The Academic Robotics Group prospectively studied 211 robotically assisted operations to assess the safety and utility of robotically assisted surgery.
All operations took place at one of four member ...institutions between June 2000 and June 2001 using the recently FDA-approved daVinci robotic system. A variety of procedures were undertaken, including antireflux surgery (69), cholecystectomy (36), Heller myotomy (26), bowel resection (17), donor nephrectomy (15), left internal mammery artery mobilization (14), gastric bypass (seven), splenectomy (seven), adrenalectomy (six), exploratory laparoscopy (three), pyloroplasty (four), gastrojejunostomy (two), distal pancreatectomy (one), duodenal polypectomy (one), esophagectomy (one), gastric mass resection (one), and lysis of adhesions (one).
Average operating room time was 188 min (range 45 to 387, SD = 83), surgical time 143 min (range 35 to 462, SD = 63), and robot time 90 min (range 12 to 235, SD = 47). Median length of stay was 1 day (range 0 to 37). There were 8 (4%) technical complications during procedures, five minor (four hook cautery dislodgement, one slipped robotic trocar) and three major (system malfunctions, two of which required conversion to standard laparoscopy). In all cases, technical problems caused only delay, without apparent altered outcome. There were medical/surgical complications in nine patients (4%). Six (3%) were considered major, including one death unrelated to the robotic procedure.
The results of robotic-assisted surgery compare favorably with those of conventional laparoscopy with respect to mortality, complications, and length of stay. Robotic-assisted surgery is safe and effective and is a new reality for American surgery. The role of these devices in surgery will expand as the technology evolves.
Despite the conventional view that a truly random V(D)J recombination process should generate a highly diverse immune repertoire, emerging reports suggest that there is a certain bias toward the ...generation of shared/public immune receptor chains. These studies were performed in viral diseases where public T cell receptors (TCR) appear to confer better protective responses. Selective pressures generating common TCR clonotypes are currently not well understood, but it is believed that they confer a growth advantage. As very little is known about public TCR clonotypes in cancer, here we set out to determine the extent of shared TCR clonotypes in the intra-tumor microenvironments of virus- and non-virus-driven head and neck cancers using TCR sequencing. We report that tumor-infiltrating T cell clonotypes were indeed shared across individuals with the same cancer type, where the majority of shared sequences were specific to the cancer type (i.e., viral versus non-viral). These shared clonotypes were not particularly enriched in EBV-associated nasopharynx cancer but, in both cancers, exhibited distinct characteristics, namely shorter CDR3 lengths, restricted V- and J-gene usages, and also demonstrated convergent V(D)J recombination. Many of these shared TCRs were expressed in patients with a shared HLA background. Pattern recognition of CDR3 amino acid sequences revealed strong convergence to specific pattern motifs, and these motifs were uniquely found to each cancer type. This suggests that they may be enriched for specificity to common antigens found in the tumor microenvironment of different cancers. The identification of shared TCRs in infiltrating tumor T cells not only adds to our understanding of the tumor-adaptive immune recognition but could also serve as disease-specific biomarkers and guide the development of future immunotherapies.
The goal of this study was to determine the optimal treatment parameters for the ablation of human esophageal epithelium using a balloon-based bipolar radiofrequency (RF) energy electrode.
...Immediately prior to esophagectomy, subjects underwent esophagoscopy and ablation of two separate, 3-cm long, circumferential segments of non-tumor-bearing esophageal epithelium using a balloon-based bipolar RF energy electrode (BARRX Medical, Inc., Sunnyvale, CA, USA). Subjects were randomized to one of three energy density groups: 8, 10, or 12 J/cm2. RF energy was applied one time (1x) proximally and two times (2x) distally. Following resection, sections from each ablation zone were evaluated using H&E and diaphorase. Histological endpoints were complete epithelial ablation (yes/no), maximum ablation depth, and residual ablation thickness after tissue slough. Outcomes were compared according to energy density group and 1x vs 2x treatment.
Thirteen male subjects (age, 49-85 years) with esophageal adenocarcinoma underwent the ablation procedure followed by total esophagectomy. Complete epithelial removal occurred in the following zones: 10 J/cm2 (2x) and 12 J/cm2 (1x and 2x). The maximum depth of injury was the muscularis mucosae: 10 and 12 J/cm2 (both 2x). A second treatment (2x) did not significantly increase the depth of injury. Maximum thickness of residual ablation after tissue slough was only 35 microm.
Complete removal of the esophageal epithelium without injury to the submucosa or muscularis propria is possible using this balloon-based RF electrode at 10 J/cm2 (2x) or 12 J/cm2 (1x or 2x). A second application (2x) does not significantly increase ablation depth. These data have been used to select the appropriate settings for treating intestinal metaplasia in trials currently under way.
