Robotic technology in surgery; a classification system of soft tissue surgical robotic devices.

BACKGROUND: The field of robotic-assisted surgery is rapidly growing as many robotic surgical devices are in development and about to enter the market. Currently, there is no universally accepted language for labeling the different robotic systems. To facilitate this communication, we created what is, to our knowledge, the first classification of surgical robotic technologies that organizes and classifies surgical robots used for endoscopy, laparoscopy and thoracoscopy. METHODS: We compiled a list of surgical robots intended to be used for endoscopy, laparoscopy, and/or thoracoscopy by searching United States, European, Hong Kong, Japan, and Korean databases for approved devices. Devices showcased at the 2023 Annual Meeting for the Society of Robotic Surgery were added. We also systematically reviewed the literature for any existing surgical robotic classifications or categorizations. We then created a multidisciplinary committee of 8 surgeons and 2 engineers to construct a proposed classification of the devices included in our search. RESULTS: We identified 40 robotic surgery systems intended to be used for endoscopy, laparoscopy and/or thoracoscopy. The proposed classification organizes robotic devices with regard to architecture, port design, and configuration (modular carts, multi-arm integrated cart, table-attachable or arm-table integration). CONCLUSION: This 3-level classification of robotic surgical devices used for endoscopy, laparoscopy and/or thoracoscopy describes important characteristics of robotic devices systematically.

Online videos of robotic-assisted cholecystectomies: more harm than good?

BACKGROUND: Many surgeons use online videos to learn. However, these videos vary in content, quality, and educational value. In the setting of recent work questioning the safety of robotic-assisted cholecystectomies, we aimed (1) to identify highly watched online videos of robotic-assisted cholecystectomies, (2) to determine whether these videos demonstrate suboptimal techniques, and (3) to compare videos based on platform. METHODS: Two authors searched YouTube and a members-only Facebook group to identify highly watched videos of robotic-assisted cholecystectomies. Three members of the Society of American Gastrointestinal and Endoscopic Surgeons Safe Cholecystectomy Task Force then reviewed videos in random order. These three members rated each video using Sanford and Strasberg's six-point criteria for critical view of safety (CVS) scoring and the Parkland grading scale for cholecystitis. We performed regression to determine any association between Parkland grade and CVS score. We also compared scores between the YouTube and Facebook videos using a t test. RESULTS: We identified 50 videos of robotic-assisted cholecystectomies, including 25 from YouTube and 25 from Facebook. Of the 50 videos, six demonstrated a top-down approach. The remaining 44 videos received a mean of 2.4 of 6 points for the CVS score (SD = 1.8). Overall, 4 of the 50 videos (8%) received a passing CVS score of 5 or 6. Videos received a mean of 2.4 of 5 points for the Parkland grade (SD = 0.9). Videos on YouTube had lower CVS scores than videos on Facebook (1.9 vs. 2.8, respectively), though this difference was not significant (p = 0.09). By regression, there was no association between Parkland grade and CVS score (p = 0.13). CONCLUSION: Publicly available and closed-group online videos of robotic-assisted cholecystectomy demonstrated inadequate dissection and may be of limited educational value. Future work should center on introducing measures to identify and feature videos with high-quality techniques most useful to surgeons.

Development and Validation of Prediction Models and Risk Calculators for Posthepatectomy Liver Failure and Postoperative Complications Using a Diverse International Cohort of Major Hepatectomies.

OBJECTIVE: The study aim was to develop and validate models to predict clinically significant posthepatectomy liver failure (PHLF) and serious complications [a Comprehensive Complication Index (CCI)>40] using preoperative and intraoperative variables. BACKGROUND: PHLF is a serious complication after major hepatectomy but does not comprehensively capture a patient's postoperative course. Adding the CCI as an additional metric can account for complications unrelated to liver function. METHODS: The cohort included adult patients who underwent major hepatectomies at 12 international centers (2010-2020). After splitting the data into training and validation sets (70:30), models for PHLF and a CCI>40 were fit using logistic regression with a lasso penalty on the training cohort. The models were then evaluated on the validation data set. RESULTS: Among 2192 patients, 185 (8.4%) had clinically significant PHLF and 160 (7.3%) had a CCI>40. The PHLF model had an area under the curve (AUC) of 0.80, calibration slope of 0.95, and calibration-in-the-large of -0.09, while the CCI model had an AUC of 0.76, calibration slope of 0.88, and calibration-in-the-large of 0.02. When the models were provided only preoperative variables to predict PHLF and a CCI>40, this resulted in similar AUCs of 0.78 and 0.71, respectively. Both models were used to build 2 risk calculators with the option to include or exclude intraoperative variables ( PHLF Risk Calculator; CCI>40 Risk Calculator ). CONCLUSIONS: Using an international cohort of major hepatectomy patients, we used preoperative and intraoperative variables to develop and internally validate multivariable models to predict clinically significant PHLF and a CCI>40 with good discrimination and calibration.

