Enhanced recovery protocol in esophagectomy, is it really worth it? A cost analysis related to team experience and protocol compliance.

Application of enhanced recovery protocols (ERP) in esophageal surgery seems to lead an advantage in terms of length of hospital staying and outcomes, but only few data exist on its cost effectiveness. Previous literature analyzed pre- and post-ERP groups, finding a cost reduction with the introduction of the pathway. We aimed to study the influence on costs of accumulating experience and compliance in an ERP group. Seventy-one patients have been treated at our institution from January 2014 to June 2017 with our ERP for Ivor-Lewis esophagectomy. Direct costs were divided into subcategories and were analyzed as a function of calendar year and compliance. Factor affecting costs were searched. Univariable analysis highlighted a significant reduction in costs over time. Increase in compliance led to a progressive cost reduction for each ERP item completed (€14 852-€11 045). While age was not found to significantly influence the cost (p = 0.341), complications seemed to nullify the effect of experience: the median was €11 507 in uncomplicated patients, and increased to €13 791 in Clavien-Dindo 3-4 (CD3-4) patients. Compliance and CD3-4 remained significant also in multivariable analysis, accomplished by quantile regression, while year of surgery lost its significance. Our results evidence how accumulating experience in ERP led to a cost reduction over time, which was mainly mediated by an increase in compliance. Indeed, compliance was the main factor in reducing ERP cost while CD3-4 complications were the most important factor in cost increasing, nullifying the benefit of compliance.

Genetic prediction of long-term survival after neoadjuvant chemoradiation in locally advanced esophageal cancer.

Candidate genes involved in DNA repair, 5-fluorouracil metabolism and drug detoxification were genotyped in 124 patients receiving neoadjuvant chemoradiation treatment for locally advanced esophageal cancer and their predictive role for long-term relapse-free survival (RFS) and cancer-specific survival (CSS) were evaluated. A panel including MTHFR 677TT, MDR1 2677GT, GSTP1 114CC, XPC 499CC and XPC 939AC+CC, defined as high-risk genotypes, discriminated subgroups with significantly different outcomes. When the panel was combined with histology, patients split into two subsets with 5-year RFS and CSS rates of 65% vs 27% (hazard ratio (HR) 3.0, P<0.0001) and 69% vs 31% (HR 2.9, P<0.0001), respectively. Combining the 5-single-nucleotide polymorphism (5-SNP) panel with pathological response defined two major informative risk classes with 5-year PFS and CSS rates of 79.4% vs 17.7% (HR 6.71, P<0.0001) and 79.3% vs 26.3% (HR 6.25, P<0.0001), respectively. This classification achieved a sensitivity of 79%, a specificity of 85.4% and an accuracy of 81.8%.

Enhanced recovery after surgery protocol in patients undergoing esophagectomy for cancer: a single center experience.

This article is about an emerging issue in esophageal surgery: enhanced recovery after surgery (ERAS) Few data are published in literature and its safety and feasibility is still debated. The focus of our paper is on the feasibility of an ERAS protocol for esophagectomy (including both the Ivor-Lewis and McKeown procedure) in a high volume center comparing to a standard perioperative protocol. We introduced a novelty item on this type of surgery: resume of oral feeding in the first postoperative day. We analyzed the dropout rate for each item and the postoperative morbidity. We studied 39 patients operated in the Upper GI division of Verona University Hospital between January 2013 and August 2014; 22 patients (ERAS group) were studied in a perspective way while 17 patients (standard group) were studied retrospectively. The enhanced recovery protocol included intraoperative fluid management, time of extubation after surgery, intensive care unit discharge, drains and nasogastric tube management, mobilization of the patient, oral food intake. We compared the results between the two groups in term of hospital stay, postoperative morbidity and mortality. We also calculated the percentage completion of the protocol, evaluating patient drop-out rates for each of the items. Patients showed an improvement in the ERAS group in terms of earlier extubation, earlier intensive care unit discharge (p < 0.01), earlier thoracic drain, urinary catheter (p < 0.01) and nasogastric tube removal (p = 0.02), earlier mobilization (p < 0.01), and resume of oral feeding (p < 0.01). Median length of hospital stays in the ERAS group was 9 days while in the standard group was 10 days (p = 0.23). Postoperative morbidity and mortality were comparable between the two groups. This study shows the feasibility and safety of an ERAS protocol for esophageal surgery in a high-volume center. These data strengthen the literature results on this argument calling for larger sample size studies.

