Multicenter study on the incidence and treatment of mediastinal leaks after esophagectomy (MuMeLe 2).

BACKGROUND: Management of mediastinal anastomotic leaks (MALs) after Ivor Lewis esophagectomy includes conservative, endoscopic, or surgical management. Endoscopic vacuum therapy (EVAC) is becoming a routine approach for MALs, although the outcomes have not been defined. This study aimed to describe the incidence, treatment, and outcomes of MALs in patients who underwent esophagectomy in 3 Italian high-volume centers that routinely use EVAC for MAL. METHODS: Patients who underwent Ivor Lewis esophagectomy between September 2018 and March 2023 were included. RESULTS: A total of 681 patients underwent Ivor Lewis esophagectomy, of whom 88 had MAL. The MAL rates for open, minimally invasive, and robotic esophagectomies were 11.5%, 13.4%, and 14.8%, respectively. Global and specific 30- and 90-day mortality rates for MAL were 0.9% and 2.1% and 6.8% and 15.9%, respectively. Nonoperative management (NOM) as the primary treatment was chosen for 62 patients. EVAC was the most common NOM (62.9%), and the most common operative management (OM) was anastomotic redo (53.8%). Diversion was the OM for 7 patients, of whom 3 patients died. Primary treatment proved successful in 40 patients. Among them, EVAC alone was successful in 35.9% of patients. Globally, endoscopic treatment, including EVAC, was successful in 79.0% of NOM and 55.7% of MALs. NOM and OM were chosen as secondary treatments for 27 and 10 patients, respectively. Secondary treatment proved successful in 21 patients. CONCLUSION: The incidence of MALs after Ivor Lewis esophagectomy is approximately 13%. Endoscopic techniques have a success rate of almost 80%, with EVAC representing a significant part of this treatment process.

Clinical predictors of postoperative complications in the context of enhanced recovery (ERAS) in patients with esophageal and gastric cancer.

The overall frequency of postoperative complications in patients with esophageal and gastric cancer diverges between studies. We evaluated the frequency and assessed the relationship between complications and demographic and clinical features. For this observational study, data were extracted from the ERAS Registry managed by the University of Verona, Italy. Patients were evaluated and compared for postoperative complications according to the consensus-based classification and the Clavien-Dindo scale. The study population was 877 patients: 346 (39.5%) with esophageal and 531 (60.5%) with gastric cancer; 492 (56.2%) reported one or more postoperative complications, 213 (61.6%) of those with esophageal and 279 (52.5%) of those with gastric cancer. When stratified by consensus-based classification, patients with esophageal cancer reported general postoperative complications more frequently (p < 0.001) than those with gastric cancer, but there was no difference in postoperative surgical complications between the two groups. Multiple logistic regression models revealed an association between postoperative complications and the Charlson Comorbidity Index (adjusted odds ratio [OR] 1.22; 95% confidence interval [CI] 1.08-1.36), operation time (adjusted OR, 1.08; 95% CI 1.00-1.15), and days to solid diet intake (adjusted OR, 1.39; 95% CI 1.20-1.59). Complications in patients with esophageal and gastric cancer are frequent, even in those treated according to ERAS principles, and are often associated with comorbidities, longer operative time, and longer time to solid diet intake.

The effect of aging on short- and long-term results after esophagectomy: an international multicenter retrospective analysis.

The optimal treatment for esophageal cancer in elderly patients is still debated and data on postoperative results are limited. This retrospective international study aims to clarify the impact of age on clinical and oncological outcomes after esophagectomy. All patients that underwent esophagectomy for cancer between 2007 and 2016 at two European high-volume Centers have been included in the study. Patients were divided into three groups according to their age: young-age group (YAG) (18-69), middle-age group (70-74) and old-age group (>74). Primary outcome was 5-year overall survival (OS), while secondary outcomes considered were 5-year disease free survival and disease related survival, 90-day morbidity and mortality, readmission rate and radicality. A total of 575 patients were included. No differences emerged in terms of morbidity and length of stay, while mortality increased with aging from 2% in YAG to 4.8% in old-aged (P = 0.003). Old-age patients had less neoadjuvant treatment (P < 0.001), a less aggressive mediastinal lymphadenectomy and presented a more advanced pathological stage. As expected, OS decreased significantly for older patients compared with the other two age groups (P = 0.044) but, on the other hand, disease free and disease related survival were comparable between the groups. Age itself should not be considered a contraindication to esophagectomy. Although in patients older than 75 years postoperative mortality is significantly increased, esophagectomy could be still an option in selected patients, favoring the use of minimally invasive techniques and enhanced recovery protocols.