Quantitative imaging features of pretreatment CT predict volumetric response to chemotherapy in patients with colorectal liver metastases.

OBJECTIVES: This study investigates whether quantitative image analysis of pretreatment CT scans can predict volumetric response to chemotherapy for patients with colorectal liver metastases (CRLM). METHODS: Patients treated with chemotherapy for CRLM (hepatic artery infusion (HAI) combined with systemic or systemic alone) were included in the study. Patients were imaged at baseline and approximately 8 weeks after treatment. Response was measured as the percentage change in tumour volume from baseline. Quantitative imaging features were derived from the index hepatic tumour on pretreatment CT, and features statistically significant on univariate analysis were included in a linear regression model to predict volumetric response. The regression model was constructed from 70% of data, while 30% were reserved for testing. Test data were input into the trained model. Model performance was evaluated with mean absolute prediction error (MAPE) and R2. Clinicopatholologic factors were assessed for correlation with response. RESULTS: 157 patients were included, split into training (n = 110) and validation (n = 47) sets. MAPE from the multivariate linear regression model was 16.5% (R2 = 0.774) and 21.5% in the training and validation sets, respectively. Stratified by HAI utilisation, MAPE in the validation set was 19.6% for HAI and 25.1% for systemic chemotherapy alone. Clinical factors associated with differences in median tumour response were treatment strategy, systemic chemotherapy regimen, age and KRAS mutation status (p < 0.05). CONCLUSION: Quantitative imaging features extracted from pretreatment CT are promising predictors of volumetric response to chemotherapy in patients with CRLM. Pretreatment predictors of response have the potential to better select patients for specific therapies. KEY POINTS: • Colorectal liver metastases (CRLM) are downsized with chemotherapy but predicting the patients that will respond to chemotherapy is currently not possible. • Heterogeneity and enhancement patterns of CRLM can be measured with quantitative imaging. • Prediction model constructed that predicts volumetric response with 20% error suggesting that quantitative imaging holds promise to better select patients for specific treatments.

TET2 Negatively Regulates Nestin Expression in Human Melanoma.

Although melanoma is an aggressive cancer, the understanding of the virulence-conferring pathways involved remains incomplete. We have demonstrated that loss of ten-eleven translocation methylcytosine dioxygenase (TET2)-mediated 5-hydroxymethylcytosine (5-hmC) is an epigenetic driver of melanoma growth and a biomarker of clinical virulence. We also have determined that the intermediate filament protein nestin correlates with tumorigenic and invasive melanoma growth. Here we examine the relationships between these two biomarkers. Immunohistochemistry staining of nestin and 5-hmC in 53 clinically annotated primary and metastatic patient melanomas revealed a significant negative correlation. Restoration of 5-hmC, as assessed in a human melanoma cell line by introducing full-length TET2 and TET2-mutated constructs, decreased nestin gene and protein expression in vitro. Genome-wide mapping using hydroxymethylated DNA immunoprecipitation sequencing disclosed significantly less 5-hmC binding in the 3' untranslated region of the nestin gene in melanoma compared to nevi, and 5-hmC binding in this region was significantly increased after TET2 overexpression in human melanoma cells in vitro. Our findings provide evidence suggesting that nestin regulation is negatively controlled epigenetically by TET2 via 5-hmC binding at the 3' untranslated region of the nestin gene, providing one potential pathway for understanding melanoma growth characteristics. Studies are now indicated to further define the interplay between 5-hmC, nestin expression, and melanoma virulence.

Non-operative management of pneumoperitoneum following cardiopulmonary resuscitation.

