Background: Chronic intractable ventricular tachycardia can cause significant morbidity and mortality. In the setting of failed intracardiac ablation, interruption of the sympathetic nerve can provide relief. We present our series of thoracoscopic sympathectomy for chronic recurrent and intractable ventricular tachycardia. Methods: We retrospectively reviewed records of sympathectomies performed at a large academic medical center between January 2018 and February 2024. We collected information regarding patients’ procedures, cardiovascular history, hospital course, postoperative cardiovascular outcomes, and mortality. Results: A total of 20 patients underwent sympathectomy for refractory cardiac arrhythmias. Two patients died in the hospital for reasons unrelated to surgery. Three patients were lost to follow-up. Of the 15 remaining patients, 2 patients died after hospitalization due to recurrent arrythmias, 1 patient died due to unknown reasons, and 12 patients were living and had follow-up. Three of these patients were without further arrythmias. Four patients had notable reduction in their symptoms. Two patients had continued episodes of ventricular tachycardia, and 3 patients proceeded to listing for heart transplantation. After surgery, 7 patients were recorded as having further ablations, with a maximum of 2 postoperative ablations. The mean number of postoperative ablations was 0.4. Conclusions: In a cohort of critically ill patients with refractory cardiac arrhythmias, sympathectomy is well tolerated. In this case series, a large proportion of patients undergoing sympathectomy experienced significant symptom reduction or complete remission of their cardiac pathologies, indicating that this procedure should be considered in select patients with refractory arrhythmias.

OBJECTIVE:To confirm the feasibility and safety of the da Vinci single-port (SP) System to perform pulmonary lobectomy procedures using a subcostal, uniportal approach. METHODS:A prospective multicenter, single-arm clinical study evaluating the performance and safety of the da Vinci SP Surgical System for pulmonary lobectomy. RESULTS:Nineteen subjects (benign, n = 1; malignant, n = 18) were enrolled at 6 academic medical centers in the United States and underwent robotic-assisted SP subcostal lobectomy. All SP lobectomy procedures were completed without conversion to multiport thoracoscopic/robotic or open approaches. No intraoperative adverse events (AEs) or unanticipated adverse device effects were observed; 13 postoperative AEs commonly experienced after lobectomy were reported, 4 of which were Clavien-Dindo grade III. The rate of complete resection (ie, R0) was 100%. The median number of nodal stations sampled was 6.5 (interquartile range [IQR], 6.0-8.0) with a median of 17.5 (IQR, 7.0-34.0) nodes resected per patient. CONCLUSIONS:Robotic SP subcostal lobectomy is feasible and is associated with acceptable perioperative and oncologic quality outcomes. Additional clinical experience and research are needed to determine whether this alternative single incision approach has clinical benefit compared to standard transthoracic, multiport robotic lobectomy.

OBJECTIVE:To evaluate the impact of delayed esophagectomy on the overall survival of esophageal cancer patients undergoing esophagectomy after CROSS. METHODS:A retrospective analysis was done of a prospective database of esophagectomy patients who underwent CROSS therapy and esophagectomy from May 2016 to January 2020. Preoperative characteristics, postoperative adverse events, recurrence rates, and survival rates were compared between patients who underwent surgery within 60 days of CROSS completion versus > 60 days. RESULTS:In total, 197 patients were included; 137 underwent surgery within 60 days (standard group, SG) versus 60 at > 60 days (delayed group, DG). Median time to surgery was 43 versus 76 days for the SG and DG groups. Median follow-up was 60 months. No differences were observed for gender, race, home state, Eastern Cooperative Oncology Group score, and tumor characteristics. DG patients were older; had higher Charlson Comorbidity Scores; and more history of myocardial infarction, stroke, and smoking, all p ≤ 0.05. DG had increased odds of major postoperative adverse events (odds ratio 2.26, 95% confidence interval 1.11-4.20). Overall survival and recurrence were similar. CONCLUSION:Following CROSS, a delay in esophagectomy beyond 60 days was not associated with worse recurrence or overall survival despite increased comorbidities and postoperative events.

