Laparoscopic training workshop to assess medical students' skill acquisition and interest in surgical careers.

BACKGROUND: With its minimally invasive approach, laparoscopic surgery has transformed the medical landscape. As the demand for these procedures escalates, there is a pressing need for adept surgeons trained in laparoscopic techniques. However, current training often falls short of catering to medical school education. This study evaluates the impact of a custom-designed laparoscopic training workshop on medical students' surgical skills and career aspirations. METHODS: This prospective experimental study was conducted at the E-Da hospital in Kaohsiung City, Taiwan. Medical students from Taiwanese medical schools undergoing Clerk 5, Clerk 6, and Postgraduate Year 1 and 2 were invited to participate. Medical students (n = 44) underwent an endoscopic skill training workshop consisting of lectures, box training, and live tissue training. The trainees performed multiple tasks before and after training using our objective evaluation system. The primary outcome was assessed before and after training through a questionnaire assessing the influence of training on students' interest in surgery as a career. The secondary outcome measured improvement in skill acquisition, comparing the task completion time pre- and post-workshop. For the primary outcome, descriptive statistics were used to summarize the questionnaire responses, and paired t-tests were performed to determine significant changes in interest levels post-workshop. For the secondary outcome, paired t-tests were used to compare the time recorded pre- and post-training. RESULTS: Post-training, participants exhibited significant proficiency gains, with task completion times reducing notably: 97 s (p = 0.0015) for Precision Beads Placement, 88.5 s (p < 0.0001) for Beads Transfer Exercise, 95 s (p < 0.0001) for Precision Balloon Cutting, and 137.8 s (p < 0.0001) for Intracorporeal Suture. The primary outcome showcased an increased mean score from 8.15 pre-workshop to 9.3 post-workshop, indicating a bolstered interest in surgery as a career. Additionally, post-training sentiment analysis underscored a predominant inclination toward surgery among 88% of participants. CONCLUSION: The custom-designed laparoscopic workshop significantly improved technical skills and positively influenced students' career aspirations toward surgery. Such hands-on training workshops can play a crucial role in medical education, bridging the gap between theoretical knowledge and practical skills and potentially shaping the future of budding medical professionals.

Pharmacogenomic study-A pilot study of the effect of pharmacogenomic phenotypes on the adequate dosing of verapamil for migraine prevention.

OBJECTIVE: To investigate factors affecting the efficacy and tolerability of verapamil for migraine prevention using individual pharmacogenomic phenotypes. BACKGROUND: Verapamil has a wide range of dosing in headache disorders without reliable tools to predict the optimal doses for an individual. METHODS: This is a retrospective chart review examining adults with existing pharmacogenomic reports at Mayo Clinic who had used verapamil for migraine. Effects of six cytochrome P450 phenotypes on the doses of verapamil for migraine prevention were assessed. RESULTS: Our final analysis included 33 migraine patients (82% with aura). The mean minimum effective and maximum tolerable doses of verapamil were 178.2(20-320) mg and 227.9(20-480) mg. A variety of CYP2C9, CYP2D6, and CYP3A5 phenotypes were found, without significant association with the verapamil doses after adjusting for age, sex, body mass index, and smoking status. CONCLUSIONS: We demonstrated a wide range of effective and tolerable verapamil doses used for migraine in a cohort with various pharmacogenomic phenotypes.

Use of Technetium-99m-Pyrophosphate Single-Photon Emission Computed Tomography/Computed Tomography in Monitoring Therapeutic Changes of Eplontersen in Patients With Hereditary Transthyretin Amyloid Cardiomyopathy.