Active surveillance for clinical complete responders after chemoradiotherapy for oesophageal squamous cell carcinoma.

BACKGROUND: Guidelines on the treatment of oesophageal squamous cell carcinoma (SCC) recommend neoadjuvant chemoradiotherapy plus surgery or definitive chemoradiotherapy. The aim of this study was to evaluate the outcome of patients with a cCR after chemoradiotherapy who underwent active surveillance. METHODS: Patients with oesophageal SCC who were treated with chemoradiotherapy between January 2016 and June 2022 were identified from an institutional database. Survival and recurrence of patients with a cCR who underwent active surveillance were compared with those of patients who underwent planned surgery. Survival was calculated according to the Kaplan-Meier method and compared between groups using the log rank test. RESULTS: The 37 patients who underwent active surveillance were older and tumours were more often located in the middle/upper-third of the oesophagus than in the surgery group of 57 patients. Median follow-up was 28.1 (i.q.r. 17.2-47.1) months for the active surveillance group and 20 (12.9-39.1) months for the surgery group. Overall survival was comparable between the two groups, with 3-year survival rates of 50 (95% c.i. 31 to 67) and 59 (40 to 73)% for the active surveillance and surgery groups respectively (P = 0.55). Three-year progression-free survival for patients who underwent active surveillance was better than in the surgery group: 70 (43 to 85) versus 58 (40 to 72)% (P = 0.02). Overall and progression-free survival was comparable between patients in the active surveillance group and 23 patients in the surgery group who had a pCR (ypT0 N0). The overall recurrence rate was comparable between the groups: 7 of 37 (19.4%) in active surveillance group versus 16 of 49 (32.6%) in surgery group (P = 0.26). Locoregional recurrence was noted more often in the active surveillance group and systemic recurrence in the surgery group. CONCLUSION: Active surveillance is feasible and safe for patients with oesophageal SCC who have a cCR after chemoradiotherapy.

The "Weekday Effect" on Enhanced Recovery after Surgery Protocol for Gastrectomy.

INTRODUCTION: While enhanced recovery after surgery (ERAS) protocol demonstrated to improve outcomes after gastrectomy, some papers evidenced a detrimental effect on postoperative morbidity related to the "weekday effect." We aimed to understand whether the day of gastrectomy could affect postoperative outcomes and compliance with ERAS items. METHODS: We included all patients that underwent gastrectomy for cancer between January 2017 and September 2021. Cohort was divided considering the day of surgery: Early group (Monday-Wednesday) and Late group (Thursday-Friday). Compliance with protocol and postoperative outcomes were compared. RESULTS: Two hundred twenty-seven patients were included in Early group, while 154 were in Late group. The groups were comparable in preoperative characteristics. No significant difference in pre/intraoperative and postoperative ERAS items' compliance was apparent between Early and Late groups, with most items exceeding the 70% threshold. Median length of stay was 6.5 days and 6 days in Early and Late groups (p = 0.616), respectively. Morbidity was 50% in both groups, with severe complications that occurred in 13% of Early patients and 15% of Late patients. Ninety-day mortality was 2%, and it was similar between the two groups. CONCLUSIONS: In a center with a standardized ERAS protocol, the weekday of gastrectomy has no significant impact on the success of each ERAS item and on postoperative surgical and oncological outcomes.

Robotic versus open Ivor-Lewis esophagectomy: A more accurate lymph node dissection without burdening the leak rate.