Tumor progression and metastasis is driven by interplays between cancer cells and their surrounding tumor microenvironment (TME). Investigating the spatiotemporal transcriptomic profile of primary and metastatic tumors sheds light on how the differences in spatial architecture shape the TME and promote tumor metastasis. Here, we profiled three primary and three lung metastatic clear cell renal cell carcinoma (ccRCC) samples using the CosMx platform, which provides a 999-gene transcriptome with spatial coordinates. After cell segmentation and annotation, we further incorporate the cellular context and spatial information to identify niches by grouping the cells with similar neighboring cells. Cell-cell communication and architecture were analyzed to understand the spatial organization in primary and metastatic ccRCC. From niche analysis, 12 distinctive niches were identified, including cancer, stroma, alveolar, tertiary lymphoid structure (TLS), and mast niches, formed by 25 different cell types. Analyzing cancer niches, we found that the metastatic TME is much more immunosuppressive compared to the TME in primary ccRCC. There is a higher infiltration of exhausted T cells, Treg and M2-like macrophages in metastases. Moreover, the fibroblasts in metastases have higher expression of VEGF and metalloproteinases, which led to angiogenesis and worse prognosis. Architecture analysis showed that lung metastatic ccRCC cells, surrounded by a stromal barrier, are not directly interacting with tumor infiltrating leukocytes (TILs), whereas primary ccRCC cells interact more with TILs. Moreover, compared to the TLSs in primary ccRCC, the ones in metastases showed features of dysfunction, which was correlated with a worse prognosis. Our results show the impact of spatial architecture on primary and metastatic ccRCC, as well as the relation between spatial organization of the cellular context and cell-cell communication. In addition, it suggests that immune cells and cancer-associated fibroblasts (CAFs) are essential components of the ccRCC TME. Their interaction constitutes a major factor not only for tumor progression but also limiting therapy response in metastatic ccRCC. Yufei Wang, Jae-Won Cho, Yasmin Nabil Laimon, Wenxin Xu, Aseman Bagheri Sheshdeh, Nithyassree Murugan, Hsien-Chi Yuan, Jon Wee, David Braun, Toni Choueiri, Catherine Wu, Sabina Signoretti, Gordon Freeman, Martin Hemberg, Wayne Marasco. ccRCC metastasis rewires tumor microenvironment to increase immunosuppression and fibrosis. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 770.

Robotic surgery is increasingly prevalent in thoracic surgery. Studies of specific kinematic data on outcomes are missing. The object of this study was to examine correlations between years in practice, robotic experience, and kinematic (motion) data on complications and readmissions. Kinematic data from the first lymph node dissection of anatomic robotic lung resections were combined with data from a prospectively maintained single institution database. Kinematic data included arm movement speed, economy of motion, and camera movement. Lobectomies and segmentectomies were matched and propensity-score weighted with inverse-probability treatment weights. Pearson’s correlations, between years in practice, robotic experience, and kinematic data; and logistic regression; between years in practice and robotic experience on complications and readmissions were done. Lobectomies, 42, and segmentectomies, 31, from 2022 to 2023 were included. After matching, lymph nodes sampled were greater with lobectomies than segmentectomies, but other data were well matched; nodes sampled with lobes 13.4 vs 7.6 with segments, p < 0.001. Years in practice and robotic experience were not correlated with complications or readmissions. Significant correlations were noted between kinematic data and robotic experience. Length of stay had a negative correlation with robotic experience, −0.16, p < 0.001. No odds ratios were significant. In this small series, decreased length of stay was correlated with increased robotic experience which was a stronger outcome determinant than practice years. The complications and readmissions were not correlated with either measure. Increasing robotic experience may help optimize patient care but additional data are needed to establish usefulness of specific kinematic data.

McKeown esophagectomy is a transthoracic esophagectomy with a cervical anastomosis that is an established mainstay for the management of benign and malignant esophageal pathology. It has gone through multiple modifications. The most current version utilizes robotic or minimally invasive ports through both the right chest and abdominal portions. There is decreased pain and hospital length of stay compared to the open technique. However, anastomotic leak and recurrent laryngeal nerve injury continue to occur. Advancements in management of complications has decreased mortality, making this surgical approach a relevant option for esophageal pathologies.