BACKGROUND: Hereditary transthyretin amyloid cardiomyopathy (hATTR-CM) is a progressive and fatal disease. Recent evidence indicates that bone scintigraphy may serve as a tool to monitor the effectiveness of hATTR-CM treatment. The objective of this study was to examine how eplontersen therapy influences the semiquantitative uptake of technetium-99m-pyrophosphate in individuals diagnosed with hATTR-CM. METHODS AND RESULTS: We retrospectively analyzed a prospective cohort from the NEURO-TTRansform trial, including patients with hATTR-CM receiving eplontersen (45 mg/4 weeks). A control group comprised patients with hATTR-CM who had not received eplontersen, inotersen, tafamidis, or patisiran. Technetium-99m-pyrophosphate single-photon emission computed tomography/computed tomography was conducted at baseline and during follow-up. Thirteen patients with hATTR-CM were enrolled, with 6 receiving eplontersen and 7 serving as the control group. The median follow-up time was 544 days. The eplontersen group exhibited a significant decrease in volumetric heart and lung ratio (3.774 to 2.979, P=0.028), whereas the control group showed no significant change (4.079 to 3.915, P=0.237). Patients receiving eplontersen demonstrated a significantly greater reduction in volumetric heart and lung ratio compared with the control group (-20.7% versus -3.4%, P=0.007). CONCLUSIONS: The volumetric heart and lung ratio used to quantify technetium-99m-pyrophosphate uptake showed a significant reduction subsequent to eplontersen treatment in individuals diagnosed with hATTR-CM. These findings suggest the potential efficacy of eplontersen in treating hATTR-CM and highlight the value of technetium-99m-pyrophosphate single-photon emission computed tomography/computed tomography as a tool for monitoring therapeutic effectiveness.

Challenges and solutions of echocardiography generalization for deep learning: a study in patients with constrictive pericarditis.

Purpose: The inherent characteristics of transthoracic echocardiography (TTE) images such as low signal-to-noise ratio and acquisition variations can limit the direct use of TTE images in the development and generalization of deep learning models. As such, we propose an innovative automated framework to address the common challenges in the process of echocardiography deep learning model generalization on the challenging task of constrictive pericarditis (CP) and cardiac amyloidosis (CA) differentiation. Approach: Patients with a confirmed diagnosis of CP or CA and normal cases from Mayo Clinic Rochester and Arizona were identified to extract baseline demographics and the apical 4 chamber view from TTE studies. We proposed an innovative preprocessing and image generalization framework to process the images for training the ResNet50, ResNeXt101, and EfficientNetB2 models. Ablation studies were conducted to justify the effect of each proposed processing step in the final classification performance. Results: The models were initially trained and validated on 720 unique TTE studies from Mayo Rochester and further validated on 225 studies from Mayo Arizona. With our proposed generalization framework, EfficientNetB2 generalized the best with an average area under the curve (AUC) of 0.96 (±0.01) and 0.83 (±0.03) on the Rochester and Arizona test sets, respectively. Conclusions: Leveraging the proposed generalization techniques, we successfully developed an echocardiography-based deep learning model that can accurately differentiate CP from CA and normal cases and applied the model to images from two sites. The proposed framework can be further extended for the development of echocardiography-based deep learning models.

Subthalamic high-beta oscillation informs the outcome of deep brain stimulation in patients with Parkinson's disease.

Background: The therapeutic effect of deep brain stimulation (DBS) of the subthalamic nucleus (STN) for Parkinson's disease (PD) is related to the modulation of pathological neural activities, particularly the synchronization in the ß band (13-35 Hz). However, whether the local ß activity in the STN region can directly predict the stimulation outcome remains unclear. Objective: We tested the hypothesis that low-ß (13-20 Hz) and/or high-ß (20-35 Hz) band activities recorded from the STN region can predict DBS efficacy. Methods: Local field potentials (LFPs) were recorded in 26 patients undergoing deep brain stimulation surgery in the subthalamic nucleus area. Recordings were made after the implantation of the DBS electrode prior to its connection to a stimulator. The maximum normalized powers in the theta (4-7 Hz), alpha (7-13 Hz), low-ß (13-20 Hz), high-ß (20-35 Hz), and low-γ (40-55 Hz) subbands in the postoperatively recorded LFP were correlated with the stimulation-induced improvement in contralateral tremor or bradykinesia-rigidity. The distance between the contact selected for stimulation and the contact with the maximum subband power was correlated with the stimulation efficacy. Following the identification of the potential predictors by the significant correlations, a multiple regression analysis was performed to evaluate their effect on the outcome. Results: The maximum high-ß power was positively correlated with bradykinesia-rigidity improvement (r s = 0.549, p < 0.0001). The distance to the contact with maximum high-ß power was negatively correlated with bradykinesia-rigidity improvement (r s = -0.452, p < 0.001). No significant correlation was observed with low-ß power. The maximum high-ß power and the distance to the contact with maximum high-ß power were both significant predictors for bradykinesia-rigidity improvement in the multiple regression analysis, explaining 37.4% of the variance altogether. Tremor improvement was not significantly correlated with any frequency. Conclusion: High-ß oscillations, but not low-ß oscillations, recorded from the STN region with the DBS lead can inform stimulation-induced improvement in contralateral bradykinesia-rigidity in patients with PD. High-ß oscillations can help refine electrode targeting and inform contact selection for DBS therapy.