BACKGROUND: Robotic-assisted minimally invasive esophagectomy (RAMIE) combines the beneficial effects of minimally invasive surgery on postoperative complications, especially on pulmonary ones, with the safety of the anastomosis performed in open surgery. Moreover, RAMIE could allow a more accurate lymphadenectomy. METHODS: We reviewed our database to identify all patients with adenocarcinoma of the esophagus treated by Ivor-Lewis esophagectomy in the period January 2014 to June 2022. Patients were divided according to the thoracic approach into RAMIE and open esophagectomy (OE) groups. We compared the groups for early surgical outcomes, 90-day mortality as well as R0 rate, and the number of lymph nodes harvested. RESULTS: We identified 47 patients in RAMIE and 159 patients in the OE group. Baseline characteristics were comparable. Operative time was significantly longer for RAMIE procedures (p < 0.01); however, we did not observe the difference in overall (RAMIE 55.5% vs. OE 61%, p = 0.76) and severe complications rate (RAMIE 17% vs. OE 22.6%, p = 0.4). The anastomotic leak rate was 2.1% after RAMIE and 6.9% after OE (p = 0.56). We did not report the difference in 90-day mortality (RAMIE 2.1% vs. OE 1.9%, p = 0.65). In the RAMIE group, we observed a significantly higher number of thoracic lymph nodes harvested, with a median of 10 lymph nodes in the RAMIE group versus 8 in the OE group (p < 0.01). CONCLUSIONS: In our experience, RAMIE has morbimortality rates comparable to OE. Moreover, it allows a more accurate thoracic lymphadenectomy which results in a higher thoracic lymph nodes retrieval rate.

Treatment of EGJ Cancer within or outside Clinical Trials: Does the Setting Matter? A Monocentric Prospective Observational Study.

INTRODUCTION: RCTs support neoadjuvant chemoradiotherapy (nCRT) followed by surgery in locally advanced esophago-gastric junction (LA-EGJ) adenocarcinoma. However, RCTs are performed in highly controlled settings with limited representativeness of real-life patients (RLS). The aim of the study was to compare the outcomes in RLS and clinical trial settings. METHODS: The outcomes of RLS, which comprised 125 patients consequently treated for LA-EGJ adenocarcinoma between 2012 and 2017, were compared with the phase II trial (PIIS), performed on 65 patients from 2003 to 2011. RESULTS: About half of RLS (51.2%) were treated with nCRT according to VR protocol, 20.8% with standard CRT according to CROSS/Al-Sarraf, 20% with chemotherapy (CT) alone. pCR was 36.8%, 28.6%, and 9.1% after VR protocol, standard CRT, and CT, respectively (p = 0.082), while 3-year overall survival (OS) was 58.6% (95% CI 43.2-71.1%), 32.8% (14.6-52.4%), and 44.8% (21.3-65.9%), respectively (p = 0.030). With respect to PIIS, RLS had a higher proportion of cN+ (94% vs. 54%; p < 0.001) and a lower proportion of pCR after CT/CRT (23% vs. 39%; p = 0.041). Three-year OS was slightly higher, although not significantly, in PIIS (58.9%, 45.1-70.2%) than RLS (47.9%, 37.4-57.7%) and nearly identical to 3-year OS in RLS treated with VR protocol. CONCLUSION: Real-life patients with EGJ adenocarcinoma have more advanced cancer at baseline, lower pathologic response to neoadjuvant treatment than patients enrolled in clinical trials, but similar survival.

Risk Factors, Diagnosis and Management of Chyle Leak Following Esophagectomy for Cancers: An International Consensus Statement.

This Delphi exercise aimed to gather consensus surrounding risk factors, diagnosis, and management of chyle leaks after esophagectomy and to develop recommendations for clinical practice. Background: Chyle leaks following esophagectomy for malignancy are uncommon. Although they are associated with increased morbidity and mortality, diagnosis and management of these patients remain controversial and a challenge globally. Methods: This was a modified Delphi exercise was delivered to clinicians across the oesophagogastric anastomosis collaborative. A 5-staged iterative process was used to gather consensus on clinical practice, including a scoping systematic review (stage 1), 2 rounds of anonymous electronic voting (stages 2 and 3), data-based analysis (stage 4), and guideline and consensus development (stage 5). Stratified analyses were performed by surgeon specialty and surgeon volume. Results: In stage 1, the steering committee proposed areas of uncertainty across 5 domains: risk factors, intraoperative techniques, and postoperative management (ie, diagnosis, severity, and treatment). In stages 2 and 3, 275 and 250 respondents respectively participated in online voting. Consensus was achieved on intraoperative thoracic duct ligation, postoperative diagnosis by milky chest drain output and biochemical testing with triglycerides and chylomicrons, assessing severity with volume of chest drain over 24 hours and a step-up approach in the management of chyle leaks. Stratified analyses demonstrated consistent results. In stage 4, data from the Oesophagogastric Anastomosis Audit demonstrated that chyle leaks occurred in 5.4% (122/2247). Increasing chyle leak grades were associated with higher rates of pulmonary complications, return to theater, prolonged length of stay, and 90-day mortality. In stage 5, 41 surgeons developed a set of recommendations in the intraoperative techniques, diagnosis, and management of chyle leaks. Conclusions: Several areas of consensus were reached surrounding diagnosis and management of chyle leaks following esophagectomy for malignancy. Guidance in clinical practice through adaptation of recommendations from this consensus may help in the prevention of, timely diagnosis, and management of chyle leaks.

