A New Risk Factor for Cervical Anastomotic Leakage-Role of The Relative Gastric Length in the Surgical Treatment of Esophageal Cancer.

BACKGROUND: Blood supply is especially weak near the gastric fundus. Making the anastomosis in this area would increase the risk of anastomotic leakage (AL). In cervical anastomosis, the gastric conduit needs to travel through the thorax. Therefore, the relative length between the stomach and the thorax is an essential factor in deciding if the poorly supplied area could be removed. This study was to explore if a small relative gastric length was a risk of cervical AL. If all other conditions are equal, could intrathoracic anastomosis be a better choice? METHODS: Patients who underwent esophagectomy with a preoperative barium swallow in West China Hospital between 2014 and 2017 were included. The length of the greater curvature and the thorax were obtained from the barium esophagogram. The ratio between the length of the greater curvature and the thorax was the relative gastric length calculated from the greater curvature (RGL-G). RESULTS: A total of 782 patients were enrolled in the final analysis. The cervical AL group had a significantly higher ratio of patients with an RGL-G less than 1.3 (26.7% vs. 8.9%, p = 0.003). The multivariate logistic regression proved that RGL-G less than 1.3 was a risk factor for cervical anastomotic leakage (p = 0.012). Correspondingly, RGL-G less than 1.3 was not a risk factor (6.3% vs. 14.3%, p = 0.289) in the intrathoracic anastomosis group. CONCLUSIONS: RGL-G less than 1.3 was a new risk factor for cervical AL, but it would not be a problem for intrathoracic anastomosis.

Pretreatment-assisted robot intrathoracic layered anastomosis: our exploration in Ivor-Lewis esophagectomy.

BACKGROUND: Minimal invasive Ivor-Lewis esophagectomy (MIIVE) with intrathoracic esophago-gastric anastomosis (EGA) is still under exploration and the preferred technique for intrathoracic anastomosis has not been established. METHODS: We retrospectively reviewed 43 consecutive patients who underwent MIIVE using the series technique called pretreatment-assisted robot intrathoracic layered anastomosis (PRILA), performed by a single surgeon between September 2018 and December 2020. The operative outcomes were analyzed. RESULTS: The mean total operation time had been reduced from 446.38±54.775 minutes (range, 354-552) in the first year to 347.70±60.420 minutes (range, 249-450) later. There were no conversions to thoracotomy. All the patients achieved R0 resection. No patient suffered from anastomotic leakage. There was no 30-day mortality. The median length of postoperative stay was 10.0 days. CONCLUSIONS: PRILA further visualizes and streamlines the process of minimal invasive intrathoracic EGA, thus ensuring the precise anastomosis. It could be considered as a feasible alternative for intrathoracic EGA in MIILE.

From McKeown to Ivor Lewis, the learning curve for thoracic lymphadenectomy over the first 100 robotic esophagectomy cases: a retrospective study.

BACKGROUND: Lymphadenectomy is an essential but challenging part of the surgical treatment for esophageal cancer. However, the previously reported learning curve for robotic esophagectomy primarily focused on only one surgical approach (McKeown or Ivor Lewis). However, both approaches must be mastered by a mature robotic surgical team to deal with different clinical conditions and satisfy patients' needs. This study aimed to show how an experienced esophageal surgical team became proficient in both McKeown and Ivor Lewis robotic esophagectomy. METHODS: A retrospective review of the first 100 cases of robot-assisted minimally invasive esophagectomy (RAMIE) by a single surgical team was performed. The cumulative sum (CUSUM) analysis was used to distinguish the change point during the learning course. A subgroup analysis was performed according to a surgical approach (McKeown or Ivor Lewis) to determine the effect of experience from one surgical approach on learning the other RAMIE technique. RESULTS: According to the tendency of the CUSUM plot, the learning curve was divided into four phases. The subgroup analysis indicated the decline of the CUSUM plot in the 3rd phase originated from the start of the Ivor Lewis approach. The attending surgeon took 23 cases to achieve a significant improvement in the number of harvested thoracic lymph nodes using the McKeown approach. Regardless of the acquired experience of McKeown RAMIE, it took another 18 cases for the surgical team to achieve significant improvement in harvesting thoracic lymph nodes using the Ivor Lewis approach. CONCLUSIONS: Twenty-three cases were needed for an experienced surgical team to improve thoracic lymphadenectomy results using McKeown RAMIE. There was another learning phase during the transition from McKeown to Ivor Lewis esophagectomy. Importantly, the acquired experience from performing McKeown RAMIE could shorten how long it takes to learn Ivor Lewis RAMIE.

