Short- and Long-Term Outcomes in Elderly Patients with Resectable Esophageal Cancer: Upfront Esophagectomy Compared to Surgery after Neoadjuvant Treatments.

Background/Objectives: Despite the increased incidence of esophageal cancer (EC) in elderly people, there are no clear guidelines for its treatment in these patients. The aim of this study was to compare the outcomes of patients ≥ 75 years with resectable EC, receiving either upfront esophagectomy or neoadjuvant treatment. Methods: We retrospectively identified 127 patients with resectable EC ≥ 75 years who underwent esophagectomy between January 2000 and December 2022 at our Clinic in the University Hospital of Padova. The included patients were stratified into two groups: patients undergoing upfront esophagectomy (SURG group) and patients receiving neoadjuvant treatment (NAT group). Results: There were no statistically significant differences in OS (p = 0.7708), DFS (p = 0.7827) and cancer-related survival (p = 0.0827) between the SURG and the NAT group, except for the OS of EAC with stage III-IV, where the NAT group experienced a significant benefit in OS (p = 0.0263). When comparing the two groups, patients receiving neoadjuvant treatment experienced a significantly higher rate of postoperative complications (p = 0.0266). At univariate analysis, neoadjuvant therapy was the only variable strongly associated with postoperative morbidity (p = 0.026). Conclusions: Considering the unique characteristics of elderly patients, the choice of a multimodal approach should be tailored to each case in a multidisciplinary setting and balanced with a potential higher risk of postoperative complications, as well as potential toxicity related to chemoradiation and reduced life expectancy.

The Prognostic Impact of Minimally Invasive Esophagectomy on Survival after Esophagectomy following a Delayed Interval after Chemoradiotherapy; A Secondary Analysis of the DICE Study.

OBJECTIVE: To evaluate prognostic differences between minimally invasive esophagectomy (MIE) and open esophagectomy (OE) in patients with surgery after a prolonged interval (>12 wk) following chemoradiotherapy (CRT). BACKGROUND: Previously, we established that a prolonged interval after CRT prior to esophagectomy was associated with poorer long-term survival. METHODS: This was an international multi-center cohort study involving seventeen tertiary centers, including patients who received CRT followed by surgery between 2010-2020. Patients undergoing MIE were defined as thoracoscopic and laparoscopic approach. RESULTS: 428 patients (145 MIE and 283 OE) had surgery between 12 weeks and two years after CRT. Significant differences were observed in ASA grade, radiation dose, clinical T stage, and histological subtype. There were no significant differences between the groups in age, sex, BMI, pathological T or N stage, resection margin status, tumor location, surgical technique, or 90-day mortality. Survival analysis showed MIE was associated with improved survival in univariate (P=0.014), multivariate analysis after adjustment for smoking, T and N stage, and histology (HR=1.69; 95% CI 1.14 to 2.5) and propensity matched analysis (P=0.02). Further subgroup analyses by radiation dose and interval after CRT showed survival advantage for MIE, in 40-50Gy dose groups (HR=1.9; 95% CI 1.2 to 3.0), and in patients having surgery within six months of CRT (HR=1.6; 95% CI 1.1 to 2.2). CONCLUSION: MIE was associated with an improved overall survival compared to OE in patients with a prolonged interval from CRT to surgery. The mechanism for this observed improvement in survival remains unknown, with potential hypotheses including a reduction in complications and improved functional recovery after MIE.

The esophageal pull-down technique improves the outcome of laparoscopic Heller-Dor myotomy in end-stage achalasia.