Current practice on the use of prophylactic drain after gastrectomy in Italy: the Abdominal Drain in Gastrectomy (ADiGe) survey.

Evidence against the use of prophylactic drain after gastrectomy are increasing and ERAS guidelines suggest the benefit of drain avoidance. Nevertheless, it is unclear whether this practice is still widespread. We conducted a survey among Italian surgeons through the Italian Gastric Cancer Research Group and the Polispecialistic Society of Young Surgeons, aiming to understand the current use of prophylactic drain. A 28-item questionnaire-based survey was developed to analyze the current practice and the individual opinion about the use of prophylactic drain after gastrectomy. Groups based on age, experience and unit volume were separately analyzed. Response of 104 surgeons from 73 surgical units were collected. A standardized ERAS protocol for gastrectomy was applied by 42% of the respondents. Most of the surgeons, regardless of age, experience, or unit volume, declared to routinely place one or more drain after gastrectomy. Only 2 (1.9%) and 7 surgeons (6.7%) belonging to high volume units, do not routinely place drains after total and subtotal gastrectomy, respectively. More than 60% of the participants remove the drain on postoperative day 4-6 after performing an assessment of the anastomosis integrity. Interestingly, less than half of the surgeons believe that drain is the main tool for leak management, and this percentage further drops among younger surgeons. On the other hand, drain's role seems to be more defined for duodenal stump leak treatment, with almost 50% of the surgeons recognizing its importance. Routine use of prophylactic drain after gastrectomy is still a widespread practice even if younger surgeons are more persuaded that it could not be advantageous.

Transthoracic esophagectomy compared to transhiatal extended gastrectomy for adenocarcinoma of the esophagogastric junction: a multicenter retrospective cohort study.

Optimal surgical treatment for Siewert type II esophagogastric junction adenocarcinoma is debated. The aim of this study was to compare transhiatal extended gastrectomy (TEG) and transthoracic esophagectomy (TTE). Patients with Siewert type II tumors who underwent a resection by TEG or TTE in two centers (Erasmus University Medical Center, Rotterdam, and University of Verona) between 2014 and 2019 were identified. To limit selection bias, patients were matched for baseline characteristics and compared with a multivariable logistic regression model. Some 159 patients treated by TEG (60 patients, 37.7%) or TTE (99 patients, 62.3%) were included. Patients in the TEG group were older, had less tumor invasion of the esophagus, and were more often excluded from neoadjuvant therapy. Post-operative morbidity was comparable (P = 0.88), while 90-day mortality was higher after TEG (90-day mortality 10.0% in TEG group vs. 2.0% in TTE group P = 0.01). R0 resection was achieved in 83.3% of patients after TEG and in 97.9% after TTE (P < 0.01), with the proximal resection margin involved in 16.6% of patients after TEG versus 0 in TTE group (P < 0.01). The 3-year overall survival was comparable (TEG: 36.5%, TTE: 48.4%, P = 0.12). At multivariable analysis, (y)pT category was an independent risk factor for 3-year recurrence. After matching, TEG was still associated with an increased risk of incomplete tumor resection (P = 0.03) and proximal margin involvement (P < 0.01), while there were no differences in post-operative morbidity (P = 0.56) and mortality (P = 0.31). Our data suggest that patients with Siewert type II tumors treated by TEG are exposed to a higher risk of positive proximal resection margin compared to TTE.