Is the routine placement of a feeding jejunostomy during esophagectomy worthwhile?-a systematic review and meta-analysis.

BACKGROUND: Malnutrition dramatically increases the risk of postoperative complications and delays patient recovery. Therefore, a feeding jejunostomy tube (FJT) is routinely placed during esophagectomy to maintain the postoperative nutrition supply. However, recently published studies have questioned the need of a FJT in every esophageal cancer patient. Because most patients can resume oral intake shortly after surgery, the nutrition-providing function of a FJT becomes much less critical. In contrast, FJT-related complications could be severe. METHODS: Relevant publications were found out by systemic searching of four medical databases (PubMed, EMBASE, Medline, and Cochrane Center Register of Controlled Trials). By reading the titles and the abstracts, potentially relevant studies were screened from the search results. The incidence of postoperative complications and FJT-related complications were calculated and compared to evaluate the efficacy of a FJT. RESULTS: Eighteen studies were included in the meta-analysis. The no-FJT group had a similar or even lower incidence of postoperative complications [anastomotic leakage (AL), pulmonary complications, and wound infections] compared with the FJT group. Ileus and FJT site infections were the most common FJT-related complications. The incidence of ileus was approximately 6% (95% CI: 3-12%), and over 63% of the patients with an ileus required re-operation to relieve the obstruction. The pooled mean rate of FJT site infections was 7% (95% CI: 6-9%). Approximately 7% of patients had dysfunction (obstruction or dislocation) of the jejunostomy tube (95% CI: 3-14%). CONCLUSIONS: The non-selective placement of a FJT during esophagectomy provides few benefits to the patients and may even increase the risk of postoperative complications. Therefore, an intraoperative FJT should be selectively prescribed, but not routinely in the surgical treatment of esophageal cancer.

Is immunonutrition superior to standard enteral nutrition in reducing postoperative complications in patients undergoing esophagectomy? A meta-analysis of randomized controlled trials.

PURPOSE: Perioperative enteral nutrition supports are recommended in esophagus cancer patients. Immunonutrition contains immuno-enhancing nutrients in addition to standard formula. These new nutrients are thought to be efficacious in reducing inflammatory response and improving postoperative immune response and they have been proved to be better than standard enteral nutrition in reducing postoperative complications in gastric cancer. However, if it would lead to a better clinical outcome in patients undergoing esophagectomy remains controversial. METHODS: A systematic literature search was performed in the online database of PubMed, Medline, EMBASE and Cochrane Library. The relevant studies were screened out of the results by reading titles and abstracts. Then, we read the full-texts to finally confirm the studies included in this meta-analysis. RESULTS: Six randomized controlled trials having enrolled 638 patients were included in the final analysis. The pooled analysis didn't show statistically significant difference between immunonutrition group and standard nutrition group in reducing postoperative complications. CONCLUSIONS: The postoperative complications are comparable between immunonutrition and the standard enteral nutrition in patients undergoing esophagectomy, but its value in severe malnutrition patients is undetermined, whereas the high tolerance and other advantages brought by the immunonutrition should not be overlooked and need to be further proved.

Role of nodal skip metastasis in patients with mid-thoracic oesophageal squamous cell carcinoma: a propensity score matching study.

