Shen, K. Robert

Regenerative medicine is transforming how we restore tissue function, leveraging advances in cell and molecular biology, biomaterials, and engineered microenvironments. While there have been notable advances and rapid progress over the past few decades, ongoing challenges persist in the technical development and effective translation of these advancements to clinical care. This perspective highlights clinically promising examples and critically assesses present challenges in translating tissue regenerative medicine therapies from the bench to the clinic. We further examine the evolving landscape of regenerative medicine by describing strategies to optimize the cellular microenvironment, the impact of patient demographics, and the use of artificial intelligence to shape the future of this field.

Abstract Gastric volvulus has been rarely associated with diaphragmatic paralysis or eventration. In this article, we present the case of a patient with idiopathic paralysis of the left hemidiaphragm that underwent treatment with a robotic thoracoscopic diaphragm plication, which was complicated by massive gastric volvulus resulting in such significant intra-abdominal hypertension that the ipsilateral diaphragm ruptured anterior to the plication suture line.

Background Bronchopleural fistula (BPF) is a dreaded complication of pulmonary resection. For high-risk patients, bronchial stump coverage with vascularized tissue has been recommended. The goal of this study was to report our experience with intrathoracic muscle transposition for bronchial stump coverage. Methods A retrospective review of all patients who underwent intrathoracic muscle flap transposition as a prophylactic measure at our institution between 1990 and 2010 was conducted. Demographics, surgical characteristics, and complication rates were abstracted and analyzed. Results A total of 160 patients were identified. The most common lung resections performed were pneumonectomy (n = 69, 43%) and lobectomy (n = 60, 38%). A total of 168 flaps were used where serratus anterior was the most common flap (n = 136, 81%), followed by intercostal (n = 14, 8%), and latissimus dorsi (n = 12, 7%). Ten patients (6%) developed BPF, and empyema occurred in 13 patients (8%). Median survival was 20 months, and operative mortality occurred in 7 patients (4%). Conclusions Reinforcement of the bronchial closure with vascularized muscle is a viable option for potentially decreasing the incidence of BPF in high-risk patients. Further randomized studies are needed to determine the efficacy of this technique for BPF prevention.

Background: Intrathoracic fistulas pose unique challenges for thoracic and reconstructive surgeons. To decrease the incidence of fistula recurrence, pedicled flaps have been suggested to buttress the repair site. The authors aimed to report their experience with muscle flap transposition for the management of intrathoracic fistulas. Methods: A retrospective review of all patients who underwent intrathoracic muscle flap transposition for the management of intrathoracic fistulas from 1990 to 2010 was conducted. Patient demographics, surgical characteristics, and complication rates were abstracted and analyzed. Results: A total of 198 patients were identified. Bronchopleural fistula was present in 156 of the patients (79 percent), and 48 had esophageal fistula (24 percent). A total of 238 flaps were used, constituting an average of 1.2 flaps per patient. After the initial fistula repair, bronchopleural fistula complicated the course of 34 patients (17 percent), and esophageal fistula occurred in 13 patients (7 percent). Partial flap loss was identified in 11 flaps (6 percent), and total flap loss occurred in four flaps (2 percent). Median follow-up was 27 months. At the last follow-up, 182 of the patients (92 percent) had no evidence of fistula, 175 (89 percent) achieved successful chest closure, and 164 (83 percent) had successful treatment. Preoperative radiation therapy and American Society of Anesthesiologists score of 4 or greater were identified as risk factors for unsuccessful treatment. Conclusions: Intrathoracic fistulas remain a source of major morbidity and mortality. Reinforcement of the fistula closure with vascularized muscle flaps is a viable option for preventing dehiscence of the repair site and can be potentially life-saving. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