Enhanced Recovery After Surgery can Improve Patient Outcomes and Reduce Hospital Cost of Gastrectomy for Cancer in the West: A Propensity-Score-Based Analysis.

BACKGROUND: Data on ERAS for gastrectomy are scarce, and the majority of the studies come from Eastern countries. Patients in the West are older and suffer from more advanced tumors that impair their clinical condition and often require neoadjuvant treatment. This retrospective study assessed the feasibility and safety of an Enhanced Recovery After Surgery (ERAS) protocol for gastrectomy in a Western center. METHODS: We conducted a single-center study of 351 patients operated for gastric cancer: 103, operated from January 2015 to December 2016, followed the standard pathway, while 248, operated from January 2017 to December 2019, followed the ERAS program. The primary outcomes considered were length of hospital stay (LOS) and direct costs. Secondary outcomes were 90-day morbidity and mortality, readmission rate, and compliance with ERAS items. A propensity score (PS) was built on confounding variables. RESULTS: Compliance with ERAS items after the program was ≥ 70%. Univariable analysis evidenced a 2-day median reduction in LOS and a median cost reduction of €826 per patient in the ERAS group. PS-based multivariable analysis confirmed a significant, 2-day decrease in median LOS and a €1097 saving after ERAS introduction. Ninety-day mortality decreased slightly in ERAS group, while complications and readmissions did not change significantly. When complications were included in the multivariable analysis, ERAS retained its significance, although the effects on LOS and cost were blunted to a median reduction of 1 day and €775, respectively. CONCLUSIONS: ERAS for gastrectomy improved patients' recovery and reduced hospital costs without changes in morbidity, mortality, or readmission.

Does Pathological Stage and Nodal Involvement Influence Long Term Oncological Outcomes after CROSS Regimen for Adenocarcinoma of the Esophagogastric Junction? A Multicenter Retrospective Analysis.

Background:After the results reported by the "Chemoradiotherapy for esophageal Cancer Followed by Surgery Study" (CROSS) trial, neo-adjuvant chemoradiotherapy became the standard treatment for locally advanced cancers of esophagus and gastroesophageal junction (GEJ). Excellent results were reported for squamocellular carcinomas (SCCs). Since the advent of the CROSS regimen, the results of surgery for esophageal adenocarcinomas (EAC) have cast some doubts about its efficacy on overall survival (OS) even in the presence of local response. This study evaluated the relation between pathological (yp) stage after CROSS regimen followed by surgery for adenocarcinoma of cardia and overall (OS) and disease-free survival (DFS). Sites of relapse after surgery were also analyzed. Methods: Patients submitted to the CROSS regimen for locally advanced EAC of the cardia followed by transthoracic esophagectomy were analyzed. Actuarial OS and DFS were analyzed and stratified according to yp stage. The site of relapse, distal and local, was also analyzed. Results: The study included 132 patients. The 50-month OS and DFS were 45% and 6.7%, respectively. No differences emerged analyzing OS according to yp stage. Time to relapse was significantly longer for yp Stage I and II, and for yp N0, compared with yp N+. Recurrence occurred in 48 cases (36.3%) with a 9 months median time to relapse. Local and distal relapse were 10 (7.5%) and 38 (28.7%) cases, respectively (p ≦ 0.001). Conclusions: Pathological stage after CROSS regimen does not relate to OS and DFS. Time to recurrence is significantly longer for yp Stages I and II and ypN0. Chemoradiotherapy in a neoadjuvant setting may influence the site of relapse, significantly reducing local recurrences.

Effect of Pyloroplasty on Gastric Conduit Emptying and Patients' Quality of Life After Ivor Lewis Esophagectomy.