BACKGROUND: The treatment of patients with end-stage achalasia with a sigmoid-shaped esophagus is particularly challenging. A modified technique (pull-down technique) has been developed to straighten the esophageal axis, but only a limited number of studies on this topic are available in the literature. This study aimed to compare the outcome of patients who underwent the pull-down technique with that of patients who had a classical laparoscopic Heller-Dor (CLHD) myotomy. METHODS: All patients with a radiologic diagnosis of end-stage achalasia who underwent an LHD myotomy between 1995 and 2022 were considered eligible for the study. All patients underwent symptom score, barium swallow, endoscopy, and manometry tests before and after the procedure was performed. Treatment failure was defined as the persistence or reoccurrence of an Eckardt score (ES) of >3 or the need for retreatment. RESULTS: Of the 94 patients who were diagnosed with end-stage achalasia (male-to-female ratio of 52:42), 60 were treated with CLHD myotomy, and 34 were treated with the pull-down technique. Of note, 2 patients (2.1%), both belonging to the CLHD myotomy group, developed a squamous cell carcinoma during the follow-up. The overall success of LHD myotomy was seen in 76 of 92 patients (82.6%). All patients in both groups achieved a lower ES after surgery. The failure rates were 27.6% (16/58) in the CLHD myotomy group and 5.9% (2/34) in the pull-down technique group (P < .01). CONCLUSION: Our findings confirm that LHD myotomy is an effective treatment of end-stage achalasia and that the pull-down technique further improves the outcome in patients with end-stage achalasia who are difficult to treat.

The Role of High-Resolution Manometry Prior to and Following Antireflux Surgery: The Padova Consensus.

BACKGROUND: In the last two decades the development of high-resolution manometry (HRM) has changed and revolutionized the diagnostic assessment of patients complain foregut symptoms. The role of HRM before and after antireflux procedure remains unclear, especially in surgical practice, where a clear understanding of esophageal physiology and hiatus anatomy is essential for optimal outcome of antireflux surgery (ARS). Surgeons and gastroenterologists (GIs) agree that assessing patients following antireflux procedures can be challenging. Although endoscopy and barium-swallow can reveal anatomic abnormalities, physiologic information on HRM allowing insight into the cause of eventually recurrent symptoms could be key to clinical decision making. METHOD: A multi-disciplinary international working group (14 surgeons and 15 GIs) collaborated to develop consensus on the role of HRM pre- and post- ARS, and to develop a postoperative classification to interpret HRM findings. The method utilized was detailed literature review to develop statements, and the RAND/University of California, Los Angeles Appropriateness Methodology (RAM) to assess agreement with the statements. Only statements with an approval rate >80% or a final ranking with a median score of 7 were accepted in the consensus. The working groups evaluated the role of HRM prior to ARS and the role of HRM following ARS. CONCLUSION: This international initiative developed by surgeons and GIs together, summarizes the state of our knowledge of the use of HRM pre- and post-ARS. The Padova Classification was developed to facilitate the interpretation of HRM studies of patients underwent ARS.

Manometric identikit of a functioning and effective fundoplication for gastroesophageal reflux disease in the high-resolution manometry ERA.

BACKGROUND: The pathophysiological and clinical value of performing High-Resolution Manometry (HRM) after laparoscopic fundoplication (LF) for gastroesophageal reflux disease (GERD) is still unclear and debated. OBJECTIVE: We sought to establish the HRM parameters indicative of functioning fundoplications, and whether HRM could distinguish them from tight or defective ones. METHODS: The study involved patients with GERD who underwent laparoscopic Nissen (LN) or Toupet (LT) fundoplication between 2010 and 2022. HRM and 24-h pH monitoring were performed before and 6 months after surgery. The study population was divided into 5 groups: LN and LT patients with normal 24h-pH findings (LNpH- and LTpH-, respectively); LN and LT patients with pathological 24h-pH findings (LNpH+ and LTpH + groups, respectively); and patients with a postoperative dysphagia intensity score >2 (Dysphagia group). The novel Hiatal Morphology (HM) classification was applied, envisaging 3 different subtypes: HM1 (normal), HM2 (intrathoracic fundoplication), and HM3 (slipped fundoplication). RESULTS: Among the 132 patients recruited during the study period, 46 were in the LNpH- group, 51 in the LTpH- group, 15 in the LNpH + group, 7 in the LTpH + group, and 5 in the Dysphagia group. In multivariate analysis, postoperative abdominal lower esophageal sphincter length (p = 0.001) and HM2 (p < 0.001) were both independently associated with surgical failure. Integrated relaxation pressure was significantly higher in the Dysphagia group than in the LNpH- group. CONCLUSION: This study generated reference HRM values for an effective LF, and confirms that using HRM to assess the neo-sphincter and HM improves the clinical assessment in cases of symptom recurrence.