Clinical characteristics and long-term outcome of cerebral cavernous malformations-related epilepsy.

OBJECTIVE: Cerebral cavernous malformations (CCMs) present variably, and epileptic seizures are the most common symptom. The factors contributing to cavernoma-related epilepsy (CRE) and drug resistance remain inconclusive. The outcomes of CRE after different treatment modalities have not yet been fully addressed. This study aimed to characterize the clinical features of patients with CRE and the long-term seizure outcomes of medical and surgical treatment strategies. METHODS: This was a retrospective cohort of 135 patients with CCM who were diagnosed in 2007-2011 and followed up for 93.6 months on average. The patients were divided into drug-resistant epilepsy (DRE; n = 29), non-DRE (n = 45), and no epilepsy (NE; n = 61). RESULTS: Temporal CCM was the factor most strongly associated with the development of both CRE and DRE. The majority of patients with single temporal CCMs had CRE (86.8%, n = 33), and 50% had DRE, whereas only 14.7% (n = 5) with a nontemporal supratentorial CCM had DRE (p < .05). The most common lesion site in the DRE group was the mesiotemporal lobe (50%). Multiple CCMs were more frequently observed in the CRE (29.2%) than the NE (11.5%) group (p < .05). In patients with CRE, multiple lesions were associated with a higher rebleeding rate (odds ratio = 11.1), particularly in those with DRE (odds ratio = 15.4). The majority of patients who underwent resective surgery for DRE (76.5%, n = 13) achieved International League Against Epilepsy Class I and II seizure outcomes even after a long disease course. SIGNIFICANCE: Temporal CCM not only predisposes to CRE but also is a major risk factor for drug resistance. The mesiotemporal lobe is the most epileptogenic zone. Multiple CCMs are another risk factor for CRE and increase the rebleeding risk in these patients. Surgical resection could provide beneficial long-term seizure outcomes in patients with DRE.

Negative-Pressure Wound Therapy Application in Fingertip Replantations and a Systematic Review.

BACKGROUND: Fingertip replantation is technically challenging. Venous congestion is one of the most common causes of replantation failure. Therefore, various venous drainage procedures and salvage techniques have been used in venous congestion. Negative-pressure wound therapy has proven beneficial in limb injuries, yet limited studies of fingertip replantation exist. This study aims to analyze risk factors in fingertip replantation and to evaluate the feasibility and clinical benefits of negative-pressure wound therapy compared with other salvage techniques. METHODS: From January of 2015 to December of 2019, 27 patients (27 digits) who experienced fingertip amputation over Tamai zone I or II underwent replantation. Salvage negative-pressure wound therapy was applied for venous congestion postoperatively. Replantation data were collected for further analysis. RESULTS: The overall survival rate of digit replantation with salvage negative-pressure wound therapy was 92.6 percent (25 of 27). The blood transfusion rate was 11.1 percent (three of 27). The average hospitalization time was 8.04 ± 1.43 days and the median duration of negative-pressure wound therapy was 6 days (range, 4 to 8 days; interquartile range, 2 days). There is no significant difference between the survival and failure groups for all risk factors evaluated. CONCLUSION: Negative-pressure wound therapy is a simple and effective salvage option to relieve venous congestion in fingertip replantation with a satisfactory survival rate, low blood transfusion rate, and short inpatient stay. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Impact on inadequate lymph node harvest on survival in T4N0 colorectal cancer: A would-be medical center experience in Taiwan.

Insufficient lymph node harvest (< 12) may lead to incorrect classification of stage I and II disease. Many studies have indicated a poor prognosis with inadequate lymph node harvest in stages I to III, but few studies have demonstrated the relationship between low lymph node harvest and T4 disease. This study aimed to identify the influence of insufficient number of lymph nodes harvested on survival in T4N0 colorectal cancer. We enrolled patients with T4N0 colorectal cancer who underwent radical resection between 2010 and 2016. A total of 155 patients were divided into 2 groups; 142 patients had ≥ 12 harvested lymph nodes, and the other 13 had < 12 lymph nodes. All patients were followed up for at least 5 years. The primary outcome was the impact of the number of lymph nodes harvested on disease-free survival and overall survival, which were investigated using Kaplan-Meier survival techniques. There were no significant differences in recurrence rate, emergent or elective surgery, laparoscopic or open surgery, or chemotherapy between the 2 groups. Kaplan-Meier analyses showed no statistical differences in 5-year disease-free survival (P = .886) and 5-year overall survival (P = .832) between the groups. There were no significant differences in disease-free survival and overall survival between patients with adequate (≥ 12) and inadequate (< 12) lymph node harvest in T4N0 colorectal cancers.

