Gastric conduit reconstruction after esophagectomy.

A high risk of complications still accompanies gastric conduit reconstruction after esophagectomy. In this narrative review, we summarize the technological progress and the problems of gastric conduit reconstruction after esophagectomy. Several types of gastric conduits exist, including the whole stomach and the narrow gastric tube. The clinical outcomes are similar between the two types of conduits. Sufficient blood supply to the conduit is mandatory for a successful esophageal reconstruction. Recently, due to the availability of equipment and its convenience, indocyanine green angiography has been rapidly spreading. When the blood perfusion of the planning anastomotic site is insufficient, several techniques, such as the Kocher maneuver, pedunculated gastric tube with duodenal transection, and additional microvascular anastomosis, exist to decrease the risk of anastomotic failure. There are two different anastomotic sites, cervical and thoracic, and mainly two reconstructive routes, retrosternal and posterior mediastinal routes. Meta-analyses showed no significant difference in outcomes between the anastomotic sites as well as the reconstructive routes. Anastomotic techniques include hand-sewn, circular, and linear stapling. Anastomoses using linear stapling is advantageous in decreasing anastomosis-related complications. Arteriosclerosis and poorly controlled diabetes are the risk factors for anastomotic leakage, while a narrow upper mediastinal space and a damaged stomach predict leakage. Although standardization among the institutional team members is essential to decrease anastomotic complications, surgeons should learn several technical options for predictable or unpredictable intraoperative situations.

Early postoperative hyperglycemia as a predictor of postoperative infectious complications and overall survival in non-diabetic patients with esophageal cancer.

BACKGROUND: Diabetes mellitus (DM) is known to be a risk factor for postoperative infectious complications (PICs). However, the significance of postoperative hyperglycemia in non-DM cases has not been well investigated. We sought to establish whether postoperative hyperglycemia is associated with PICs and survival among patients with esophageal cancer, with a focus on non-DM cases. METHODS: A total of 430 patients who underwent subtotal esophagectomy for esophageal cancer between 2014 and 2018 were enrolled. Postoperative blood glucose was measured by arterial blood gas test every 8 h from postoperative day (POD) 1 to POD4. The association between hyperglycemia (mean ≥ 200 mg/dl) and PICs or long-term outcomes on each POD was investigated. RESULTS: There were 53 DM and 377 non-DM cases. PICs occurred in 127 patients. In the multivariate analysis of all cases, PICs were associated with hyperglycemia on POD1 or -2 (odds ratio [OR] = 1.69, 95% CI, 1.05-2.73, P = 0.031 for POD1; OR = 2.55, 95% CI, 1.10-5.93, P = 0.029 for POD 2). Among non-DM cases, the association was more evident, and persisted until POD4 (OR = 1.94, 95% CI, 1.16-3.24, P = 0.012 for POD1; OR = 3.68, 95% CI, 1.28-10.6, P = 0.016 for POD2; OR = 3.07, 95% CI, 1.11-8.51, P = 0.031 for POD4). Survival analyses limited to R0 cases revealed hyperglycemia on POD2 as an independent prognostic factor in all cases (N = 412) [hazard ratio (HR) = 2.61, 95%CI, 1.21-5.63, P = 0.014], with the prognostic impact more evident among non-DM cases (N = 360) (HR = 4.38, 95% CI, 1.82-10.57, P = 0.0010). CONCLUSION: Postoperative hyperglycemia is associated with PICs and worse survival after esophagectomy, particularly in patients without DM.

Quantitative Evaluation of Periodontitis for Predicting the Occurrence of Postoperative Pneumonia After Oncologic Esophagectomy.