Delayed Surgical Intervention After Chemoradiotherapy in Esophageal Cancer: (DICE) Study.

OBJECTIVE: To determine the impact of delayed surgical intervention following chemoradiotherapy (CRT) on survival from esophageal cancer. BACKGROUND: CRT is a core component of multimodality treatment for locally advanced esophageal cancer. The timing of surgery following CRT may influence the probability of performing an oncological resection and the associated operative morbidity. METHODS: This was an international, multicenter, cohort study, including patients from 17 centers who received CRT followed by surgery between 2010 and 2020. In the main analysis, patients were divided into 4 groups based upon the interval between CRT and surgery (0-50, 51-100, 101-200, and >200 days) to assess the impact upon 90-day mortality and 5-year overall survival. Multivariable logistic and Cox regression provided hazard ratios (HRs) with 95% CIs adjusted for relevant patient, oncological, and pathologic confounding factors. RESULTS: A total of 2867 patients who underwent esophagectomy after CRT were included. After adjustment for relevant confounders, prolonged interval following CRT was associated with an increased 90-day mortality compared with 0 to 50 days (reference): 51 to 100 days (HR=1.54, 95% CI: 1.04-2.29), 101 to 200 days (HR=2.14, 95% CI: 1.37-3.35), and >200 days (HR=3.06, 95% CI: 1.64-5.69). Similarly, a poorer 5-year overall survival was also observed with prolonged interval following CRT compared with 0 to 50 days (reference): 101 to 200 days (HR=1.41, 95% CI: 1.17-1.70), and >200 days (HR=1.64, 95% CI: 1.24-2.17). CONCLUSIONS: Prolonged interval following CRT before esophagectomy is associated with increased 90-day mortality and poorer long-term survival. Further investigation is needed to understand the mechanism that underpins these adverse outcomes observed with a prolonged interval to surgery.

Minimally invasive Ivor Lewis esophagectomy in the elderly patient: a multicenter retrospective matched-cohort study.

Introduction: Several studies reported the advantages of minimally invasive esophagectomy over the conventional open approach, particularly in terms of postoperative morbidity and mortality. The literature regarding the elderly population is however scarce and it is still not clear whether elderly patients may benefit from a minimally invasive approach as the general population. We sought to evaluate whether thoracoscopic/ laparoscopic (MIE) or fully robotic (RAMIE) Ivor-Lewis esophagectomy significantly reduces postoperative morbidity in the elderly population. Methods: We analyzed data of patients who underwent open esophagectomy or MIE/RAMIE at Mainz University Hospital and at Padova University Hospital between 2016 and 2021. Elderly patients were defined as those ≥ 75 years old. Clinical characteristics and the postoperative outcomes were compared between elderly patients who underwent open esophagectomy or MIE/RAMIE. A 1-to-1 matched comparison was also performed. Patients < 75 years old were evaluated as a control group. Results: Among elderly patients MIE/RAMIE were associated with a lower overall morbidity (39.7% vs. 62.7%, p=0.005), less pulmonary complications (32.8 vs. 56.9%, p=0.003) and a shorter hospital stay (13 vs. 18 days, p=0.03). Comparable findings were obtained after matching. Similarly, among < 75 years-old patients, a reduced morbidity (31.2% vs. 43.5%, p=0.01) and less pulmonary complications (22% vs. 36%, p=0.001) were detected in the minimally invasive group. Discussion: Minimally invasive esophagectomy improves the postoperative course of elderly patients reducing the overall incidence of postoperative complications, particularly of pulmonary complications.