Background: Delayed gastric emptying (DGE) is a common complication after esophagectomy with gastric tube reconstruction. It is still unclear whether a pyloric drainage procedure might reduce the risk of DGE. Methods: We identified in our database all patients subjected to Ivor Lewis esophagectomy after neoadjuvant chemoradiotherapy in the period 2000-2012. In the period 2000-2009, we performed a routine pyloroplasty (pyloroplasty group, PP group, 15 patients), after 2009 we did not perform any type of pyloric drainage procedure (nonpyloroplasty group, NPP group, 11 patients). We compared the groups with subjective questionnaires to assess the perceived quality of life (QoL) (QLQ-C30 and OES-18) and with objective test to study the gastric tube emptying (timed barium swallow test, scintigraphy, 24 hours' pH-metry). Results: No difference was observed in questionnaires QLC-C30 and OES-18 scores: 73% of patients in PP group and 63% in NPP group scored their overall QoL as good to excellent (QLC-C30). We did not report difference in timed barium swallow test results and in scintigraphy results. Twenty-four-hour pH-metry results showed in PP group a nonsignificant higher number of acid reflux episodes (NPP group 23.2 ± 9.5 versus PP group 41.3 ± 10.7, P = .29) and a longer time with pH <4 (NPP group 0.89% ± 1.6% versus PP group 3.1% ± 2.1%, P = .24). Conclusions: In our series, pyloroplasty was not associated with improved long-term QoL nor with better gastric conduit emptying. Further studies are needed to confirm these findings.

Effectiveness of endoscopic vacuum therapy as rescue treatment in refractory leaks after gastro-esophageal surgery.

The treatment of leak after esophageal and gastric surgery is a major challenge. Over the last few years, endoscopic vacuum therapy (E-VAC) has gained popularity in the management of this life-threatening complication. We reported our initial experience on E-VAC therapy as rescue treatment in refractory anastomotic leak and perforation after gastro-esophageal surgery. From September 2017 to December 2019, a total of 8 E-VAC therapies were placed as secondary treatment in 7 patients. Six for anastomotic leak (3 cervical, 1 thoracic, 2 abdominal) and 1 for perforation of the gastric conduit. In 6 cases, E-VAC was placed intracavitary; while in the remaining 2, the sponge was positioned intraluminal (one patient was treated with both approaches). A total of 60 sponges were used in the whole cohort. The median number of sponge insertions was 10 (range: 5-14) with a median treatment duration of 41 days (range: 19-49). A complete healing was achieved in 4 intracavitary (67%) and in 1 intraluminal (50%) E-VAC. We observed only one E-VAC-related complication: a bleeding successfully managed endoscopically. E-VAC therapy seems to be a safe and effective tool in the management of leaks and perforations after upper GI surgery, although with longer healing time when it is used as secondary treatment.

RAMIE: tradition drives innovation-feasibility of a robotic-assisted intra-thoracic anastomosis.

Due to the difficulties in the intra-thoracic esophagogastric anastomosis creation, totally minimally invasive Ivor Lewis esophagectomy (MIE) did not encountered a large diffusion, preferring hybrid techniques or cervical anastomosis. Robot-assisted minimally invasive esophagectomy (RAMIE) has gained popularity due to an easy reproducibility of the open anastomotic technique. In this feasibility study, we described the RAMIE technique introduced in our Center, providing innovative details for a mechanical end-to-end anastomosis. With patient in prone position, esophagectomy is conducted through the meso-esophagus plan. Robotic hand-sewn purse-string is realized above Azygos vein. A 4-cm thoracotomy in the fifth intercostal space is performed by enlarging the trocar incision. The tubulization is performed to create an access pouch for the introduction of the circular stapler. After the creation of the end-to-end anastomosis, the access pouch is resected and a robotic over-sewn is realized. From January 2020 until July 2020, ten patients were enrolled. No restriction in term of age, BMI, ASA grade or previous surgery were applied. Median operative time was 700 min. R0 resection was achieved in all cases with a good lymph node harvesting. No anastomotic leak or stricture were observed. One chyle leak was treated conservatively. Median length of stay was 8 days and 90 days mortality was 0%. This study evidenced how robotic surgery allowed us to perform the same anastomosis of our open technique with good oncological results and morbidity and length of stay comparable with our previous results. Of note, longer operative time has been recorded. Further studies after the completion of the learning curve are necessary to address more definite conclusions.

Impact of COVID-19 outbreak on esophageal cancer surgery in Northern Italy: lessons learned from a multicentric snapshot.