Improved antitumor responses have been observed in patients after combination radiation therapy (RT) and immune checkpoint blockade (ICB). Whether these clinical responses are linked to the host ...systemic immune system has not been elucidated.
In this single-institution prospective observational study, peripheral blood was longitudinally collected from 10 patients with metastatic disease who had responded to anti-PD-1/anti-PD-L1 ICB and received RT (8-50 Gy in 1-5 fractions) upon disease progression at the following timepoints: baseline (pre-RT), 1 to 2 weeks post-RT, and post-ICB (cycle 1) on reintroduction post-RT. To thoroughly characterize the interaction between combined RT-ICB and the host immune system, we performed high-dimensional, mass cytometry–based immunophenotyping of circulating lymphocytes using a 40-marker panel addressing lineage, differentiation, activation, trafficking, cytotoxicity, and costimulatory and inhibitory functions. Phenotypic expression of circulating lymphocytes was compared across patients and time points and correlated with post-RT tumor responses.
Foremost, we demonstrated excellent posttreatment clinical responses, including 4 local responses with >50% reduction in radiated tumor size, 1 out-of-field response, and 4 patients who resumed ICB for >1 year. Baseline and post-RT immune states were highly heterogeneous among patients. Despite this interindividual heterogeneity in baseline immune states, we observed a systemic immune reaction to RT-ICB common across patients, histology, and radiation sites; a subset of pre-existing Ki-67+ CD8+ T cells were increased post-RT and further expanded upon reintroduction of ICB post-RT (2.3-fold increase, P = .02). Importantly, RT did not alter the phenotypic profile of these Ki-67+ CD8+ T cells, which was characterized by a distinct activated and differentiated effector phenotype.
Collectively, these findings point toward a sustained reinvigoration of host antitumor immunity after RT-ICB and suggest an expansion in activated Ki-67+ CD8+ T cells as a possible demonstration of this synergy, thereby providing new insights that may support the development of optimal sequencing strategies.
Ex-ante identification of the last year in life facilitates a proactive palliative approach. Machine learning models trained on electronic health records (EHR) demonstrate promising performance in ...cancer prognostication. However, gaps in literature include incomplete reporting of model performance, inadequate alignment of model formulation with implementation use-case, and insufficient explainability hindering trust and adoption in clinical settings. Hence, we aim to develop an explainable machine learning EHR-based model that prompts palliative care processes by predicting for 365-day mortality risk among patients with advanced cancer within an outpatient setting.
Our cohort consisted of 5,926 adults diagnosed with Stage 3 or 4 solid organ cancer between July 1, 2017, and June 30, 2020 and receiving ambulatory cancer care within a tertiary center. The classification problem was modelled using Extreme Gradient Boosting (XGBoost) and aligned to our envisioned use-case: "Given a prediction point that corresponds to an outpatient cancer encounter, predict for mortality within 365-days from prediction point, using EHR data up to 365-days prior." The model was trained with 75% of the dataset (n = 39,416 outpatient encounters) and validated on a 25% hold-out dataset (n = 13,122 outpatient encounters). To explain model outputs, we used Shapley Additive Explanations (SHAP) values. Clinical characteristics, laboratory tests and treatment data were used to train the model. Performance was evaluated using area under the receiver operating characteristic curve (AUROC) and area under the precision-recall curve (AUPRC), while model calibration was assessed using the Brier score.
In total, 17,149 of the 52,538 prediction points (32.6%) had a mortality event within the 365-day prediction window. The model demonstrated an AUROC of 0.861 (95% CI 0.856-0.867) and AUPRC of 0.771. The Brier score was 0.147, indicating slight overestimations of mortality risk. Explanatory diagrams utilizing SHAP values allowed visualization of feature impacts on predictions at both the global and individual levels.
Our machine learning model demonstrated good discrimination and precision-recall in predicting 365-day mortality risk among individuals with advanced cancer. It has the potential to provide personalized mortality predictions and facilitate earlier integration of palliative care.
The index case of the Ebola virus disease epidemic in West Africa is believed to have originated in Guinea. By June 2014, Guinea, Liberia, and Sierra Leone were in the midst of a full-blown and ...complex global health emergency. The devastating effects of this Ebola epidemic in West Africa put the global health response in acute focus for urgent international interventions. Accordingly, in October 2014, a World Health Organization high-level meeting endorsed the concept of a phase 2/3 clinical trial in Liberia to study Ebola vaccines. As a follow-up to the global response, in November 2014, the Government of Liberia and the US Government signed an agreement to form a research partnership to investigate Ebola and to assess intervention strategies for treating, controlling, and preventing the disease in Liberia. This agreement led to the establishment of the Joint Liberia–US Partnership for Research on Ebola Virus in Liberia as the beginning of a long-term collaborative partnership in clinical research between the two countries. In this article, we discuss the methodology and related challenges associated with the implementation of the Ebola vaccines clinical trial, based on a double-blinded randomized controlled trial, in Liberia.