OBJECTIVES: Nodal skip metastasis (NSM) is a common phenomenon in mid-thoracic oesophageal squamous cell carcinoma (MT-OSCC); however, the prognostic implications of NSM in patients with MT-OSCC remain unclear. METHODS: This retrospective study enrolled 300 patients with MT-OSCC who underwent radical oesophagectomy and who had pathologically confirmed lymph node metastasis from January 2014 to December 2016. The patients were divided into 2 groups according to the presence or absence of NSM. Propensity score matching was applied to minimize patient selection bias. The impact of NSM on overall survival (OS) was assessed by Kaplan-Meier and multiple Cox proportional hazards analyses. The median follow-up time was 57 months. RESULTS: The NSM rate in the entire cohort was 22.0% (66/300). Pathological N (pN) stage (P < 0.001) and sex (P = 0.001) were identified as significant independent risk factors for NSM. NSM was more frequent in pN1 compared with pN2 patients (87.9% vs 12.1%, P < 0.001) and no NSM was found in pN3. NSM(+) patients had better prognoses than NSM(-) patients (Kaplan-Meier; 3-year OS, 62.1% vs 34.1%, P < 0.001). Propensity score matching produced 51 matched pairs, and the 3-year OS was still better in the NSM(+) compared with the NSM(-) group (66.7% vs 40.0%, P = 0.025). Multivariable Cox analysis confirmed NSM(+) as an independent factor favouring OS in patients with MT-OSCC. CONCLUSIONS: NSM usually occurs at pN1 stage in patients with MT-OSCC, and is associated with a favourable prognosis.

Predictors for the clinical benefit of anti-PD-1/PD-L1 therapy in advanced gastroesophageal cancer: a meta-analysis of clinical trials.

BACKGROUND: The overall objective response rate (ORR) of published clinical trials in advanced gastroesophageal cancer patients who received anti-program-death-1 (anti-PD-1) or program-death-legend-1 (anti-PD-L1) therapy was only 10%. This ratio is far away from satisfying. It is necessary to identify patients who are more likely to benefit from the treatment. This study aimed to identify the factors with which the patients would have a higher response rate to anti-PD-1/anti-PD-L1 therapy. METHODS: The study was carried out according to the Cochrane handbook for systemic reviews of intervention. The comparisons were conducted according to the patients' characteristics to distinguish the factors with which the patients would have a higher response rate and better survival from the therapy. RESULTS: One thousand and nine hundred ninety-eight patients with advanced gastroesophageal cancer receiving anti-PD-1 or anti-PD-L-1 therapy were enrolled totally. Both the anti-PD-1 and anti-PD-L-1 therapy were significantly more efficacy in patients with high expression of PD-L1. Adenocarcinoma patients with high microsatellite instability (MSI-H) were more likely to benefit from anti-PD-1 therapy. Patients with a better Eastern Cooperative Oncology Group (ECOG) performance status had a significantly higher ORR and disease control rate (DCR). The treatment also had a better performance in improving the overall survival (OS) and progression-free survival (PFS) in patients with high expression of PD-L1. CONCLUSIONS: The expression level of PD-L1, MSI, and ECOG performance status could be the predictors of achieving clinical benefit from anti-PD-1/anti-PD-L1 therapy in advanced gastroesophageal cancer.

Fixed in the neck or pushed back into the thorax?-Impact of cervical anastomosis position on anastomosis healing.

BACKGROUND: Cervical anastomotic leakage remains a great challenge for thoracic surgeons in the surgical treatment of esophageal cancer. Among the factors affecting cervical anastomosis healing, the surgical technique is the key controllable element. This study aimed to identify the risk factors of cervical anastomotic leakage after McKeown esophagectomy, especially those controllable surgical factors. METHODS: A retrospective review of patients who underwent McKeown esophagectomy in the past eight years in West China Hospital was performed. Patients with cervical anastomotic leakage were assigned to leakage group (LG) while the left was enrolled in the none-leakage group (NLG). Multivariate logistic regression analysis was used to identify independent risk factors of anastomotic leakage. RESULTS: A total of 518 patients were enrolled in the final analysis. In the baseline comparison, the difference in fixation of anastomosis in the neck, anastomosis mode, diabetes, and hypertension between the LG and NLG reached statistically significant. Moreover, the statistical difference of cervical fixation, anastomosis mode, and hypertension remained significant in the multivariate logistic regression analysis. CONCLUSIONS: The cervical anastomosis fixation, anastomosis mode, and hypertension are independent risk factors of gastroesophageal cervical anastomotic leakage.