BACKGROUND: Periodontitis is a biofilm-associated inflammatory periodontal disease associated with postoperative complications after esophagectomy. However, few studies have evaluated the inflammatory burden posed by periodontitis quantitively for patients undergoing oncologic esophagectomy. This study aimed to clarify the relationship between periodontitis and postoperative pneumonia using periodontal inflammatory surface area (PISA). METHODS: The study analyzed 251 patients who underwent esophagectomy for esophageal cancer. The patients were classified into low-PISA and high-PISA groups according to preoperative PISA, and the relationship between the occurrence and severity of postoperative pneumonia was investigated. RESULTS: The high-PISA group (n = 69) included more males (P < 0.001) and patients with poor performance status (P < 0.024). Postoperative pneumonia occurred more frequently in the high-PISA group than in the low-PISA group (31.9 % vs. 15.9 %; P = 0.008), whereas the incidences of other complications did not differ significantly. In addition, the incidence of severe pneumonia was significantly higher in the high-PISA group (7.2 % vs. 1.6 %; P = 0.038). In the multivariable analysis for adjustment of preoperative confounders, age older than 70 years (odds ratio [OR], 2.62; P = 0.006), high PISA (OR, 2.45; P = 0.012), and smoking history (OR, 2.78; P = 0.006) were the independent variables predicting postoperative pneumonia. CONCLUSION: Preoperative higher PISA was significantly associated with the occurrence of overall and severe postoperative pneumonia. The quantitative evaluation of periodontitis using PISA is a useful measure for predicting postoperative pneumonia, and intensive periodontal intervention may contribute to decreasing postoperative pneumonia.

McKeown Versus Ivor-Lewis Esophagectomy for Patients with a History of Total Pharyngolaryngectomy: A Comparison Study.

BACKGROUND: Oncologic esophagectomy in patients with a history of total pharyngolaryngectomy (TPL) is challenging. There are two different esophagectomy procedures: total esophagectomy with cervical anastomosis (McKeown) and subtotal esophagectomy with intrathoracic anastomosis (Ivor-Lewis). Differences in outcomes between McKeown and Ivor-Lewis esophagectomies for patients with this history remain unclear. METHODS: We retrospectively reviewed 36 patients with a history of TPL who underwent oncologic esophagectomy and compared the clinical outcomes between the procedures. RESULTS: Twelve (33.3%) and 24 (66.7%) patients underwent McKeown and Ivor-Lewis esophagectomies, respectively. McKeown esophagectomy was more frequently performed for the supracarinal tumors (P = 0.002). Other baseline characteristics, including the history of radiation therapy, were comparable between the groups. Postoperatively, the incidences of pneumonia and anastomotic leakage were higher in the McKeown group than in the Ivor-Lewis group (P = 0.029 and P < 0.001, respectively). Neither tracheal necrosis nor remnant esophageal necrosis was observed. The overall and recurrence-free survival rates were comparable between the groups (P = 0.494 and P = 0.813, respectively). CONCLUSIONS: When performing esophagectomy for patients with a history of TPL, if it is oncologically acceptable and technically available, Ivor-Lewis is preferable over McKeown esophagectomy for avoiding postoperative complications.

Prognostic significance of circulating basophil counts in patients who underwent esophagectomy for esophageal cancer.

PURPOSE: Recent reports have suggested that basophils influence allergic reactions and tumor immunity. In this study, we aimed to elucidate the association between preoperative circulating basophil (CB) counts and the outcomes of patients who underwent esophagectomy for esophageal cancer. METHODS: A total of 783 consecutive patients who underwent esophagectomy for esophageal cancer were eligible. The clinicopathological factors and prognoses were compared between the groups stratified by the preoperative counts of CB. RESULTS: There were more advanced clinical T and N stages in the low CB group than in the high CB group (P = 0.01 and = 0.04, respectively). The incidences of postoperative complications were comparable between the groups. The low CB count was associated with unfavorable overall and recurrence-free survivals (P = 0.04 and 0.01, respectively). In the multivariate analysis, low CB count was one of the independent prognostic factors for poor recurrence-free survival (HR 1.33; 95% CI 1.04-1.70; P = 0.02). In addition, hematogenous recurrence occurred more frequently in the low CB group than in the high CB group (57.6% vs. 41.4%, P = 0.04). CONCLUSION: A preoperative low CB count was an unfavorable prognosticator in patients who underwent esophagectomy for esophageal cancer.

Robotic-Assisted Esophagectomy: Current Situation and Future Perspectives.

