has been acknowledged as a process that develops an abnormal fibrotic capsule associated with the immune response to allogeneic materials. However, the signaling pathways leading to the nasal fibrosis remain poorly investigated. We aimed to explore the molecular mechanism underlying the pathogenesis of nasal capsular contracture, with a specific research interest in the signaling pathways involved in fibrotic development at the advanced stage of contracture. By examining our recently obtained RNA sequencing data and global gene expression profiling between grade II and grade IV nasal capsular tissues, we found that both the RAP1 and JAK/STAT signaling pathways were hyperactive in the contracted capsules. This was verified on quantitative real-time PCR which demonstrated upregulation of most of the representative component signatures in these pathways. Loss-of-function assays through siRNA-mediated Rap1 silencing and/or small molecule-directed inhibition of JAK/STAT pathway in ex vivo primary nasal fibroblasts caused a series of dramatic behavioral and functional changes, including decreased cell viability, increased apoptosis, reduced secretion of proinflammatory cytokines, and synthesis of type I collagen, compared to control cells, and indicating the essential role of the RAP1 and JAK/STAT signaling pathways in nasal capsular fibrosis. Our results sheds light on targeting downstream signaling pathways for the prevention and therapy of silicone implant-induced nasal capsular contracture.