Neoadjuvant concurrent chemoradiotherapy for locally advanced esophageal cancer in a single high-volume center.

BACKGROUND: Neoadjuvant chemoradiotherapy (CRT) is now considered the standard of care by many centers in the treatment of both squamous cell carcinoma (SCC) and adenocarcinoma of the esophagus. This study evaluates the effectiveness of a neoadjuvant CRT protocol, as regards pathological complete response (pCR) rate and long-term survival. METHODS: From 2003 to 2011, at Upper G.I. Surgery Division of Verona University, 155 consecutive patients with locally advanced esophageal cancers (90 SCC, 65 adenocarcinoma) were treated with a single protocol of neoadjuvant CRT (docetaxel, cisplatin, and 5-fluorouracil with 50.4 Gy of concurrent radiotherapy). Response to CRT was evaluated through percentage of pathological complete response (pCR or ypT0N0), overall (OS) and disease-related survival (DRS), and pattern of relapse. RESULTS: One hundred thirty-one patients (84.5 %) underwent surgery. Radical resection (R0) was achieved in 123 patients (79.3 %), and pCR in 65 (41.9 %). Postoperative mortality was 0.7 % (one case). Five-year OS and DRS were respectively 43 and 49 % in the entire cohort, 52 and 59 % in R0 cases, and 72 and 81 % in pCR cases. Survival did not significantly differ between SCC and adenocarcinoma, except for pCR cases. Forty-nine patients suffered from relapse, which was mainly systemic in adenocarcinoma. Only three out of 26 pCR patients with previous adenocarcinoma developed relapse, always systemic. CONCLUSIONS: This study suggests that patients treated with the present protocol achieve good survival and high pCR rate. Further research is necessary to evaluate whether surgery on demand is feasible in selected patients, such as pCR patients with adenocarcinoma.

Utility of Abdominal Drain in Gastrectomy (ADiGe) Trial: study protocol for a multicenter non-inferiority randomized trial.

BACKGROUND: Prophylactic use of abdominal drain in gastrectomy has been questioned in the last 15 years, and a 2015 Cochrane meta-analysis on four RCTs concluded that there was no convincing evidence to the routine drain placement in gastrectomy. Nevertheless, the authors evidenced the moderate/low quality of the included studies and highlighted how 3 out of 4 came from Eastern countries. After 2015, only retrospective studies have been published, all with inconsistent results. METHODS: ADiGe (Abdominal Drain in Gastrectomy) Trial is a multicenter prospective randomized non-inferiority trial with a parallel design. It aimed to verify whether avoiding routine use of abdominal drain is burdened with complications, particularly an increase in postoperative invasive procedures. Patients with gastric cancer, scheduled for subtotal or total gastrectomy with curative intent, are eligible for inclusion, irrespective of previous oncological treatment. The primary composite endpoint is reoperation or percutaneous drainage procedures within 30 postoperative days. The primary analysis will verify whether the incidence of the primary composite endpoint is higher in the experimental arm, avoiding routine drain placement, than control arm, undergoing prophylactic drain placement, in order to falsify or support the null hypothesis of inferiority. Secondary endpoints assessed for superiority are overall morbidity and mortality, Comprehensive Complications Index, incidence and time for diagnosis of anastomotic and duodenal leaks, length of hospital stay, and readmission rate. Assuming one-sided alpha of 5%, and cumulative incidence of the primary composite endpoint of 6.4% in the control arm and 4.2% in the experimental one, 364 patients allow to achieve 80% power to detect a non-inferiority margin difference between the arm proportions of 3.6%. Considering a 10% drop-out rate, 404 patients are needed. In order to have a balanced percentage between total and subtotal gastrectomy, recruitment will end at 202 patients for each type of gastrectomy. The surgeon and the patient are blinded until the end of the operation, while postoperative course is not blinded to the patient and caregivers. DISCUSSION: ADiGe Trial could contribute to critically re-evaluate the role of prophylactic drain in gastrectomy, a still widely used procedure. TRIAL REGISTRATION: Prospectively registered (last updated on 29 October 2020) at ClinicalTrials.gov with the identifier NCT04227951 .