Robotic-assisted minimally invasive esophagectomy (RAMIE) has been rapidly spreading worldwide as a novel minimally invasive approach for esophageal cancer. This narrative review aimed to elucidate the current situation and future perspectives of RAMIE for esophageal cancer. References were searched using PubMed and Embase for studies published up to 8 April 2023. Search terms included "esophagectomy" or "esophageal cancer" and "robot" or "robotic" or "robotic-assisted." There are several different uses for the robot in esophagectomy. Overall complications are equivalent or may be less in RAMIE than in open esophagectomy and conventional (thoracoscopic) minimally invasive esophagectomy. Several meta-analyses demonstrated the possibility of RAMIE in reducing pulmonary complications, although the equivalent incidence was observed in two randomized controlled trials. RAMIE may increase the number of dissected lymph nodes, especially in the left recurrent laryngeal nerve area. Long-term outcomes are comparable between the procedures, although further research is required. Further progress in robotic technology combined with artificial intelligence is expected.

Postoperative Complications Following Pharyngolaryngectomy With Total Esophagectomy: Comparison Between Cervical and Anterior Mediastinal Tracheostomy.

OBJECTIVES: Pharyngolaryngectomy with total esophagectomy (PLTE) is associated with high morbidity and mortality rates. Cervical tracheostomy (CT) is the first choice of tracheostomy, whereas anterior mediastinal tracheostomy (AMT) is sometimes required due to tumor extension or insufficient blood supply to the tracheal tip. However, the differences in the outcomes between CT and AMT after PLTE remain unclear. METHODS: We retrospectively reviewed 67 patients who underwent PLTE and compared the clinical features and postoperative complications between patients with CT and AMT. The characteristics and the outcomes were compared between the groups stratified by the causes of AMT. RESULTS: Of the 67 patients, 42 (62.7%) patients underwent PLTE with CT (CT group), whereas 25 (37.3%) underwent PLTE with AMT (AMT group). The AMT group included more cervicothoracic esophageal cancers and had showed an advanced T stage compared to the CT group (P < .01 and .01, respectively). The incidences of pneumonia and surgical site infection (SSI) were more frequent in the AMT group than in the CT group (P = .03 and .01, respectively). Surgery-related mortality was only observed in the AMT group. In the AMT group, 17 (68.0%) and 8 (32.0%) patients underwent AMT because of tumor extension and insufficient supply to the tracheal tip. The latter cases underwent transthoracic esophagectomy more frequently than former cases (P = .03). CONCLUSION: AMT after PLTE had more postoperative complications and mortality than CT. In cases that may need AMT, a transhiatal approach is preferable over transthoracic esophagectomy to avoid fatal complications when oncologically permissive.

Fecal Microbes Associated with the Outcomes After Esophagectomy in Patients with Esophageal Cancer.

BACKGROUND: Although accumulating evidence suggests that an imbalanced gut microbiota leads to cancer progression, few studies demonstrated the implication in patients who underwent oncologic esophagectomy. This study aimed to elucidate the association between gut microbes and the outcomes after oncologic esophagectomy, as well as the host's inflammatory/nutritional status. METHODS: Overall, 783 consecutive patients who underwent oncologic esophagectomy were eligible. We investigated the microbiota detected by fecal culture tests and then assessed the association between the gut microbiota and patient characteristics, short-term outcomes, and long-term survival. RESULTS: Seventeen different species could be cultivated. We comprehensively examined the impact of each detected microbe on survival. The presence of Bacillus species (Bacillus sp.; 26.8%) was associated with favorable prognosis on overall and cancer-specific survival (p = 0.02 and 0.02, respectively). Conversely, the presence of Proteus mirabilis (P. mirabilis; 3.4%) was associated with unfavorable overall and recurrence-free survivals (p = 0.02 and < 0.01, respectively). Multivariate analysis showed that the presence of P. mirabilis was one of the independent prognostic factors for poor recurrence-free survival (p < 0.01). Patients with Bacillus sp. had lower modified Glasgow prognostic score and better response to preoperative treatment than those without (p = 0.01 and 0.03, respectively). Meanwhile, patients with P. mirabilis were significantly associated with higher systemic inflammation scores and increased postoperative pneumonia incidence than those without (p = 0.01 and 0.02, respectively). CONCLUSIONS: Preoperative fecal microbiota was associated with the host's inflammatory and nutritional status and may influence the outcomes after oncologic esophagectomy.

Treatment Strategy for Esophageal Squamous Cell Carcinoma With Endoscopic Intramural Metastasis.

