Background
Carcinoid tumors are masses originating from neuroendocrine cells and are one of the rarest forms of endocrine cancer. Minimal literature exists regarding neuroendocrine tumors arising from the mediastinum, let alone the thymus. This is likely secondary to its rarity, with a reported incidence of 0.2 per million in the United States.
Case Presentation
When diagnosing a neuroendocrine tumor, it is crucial to distinguish the combined neuroendocrine and epithelial characteristics of the neoplasm, acknowledge its potential aggressiveness, and establish additional markers for prognosis and prediction. In the following review, we present a case of a 64-year-old male with an incidental finding of an atypical thymic neuroendocrine tumor. A radical robotic-assisted thymectomy was performed, and adjuvant radiotherapy was administered. 
Discussion
Atypical thymic neuroendocrine tumors remain a niche disease, presenting a unique challenge due to rarity, diverse characteristics, and aggressiveness. Though lacking consensus or best-practice guidelines, surgery is considered the most curative treatment modality. Proving the variability of this type of tumor, however, radiation therapy has had unclear and inconsistent effects on long-term survival, either enhancing clinical outcomes or failing to improve 5-year survival rates. Overall, survival rates for thymic neuroendocrine tumors are lower than those of the gastrointestinal tract, highlighting the need for better therapeutic strategies to maintain the highest level of care for such patients.

Thymic Atypical Carcinoid Tumors vs. Gastrointestinal Neuroendocrine Tumors - 
Are They Really the Same Disease?

Background
Lung cancer is the leading cause of cancer deaths worldwide. The increasing use of minimally invasive surgical approaches has expanded the scope of treatment options for patients with lung cancer. However, these operations are not risk-free as there have been several reported cases of intraoperative catastrophes, with major hemorrhage from the pulmonary artery being the most common. The objective of this study was to develop a computer vision-based approach to reliably identify the pulmonary artery during robotic right lower lobectomies. 

Methods
Twelve patients with biopsy-proven Stage I non-small-cell lung cancer of the right lower lobe underwent robotic lobectomy with mediastinal lymph node dissection. Complete videos of each operation were obtained, and video fragments of the pulmonary artery were identified by two board-certified thoracic surgeons. Annotation masks of the pulmonary artery were then created using Computer Vision Annotation Tool, an open-source web-based annotation tool. The labeled data was next used to train a state-of-the-art instance segmentation algorithm called Mask Regional-Convolutional Neural Network (Mask R-CNN) using an 80:20 random sample split from ten cases for training and validation, respectively. Two cases were utilized for generalization testing. Three custom performance metrics commonly utilized in deep learning-based instance segmentation were used to evaluate our approach: Intersection over Union (IoU), Average Precision at IoU threshold of 50% (AP50) and at 75% (AP75). 

Results
Annotation masks of the pulmonary artery were created in 4,139 images across twelve cases of robotic right lower lobectomy. 2,893 and 684 annotated images across ten (83.3%) cases were used for training and validation, respectively; and 261 and 301 annotated images from two (16.7%) cases were used for generalization testing. A mean IoU of 87.7% was achieved in the validation dataset. The AP50 attained by our model was 96.7% and AP75 was 82.3%. In generalizability testing, when the model was tested on data never exposed to it, it was able to partially generalize with a mean IoU of 86.0%. 

Conclusion
Our study shows that our Mask R-CNN model was able to identify surgical anatomy during robotic lobectomy with high accuracy in the validation dataset. While still at an early stage, more variable labeled data and collaborative efforts are needed to improve the generalizability of our model. We envision such a computer vision system to be valuable in early surgeon training and incorporate future real-time augmentation of video feedback to improve outcomes.






Using Artificial Intelligence for Automatic Detection of the Pulmonary Artery During Robotic Right Lower Lobectomies

Background: Endoscopy is commonly used to diagnose upper gastrointestinal (GI) system disorders. However, excess mucus can significantly impair visualization, and reducing mucus intra-procedurally can increase procedure time. Several studies have evaluated the efficacy of pre-medication with mucolytic agents prior to gastroscopy to improve the diagnostic yield of endoscopy and reduce procedural time. Here, we systematically review recent evidence assessing the efficacy of mucolytic agents, including N-acetyl cysteine (NAC), in improving visibility in upper GI endoscopy.
Methods: Studies were identified by interrogating the PubMed database using the search terms "endoscopy" and "N-acetyl cysteine" for the period of 2016-2023. Only randomized control trials were included in the search. Records written in languages other than English were excluded. Ten (10) records matching these criteria were retrieved. Title and abstract screening resulted in five (5) records, which were subsequently extracted.
Results: The studies were conducted in the United Kingdom, Chile, Portugal, Thailand, and the Czech Republic. Four (4) studies consisted of randomized, double-blinded, placebo-controlled trials, while the remaining study was a randomized, non-blinded controlled trial. Four (4) of the studies showed that pre-administration of NAC (600 mg) plus simethicone (100 mg) significantly improved the visibility of the upper GI tract (esophagus, stomach, and duodenum) when compared to placebo control. The only study that failed to show an improvement in visibility scores was attributed to sub-threshold doses of NAC (400 mg) and simethicone (20 mg). Although none of the studies included an arm consisting of NAC alone, one study comparing simethicone +/- NAC showed superior visibility when NAC was administered at a high dose (1000 mg), while another study comparing simethicone +/- NAC failed to show improvement when NAC was administered at a moderate dose (600 mg). Lastly, one study found that the procedure time and volume of mucosal cleansing solution required were significantly reduced when NAC and simethicone were administered together.