How Long Does It Take to Acquire Mastery of Performance in Laparoscopic Living Donor Nephrectomy? A Center-Based and Surgeon-Based Operative Time CUSUM Analysis.

BACKGROUND: The safety of laparoscopic donor nephrectomy (LDN) has been widely documented, but its challenging learning curve (LC) requires an insightful assessment to expand its application. The aim of this study was to evaluate LC of LDN in a high-volume transplant center. METHODS: Three hundred forty-three LDNs performed from 2001 to 2018 were evaluated. CUSUM analysis based on the operative time was used to assess the number of cases required to reach mastery in the technique for both the entire surgical team and for the 3 main surgeons considered separately. Analysis of association between demographics, perioperative characteristics, and complications within the different LC phases was conducted. RESULTS: Mean operative time was 228.9 minutes. Mean length of stay was 3.8 days and mean warm ischemia time (WIT) was 170.8 seconds. Surgical and medical complication rates were 7.3% and 6.4%, respectively. The CUSUM-LC showed a requirement of 157 cases (for surgical team) and 75 cases (for single surgeons) to reach competence in the procedure. Patient baseline characteristic showed no differences among the LC phases. Compared with the initial LC phase, hospital stay was significantly lower at the end of the LC whereas WIT results were longer in the LC descendent phase. CONCLUSIONS: This study confirms the safety and efficacy of LDN, with a low rate of complications. This analysis suggests that about 75 procedures are required to reach competence and 93 cases to achieve mastery level of skill for a single surgeon. It can be hypothesized that, in a high-volume transplant enter, the time to guarantee training in LDN is compatible with the duration of a clinical fellowship.

Safety and Efficacy of Surgery for Metastatic Tumor to the Pancreas: A Single-Center Experience.

Pancreatic metastases from other neoplasms are rare. The role of surgery for this clinical entity is unclear. The aim of this study was to investigate the role of resection in patients with pancreatic secondary lesions. We observed 44 patients with pancreatic metastases from other tumors. Renal cell carcinoma was the most common primary tumor (n = 19, 43.2%). Thirty-seven patients underwent surgery, and pancreatic resection with curative intent was feasible in 35 cases. Fifteen patients (43.2%) experienced major postoperative complications (Clavien-Dindo > 2), and postoperative mortality rate was 5.4%. The median overall survival and disease-free survival were 38 (range 0-186) and 11 (range 0-186) months, respectively. Overall survival and disease-free survival were significantly longer for pancreatic metastases from renal cell carcinoma when compared to other primary tumors. Multivariate analysis confirmed a pathological diagnosis of metastasis from RCC as an independent prognostic factor for overall survival (OR 2.48; 95% CI, 1.00-6.14; p = 0.05). In conclusion, radical resection of metastases to the pancreas is feasible and safe, and may confer a survival benefit for selected patients. There is a clear benefit of metastasectomy in terms of patient survival for metastases from renal cell carcinoma, while for those with other primary tumors, surgery seems to be mainly palliative.

Laparoscopic Heller-Dor Is a Persistently Effective Treatment for Achalasia Even in Pediatric Patients: A 25-Year Experience at a Single Tertiary Center.