PURPOSE: Intramural metastasis (IM) in esophageal squamous cell carcinoma (ESCC) is sometimes found, and the prognosis of ESCC patients with pathologically diagnosed IM is known to be dismal. However, there are few reports on ESCC patients with clinically diagnosed IM. METHODS: This study assessed 2,772 ESCC patients who underwent endoscopy for initial evaluation. Among them, 85 patients (3.1%) were diagnosed with endoscopic IM. In this study, we investigated these patients' characteristics, survival among the groups stratified by the treatment modalities, and survival predictors. RESULTS: Of 85 patients, 76 (89.4%) had T3 or T4 tumors, 73 (85.9%) had nodal metastases, and 36 (42.4%) had M1 diseases. Curative-intent treatment could be given to 63 patients (74.1%) with a median survival time (MST) of 15.6 months (95% CI: 10.7-20.4). As initial treatment, upfront surgery (US), neoadjuvant chemotherapy (NAC) using cisplatin and 5-fluorouracil (CF), neoadjuvant chemoradiotherapy, and definitive chemoradiotherapy (dCRT) were given to 17 (27.0%), 27 (42.9%), 2 (3.2%), and 17 patients (27.0%), respectively. dCRT was preferred for T4 tumors compared with US or NAC (P = 0.02). The MST of US and NAC patients was 19.3 (95% CI: 12.9-25.6) and 23.4 months (95% CI: 9.4-37.4), respectively. No significant difference was noted between US and NAC patients (P= 0.89). CONCLUSION: The prognosis of ESCC patients with endoscopic IM is poor even if curative-intent treatment is done. Moreover, no significant survival benefit of NAC with CF for these patients was observed when compared with US.

Is Prophylactic Cervical Drainage Effective in Patients Undergoing McKeown Esophagectomy Reconstructed Through the Retrosternal Route with Two-Field Lymphadenectomy?

BACKGROUND: McKeown esophagectomy with two-field lymphadenectomy is the treatment of choice for oncologic esophagectomy. A cervical drain is placed in cases after modern two-field lymph node dissection (M2FD) to provide information on anastomotic leakage. However, the necessity of prophylactic cervical drainage during surgery remains unknown. This study aimed to clarify the clinical significance of cervical drainage in patients who underwent McKeown esophagectomy with M2FD. METHODS: A total of 293 patients underwent McKeown surgery with two-field lymphadenectomy at our institute between January 2013 and December 2019. We compared the day of drain removal, amount of drainage volume, and the appearance of drainage fluid between patients with and without anastomotic leakage. RESULTS: McKeown esophagectomy reconstructed through the retrosternal route is 203 patients (69.3%) of all. Nineteen patients (6.5%) experienced anastomotic leakage. The amount of cervical drain discharge was comparable between patients with and without anastomotic leakage. In addition, no purulent or salivary discharge was observed in patients with anastomotic leakage. There was no difference in the median day of drain removal between the groups. The initial clinical findings for the diagnosis of anastomotic leakage were surgical site infection in 10 (52.6%), fever in 5 (26.3%), prolonged inflammation in a blood test in 3 (15.8%), and bloody discharge from the chest tube in 1 (5.3%). There was no mortality due to any cause. CONCLUSION: A prophylactic cervical drain may not be mandatory in patients with esophageal cancer undergoing McKeown esophagectomy reconstructed through the retrosternal route with two-field lymphadenectomy.

C-reactive protein to prealbumin ratio: a useful inflammatory and nutritional index for predicting prognosis after curative resection in esophageal squamous cell carcinoma patients.