Preoperative dilated esophagus is associated with a high risk of intrathoracic anastomotic leakage for patients with esophageal cancer.

BACKGROUND: The association between the preoperative condition of the esophagus and anastomotic leakage has seldom been studied. We observed a dominant dilation of the esophagus under barium esophagography in some esophageal cancer patients. In consideration of the larger circular stapler are applied in colorectal surgery, we wonder if larger circular stapler should be applied in these patients to fit the larger esophagus. The larger size of the circular stapler also could decrease the incidence of anastomosis stricture. Thus, we made this study to explore if patients with a dilated esophagus were facing a higher risk of anastomotic leakage when applying the 25 mm circular stapler. METHODS: A retrospective review of patients undergoing gastroesophageal intrathoracic anastomosis using a 25 mm circular stapler was performed. Patients with endoscopy or barium esophagography confirmed anastomotic leakage was assigned to leakage group (LG) while the left was enrolled in no leakage group (NLG). The measurement of the diameter of the esophagus was carried out at the level of 5 centimeters away from the upper margin of the tumor on esophagography. RESULTS: LG had a greater intraluminal mucosal phase diameter (IMPD) than NLG (P=0.010). The ROC curve indicated 1.79 cm as the cutoff value for IMPD. Patients with IMPD greater than 1.79 cm had a statistically significant higher rate of leakage. In the multivariate logistic regression analysis, dilated IMPD was proven to be a risk factor of 25 mm-circular-stapler anastomotic leakage. CONCLUSIONS: Patients with an IMPD over 1.79 mm are facing a higher risk of intrathoracic anastomosis leakage when applying the 25 mm circular stapler. Larger circular stapler or hand-sewn would be the better choice for these patients.

The efficacy of ischemic conditioning in the prevention of gastroesophageal anastomotic complications: a meta-analysis.

BACKGROUND: The blood supply to the gastric conduit is thought to be the most crucial factor affecting the healing of the gastroesophageal anastomosis. By selective ligation or embolization of gastric vessels, ischemic conditioning (IC) could promote the hypertrophy and neovascularization of the remaining gastric vessels. So that it could help the stomach adapt to the decline of blood supply before esophagectomy. However, the safety and efficacy of the technique still needs to be proved. Several new studies on this topic have been published recently. We conduct this meta-analysis to update the evidence on this topic. METHODS: A logistic searching strategy was designed to find out related publications on four medical databases (PubMed, EMBASE, Medline, and Cochrane Central Register of controlled trials). The included studies were confirmed by reading the title, abstract, or full text. Based on these included studies, the comparison of postoperative outcomes between patients who received IC and those did not was made. After that, the safety and efficacy of IC were assessed. RESULTS: Fourteen studies were enrolled in the meta-analysis. The pooled analysis showed IC reduced the incidence of anastomotic leakage significantly. And both the embolization and laparoscopic ligation approach were effective. The subgroup analysis indicated the interval between IC and esophagectomy should be over two weeks before the IC worked. The IC also could decrease the anastomotic stricture rate dominantly. What's more, the IC didn't increase the mortality. CONCLUSIONS: This meta-analysis proved that ischemic conditioning is a safe intervention that could reduce anastomotic complications effectively. Future randomized controlled clinical trials are needed to provide high-level evidence on this topic.

Predictive Value of Excision Repair Cross-Complementation Group 1 in the Response to Platinum-Based Chemotherapy in Esophageal Cancer: A Meta-Analysis.