Minor Traumatic Intracranial Hemorrhage: Identifying Prognostic Factors and Comparing Patients with Favorable and Unfavorable Outcomes.

BACKGROUND: Whether patients with minor traumatic intracranial hemorrhage (MTICH) require intensive care remains uncertain. This study aimed to identify the factors affecting the postinjury neurologic outcomes of patients with MTICH to determine optimal care. METHODS: We retrospectively reviewed the data of all patients with trauma discharged from a tertiary trauma center during a 2-year period and included adult patients with isolated MTICH. Patient Glasgow Outcome Scale (GOS) score at discharge was the primary outcome measurement. A GOS score of 4 or 5 was defined as a favorable outcome, and a score of 1-3 was considered an unfavorable outcome. We compared the clinical data between favorable and unfavorable outcome groups to determine the differences between groups. RESULTS: Of the 11,814 patients considered, we identified 534 patients who met the inclusion criteria. Older adults accounted for 35.4% of the study cohort. Only 4 complications (0.7%) and 1 mortality (0.2%) were observed during hospitalization. The number of patients who requiring brain surgery, transfusion, mechanical ventilation, pressor, or invasive monitor was 5 (0.9%), 5 (0.9%), 3 (5.6%), 0 (0%), and 0 (0%), respectively. After multivariate analysis, we discovered that comorbidities, brain surgery requirement, respiratory rate, and Trauma Injury Severity Score were strongly associated with patient GOS score at discharge. CONCLUSIONS: MTICH rarely resulted in permanent morbidity and mortality. Older patients exhibited higher incidences of MTICH and were at a higher risk for unfavorable outcomes.

Lower starting dose of afatinib for the treatment of metastatic lung adenocarcinoma harboring exon 21 and exon 19 mutations.

BACKGROUND: Afatinib has shown favorable response rates (RRs) and longer progression free survival (PFS) in lung cancer patients harboring EGFR mutations compared with standard platinum-based chemotherapy. However, serious adverse drug reactions (ADRs) limit the clinical application of afatinib. METHODS: We designed a retrospective study, enrolling all patients with metastatic lung adenocarcinoma who were diagnosed and treated with 30 or 40 mg daily afatinib as their initial treatment in three Kaohsiung Medical University-affiliated hospitals in Taiwan. RESULTS: A total of 179 patients were enrolled in the study, of which 102 (57%) and 77 (43%) received 30 mg and 40 mg afatinib daily as their initial treatment, respectively. The patients initially using 30 mg afatinib daily had a similar RR (75% vs. 83%, p = 0.1672), median PFS (14.5 vs. 14.8 months, log-rank p = 0.4649), and median OS (34.0 vs. 25.2 months, log-rank p = 0.5982) compared with those initially using 40 mg afatinib daily. Patients initially receiving 30 mg afatinib daily had fewer ADRs compared with those using 40 mg daily. The overall incidence of moderate and severe ADRs was significantly lower in patients receiving 30 mg afatinib daily compared with those using 40 mg daily (49% vs. 77%, p = 0.002); similar findings was observed in terms of severe ADRs (7% vs. 24%, p < 0.0001). CONCLUSION: Patients receiving 30 mg afatinib daily as their initial treatment had similar RR, PFS, OS, but significantly fewer serious ADRs, as compared with those using 40 mg as their starting dose.

Effects of Focal Radiation on [18 F]-Fluoro-D-Glucose Positron Emission Tomography in the Brains of Miniature Pigs: Preliminary Findings on Local Metabolism.