BACKGROUND: Esophageal achalasia (EA) is a rare primary motility disorder in any age group, and particularly rare in the pediatric population, with a reported incidence of 0.18 per 100,000 children a year. EA in pediatric age is currently treated in the same way as in adults, but this approach is based on only a few studies on small case series. The aim of this retrospective study was to assess the long-term outcome of the laparoscopic Heller-Dor (LHD) procedure when performed in pediatric patients with EA at our university hospital. MATERIALS AND METHODS: We considered children and adolescents younger than 16 years old diagnosed with EA and treated with LHD between 1996 and 2022. Clinical data were prospectively collected in an ongoing database. Symptoms were recorded and their severity was calculated using the Eckardt score. Barium swallow, esophageal manometry (conventional or high-resolution), and endoscopy were performed before and after the surgical procedure. RESULTS: During the study period, 40 children with a median age of 14 years (interquartile range [IQR]: 11-15) underwent LHD. At a median follow-up of 10.5 years (IQR: 4.5-13.9), a good outcome was achieved in 36/40 patients (90%). Two of the four patients whose surgical procedure failed underwent complementary pneumatic dilations successfully, thus increasing the overall success rate to 95%. A previous endoscopic treatment (in five patients) did not affect the final outcome (p = 0.49). An intraoperative mucosal lesion was detected in only one patient (2.5%) and was repaired at the time without further consequences. During the follow-up, 22 patients underwent endoscopy, and 17 had pH monitoring as well: only 2 of these patients showed reflux esophagitis at endoscopy (one of them with abnormal findings on pH monitoring), amounting to a 9.1% rate of instrumentally confirmed postoperative reflux. CONCLUSION: LHD is a safe and persistently effective treatment for EA in pediatric age, with a success rate comparable with what is usually obtained in adults, and better than what has been reported to date in the pediatric literature. Adding a fundoplication certainly helps ensure an optimal long-term control of any gastroesophageal reflux induced by the myotomy.

ESDE-MIE fellowship: a descriptive analysis of the first experiences.

Esophageal resection is a high-risk and technically demanding procedure, with a long proficiency-gain curve. The European Society Diseases of the Esophagus (ESDE)-Minimally Invasive Esophagectomy (MIE) training program was launched in 2018 for European surgeons willing to train and to begin a career undertaking MIE. The aim of this study was to evaluate the first experience of the ESDE-MIE fellowship and relate this to the initially predetermined core principles and objectives of the program. Between October 2021 and May 2022, the participating fellows, in collaboration with the ESDE Educational Committee, initiated a survey to assess the outcome and experience of these fellowships. Data from each individual fellowship were analysed and reported in a descriptive manner. Between 2018 and 2022, in total, five fellows have completed the ESDE-MIE fellowship program. Despite the COVID-19 outbreak just the year after its launch, predetermined clinical and research goals were achieved in all cases. Each of the fellows were able to assist in a median of 40 (IQR 27-69) MIE and/or Robot assisted (RA)MIE procedures, of a total median of 115 (IQR 83-123) attended Upper GI cases. After the fellowship, MIE has been fully adopted by the fellows who returned to their home institutions as Upper GI surgeons. The fellowship was concluded by the European Union of Medical Specialists (UEMS) Multidisciplinary Joint Committee (MJC) certification in Upper GI Surgery, which was successfully obtained by all who took part. Based on the experience of the first five fellows, the ESDE-MIE training fellowship meets with the expected needs even despite the COVID-19 outbreak in 2019. Furthermore, these fellows have returned home and integrated MIE into their independent surgical practice, affirming the ability of this program to train the next generation of MIE surgeons, even in the most challenging of circumstances.

Semiprone thoracoscopic approach during totally minimally invasive Ivor-Lewis esophagectomy seems to be beneficial.

Minimally invasive Ivor-Lewis Esophagectomy (MIE) is widely accepted as a surgical treatment of resectable esophageal cancer. Aim of this paper is to describe the surgical details of our standardized MIE technique and its safety. We also evaluate the esophageal mobilization in semiprone compared to the left lateral position. A retrospective analysis of 141 consecutive patients who underwent Ivor-Lewis esophagectomy for cancer, from February 2016 to September 2021, was conducted. All the procedures were performed by totally thoraco-laparoscopic with an intrathoracic end-to-side circular stapled anastomosis. Thoracic phase was performed in left lateral position (LLP-group, n=47) followed by a semiprone position (SP-group, n=94). The intraoperative and postoperative outcomes were prospectively collected and analyzed. The procedure was completed without intraoperative complication in 94.68% of cases in SP-group and in 93.62% of cases in LLP-group (P=0.99). The total operative time and thoracic operative time were significantly shorter in SP-group (P=0.0096; P=0.009). No statistically significant differences were detected in postoperative outcomes between the groups, except for anastomotic strictures (higher in LLP-group, P=0.02) and intensive care unit stay (longer in LLP-group, P=00.1). No reoperation was needed in any cases. Surgical radicality was comparable; the median of harvested lymph nodes was significantly higher in SP-group (P<0.0001). The present semiprone technique of thoraco-laparoscopic Ivor-Lewis esophagectomy is safe and feasible but may also provide some advantages in terms of lymph nodes harvested and total operation time.