PURPOSE: Although C-reactive protein to prealbumin ratio (CPR) can predict the outcomes of several types of cancer surgeries, little is known about the implication of CPR in patients undergoing esophagectomy for esophageal squamous cell carcinoma (ESCC). METHODS: Between 2009 and 2018, 682 consecutive ESCC patients who underwent curative esophagectomy were enrolled. The clinicopathological factors and prognoses were compared between the groups stratified by preoperative CPR levels. A logistic regression model was used to determine the risk factors of postoperative pneumonia. Survival curves were constructed using the Kaplan-Meier method and compared using the log-rank test. The Cox proportional hazards model was used to elucidate prognostic factors. RESULTS: There were more elderly patients, more males, and more advanced clinical T and N categories in the high CPR group than in the low CPR group. Also, the incidence of postoperative pneumonia was significantly higher in the high CPR group than in the low CPR group (32.4% vs. 20.3%, p < 0.01). In multivariate analyses, high CPR was one of the independent predictive factors for postoperative pneumonia (OR, 1.71; 95% CI, 1.15-2.54; p < 0.03). Moreover, high CPR was an independent prognostic factor for overall, cancer-specific, and recurrence-free survivals (HR 1.62; 95% CI 1.18-2.23; p < 0.01, HR 1.57; 95% CI 1.08-2.32; p = 0.02, HR 1.42; 95% CI 1.06-1.90; p = 0.02). CONCLUSION: Preoperative CPR was found to be a useful inflammatory and nutritional indicator for predicting the occurrence of pneumonia and prognosis in patients with ESCC undergoing esophagectomy.

Long-Term Insufficiency of Oral Intake after Esophagectomy: Who Needs Intense Nutritional Support after Esophagectomy?

BACKGROUND: Patients with esophageal cancer are at a high risk of malnutrition after esophagectomy, and nutritional support may at times be required for several months following surgery. In this study, we aimed to clarify the clinical features and preoperative risk factors of patients with long-term insufficiency of oral intake after esophagectomy by evaluating the duration of feeding enterostomy placement. METHODS: A total of 306 patients who underwent esophagectomy, reconstruction with gastric conduit, and feeding enterostomy creation were retrospectively reviewed. We analyzed the clinical features and preoperative risk factors for long-term placement of feeding enterostomy. RESULTS: The feeding enterostomy tube was removed less than 90 days after esophagectomy in 234 patients (76.5%) (short group), whereas 72 patients still needed enteral nutrition after 90 days (23.5%; long group). Although severe malnutrition was observed more frequently in the long group compared with the short group (p = 0.021), overall survival time was comparable between the groups (p = 0.239). Multivariate analysis revealed that higher age (odds ratio [OR] 1.04; 95% confidence interval [CI], 1.01-1.07; p = 0.021), poor performance status (OR 2.94; 95% CI, 1.10-7.87; p = 0.032), and lower preoperative body weight (BW) (OR 0.96; 95% CI, 0.94-0.99; p = 0.009) were the independent variables predicting the long-time placement of feeding enterostomy. CONCLUSION: Nutritional support via feeding enterostomy for more than 90 days after esophagectomy was required in 23.5% of patients. The elderly, poor performance status, and lower BW were the independent preoperative factors for predicting the long-term placement of feeding enterostomy.

Current status of robot-assisted minimally invasive esophagectomy: what is the real benefit?

Robot-assisted minimally invasive esophagectomy (RAMIE) for esophageal cancer has been performed increasingly frequently over the last few years. Robotic systems with articulated devices and tremor filtration allow surgeons to perform such procedures more meticulously than by hand. The feasibility of RAMIE has been demonstrated in several retrospective comparative studies, which showed similar short-term outcomes to conventional minimally invasive esophagectomy (cMIE). Considering the number of harvested lymph nodes, RAMIE may be superior to cMIE in terms of left upper mediastinal lymph node dissection. However, whether or not the addition of a robotic system to cMIE can help improve perioperative and oncological outcomes remains unclear. Given the lack of established evidence from randomized controlled trials, we must await the results of ongoing studies to reach any meaningful conclusions. Further advancements in robotic platforms, as well as the reduction in medical expenses, will be essential to demonstrate the real benefit of RAMIE.

Additional Treatment Following Noncurative Endoscopic Resection for Esophageal Squamous Cell Carcinoma: A Comparison of Outcomes between Esophagectomy and Chemoradiotherapy.