Abstract Background Hiatal hernia post esophagectomy is a delayed postoperative complication. Historically, in open surgery, the incidence is rare. The increased utilization of minimally invasive methods has increased the incidence of hiatal hernias. Current literature is limited to case series. There is even less on frequency and management of re-recurrent cases. Our objectives were to identify the incidence of hiatal hernia post esophagectomy and the outcomes of the recurrent cases. Methods A retrospective analysis of prospective data at a single center was conducted on esophagectomies performed 2017 to 2022. Non-gastric conduit reconstructions were excluded. Baseline patient demographics including comorbidities, type of tumor, neoadjuvant therapy, surgical approach (open versus minimally invasive [MIE]), and conduit construction were recorded. Radiographic presence of non-gastric conduit abdominal contents was defined as hiatal hernia. Time of hiatal hernia occurrence, details of the repair and timing re-recurrence was recorded. Associated factors described in literature including baseline demographics, neoadjuvant therapy, operative technique, conduit diameter and use of pexy techniques were analyzed with univariate analysis. P<0.05 was considered significant. Results A total of 565 esophagectomies met inclusion criteria, 78% (439/565) were MIE. Robotic-assisted comprised 33% (143/439) of the MIE cohort. A hiatal hernia was identified in 3% of patients (15/565). All had malignancy and were Ivor Lewis (11/15, 73%) or 3-hole (4/15, 27%). The majority had an MIE (13/15, 86%), one had open esophagectomy (6%), and one had hybrid (1/15, 6%). There was no difference in risk factors between the hernia and non-hernia groups. Median time to hernia was 5 months (IQR: 4, 12). All underwent repair. Recurrent hernia occurred in 33% of patients (5/15), all within the robotic-assisted MIE. Conclusion Hiatal hernia post esophagectomy occurred in 3% of cases, and most cases occurred within the MIE group. Recurrence of hernias occurred in robotic-assisted esophagectomy patients. Analysis of patient-specific factors such as prior hiatal hernia, body-mass index, neoadjuvant therapy, operative technique, conduit pexy technique all did not reveal significant correlation with hiatal hernia development. The recurrence of hiatal hernia all required redo repairs. Though we had no deaths in the hiatal hernia cohort, repeat surgeries affect morbidity in esophagectomy patients. Further analysis is needed to identify ways to minimize hernia recurrence in minimally invasive esophagectomy.

Background: The esophagectomy surgical Apgar score (eSAS) has been found to be a predictor of postoperative complications in esophagectomy. In our previous study, we built a graphic nomogram based on eSAS and demonstrated that it can effectively predict the risk of major morbidity after esophagectomy. In this study, we aimed to assess the benefits of using an eSAS-based nomogram model as a postoperative risk-based triage system for patients undergoing esophagectomy. Methods: We enrolled 119 patients diagnosed with esophageal carcinoma and randomly assigned them to a nomogram group (NG) or control group (CG) from January 2019 to December 2020. Patients in the NG were assigned to a low-risk group and high-risk group based on the nomogram. Patients in the high-risk group were admitted to the intensive care unit (ICU) after esophagectomy. Risk estimation in the CG patients was based on the surgeon's clinical experience. Thirty-day major complications, postoperative hospital stay, hospital costs, and quality of life (QOL) during the follow-up were compared between the two groups. Results: Baseline clinicopathological characteristics were comparable between the NG (n=58) and CG (n=61). All patients underwent esophagectomy. Postoperative complications were significantly higher in the CG (30, 49.2%) than in the NG (14, 24.1%) (P=0.008), with pneumonia being the most common (CG: 23, 37.7%; NG: 12, 20.7%; P=0.042). There was no significant difference in anastomotic leakage (NG: 1, 1.7%; CG: 6, 9.8%; P=0.12). Postoperative median hospital stay was shorter in the NG (14 days) than in the CG (16 days) (P=0.041). Hospital costs (NG: ¥60,045.1; CG: ¥63,961.5; P=0.21) and postoperative QOL did not differ significantly between groups. Conclusions: An eSAS-based nomogram as a triage system can reduce the overall occurrence of postoperative complications and shorten postoperative hospital stay without increasing hospital costs. Trial Registration: Chinese Clinical Trial Registry ChiCTR1900021636.

Background: Reported advantages to robotic thoracic surgery include shorter length of stay (LOS), improved lymphadenectomy, and decreased complications. It is uncertain if these benefits occur when introducing robotics into a well-established video-assisted thoracoscopy (VATS) practice. We compared the two approaches to investigate these advantages. Materials and methods: IRB approval was obtained for this project. Patients who underwent segmentectomy or lobectomy from May 2016-December 2018 were propensity-matched 2: 1 (VATS: robotic) and compared using weighted logistic regression with age, gender, Charlson Comorbidity Index, surgery type, stage, Exparel, and epidural as covariates. Complication rates, operation times, number of sampled lymph nodes, pain level, disposition, and LOS were compared using Wilcoxon rank-sum and with Rao-Scott Chi-squared tests. Results: 213 patients (142 VATS and 71 robot) were matched. Duration of robotic cases was longer than VATS (median 186 min (IQR 78) vs. 164 min (IQR 78.75); p < 0.001). Significantly more lymph nodes (median 11 (IQR 7.50) vs. 8 (IQR 7.00); p = 0.004) and stations were sampled (median 4 (IQR 2.00) vs. 3 (IQR 1.00); p < 0.001) with the robot. Interestingly, robotic resections had higher 72-hour pain scores (median 3 (IQR 3.25) vs. 2 (IQR 3.50); p = 0.04) and 48-hour opioid usage (median 37.50 morphine milligram equivalents (MME) (IQR 45.50) vs. 22.50 MME (IQR 37.50); p = 0.01). Morbidity, LOS, and disposition were similar (all p > 0.05). Conclusions: The robotic approach facilitates better lymph node sampling, even in an established VATS practice.