Laparoscopic transhiatal suture and gastric valve as a safe and feasible treatment for Boerhaave's syndrome: an Italian single center case series study.

BACKGROUND: Boerhaave's syndrome (BS) is a rare life-threating condition with poor prognosis. Unfortunately, due to its very low incidence, no clear evidences or definitive guidelines are currently available: in detail, surgical strategy is still a matter of debate. Most of the case series reports thoracic approach as the most widely used; conversely, transhiatal abdominal management is just described in sporadic case reports. In our center, the laparoscopic approach has been adopted for years: in the present study, we aim to show his feasibility by reporting the outcomes of the largest clinical series available to date. METHODS: Clinical records of patients admitted for BS to the General and Upper GI Surgery Division of Verona from February 2014 to December 2019 were retrospectively collected. Clinico-pathological characteristics, preoperative workup, surgical management, and outcomes were analyzed. RESULTS: Seven patients were admitted; epigastric/thoracic pain and vomiting were the most frequent symptoms at diagnosis. Laboratory findings were not specific; conversely, radiological imaging always revealed abnormal findings: particularly, CT had excellent sensitivity in detecting signs of esophageal perforation. All but one case had diagnostic workup and received surgery within 24 h. Every patient had laparoscopic transhiatal direct suture and gastric valve; 2 patients (28.6%) also needed a thoracoscopic toilette. Postoperative complications occurred in 4 patients (57%), but in only two of them (29%), the complication was severe according to Clavien-Dindo classification (both received thoracentesis or thoracic drainage for pleural effusion). Of note, no cases of postoperative esophageal leak were recorded. Postoperative mortality was 14% due to one patient who died for cardiovascular complications. Most of the patients (71.4%) were admitted to ICU after surgery (average length, 8.8 days); mean hospital stay was 14.7 days. No patients had readmissions. CONCLUSIONS: To our knowledge, this is the largest case series reporting laparoscopic management of BS. We show that laparoscopy is a safe and feasible approach associated with a shorter length of hospital stay when compared with clinical series in which thoracic approach had been chosen. Of note, laparoscopic management would be easily adopted by surgical centers treating benign gastro-esophageal junction entailing a proper management more widely.

Perianastomotic drainage in Ivor-Lewis esophagectomy, does habit affect utility? An 11-year single-center experience.