Coronavirus Disease-19 (COVID-19) outbreak has significantly burdened healthcare systems worldwide, leading to reorganization of healthcare services and reallocation of resources. The Italian Society for Study of Esophageal Diseases (SISME) conducted a national survey to evaluate changes in esophageal cancer management in a region severely struck by COVID-19 pandemic. A web-based questionnaire (26 items) was sent to 12 SISME units. Short-term outcomes of esophageal resections performed during the lockdown were compared with those achieved in the same period of 2019. Six (50%) centers had significant restrictions in their activity. However, overall number of resections did not decrease compared to 2019, while a higher rate of open esophageal resections was observed (40 vs. 21.7%; P = 0.034). Surgery was delayed in 24 (36.9%) patients in 6 (50%) centers, mostly due to shortage of anesthesiologists, and occupation of intensive care unit beds from intubated COVID-19 patients. Indications for neoadjuvant chemo (radio) therapy were extended in 14% of patients. Separate COVID-19 hospital pathways were active in 11 (91.7%) units. COVID-19 screening protocols included nasopharyngeal swab in 91.7%, chest computed tomography scan in 8.3% and selective use of lung ultrasound in 75% of units. Postoperative interstitial pneumonia occurred in 1 (1.5%) patient. Recovery from COVID-19 pandemic was characterized by screening of patients in all units, and follow-up outpatient visits in only 33% of units. This survey shows that clinical strategies differed considerably among the 12 SISME centers. Evidence-based guidelines are needed to support the surgical esophageal community and to standardize clinical practice in case of further pandemics.

18F-FDG PET/CT Metrics Are Correlated to the Pathological Response in Esophageal Cancer Patients Treated With Induction Chemotherapy Followed by Neoadjuvant Chemo-Radiotherapy.

BACKGROUND AND OBJECTIVE: The aim of this study was to assess the ability of Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography (18F-FDG PET/CT) to provide functional information useful in predicting pathological response to an intensive neoadjuvant chemo-radiotherapy (nCRT) protocol for both esophageal squamous cell carcinoma (SCC) and adenocarcinoma (ADC) patients. MATERIAL AND METHODS: Esophageal carcinoma (EC) patients, treated in our Center between 2014 and 2018, were retrospectively reviewed. The nCRT protocol schedule consisted of an induction phase of weekly administered docetaxel, cisplatin, and 5-fluorouracil (TCF) for 3 weeks, followed by a concomitant phase of weekly TCF for 5 weeks with concurrent radiotherapy (50-50.4 Gy in 25-28 fractions). Three 18F-FDG PET/CT scans were performed: before (PET1) and after (PET2) induction chemotherapy (IC), and prior to surgery (PET3). Correlation between PET parameters [maximum and mean standardized uptake value (SUVmax and SUVmean), metabolic tumor volume (MTV), and total lesion glycolysis (TLG)], radiomic features and tumor regression grade (TGR) was investigated. RESULTS: Fifty-four patients (35 ADC, 19 SCC; 48 cT3/4; 52 cN+) were eligible for the analysis. Pathological response to nCRT was classified as major (TRG1-2, 41/54, 75.9%) or non-response (TRG3-4, 13/54, 24.1%). A major response was statistically correlated with SCC subtype (p = 0.02) and smaller tumor length (p = 0.03). MTV and TLG measured prior to IC (PET1) were correlated to TRG1-2 response (p = 0.02 and p = 0.02, respectively). After IC (PET2), SUVmean and TLG correlated with major response (p = 0.03 and p = 0.04, respectively). No significance was detected when relative changes of metabolic parameters between PET1 and PET2 were evaluated. At textural quantitative analysis, three independent radiomic features extracted from PET1 images ([JointEnergy and InverseDifferenceNormalized of GLCM and LowGrayLevelZoneEmphasis of GLSZM) were statistically correlated with major response (p < 0.0002). CONCLUSIONS: 18F-FDG PET/CT traditional metrics and textural features seem to predict pathologic response (TRG) in EC patients treated with induction chemotherapy followed by neoadjuvant chemo-radiotherapy. Further investigations are necessary in order to obtain a reliable predictive model to be used in the clinical practice.

Long-Term Outcomes of Induction Chemotherapy Followed by Chemo-Radiotherapy as Intensive Neoadjuvant Protocol in Patients with Esophageal Cancer.