OBJECTIVES: It would be a medically important advance if durable and focal neuromodulation of the brain could be delivered noninvasively and without ablation. This ongoing study seeks to elucidate the effects of precisely delivered ionizing radiation upon focal brain metabolism and the corresponding cellular integrity at that target. We hypothesize that focally delivered ionizing radiation to the brain can yield focal metabolic changes without lesioning the brain in the process. MATERIALS AND METHODS: We used stereotactic radiosurgery to deliver doses from 10 Gy to 120 Gy to the left primary motor cortex (M1) of Lee Sung miniature pigs (n = 8). One additional animal served as a nonirradiated control. We used positron emission tomography-computed tomography (PET-CT) to quantify radiation dose-dependent effects by calculating the ratio of standard uptake values (SUV) of 2-deoxy-2-[18 F]-fluoro-D-glucose (18 F-FDG) between the radiated (left) and irradiated (right) hemispheres across nine months. RESULTS: We found that the FDG-PET SUV ratio at the targeted M1 was significantly lowered from the pre-radiation baseline measurements for animals receiving 60 Gy or higher, with the effect persisting at nine months after radiosurgery. Only at 120 Gy was a lesion suggesting ablation visible at the M1 target. Animals treated at 60-100 Gy showed a reduced signal in the absence of an identifiable lesion, a result consistent with the occurrence of neuromodulation. CONCLUSION: Focal, noninvasive, and durable changes in brain activity can be induced without a magnetic resonance imaging (MRI)-visible lesion, a result that may be consistent with the occurrence of neuromodulation. This approach may provide new venues for the investigation of neuromodulatory treatments for disorders involving dysfunctional brain circuits. Postmortem pathological analysis is needed to elucidate whether there have been morphological changes not detected by MRI.

Outcomes of conventional versus virtual surgical planning of orthognathic surgery using surgery-first approach for class III asymmetry.

OBJECTIVES: To determine if patient outcome variables differ between conventional and virtual surgical planning of orthognathic surgery for class III asymmetry. MATERIAL AND METHODS: This retrospective case-control study examined 95 patients with class III asymmetry who had been consecutively treated with at least a Le Fort I osteotomy and a bilateral sagittal split osteotomy with a surgery-first approach. Two groups were examined: 51 patients treated with conventional surgical planning and 44 with virtual surgical planning. After treatment, quantitative assessment was determined with measurements of midline symmetry, contour symmetry, and overall facial symmetry using standardized frontal photographs. Subject assessments were analyzed with questionnaires regarding self-perception of overall appearance, satisfaction with appearance, and quality of life. RESULTS: Conventional and virtual surgical planning resulted in significant improvements in outcomes for all patients. However, facial midline and overall facial symmetry were significantly greater for the virtual compared with the conventional group. There were no significant differences in subjective measures of appearance, satisfaction with appearance, and quality of life for patients treated with conventional or virtual surgical planning; measures were high for both groups. CONCLUSIONS: Conventional and virtual surgical planning of surgery-first bimaxillary orthognathic surgery resulted in quantitative and qualitative improvements in facial symmetry. Although patient satisfaction was similar for both approaches, virtual surgical planning was superior to conventional surgical planning for the improvement of midline and overall asymmetry. CLINICAL RELEVANCE: Improvements with virtual surgical planning in facial midline, facial contour, and overall facial symmetry are as good as or better than conventional surgical planning.

The Medial Subcoronoid Process Region as a Novel Source of Bone Grafts in Orthognathic Surgery and Genioplasty.

BACKGROUND: Since 2012, the authors have adopted the medial subcoronoid process bone interpositional grafting in OGS and genioplasty procedures. The purpose of this study was to present the technical details and clinical outcomes of this alternative bone interpositional grafting for LeFort I and chin osteotomies. METHODS: Consecutive patients (n = 50) who underwent single-splint bimaxillary OGS with or without genioplasty and received medial subcoronoid bone interpositional grafting were included. Standardized facial and intraoral photographs at early and late postoperative periods (12.2 ±â€Š3.3 and 44.8 ±â€Š8.4 months postsurgery, respectively) were blindly rated to assess facial symmetry, chin, and occlusion status based on qualitative rating scales. Complication and reoperation rates were also reviewed. RESULTS: The medial subcoronoid bone interpositional grafts were adopted to stabilize different LeFort I maxillary movement types or lengthening/advancing genioplasty (36 and 14 patients, respectively). Overall, the early facial symmetry, chin, and occlusion status were maintained at late evolutions. None of the patients had donor-site or bone graft-related complications (i.e., bad split, undesired mandible fracture, infection, fibrous union, nonunion, and/or permanent neurosensory deficit) or revisionary surgery during follow-up. CONCLUSION: The medial subcoronoid process bone grafting was a feasible alternative for bone interpositional defects of LeFort I and chin osteotomies with no significant morbidity and avoiding secondary donor sites.