Spontaneous pneumoperitoneum in a patient with a tracheostomy tube following cardiopulmonary resuscitation is exceedingly rare, with little experimental nor observational data to guide evidence-based management. We present the case of a 75-year-old woman with a tracheostomy tube who developed pneumoperitoneum following CPR. The patient experienced pulseless electrical activity arrest requiring nine rounds of chest compressions to return to spontaneous circulation. Computerized tomography demonstrated pneumothoraces, subcutaneous emphysema and extensive intraperitoneal, extraperitoneal and retroperitoneal free air without evidence of visceral perforation. The patient's abdomen was distended without tenderness, guarding or rebound. She had a white blood cell count mildly elevated from her baseline levels. The management plan of serial abdominal exams without operative intervention was chosen given the absence of clinical and laboratory signs of peritonitis. This case highlights the importance of developing a standardized management algorithm for patients with pneumoperitoneum in the setting of tracheostomy tubes without evidence of perforation.

Choledochal Cyst or Benign Biliary Dilation: Is Resection Always Necessary?

BACKGROUND: Choledochal cysts (CC) are often diagnosed during the first few decades of life, when, due to the risk of malignancy, resection is advised. With an increasing number of patients undergoing abdominal imaging, many older patients have recently been radiographically diagnosed with biliary duct enlargement that meets the criteria of choledochal cysts. The management in these patients is less well defined, but resection is often recommended as it is for younger patients. We sought to better understand the significance of these biliary duct anomalies in adults. METHODS: We retrospectively reviewed all patients 18 years and older at our institution, who were given a radiographic diagnosis of choledochal cyst during the interval 2006-2019. Demographics, comorbidities, complications, readmissions, and follow-up imaging were evaluated. RESULTS: We identified 22 patients, of whom 40.9% (n = 9) underwent an operation. The remainder was observed. Median duct size was 15 mm (range 2-25 mm). There were no significant differences in demographics between the two cohorts. Of those who underwent resection, none had evidence of high-grade dysplasia or invasive carcinoma upon final pathology. However, 33.3% (n = 3) had subsequent readmissions for complications, including post-operative nausea and vomiting, cholangitis, and anastomotic stenoses that required stenting. In the observation group, there was no obvious growth of the cysts or development of worrisome features to suggest malignant degeneration (median follow-up = 68 months). CONCLUSION: A radiographic diagnosis of choledochal cyst in older adults is likely a different entity than those diagnosed in childhood. Close surveillance of these biliary duct anomalies in older adults may be a better option than resection and reconstruction with the associated risks of long-term morbidity.

Scan time, reliability and accuracy of craniofacial measurements using a 3D light scanner.

AIM: To evaluate time, reliability and accuracy of craniofacial measurements with a 3D light scanner, considering prior demarcation of surface points on the face. MATERIALS AND METHODS: Eleven facial measurements of 15 volunteers were obtained by a scanner (Artec Eva TM) and by a caliper directly on the face, with or without demarcation of facial reference points. Inter and intra-method comparison were examined by intraclass correlation coefficient and analysis of random error by the Dahlberg formula. Agreement between the methods was analyzed by the Bland-Altman. A Wilcoxon test was used to compare the time for each method, at p < 0.05. RESULTS: Marking points on the face improved accuracy for both methods. In the inter-methods analysis with landmarks, the scanner showed excellent reliability in all measures (ICC = 0.92-0.97, p < 0.0001). Measurements accuracy with scanner was around 2 mm when the points were not previously marked and about 1 mm when the points were marked. Measures taken with the scanner, however, took twice as long, compared with the direct method. CONCLUSIONS: Craniofacial measurements obtained with scanner showed excellent reliability and accuracy, which qualifies this method for clinical and scientific use. Accuracy is improved when the points were previously marked on face. However, the time needed to obtain measurements is greater than about 4 min for the direct method.

Biological significance of 5-hydroxymethylcytosine in oral epithelial dysplasia and oral squamous cell carcinoma.