This study aimed to determine the optimal treatment parameters for the ablation of intestinal metaplasia (IM) containing high-grade dysplasia (HGD) using a balloon-based ablation system for patients ...undergoing esophagectomy.
Immediately before esophagectomy, patients underwent ablation of circumferential segments of the esophagus containing IM-HGD using the HALO360 system. The treatment settings were randomized to 10, 12, or 14 J/cm2 for two, three, or four applications. After esophagectomy, multiple sections from ablation zones were microscopically evaluated. Histologic end points included maximum ablation depth (histologic layer) and complete ablation of all IM-HGD (yes/no).
Eight men with a mean age of 57 years (range, 45-71 years) were treated, and 10 treatment zones were created. There were no device-related adverse events. At resection, there was no evidence of a transmural thermal effect. Grossly, ablation zones were clearly demarcated sections of ablated epithelium. The maximum ablation depth was the lamina propria or muscularis mucosae. The highest energy (14 J/cm2, 4 applications) incurred edema in the superficial submucosa, but no submucosa ablation. Complete ablation of IM and HGD occurred in 9 of 10 ablation zones (90%), defined as complete removal of the epithelium with only small foci of "ghost cells" representing nonviable, ablated IM-HGD and demonstrating loss of nuclei and cytoarchitectural derangement. One focal area of viable IM-HGD remained at the margin of one ablation zone (12 J/cm2, 2 applications) because of incomplete overlap.
Complete ablation of IM-HGD without ablation of submucosa is possible using the HALO360 system. Ablation depth is dose related and limited to the muscularis mucosae. In one patient, small residual foci of IM-HGD at the edge of the ablation zone were attributable to incomplete overlap, which can be avoided. This study, together with nonesophagectomy IM-HGD trials currently underway, will identify the optimal treatment parameters for IM-HGD patients who would otherwise undergo esophagectomy or photodynamic therapy.
Few Western studies have focused on percutaneous techniques using percutaneous transhepatic choledochoscopy (PTHC) and holmium:yttrium-aluminum-garnet (YAG) laser to ablate biliary calculi in ...patients unable or unwilling to undergo endoscopic or surgical removal of the calculi. The authors report the efficacy of the holmium:YAG laser in clearing complex biliary calculi using percutaneous access techniques.
This study retrospectively reviewed 13 non-Asian patients with complex secondary biliary calculi treated percutaneously using holmium:YAG laser. Percutaneous access was accomplished via left, right, or bilateral hepatic ducts and upsized for passage of a 7-Fr video choledochoscope. Lithotripsy was performed under choledochoscopic vision using a holmium:YAG laser with 200- or 365-microm fibers generating 0.6 to 1.0 joules at 8 to 15 Hz. Patients underwent treatment until stone clearance was confirmed by PTHC. Downsizing and subsequent removal of percutaneous catheters completed the treatment course.
Seven men and six women with an average age of 69 years underwent treatment. All the patients had their biliary tract stones cleared successfully. Of the 13 patients, 3 were treated solely as outpatients. The average length of percutaneous access was 108 days. At this writing, one patient still has a catheter in place. The average number of holmium:YAG laser treatments required for stone clearance was 1.6, with no patients requiring more than 3 treatments. Of the 13 patients, 8 underwent a single holmium:YAG laser treatment to clear their calculi. Prior unsuccessful attempts at endoscopic removal of the calculi had been experienced by 7 of the 13 patients. Five patients underwent percutaneous access and subsequent stone removal as their sole therapy for biliary stones. Five patients were cleared of their calculi after percutaneous laser ablation of large stones and percutaneous basket retrieval of the remaining stone fragments. There was one complication of pain requiring admission, and no deaths.
The use of PTHC with holmium:YAG laser ablation is safe and efficacious, but requires prolonged biliary access and often multiple procedures to ensure clearance of all calculi.
A new type of computer-enhanced telemanipulator device for "robotic" laparoscopic surgery was recently approved. We prospectively evaluated the initial patients undergoing procedures with this new ...device at our institution.
Patient demographics, operative indications, port placement, operative time, robot time, complications, and hospital stay were recorded. Follow-up evaluation was appropriate for the individual procedure.
Initially, 35 cases were managed. There were 22 anti-reflux procedures, 9 Heller myotomies, 1 pyloroplasty, 1 distal pancreatectomy with splenectomy, 1 esophagectomy with intrathoracic anastomosis, and 1 diagnostic laparoscopy. The operative times ranged from 88 to 458 min. The robot use times were between 16 and 185 min. There were no device-related complications.
Computer-enhanced robotic telesurgery is a safe and effective treatment method for a variety of diseases of the proximal gastrointestinal tract. Further study is needed to determine the benefits of this approach as compared with current technology.
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