Cryolite (Na3AlF6) crystallization for fluoride recovery using an electrolytic process equipped with a sacrificial aluminum anode.

An electro-crystallization process equipped with a sacrificial aluminum anode was operated under an optimum condition to promote the formation of crystalline cryolite for the recovery of fluoride from synthetic F-containing wastewater. The effects of pH, Al/F molar ratio, initial F concentration, and electrolytes were investigated experimentally, and the results were compared with data obtained from chemical equilibrium modeling. Cryolite was successfully produced under optimum pH values of 5 to 6 and Al/F molar ratios of less than 1/6. The F removal increased with increasing Al/F molar ratio until reaching the molar ratio of 1/6 and decreased thereafter due to the formation of AlFn3-n species. The adsorption of AlFn3-n by Al(OH)3 precipitates contributed part of F removal. The removal efficiency reached 100% when the initial fluoride concentration was high while it was around 90% with the low initial fluoride concentration. XRD and SEM/EDX analysis showed that the obtained solids matched well to the commercial cryolite. Finally, the operating costs of chemical-crystallization (the process with Al ions added chemically) and electro-crystallization were compared, and the cost of the former was less than the latter. Energy consumption was the main contributor to the operating cost of the electro-crystallization process.

Clinical Utility of FDG PET/CT in Patients with Autoimmune Pancreatitis: a Case-Control Study.

Autoimmune pancreatitis (AIP) shares overlapping clinical features with pancreatic cancer (PC). Importantly, treatment of the two conditions is different. We investigated the clinical usefulness of 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) in patients with suspected AIP before treatment. From September 2008 to July 2016, 53 patients with suspected AIP at National Taiwan University Hospital had PET/CT prior to therapy to exclude malignancy and evaluate the extent of inflammation. Their scans were compared with those from 61 PC patients. PET imaging features were analyzed using logistic regression. Significant differences in pancreatic tumor uptake morphology, maximum standardized uptake value, high-order primary tumor texture feature (i.e. high-gray level zone emphasis value), and numbers and location of extrapancreatic foci were found between AIP and PC. Using the prediction model, the area under curve of receiver-operator curve was 0.95 (P < 0.0001) with sensitivity, specificity, positive predictive, and negative predictive values of 90.6%, 84.0%, 87.9%, and 87.5% respectively, in differentiating AIP from PC. FDG PET/CT offers high sensitivity, albeit slightly lower specificity in differentiating AIP from PC. Nonetheless, additional systemic inflammatory foci detected by the whole body PET/CT help confirm diagnosis of AIP in these patients before initiating steroid therapy, especially when biopsy is inconclusive.

The Role of Local Bupivacaine Irrigation in Postoperative Pain Control After Augmentation Mammoplasty: A Systematic Review and Meta-Analysis.

BACKGROUND: The objective of this study is to analyze the efficacy of local bupivacaine irrigation after augmentation mammoplasty for the control of postoperative pain. METHODS: A systematic review and meta-analysis was conducted including all randomized controlled trials (RCTs) that compared the irrigation of bupivacaine (±ketorolac) versus normal saline or no irrigation for pain control after breast augmentation. The primary outcome was postoperative pain measured by visual analog scale. The study protocol was established a priori according to the recommendations of the Cochrane Collaboration. A bibliographical search was conducted in September 2015 in the following Cochrane Library databases: CENTRAL, MEDLINE, EMBASE, and Scielo. The strategy used for the search was ((augmentation AND ("mammoplasty"[MeSH Terms] OR "mammoplasty")) OR (("breast"[MeSH Terms] OR "breast") AND augmentation)) AND (("pain, postoperative"[MeSH Terms])). RESULTS: Four RCTs with a total of 264 participants were included. Two trials compared bupivacaine alone versus placebo (normal saline or no irrigation) and 3 trials compared bupivacaine plus ketorolac versus placebo. The combined irrigation of bupivacaine and ketorolac showed a clinically significant reduction of pain in the first postoperative hour and on postoperative day 5. The irrigation with bupivacaine compared with placebo significantly reduced pain assessed on postoperative day 4. CONCLUSION: The irrigation of bupivacaine with or without ketorolac was associated with a reduction of postoperative pain compared with control groups for the first 5 postoperative days. Due to the few number of trials included, these results should be correlated further clinically.