One of the major hurdles that has hindered the success of chimeric antigen receptor (CAR) T cell therapies against solid tumors is on-target off-tumor (OTOT) toxicity due to sharing of the same epitopes on normal tissues. To elevate the safety profile of CAR-T cells, an affinity/avidity fine-tuned CAR was designed enabling CAR-T cell activation only in the presence of a highly expressed tumor associated antigen (TAA) but not when recognizing the same antigen at a physiological level on healthy cells. Using direct stochastic optical reconstruction microscopy (dSTORM) which provides single-molecule resolution, and flow cytometry, we identified high carbonic anhydrase IX (CAIX) density on clear cell renal cell carcinoma (ccRCC) patient samples and low-density expression on healthy bile duct tissues. A Tet-On doxycycline-inducible CAIX expressing cell line was established to mimic various CAIX densities, providing coverage from CAIX-high skrc-59 tumor cells to CAIX-low MMNK-1 cholangiocytes. Assessing the killing of CAR-T cells, we demonstrated that low-affinity/high-avidity fine-tuned G9 CAR-T has a wider therapeutic window compared to high-affinity/high-avidity G250 that was used in the first anti-CAIX CAR-T clinical trial but displayed serious OTOT effects. To assess the therapeutic effect of G9 on patient samples, we generated ccRCC patient derived organotypic tumor spheroid (PDOTS) ex vivo cultures and demonstrated that G9 CAR-T cells exhibited superior efficacy, migration and cytokine release in these miniature tumors. Moreover, in an RCC orthotopic mouse model, G9 CAR-T cells showed enhanced tumor control compared to G250. In summary, G9 has successfully mitigated OTOT side effects and in doing so has made CAIX a druggable immunotherapeutic target.

Background:Neoadjuvant chemoradiation therapy (nCRT) followed by esophagectomy is the standard treatment for resectable, locally advanced esophageal cancer. The ideal timing between neoadjuvant therapy and esophagectomy is unclear. Delayed esophagectomy is associated with worse outcomes. We investigated which factors impacted time to esophagectomy in our patients. Methods:We conducted a retrospective analysis of prospectively collected data of patients with pT0-3N0-2 esophageal cancers who underwent CROSS trimodality therapy from May 2016 to January 2020. Sociodemographic factors, comorbidities, and neoadjuvant factors (location of CRT, treatment toxicity, discontinuation of treatment) were compared between patients who underwent surgery within 60 days and those after 60 days. Results:In total, 197 patients were analyzed of whom 137 underwent esophagectomy within 60 days (early surgery, ES) and 60 were outside that window (delayed surgery, DS). More DS patients had a history of myocardial infarction (MI) or stroke (both 11.67% vs. 3.65%, P=0.05) and required CRT dose reduction (16.67% vs. 6.57%, P=0.04). Fewer DS patients received CRT at Dana-Farber Cancer Institute (DFCI) or a DFCI satellite site (33.33% vs. 58.4%, P=0.01) and saw our surgeons before CRT completion (68.33% vs. 89.78%, P=0.001). CRT at DFCI [odds ratio (OR) 2.63, P=0.01] or a satellite site (OR 3.07, P=0.01) and evaluation by a thoracic surgeon (OR 4.07, P=0.001) shortened time to esophagectomy. History of MI (OR 0.29, P=0.04), stroke (OR 0.29, P=0.04), and CRT dose reduction (OR 0.35, P=0.03) delayed time to esophagectomy. Conclusions:Improving access to multispecialty cancer centers and increasing satellite sites may improve time to esophagectomy.