Abstract Background Pneumatosis intestinalis has long been a marker of advanced bowel ischemia and prompts urgent laparotomy. In post-operative settings, the presence of pneumatosis represents a significant management dilemma. We share a case-series of post-esophagectomy patients with pneumatosis intestinalis and no corollary intra-abdominal pathologic findings on re-exploration. Methods January 2000 to December 2017, 1760 patients underwent Ivor-Lewis esophagectomy or gastrectomy with jejunostomy-tube placement. Charts were reviewed retrospectively to identify patients with pneumatosis intestinalis discovered in the post-operative period. Demographic data, operative details and postoperative course were reviewed including incidence and details of re-exploration. Results Eleven patients met inclusion criteria. Nine were male (81.8%) and mean age was 69 years. All patients had radiographic confirmation of pneumatosis intestinalis and in many cases portal venous gas (Figure 1). Clinical course was variable without discernable trends in vitals or laboratory values. Development of significant postoperative ileus along with delivery of enteral tube feeds through a jejunostomy tube preceded development of the pneumatosis in all patients. Nine patients were re-explored and none had evidence of bowel ischemia. Conclusion The finding of pneumatosis intestinalis in the post-operative setting can be alarming and pose a management dilemma. With the advent of improved and readily available imaging, there has been an increase in findings that have no corollary physical symptomatology. In this series of patients, despite dramatic radiographic findings, none had ischemic bowel. Pneumatosis intestinalis alone in patients who have undergone esophagectomy should not be considered an indication for emergency re-exploration. Disclosure All authors have declared no conflicts of interest.

Abstract Background The purpose of this study was to evaluate the survival difference in clinical T2N0 esophageal cancer patients receiving neoadjuvant chemoradiotherapy (CRT) vs. upfront surgery. Methods Between 1/1/1995 to 12/31/2012, a prospectively maintained database was used to identify patients with cT2N0 esophageal adeno- and squamous cell carcinoma. Exclusion criteria included: lack of endoscopic esophageal ultrasonographic (EUS) staging, incomplete resection, and prior treatment with endoscopic mucosal or submucosal resection. Cox-proportional hazard ratios were used to compare the primary outcomes of overall (OS) and disease-free survival (DFS). Secondary outcomes included: rate of postoperative complications, rate of pathologic upstaging/response, and induction/adjuvant treatment completion rate. Pre-hoc subgroup analysis compared pathologically upstaged patients receiving upfront surgery followed by adjuvant chemotherapy to those treated with neoadjuvant CRT. Results A total of 161 cT2N0 esophageal cancer patients were identified based on EUS staging. Upfront surgery was offered to 134 patients (83%), with 27 patients (17%) receiving induction CRT. Univariate analysis did not demonstrate any significant baseline differences between the two groups. In the upfront surgery group, 53 (39.6%), 28 (20.9%) and 53 (39.6%) patients were pathologically down-staged, accurately staged and upstaged respectively. Upstaging was higher in the upfront surgery group (53/134, 39.6% vs. 4/27, 14.8%; P = 0.02), while 11/27 (40.7%) patients receiving neoadjuvant CRT demonstrated complete pathologic response. Of those eligible for adjuvant chemotherapy, only 21/55 (38.2%) received treatment. In the neoadjuvant CRT group, 51.9% completed all planned therapy, compared to 23.6% of patients treated with upfront surgery followed by adjuvant chemotherapy (P = 0.01). Cox proportional hazard ratio did not demonstrate an advantage to induction CRT in terms of OS (HR = 1.64, P = 0.43) or DFS (HR = 1.36, P = 0.69). In general, patients with pathologic upstaging had worse OS (HR = 2.73, P = 0.001) and DFS (HR = 4.18, P = 0.003). Conclusion EUS was only accurate in staging T2N0 patients in 20.9% of cases. While neoadjuvant CRT did not confer a survival advantage, these results likely reflect the low number of patients being referred for induction therapy. Neoadjuvant CRT was however associated with lower rates of pathologic upstaging and higher rates of treatment completion. Further research should evaluate the survival outcomes in pathologically upstaged cT2N0 patients not receiving neoadjuvant therapy. Disclosure All authors have declared no conflicts of interest.