BACKGROUND: A phase II intensive neoadjuvant chemo-radiotherapy (nCRT) protocol for esophageal cancer (EC) was previously tested at our Center with promising results. We here present an observational study to evaluate the efficacy of the protocol also in "real life" patients. METHODS: We retrospectively reviewed 122 ECs (45.1% squamous cell (SCC) and 54.9% adenocarcinoma (ADC)) treated with induction docetaxel, cisplatin, and 5-fluorouracil (TCF), followed by concomitant TCF and radiotherapy (50-50.4 Gy/25-28 fractions), between 2008 and 2017. Primary endpoints were overall survival (OS), event-free survival (EFS) and pathological complete response (pCR). RESULTS: With a median follow-up of 62.1 months (95% CI 50-67.6 months), 5-year OS and EFS rates were 54.8% (95% CI 44.7-63.9) and 42.7% (95% CI 33.1-51.9), respectively. A pCR was observed in 71.1% of SCC and 37.1% of ADC patients (p = 0.001). At multivariate analysis, ypN+ was a significant prognostic factor for OS (Hazard Ratios (HR) 4.39 [95% CI 2.36-8.18]; p < 0.0001), while pCR was a strong predictor of EFS (HR 0.38 [95% CI 0.22-0.67]; p < 0.0001). CONCLUSIONS: The nCRT protocol achieved considerable long-term survival and pCR rates also in "real life" patients. Further research is necessary to evaluate this protocol in a watch-and-wait approach.

Gastric conduit perforation after Ivor Lewis esophagectomy successfully treated with endoscopic vacuum therapy (E-VAC): a case report.

Gastric conduit perforation is a life-threatening complication after esophagectomy and currently there is no consensus about its optimal management. Endoscopic vacuum therapy (E-VAC) is a promising technique for the treatment of leaks and perforations after upper gastro-intestinal surgery. We report the case of a 65 years-old male patient who underwent an Ivor Lewis esophagectomy for esophago-gastric junction adenocarcinoma. He referred to our Emergency Department for septic shock and right hydropneumothorax. We performed an emergency thoracoscopy with intraoperative esophagogastroduodenoscopy which showed a pre-pyloric perforation of the gastric conduit. The perforation was initially treated with unsuccessful primary surgical closure and subsequently by means of E-VAC, firstly placed intraluminal and then intracavitary. With the latter technique, we assisted to a progressive clinical improvement until the definitive healing of the perforation. To our knowledge, this is the first case of a gastric tube perforation after esophagectomy successfully treated with E-VAC.

Feasibility and safety of an enhanced recovery protocol (ERP) for upper GI surgery in elderly patients (≥ 75 years) in a high-volume surgical center.

Enhanced recovery protocols (ERP) have demonstrated their efficacy after esophagectomy and gastrectomy but little is known about their feasibility and safety in elderly patients. Patients submitted to Ivor-Lewis esophagectomy or gastrectomy for cancer between January 2016 and June 2019 were divided into three age groups: young-age group, YG (≤ 65 years, n = 130); middle-age group, MG (66-74 years, n = 101); old-age group, OG (≥ 75 years, n = 74). The groups were compared for adherence to our ERP, morbidity and mortality rates. After esophagectomy, adherence to ERP was comparable between the three groups, overall morbidity was higher in OG, without statistically significant difference, while the incidence of cardiac complications was significantly higher in OG (p = 0.02). After gastrectomy, OG presented a lower adherence to urinary catheter removal and to early mobilization. No difference in overall morbidity rate was observed (p = 0.13). The median length of stay was comparable both after esophagectomy (p = 0.075) and gastrectomy (p = 0.07). Multivariable analysis showed that age ≥ 75 years was not associated with a higher risk of ERP failure either after esophagectomy (p = 0.59) or after gastrectomy (p = 0.83). After esophagectomy, the risk of failure of the ERP program was higher for patients with ASA grade 3-4 (p = 0.03) and for those with postoperative complications (p < 0.001) while after gastrectomy only postoperative complications were associated to higher risk of ERP failure (p < 0.001). In our series, adherence to ERP protocol of patients ≥ 75 years old was similar to that of younger patients after esophagectomy and gastrectomy, without a significant increase in morbi-mortality rates.