HISTORIQUE: La présente étude vise à analyser l'efficacité de l'infiltration locale de bupivacaïne pour contrôler la douleur postopératoire après une mammoplastie d'augmentation. MÉTHODOLOGIE: Les chercheurs ont procédé à une analyse systématique et à une méta-analyse incluant tous les essais aléatoires et contrôlés (EAC) qui comparaient l'infiltration de bupivacaïne (±kétorolac) à un soluté physiologique normal ou à l'absence d'infiltration pour contrôler la douleur après une augmentation mammaire. Le résultat clinique primaire était la douleur postopératoire mesurée d'après une échelle analogique visuelle. Les chercheurs ont établi le protocole de l'étude a priori, conformément aux recommandations de la Collaboration Cochrane. En septembre 2015, ils ont effectué une recherche bibliographique dans les bases de données suivantes de la Bibliothèque Cochrane : CENTRAL, MEDLINE, EMBASE et Scielo, à l'aide des termes suivants : augmentation ET mammoplasty (termes du MeSH) OU mammoplasty, OU breast (termes du MeSH) OU breast ET augmentation ET pain, postoperative (termes du MeSH). RÉSULTATS: Quatre EAC, totalisant 264 participants, ont été inclus dans l'étude. Deux essais comparaient la bupivacaïne utilisée seule à un placebo (soluté physiologique normal ou absence d'infiltration) et trois essais, la bupivacaïne associée au kétorolac à un placebo. L'infiltration combinée de bupivacaïne et de kétorolac a démontré une réduction cliniquement significative de la douleur pendant l'heure suivant l'opération ainsi que le cinquième jour suivant l'opération. Par rapport à un placebo, l'infiltration de bupivacaïne réduisait considérablement la douleur évaluée le quatrième jour suivant l'opération. CONCLUSION: Pendant les cinq premiers jours suivant l'opération, l'infiltration de bupivacaïne, associée ou non à du kétorolac, entraînait une diminution de la douleur postopératoire par rapport à celle ressentie par les groupes témoins. Étant donné le peu d'essais en cause, il faudrait corréler ces résultats en clinique.

Dysregulation of Rab37-Mediated Cross-talk between Cancer Cells and Endothelial Cells via Thrombospondin-1 Promotes Tumor Neovasculature and Metastasis.

Purpose: Accumulating evidence indicates that factors secreted by cancer epithelial cells shape the tumor microenvironment to promote cancer invasion and metastasis. Recent studies also shed light on alterations of Rab small GTPase-mediated exocytosis in tumorigenesis. However, the mechanisms for Rab-mediated exocytosis in tumor microenvironment remain elusive. We aimed to investigate the interplay between Rab37-mediated exocytosis and tumor microenvironment, focusing on endothelial cell motility and angiogenesis.Experimental Design: We performed fluorescence IHC for Rab37, thrombospondin-1 (TSP1, an antiangiogenesis factor), and angiogenesis marker CD31 in 183 surgically resected esophageal squamous cell carcinoma (ESCC) patient samples. Cell migration, invasion, angiogenesis, and tumor metastasis were measured.Results: ESCC patients with low expression of Rab37 or TSP1 significantly correlated with high CD31 expression and were associated with worse progression-free survival. The multivariate Cox regression analysis showed that concordant low expression of both Rab37 and TSP1 was an independent prognostic factor of ESCC patients. Rab37-mediated exocytosis of TSP1 led to the inhibition of neovasculature in vitro and in vivo Secreted TSP1 from cancer cells with Rab37 exocytic function inhibited the p-FAK/p-paxillin/p-ERK migration signaling in both cancer epithelial cells and their surrounding endothelial cells. Dysfunction of Rab37 or loss of TSP1 abrogated the suppressive effects on angiogenesis and metastasis.Conclusions: Our findings suggest that Rab37-mediated TSP1 secretion in cancer cells suppresses metastasis and angiogenesis via a cross-talk with endothelial cells and reveal a novel component of the vesicular exocytic machinery in tumor microenvironment and tumor progression. Dysregulation of Rab37/TSP1 axis has clinical implications for prognosis prediction. Clin Cancer Res; 23(9); 2335-45. ©2016 AACR.