Conclusion: Our survey of recent randomized control trials supports that pre-medication with NAC (600-1000 mg) and simethicone (100 mg) significantly improves the visibility of the upper GI mucosal surfaces during upper endoscopic procedures and, therefore, may improve diagnostic yield in settings where visibility is impaired. This approach may be particularly useful in lower-resource settings where less sophisticated endoscopic tools are utilized.

Efficacy of N-Acetyl Cysteine in the Prevention of Post-Operative Atrial Fibrillation and Acute Kidney Injury Post-Cardiac Surgery: A Systematic Review

Introduction
Despite high response rates to osimertinib in patients with EGFRm+ NSCLC, resistance inevitably develops. HER2 overexpression and amplification is detected in 13% of NSCLC-patients with acquired TKI-resistance. Here, we evaluated the efficacy and toxicity of T-DM1 and osimertinib in patients with HER2 overexpression and/or amplification after progression on osimertinib. We report a pre-planned interim analysis.

Methods
In this multicenter single arm phase II study (NCT03784599), patients with EGFRm+ NSCLC, progressing on EGFR TKI treatment and with HER2 IHC ≥2+ in ≥10% of the cells were included. Patients were treated with T-DM1 3.6 mg/kg (IV) every 3 weeks and osimertinib 80 mg QD. Primary endpoints were to assess the ORR after 12 weeks and to evaluate safety. 
Responses were assessed every 6 weeks (RECIST 1.1). Treatment was continued until progression or unacceptable toxicity. Sample size was calculated using Simon’s two stage minimax design (H0=41%, H1>55%, 80% power, one-sided type I error rate of 10%, sample size: 58 patients, cohort A ORR 16/36 in order to proceed to cohort B).

Results
From 01-2019 until 04-2021, 27 patients were included and started with T-DM1. ORR and DCR after 12 weeks of treatment were 13% (3/23) and 43% (10/23). Four patients are not yet evaluable for the primary endpoint. Median DCR in HER2 IHC2+ and 3+ cohorts were was 36% (5/14) and 55% (5/9), respectively. PFS was 2.8 months (95% CI, 2.3-3.3 months), median duration of disease control was 20 weeks (range 4-47 weeks). Grade 2/3 adverse events (AEs) occurred in 29%/21% of patients, including pneumonitis, LVEF decrease, fatigue, erythema and CK elevation. There were no grade 4 or 5 therapy-related AEs.

Conclusion
TRAEMOS is the first trial combining T-DM1 and osimertinib in EGFRm+ NSCLC patients to target HER2 bypass track resistance. Safety profile was favorable compared to cytotoxic chemotherapy, however this treatment strategy showed limited efficacy. Further clinical evaluation of this regimen is not warranted.

Trastuzumab-emtansine (T-DM1) and osimertinib (TRAEMOS) combination treatment to target HER2 bypass track resistance in EGFR mutation positive (EGFRm+) NSCLC

Introduction
Resistance to osimertinib inevitably occurs in the majority of patients. We aimed to identify the resistance mechanism (RM) using paired liquid and tissue biopsies in patients that progressed on 2nd line osimertinib and to determine progression free survival (PFS) of post-osimertinib therapy. 

Methods
From 09-2019 to 02-2021, 50 patients that progressed on 2nd line osimertinib treatment were enrolled. Liquid biopsies were analyzed using AVENIO ctDNA Expanded Panel, and tissue biopsies underwent DNA and RNA NGS. Results were discussed in a Molecular Tumor Board (MTB), leading to tailored treatment advise. Post-MTB treatment was monitored every 6-8 weeks with CT. 

Results
The EGFR mutation (m) was detected in 37/50 plasma samples (74%) and 48/50 tumor biopsies (96%). Matched results were available for 35/50 patients (70%). For 39/50 patients (78%) ≥1 RM could be identified in plasma and/or tissue, of which 15 showed ≥2 RMs. Most prevalent RMs were MET amplification (38%) and EGFR C797Ss (16%). 
23 patients received targeted therapy (TT) and 16 patients chemotherapy (CTX). Four received best supportive care. Six continued osimertinib, 3 of whom received additional local therapy. One had not yet started CTX. Median PFS was 5.2 months for CTX (95%CI 3.9 – 6.5 months), 3.3 months for TT (95%CI 1.4 – 5.2 months). Median FU was 9.1 months for (CTX) and 7.2 months for TT. For patients receiving TT after progression on osimertinib, the number of identified RMs impacted PFS. PFS for patients who had 1 RM was 5.8 months (95%CI 4.2 – 7.5 months), 3.2 months for those with ≥2 RMs (95%CI 0.2 – 6.2 months).
Ten patients were biopsied after progression on TT. The targeted RM was no longer detected in 7/10 (70%) biopsy samples, while a new RM was detected in 5/10 (50%).

Conclusion
When paired liquid and tissue biopsies were used to guide treatment after progression on 2nd line osimertinib, no large difference in PFS was observed between CTX and TT in an exploratory analysis on clinical data. A relatively short duration of response to TT after progression on osimertinib may be due to the prevalence of multiple RMs.

Underline digital video library

Thymic Atypical Carcinoid Tumors vs. Gastrointestinal Neuroendocrine Tumors - Are They Really the Same Disease?

Using Artificial Intelligence for Automatic Detection of the Pulmonary Artery During Robotic Right Lower Lobectomies

Efficacy of N-Acetyl Cysteine in the Prevention of Post-Operative Atrial Fibrillation and Acute Kidney Injury Post-Cardiac Surgery: A Systematic Review

Trastuzumab-emtansine (T-DM1) and osimertinib (TRAEMOS) combination treatment to target HER2 bypass track resistance in EGFR mutation positive (EGFRm+) NSCLC

Paired liquid and tissue biopsies to guide treatment for patients that progress on 2nd line osimertinib treatment (OSIRIS)

Thyroid Board Review

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