Laparoscopic Heller-Dor is an effective long-term treatment for end-stage achalasia.

BACKGROUND: The end-stage achalasia is a difficult condition to treat, for the esophageal diameter and conformation of the gullet, that may progress to a sigmoid shape. The aim of this study was to examine the outcome of Laparoscopic Heller-Dor in patients with end-stage achalasia, comparing them with patients who had mega-esophagus without a sigmoid shape. METHODS: From 1992 to 2020, patients with a diagnosis of sigmoid esophagus, or radiological stage IV achalasia (the SE group), and patients with a straight esophagus larger than 6 cm in diameter, or radiological stage III achalasia (the NSE group), were all treated with LHD. The two groups were compared in terms of patients' symptoms, based on the Eckardt score, and on barium swallow, endoscopy and manometry performed before and after the treatment. The failure of the treatment was defined as an Eckardt score > 3, or the need for further treatment. RESULTS: The study involved 164 patients: 73 in the SE group and 91 in the NSE group. No intra- or postoperative mortality was recorded. The median follow-up was 51 months (IQR 25-107). The outcome was satisfactory in 71.2% of patients in the SE group, and in 89% of those in the NSE group (p = 0.005). CONCLUSIONS: SE is certainly the worst condition of the disease and the final outcome of LHD, in term of symptom control, is inferior compared to NSE. Despite this, almost 3/4 of the SE patients experienced a significant relieve in symptoms after LHD, which may therefore still be the first surgical option to offer to these patients, before considering esophagectomy.

Plasma proteome profiling of healthy subjects undergoing bed rest reveals unloading-dependent changes linked to muscle atrophy.

BACKGROUND: Inactivity and unloading induce skeletal muscle atrophy, loss of strength and detrimental metabolic effects. Bed rest is a model to study the impact of inactivity on the musculoskeletal system. It not only provides information for bed-ridden patients care, but it is also a ground-based spaceflight analogue used to mimic the challenges of long space missions for the human body. In both cases, it would be desirable to develop a panel of biomarkers to monitor muscle atrophy in a minimally invasive way at point of care to limit the onset of muscle loss in a personalized fashion. METHODS: We applied mass spectrometry-based proteomics to measure plasma protein abundance changes in response to 10 days of bed rest in 10 young males. To validate the correlation between muscle atrophy and the significant hits emerging from our study, we analysed in parallel, with the same pipeline, a cohort of cancer patients with or without cachexia and age-matched controls. Our analysis resulted in the quantification of over 500 proteins. RESULTS: Unloading affected plasma concentration of proteins of the complement cascade, lipid carriers and proteins derived from tissue leakage. Among the latter, teneurin-4 increased 1.6-fold in plasma at bed rest day 10 (BR10) compared with BR0 (6.E9 vs. 4.3E9, P = 0.02) and decreased to 0.6-fold the initial abundance after 2 days of recovery at normal daily activity (R + 2, 2.7E9, P = 3.3E-4); the extracellular matrix protein lumican was decreased to 0.7-fold (1.2E9 vs. 8.5E8, P = 1.5E-4) at BR10 and remained as low at R + 2. We identified six proteins distinguishing subjects developing unloading-mediated muscle atrophy (decrease of >4% of quadriceps cross-sectional area) from those largely maintaining their initial muscle mass. Among them, transthyretin, a thyroid hormone-binding protein, was significantly less abundant at BR10 in the plasma of subjects with muscle atrophy compared with those with no atrophy (1.6E10 vs. 2.6E10, P = 0.001). Haptoglobin-related protein was also significantly reduced in the serum of cancer patients with cachexia compared with that of controls. CONCLUSIONS: Our findings highlight a combination or proteomic changes that can be explored as potential biomarkers of muscle atrophy occurring under different conditions. The panel of significant proteomic differences distinguishing atrophy-prone and atrophy-resistant subjects after 10 days of bed rest need to be tested in a larger cohort to validate their potential to predict inactivity-triggered muscle loss in humans.