OBJECTIVES: The aim of this study was to determine the levels of 5-hydroxylmethylcytosine (5-hmC) in oral epithelial dysplasia (OED) and oral squamous cell carcinoma (OSCC) compared with those in benign, reactive inflammatory lesions and to explore whether DNA hydroxymethylation may serve as a novel biomarker for early diagnosis and prognosis of OSCC. STUDY DESIGN: The study included normal mucosa from uninvolved margins of 9 fibromas, 10 oral lichen planus, 15 OED, and 23 OSCC. Cultured human keratinocyte lines from benign oral mucosa, OED, and OSCC, as well as a murine model in which OSCC was induced with 4-nitroquinoline-1-oxide, were also evaluated. RESULTS: Progressive loss of 5-hmC from benign oral mucosal lesions to OED and OSCC was documented in patient samples. Decreased levels in 5-hmC that typify OED and OSCC were also detectable in human cell lines. Moreover, we characterized similar alterations in 5-hmC in an animal model of OED/OSCC. CONCLUSIONS: This study demonstrated that 5-hmC distinguishes OED and OSCC from benign lesions with high sensitivity and specificity. Consequently, loss of 5-hmC may be useful for the diagnosis of OED with potential implications for therapy of OSCC.

Ligand-activated BMP signaling inhibits cell differentiation and death to promote melanoma.

Oncogenomic studies indicate that copy number variation (CNV) alters genes involved in tumor progression; however, identification of specific driver genes affected by CNV has been difficult, as these rearrangements are often contained in large chromosomal intervals among several bystander genes. Here, we addressed this problem and identified a CNV-targeted oncogene by performing comparative oncogenomics of human and zebrafish melanomas. We determined that the gene encoding growth differentiation factor 6 (GDF6), which is the ligand for the BMP family, is recurrently amplified and transcriptionally upregulated in melanoma. GDF6-induced BMP signaling maintained a trunk neural crest gene signature in melanomas. Additionally, GDF6 repressed the melanocyte differentiation gene MITF and the proapoptotic factor SOX9, thereby preventing differentiation, inhibiting cell death, and promoting tumor growth. GDF6 was specifically expressed in melanomas but not melanocytes. Moreover, GDF6 expression levels in melanomas were inversely correlated with patient survival. Our study has identified a fundamental role for GDF6 and BMP signaling in governing an embryonic cell gene signature to promote melanoma progression, thus providing potential opportunities for targeted therapy to treat GDF6-positive cancers.

Osseous oral hyaline ring granuloma mimicking a mandible tumor in a child with congenital agenesis of the corpus callosum.

BACKGROUND: Hyaline ring granuloma (HRG) of the oral cavity is an uncommon disorder considered to be a foreign-body reaction resulting from implantation of food vegetable particles. Microscopically, it is characterized by the presence of structures of hyaline rings in an inflamed fibrous tissue background, which contains multinucleated giant cells. MATERIAL AND METHODS: We present the case of a 4-year-old boy diagnosed with a mandible osseous HRG, which showed clinical and tomographic aspects suggestive of an aggressive bone tumor. RESULTS: The patient underwent surgical exploration and histopathologic analysis showed fragments composed predominantly of widespread dense connective tissue with an acute and chronic inflammatory infiltrate containing multinucleated giant cells and scattered areas of eosinophilic material associated with hyaline rings, strongly suggestive of vegetable particles. The eosinophilic material was positive for periodic acid-Schiff (PAS) and resistant to diastase digestion. These features led to diagnosis of osseous HRG. Scanning electron microscopy (SEM) analysis was performed for illustrative purposes and the multiple structures resembling vegetable particles were characterized in more detail. CONCLUSIONS: Although rare, this case highlights the importance of the clinician's awareness regarding the existence of an osseous counterpart of HRG. Key words:Agenesis of the corpus callosum, child, hyaline ring granuloma, intraosseous, mandible, pulse granuloma.

Pulp Obliteration in a Patient with Sclerodermatous Chronic Graft-versus-Host Disease.

Dental pulp calcification is a common finding associated with localized dental trauma, genetic disorders, and systemic inflammatory diseases. Chronic graft-versus-host disease (cGVHD) is a frequent complication after allogeneic hematopoietic cell transplantation (allo-HCT) characterized by immune-mediated injury to the skin, mouth, eyes, liver, and other tissues, resulting in significant disability and reduced quality of life. We report a patient with sclerodermatous cGVHD who presented with general pulp calcification in all teeth 5 years after allo-HCT. A review of full mouth dental radiographs obtained just before allo-HCT revealed normal-appearing pulp chambers. Based on prior reports of generalized pulp calcification associated with progressive systemic sclerosis, we hypothesized that the etiology was likely related to the presence of cGVHD with associated vascular and fibrotic tissue changes within the pulp vasculature. Clinicians should consider cGVHD in the differential diagnosis of generalized pulp calcification.