Objective: The impact of conduit dimensions and location of esophagogastric anastomosis on long-term quality of life after esophagectomy remains unexplored. We investigated the association of these parameters with surgical outcomes and patient-reported quality of life at least 18 months after esophagectomy. Methods: We identified all patients who underwent esophagectomy for cancer from 2018 to 2020 in our institution. We reviewed each patient's initial postoperative computed tomography scan measuring the gastric conduit's greatest width (centimeters), linear staple line length (centimeters), and relative location of esophagogastric anastomosis (vertebra). Quality of life was ascertained using patient-reported outcome measures. Perioperative complications, length of stay, and mortality were collected. Multivariate regressions were performed. Results: Our study revealed that a more proximal anastomosis was linked to an increased risk of pulmonary complications, a lower recurrence rate, and greater long-term insomnia. Increased maximum intrathoracic conduit width was significantly associated with trouble enjoying meals and reflux long term after esophagectomy. A longer conduit stapled line correlated with fewer issues related to insomnia, improved appetite, less dysphagia, and significantly enhanced "social," "role," and "physical'" aspects of the patient's long-term quality of life. Conclusions: The dimensions of the gastric conduit and the height of the anastomosis may be independently associated with outcomes and long-term quality of life after esophagectomy for cancer. (JTCVS Open 2024;17:306-19)

Verrucous esophageal carcinoma is an extremely rare subtype of squamous cell carcinoma of the esophagus that is characterized by a friable exophytic mass but is often deceptively low-grade and superficially well-differentiated on mucosal biopsies, making pathologic diagnosis challenging. Distant metastasis is rare in these tumors. Therefore, early diagnosis is crucial as surgical resection is frequently curative. Conversely, delay in diagnosis can lead to extensive local invasion and result in severe morbidity and death. In this article, we will outline the history of verrucous esophageal carcinoma, review the current clinical understanding based on cases of verrucous carcinoma described thus far, and discuss recent advances in understanding of the pathogenesis of verrucous esophageal carcinoma that may aid in molecular diagnostics.

The role of Human papillomavirus (HPV) infection in esophageal squamous cell carcinoma (ESCC) is a topic of ongoing debate. This study used two screening approaches to look for evidence of HPV infection in esophageal squamous cell carcinoma. We initially checked for HPV infection in a randomly selected group of 53 ESCC cases. We did not detect any tumors positive for high-risk HPV. However, during clinical practice, we identified an HPV-positive ESCC in the distal esophagus, which tested positive for HPV16. This index case was TP53 wild-type, as determined by next-generation DNA sequencing (NGS). Since TP53 mutations are rare in other HPV-driven cancers, we improved our screening method by limiting our screen to a subset of ESCC cases without TP53 mutations. A second screen of 95 ESCCs (from 93 patients) sequenced by NGS revealed an additional 7 ESCCs with TP53 wild-type status (7.3% of the total). Of the 7 cases, 2 cases were found to be high-risk HPV positive. Both patients also tested positive for circulating cell-free HPV DNA and had a complete response to neoadjuvant chemoradiation. The index patient had microscopic residual tumor following neoadjuvant therapy. The patient underwent adjuvant immunotherapy and remained disease free after 22 months of surveillance. This study affirms the transcriptionally active status of high-risk HPV in a minority of ESCC patients in North America.

We read with great interest the commentary entitled "A Deeper Look at Dilations After Minimally Invasive Esophagectomy."1 We appreciate that the journey toward the "'optimal" minimally invasive esophagectomy (MIE) approach is far from complete as exciting technologies and techniques continue to be introduced. In addition to the use of indocyanine green for evaluating anastomotic ischemia, we believe new anastomotic techniques, aided by the introduction of the robotic approach, have the potential to impart significant benefit on operative outcomes.

BACKGROUND:Sternotomy is the traditional approach for thymectomy. However, over the last 2 decades, minimally invasive surgical approaches (multiport thoracoscopic and robotic-assisted surgery) have proven feasible, offering similar survival, lower morbidity, and shorter length of stay. Single-port (SP) subxiphoid thymectomy potentially offers less pain and allows bilateral visualization of the mediastinum. METHODS:A prospective, multicenter, single-arm clinical study was conducted to evaluate the performance and safety of the da Vinci SP surgical system (Intuitive) for thymectomy through a subxiphoid incision. Primary performance end points included ability to achieve R0 resection and completion of the procedure without conversion. The primary safety end point was all adverse events up to 30 days postoperatively. RESULTS:The study enrolled 13 individuals (benign, n = 6; malignant, n = 7) at 6 centers in the United States. All SP thymectomy procedures were completed through a small (mean, 3.8 cm) subxiphoid incision without conversion to other minimally invasive or open approaches. For malignant cases, the rate of complete resection was 100%. No study participants experienced any intraoperative or serious adverse events. No unanticipated adverse device effects were reported. CONCLUSIONS:Thymectomy using the da Vinci SP surgical system through a subxiphoid approach is feasible, and there are no early indications of safety or procedural concerns. Larger clinical studies are warranted to further evaluate the relative benefits and limitations of the SP system compared with multiport robotic thymectomy.