Anastomotic leakage (AL) is a deadly complication after Ivor-Lewis esophagectomy. The use of an anastomotic drainage (AD), to diagnose and to potentially treat the leakage, is still a widespread practice. At present, scientific literature is lacking in this topic and its use is based on each center experience. We performed a retrospective analysis of 239 consecutive patients who underwent an Ivor-Lewis esophagectomy in our Department from 01/01/2006 to 31/12/2017. Until 28/02/2014, a transthoracic anastomotic drainage was routinely placed in 119 patients (anastomotic-drain group). Drainage removal was planned on POD 5 after the resume of oral intake. In the remaining 120 cases, no drainage was placed (no anastomotic-drain group). We compared the two groups to assess whether the anastomotic drainage had an impact on the timing of the anastomotic leakage diagnosis and treatment. In our series, we observed 9 anastomotic leaks in the first group (7.6%) and 3 in the second one (2.5%). In the anastomotic-drain group, median time for leak diagnosis was 10 days, and notably, in seven cases, the anastomotic drainage was already removed. Considering all the patients who experienced an AL, a re-operation was mandatory in one case, while endoscopic treatment was chosen for five cases and conservative treatment was adopted in three cases. The median hospital length of stay in these patients was 31 days. In the no anastomotic-drain group, one patient with anastomotic leakage was treated conservatively and discharged after 34 days. The other two cases were re-operated and an esophageal prosthesis was placed in both cases, and these patients were discharged, respectively, on POD 28 and POD 38. Concluding, the role of the anastomotic drain in Ivor-Lewis esophagectomy is still unclear. There is a shortage of the literature on this topic and our experience shows that the anastomotic drain has a limited sensibility in AL diagnosis and cannot replace the clinical signs and symptoms. Moreover, the drain it is often removed before the leakage becomes visible. In selected patients with a less severe leak, the anastomotic drain can be an effective treatment, but often a percutaneous drainage, it is an effective alternative choice. In severe dehiscence with sepsis, a reoperation remains the mainstay to control the mediastinal contamination and to eventually treat the leakage.

Acute bleeding obstruction pancreatitis after Roux-en-Y anastomosis in total gastrectomy: a single center experience.

Anastomotic intraluminal bleeding is a well-known complication after total gastrectomy. Nevertheless, few data are published on acute bleeding obstruction pancreatitis (BOP) due to a bleeding from the jejunojejunostomy (JJ). In this paper we describe our experience. A total of 140 gastrectomies for EGJ cancer were performed in our Institute from January 2012 to January 2017. All reconstructions were performed with a Roux-en-Y anastomosis: a mechanical end-to-side esophago-jejunostomy and a mechanical end-to-side JJ. Three patients suffered from a bleeding at the JJ with a consequent BOP. We analyzed the time of diagnosis, the treatment and the outcomes. The three patients presented anemia at the laboratory findings on postoperative day (POD) 1. In patient I laboratory findings of acute pancreatitis were found in POD 2. CT scan was performed and showed signs of BOP. Endoscopic treatment was tried without success. Therefore, patient underwent surgery: JJ take down, bleeding control and anastomosis rebuild were performed. In spite of this the patient died of MOF in POD 4. Patient II had a persistent anemia treated with blood transfusions until POD 3, when laboratory tests showed increased lipase and bilirubin levels. Patient was successfully treated with endoscopy but several blood transfusions and a prolonged recovery were necessary. Patient III had laboratory findings of acute pancreatitis on POD 1. Immediate surgery was performed and patient was discharged on POD 9 without sequelae. BOP is a rare but deadly complication after Roux-en-Y anastomosis. An early diagnosis and an aggressive treatment seem to improve the outcome.

[Spectrum of laparoscopic surgery for gastric tumors]. / Spektrum der laparoskopischen Chirurgie bei Magentumoren.

Minimally invasive operative procedures are increasingly being used for treating tumors of the upper gastrointestinal tract. While minimally invasive surgery (MIS) has become established as a standard procedure for benign tumors and gastrointestinal stromal tumors (GIST) based on current studies, the significance of MIS in the field of gastric cancer is the topic of heated debate. Until now the majority of studies and meta-analyses on gastric cancer have come from Asia and these indicate the advantages of MIS in terms of intraoperative blood loss, minor surgical complications and swifter convalescence although without any benefits in terms of long-term oncological results and quality of life. Unlike in Germany, gastric cancer in Asia with its unchanged high incidence rate, 50 % frequency of early carcinoma and predominantly distal tumor localization is treated at high-volume centres. Due to the proven marginal advantages of MIS over open resection described in the published studies no general recommendation for laparoscopic surgery of gastric cancer can currently be given.