Transoral septotomy with septum traction is an effective treatment for recurrent Zenker diverticulum.

Symptoms of Zenker diverticulum can recur whatever the type of primary treatment administered. A modified transoral stapler-assisted septotomy (TS) was introduced in clinical practice a few years ago to improve the results of this mini-invasive technique. The aim of this prospective, controlled study was to assess the outcome of TS in patients with recurrent Zenker diverticulum (RZD), as compared with patients with treatment-naïve Zenker diverticulum (NZD). Patients diagnosed with NZD or RZD, and treated with TS between 2015 and 2021 were compared. Symptoms were recorded and scored using a detailed questionnaire. Barium swallow and endoscopy were performed before and after the TS procedure. In sum, 89 patients were enrolled during the study period: 68 had NZD and 21 had RZD. The patients' demographic and clinical data were similar in the two groups. Three mucosal lesions were detected intra-operatively, and one came to light at post-operative radiological assessment in the NZD group. No mucosal lesions were detected in the RZD group. The median follow-up was 36 months (interquartile range 23-60). The treatment was successful in 97% NZD patients and 95% of RZD patients (P = 0.56). This is the first comparative study based on prospectively collected data to assess the outcome of TS in patients with RZD. Traction on the septum during the procedure proved effective in the treatment of RZD, achieving a success rate that was excellent, and comparable with the outcome in treating NZD.

Bio-Engineered Scaffolds Derived from Decellularized Human Esophagus for Functional Organ Reconstruction.

Esophageal reconstruction through bio-engineered allografts that highly resemble the peculiar properties of the tissue extracellular matrix (ECM) is a prospective strategy to overcome the limitations of current surgical approaches. In this work, human esophagus was decellularized for the first time in the literature by comparing three detergent-enzymatic protocols. After decellularization, residual DNA quantification and histological analyses showed that all protocols efficiently removed cells, DNA (<50 ng/mg of tissue) and muscle fibers, preserving collagen/elastin components. The glycosaminoglycan fraction was maintained (70-98%) in the decellularized versus native tissues, while immunohistochemistry showed unchanged expression of specific ECM markers (collagen IV, laminin). The proteomic signature of acellular esophagi corroborated the retention of structural collagens, basement membrane and matrix-cell interaction proteins. Conversely, decellularization led to the loss of HLA-DR expression, producing non-immunogenic allografts. According to hydroxyproline quantification, matrix collagen was preserved (2-6 µg/mg of tissue) after decellularization, while Second-Harmonic Generation imaging highlighted a decrease in collagen intensity. Based on uniaxial tensile tests, decellularization affected tissue stiffness, but sample integrity/manipulability was still maintained. Finally, the cytotoxicity test revealed that no harmful remnants/contaminants were present on acellular esophageal matrices, suggesting allograft biosafety. Despite the different outcomes showed by the three decellularization methods (regarding, for example, tissue manipulability, DNA removal, and glycosaminoglycans/hydroxyproline contents) the ultimate validation should be provided by future repopulation tests and in vivo orthotopic implant of esophageal scaffolds.

Multimodal treatment of radiation-induced esophageal cancer: Results of a case-matched comparative study from a single center.