Increased GVHD-related mortality with broad-spectrum antibiotic use after allogeneic hematopoietic stem cell transplantation in human patients and mice.

Intestinal bacteria may modulate the risk of infection and graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Allo-HSCT recipients often develop neutropenic fever, which is treated with antibiotics that may target anaerobic bacteria in the gut. We retrospectively examined 857 allo-HSCT recipients and found that treatment of neutropenic fever with imipenem-cilastatin and piperacillin-tazobactam antibiotics was associated with increased GVHD-related mortality at 5 years (21.5% for imipenem-cilastatin-treated patients versus 13.1% for untreated patients, P = 0.025; 19.8% for piperacillin-tazobactam-treated patients versus 11.9% for untreated patients, P = 0.007). However, two other antibiotics also used to treat neutropenic fever, aztreonam and cefepime, were not associated with GVHD-related mortality (P = 0.78 and P = 0.98, respectively). Analysis of stool specimens from allo-HSCT recipients showed that piperacillin-tazobactam administration was associated with perturbation of gut microbial composition. Studies in mice demonstrated aggravated GVHD mortality with imipenem-cilastatin or piperacillin-tazobactam compared to aztreonam (P < 0.01 and P < 0.05, respectively). We found pathological evidence for increased GVHD in the colon of imipenem-cilastatin-treated mice (P < 0.05), but no difference in the concentration of short-chain fatty acids or numbers of regulatory T cells. Notably, imipenem-cilastatin treatment of mice with GVHD led to loss of the protective mucus lining of the colon (P < 0.01) and the compromising of intestinal barrier function (P < 0.05). Sequencing of mouse stool specimens showed an increase in Akkermansia muciniphila (P < 0.001), a commensal bacterium with mucus-degrading capabilities, raising the possibility that mucus degradation may contribute to murine GVHD. We demonstrate an underappreciated risk for the treatment of allo-HSCT recipients with antibiotics that may exacerbate GVHD in the colon.

Reactive tonsillar enlargement showing strong 18F-FDG uptake during the follow-up of follicular lymphoma.

The 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) has become a standard procedure for the diagnosis, staging, and restaging in lymphoma patients. However, a relative high rate of false-positive results has been reported. We report a case of a 40-year-old man with a previous history of a nodal follicular lymphoma, stage IVA, treated with R-CHOP, which showed strong 18F-FDG uptake in the Waldeyer's tonsillar ring during his follow-up, being considered highly suspicious of relapsed lymphoma. A surgical removal of the palatine tonsils and adenoids was performed, which showed reactive follicular hyperplasia. Furthermore, bone marrow biopsy revealed absence of neoplasia. The patient is still in follow-up with no signs of recurrent lymphoma. This case illustrates that, despite the high sensitivity for the detection of recurrent lymphoma, 18F-FDG uptake should be interpreted with great caution and confirmatory studies should be performed before any therapy.

Evolution of sexual dimorphism in the digit ratio 2D:4D--relationships with body size and microhabitat use in iguanian lizards.

The ratio between lengths of digit II and IV (digit ratio 2D:4D) is a morphological feature that likely affects tetrapod locomotor performances in different microhabitats. Modifications of this trait may be triggered by changes in steroids concentrations during embryo development, which might reflect direct selection acting on digit ratio or be solely a consequence of hormonal differences related for example to body size. Here we apply both conventional and phylogenetic analyses on morphological data from 25 lizard species of 3 families of Iguania (Iguanidae, Polychrotidae, and Tropiduridae), in order to verify whether selective pressures related to locomotion in different microhabitats could override the prenatal developmental cues imposed on the digit ratio 2D:4D by differences in body size between males and females. Data suggest that this trait evolved in association with ecological divergence in the species studied, despite the clear effect of body size on the digit ratio 2D:4D. The ecological associations of size-corrected digit ratios were restricted to one sex, and females of species that often use perches exhibited small digit ratios in the front limbs, which translated into larger sexual dimorphism indexes of arboreal species. The results, together with the subsequent discussion, provide outlines for further investigation about possible developmental mechanisms related to the evolution of adaptive changes in digit lengths that may have occurred during the evolution of ecological divergence in squamates.