INTRODUCTION: Platinum is widely used in the treatment of esophageal cancer. In clinical practice, it is significant to distinguish patients who respond to platinum from those who do not. Excision repair cross-complementation group 1 (ERCC1) is thought to be the key in the resistance to platinum. However, whether it is related to the platinum-based chemotherapy response on real esophageal cancer patients is controversial. We conducted this meta-analysis to explore the association between ERCC1 polymorphisms, its expression levels and platinum-based chemotherapy response, and identify the most sensitive genotypes. METHODS: The study was carried out according to the Cochrane handbook for systemic reviews of intervention. The study protocol has been registered on PROSPERO. RESULTS: Three studies were included in the analysis of C8092A polymorphisms, 5 in the C118T, and another 6 in ERCC1 expression levels. In C118T polymorphisms, compared to wild genotype, patients with mutant genotypes had a significantly higher response rate. As for C8092A polymorphisms, the mutant genotypes also presented a better response than the wild genotype. The pooled analysis indicated a significantly higher response rate in patients with a low expression of ERCC1. CONCLUSIONS: ERCC1 is a valuable biomarker for platinum-based chemotherapy in esophageal cancer. Patients with ERCC1 mutations or low-level ERCC1 expression are more sensitive to platinum-based chemotherapy.

Role of everolimus in the treatment of advanced neuroendocrine tumor: a meta-analysis of randomized trials.

PURPOSE: There are two fundamentally groups of neuroendocrine neoplasms: neuroendocrine tumors (NETs) and neuroendocrine carcinomas (NECs). Target therapy plays a quite important role in the treatment of NETs. However, whether everolimus (mTOR inhibitor) could improve the overall survival (OS) of NETs is contradictory and the efficacy of the agent in NETs from specific organ is lacking analysis. This meta-analysis enrolled the relevant published trials to see the results in a large sample size and further analyzed the efficacy of everolimus according to the tumor origin. METHODS: A systemic search was performed on four major medical databases and related studies were screened out of the result. All the works were done by two reviewers independently and then checked with each other. RESULTS: Finally, 5 articles and 4 conference abstracts from 3 trials were included. All of the trials indicated a statistically significant difference of progression free survival (PFS) in patients receiving everolimus. And the statistic difference remained significant when it came to the NETs from specific organ (overall HR=0.42, 95%CI 0.35, 0.51). As for OS, all the three trials showed no statistically significant difference between the experimental group (patients receiving everolimus) and control group (patients receiving placebo) and the pooled analysis also indicated no significant difference (HR=0.95, 95%CI 0.71,1.25, p=0.695). CONCLUSION: Everolimus is effective in improving the PFS of NETs and the statistical difference remained significant when it came to the NETs from specific organs.

The influence of heparin on coagulation function of patients undergoing video-assisted major thoracic surgery.

BACKGROUND: Venous thromboembolism (VTE) remains a common complication after major thoracic surgery, especially resection of lung or esophagus cancer. This trial aims to explore the influence of preoperative usage of heparin on coagulation function of patients treated with video-assisted major thoracic surgery. METHODS: This prospective randomized control trial collected 91 patients who are diagnosed with lung or esophagus cancer intending to accept video-assisted neoplasm resection from June 2016 to May 2017 in West China Hospital, Sichuan University. After admission to hospital, the patients received heparin sodium (unfractionated heparin) 5,000 U twice a day before operation. The change of blood platelet count (PLT), prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), fibrinogen (FIB), international normalized ratio (INR) was collected and analyzed at the points of admission to hospital and post-operation. RESULTS: The mean value of all coagulation parameters (PLT, PT, APTT, TT, INR, FIB) were in normal range both before and after operation. Postoperative PLT and FIB were not significantly different from preoperative PLT and FIB respectively (P>0.05). Preoperative PT, APTT, and INR increased significantly compared to pre-operation respectively (P<0.05). Postoperative TT significantly decreased when compared to preoperative TT (P<0.05). Preoperative and postoperative abnormal rate of PT or APTT or TT or INR (number of abnormal cases/all cases) was not different significantly respectively (P>0.05). Postoperative mean drainage was 240 mL/d, mean time of hospital stay was 7.50 days, drainage tube was maintained for 4.22 days on average. CONCLUSIONS: All patients underwent video-assisted major thoracic surgery with preoperative use of heparin, there were significant differences in coagulation function after operation. However, mean values of all coagulation parameters stayed normal range clinically. In a word, the method showed no influence on coagulation function clinically.