PURPOSE: Radiation-induced esophageal cancer (RIEC) is a rare but severe late consequence of radiotherapy. The literature regarding this topic is predominately limited in describing the risk of this disease. Tumor behavior, treatment strategies, and prognosis of this cancer remain poorly defined. PATIENTS AND METHODS: We collected data of patients who were referred to our unit between 2000 and 2020 for RIEC. After tumor board discussion, upfront surgery or neoadjuvant therapy and surgery were indicated as the main treatment. Preoperative characteristics, long-term and short-term postoperative outcomes of RIEC patients were compared with a 1:1 clustering-matched cohort of patients affected by primary esophageal cancer (PEC). RESULTS: At pre-matching, 54 RIEC and 936 PEC patients were enrolled. The median time between primary irradiation and diagnosis of RIEC was 13.5 years, and the median primary radiation dose was 60 Gy. Compared to the unmatched cohort of PECs, RIEC patients were more frequently female (p = 0.0007), had earlier detection of disease (p = 0.03) and presented more frequently with upper esophageal cancers (p < 0.0001). Neoadjuvant treatment was used less frequently in RIEC patients (p < 0.0001). After matching, the 51 RIEC and 50 PEC patients showed comparable results in terms of exposure to neoadjuvant treatment, surgical radicality and survival outcomes. RIEC patients had more severe postoperative complications (p = 0.04) and a higher proportion of pulmonary complications (p = 0.04). CONCLUSIONS: Curative treatments are feasible for RIEC. Neoadjuvant chemotherapy or chemoradiation can be used in this subgroup, treatment response and long-term outcomes are comparable to those of PEC. The risk of postoperative complications is probably related to the detrimental effect of primary irradiation on lung function.

Robotic-assisted surgery for esophageal submucosal tumors: a single-center case series.

Esophageal submucosal tumors (SMTs) are rare heterogenous clinical entities. The surgical resection can be performed in different surgical approaches. However, the robotic surgical strategy is poorly documented in the treatment of SMTs. We present our series of operated esophageal SMTs approached via robotic-assisted surgery. Six patients with symptomatic esophageal submucosal tumors underwent robotic surgery within a 3-year period. The performed procedures were robotic-assisted enucleation, robotic esophagectomy (RAMIE) and reverse hybrid robotic esophagectomy. Patients' clinical data, intra/postoperative outcomes, and histopathological features were retrieved from the institution's prospective database. Five of six patients were scheduled for upfront surgery: four underwent robotic enucleation (three leiomyoma and one suspected GIST) and one underwent reverse hybrid robotic esophagectomy (suspected GIST). One patient, diagnosed with GIST, was treated with neoadjuvant Imatinib therapy, before undergoing a RAMIE. No major intra-operative complications were recorded. Median length of stay was 7 days (6-50), with a longer post-operative course in patients who underwent esophagectomy. Clavien-Dindo > 3a complications occurred in two patients, aspiration pneumonia and delayed gastric emptying. The final histopathological and immuno-histochemical diagnosis were leiomyoma, well-differentiated GIST, low-grade fibromyxoid sarcoma and Schwannoma. Robotic-assisted surgery seems to be a promising option for surgical treatment strategies of benign or borderline esophageal submucosal tumors.

End to side circular stapled anastomosis during robotic-assisted Ivor Lewis minimally invasive esophagectomy (RAMIE).

Robotic-assisted minimally invasive esophagectomy (RAMIE) represents an established approach for the treatment of esophageal cancer. Aim of this study is to evaluate the feasibility and safety of our technique for performing the intrathoracic anastomosis during RAMIE.All the procedures were performed by the same surgeon using the same technique for performing the intrathoracic anastomosis. Intraoperative and postoperative outcomes were recorded. Postoperative complications were classified according to the Esophagectomy Complications Consensus Group (ECCG); the primary outcome was the evaluation of the feasibility and safety of our technique. From 2016 to 2021, 204 patients underwent Ivor Lewis RAMIE at our Center. Two patients (0.9%) were converted during the thoracic phase. The anastomosis was completed in all the other patients forming complete anastomotic rings. The median duration for the robotic-assisted thoracoscopic phase was 224 minutes. Twenty-two of the RAMIE-Ivor Lewis patients had an anastomotic leakage (10.3%). The overall 90-day postoperative mortality was 1.9%. The procedure resulted to be feasible and safe in our cohort of patients.