BACKGROUND: Endoscopic resection (ER) has been widely implemented for cT1N0 esophageal squamous cell carcinoma (ESCC). Additional therapy, including esophagectomy and chemoradiotherapy (CRT), is sometimes required after noncurative ER. METHODS: We retrospectively reviewed 108 patients who received any additional treatment following noncurative ER (positive vertical margins, lymphovascular invasion, or invasion depth of submucosa or more), and compared the short- and long-term outcomes between the two treatment modalities. RESULTS: Of 108 patients, 56 underwent esophagectomy (E group), and 52 received CRT (CRT group). A positive vertical margin was observed in 17 (14.8%) patients and high risks of occult lymph node metastasis were observed in 91 (85.2%) patients, as well as lymphovascular invasion in 35 (32.4%) patients, invasion depth of the submucosa or more in 27 (25.0%) patients, and both in 29 (26.9%) patients. The E group patients were significantly younger (p = 0.046) and tended to present with larger tumors than those in the CRT group (p = 0.057). Lymphatic invasion was more frequent in the E group (p = 0.019), and, furthermore, one treatment-related death was observed in the E group. There were no significant differences between the groups in overall and disease-specific survival (p = 0.406 and 0.151, respectively), however, recurrence was only observed in the CRT group. CONCLUSION: Both esophagectomy and CRT are safe and effective as additional treatments after noncurative ER in patients with ESCC. Esophagectomy is oncologically safe, whereas a risk of postoperative morbidity and mortality remains. Although the adverse events are acceptable, CRT has a certain degree of risk of disease recurrence.

Airflow Limitation Predicts Postoperative Pneumonia after Esophagectomy.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is known to be a risk factor of pneumonia after esophagectomy. In this study, we investigated the relationship of airflow limitation with the occurrence and the severity of pneumonia in esophageal cancer patients who underwent esophagectomy. METHODS: We enrolled 844 patients who underwent curative esophagectomy between 2009 and 2018. The airflow limitation was evaluated using the percent-predicted forced expiratory volume at 1 s (%FEV1) with spirometry. RESULTS: There were 597 (70.7%), 141 (16.7%), 68 (8.1%), and 38 patients (4.5%) with %FEV1 of ≥ 90%, 80-90%, 70-80%, and < 70% categories, respectively. One hundred and ninety-one patients (22.6%) occurred pneumonia, and the incidences of pneumonia in each category of patients were 18.8%, 28.4%, 29.4%, and 50.0%, respectively. In multivariate analysis, the categories of 80%-90%, 70-80%, and < 70% were significantly associated with a higher incidence of postoperative pneumonia (OR 1.57; 95% CI 1.02-2.43, OR 1.87; 95% CI 1.04-3.36, OR 3.34; 95% CI 1.66-6.71, respectively), with the %FEV1 category of ≥ 90% as reference. The incidence of severe pneumonia of Clavien-Dindo grade III or higher was also significantly associated with the %FEV1. In patients without COPD, the incidence of pneumonia was significantly higher in those with %FEV1 < 90% than in those with %FEV1 ≥ 90% (32.2% versus 17.5%, p < 0.001). CONCLUSIONS: The airflow limitation can help predict the occurrence of pneumonia after esophagectomy in patients with and without COPD. Exclusive preventive measures should be considered in patients with reduced %FEV1 undergoing esophagectomy.

Influence of Damaged Stomach on Anastomotic Leakage following Cervical Esophagogastrostomy in Patients with Esophageal Cancer.

BACKGROUND: Anastomotic leakage (AL) is one of the most common complications after esophagectomy. Although some patients have a history of peptic ulcers or other prior stomach diseases, the influence of a damaged stomach (DS) on AL incidence remains unclear. Therefore, we investigated the association between DS and incidence of AL in patients who underwent esophagectomy. PATIENTS AND METHODS: Between 2015 and 2019, a total of 447 consecutive patients who underwent cervical esophagogastrostomy using gastric tube following esophagectomy were enrolled. DS was defined on the basis of endoscopic findings of ulcers or scars due to medical history or prior treatment. We compared the incidence of AL between patients with DS and those with a healthy stomach (HS). Univariate and multivariate logistic regression analyses were used to identify factors that could predict AL incidence. RESULTS: Fifty-one patients (11.4%) had DS. Causes of DS included peptic ulcer (n = 36), endoscopic resection for early gastric cancer (n = 9), percutaneous endoscopic gastrostomies (n = 5), and post-chemotherapy scar for gastric malignant lymphoma (n = 1). Overall, AL occurred in 35 patients (7.8%). The incidence of AL in the DS group was significantly higher than in the HS group (15.7 vs. 6.8%, p = 0.03). DS was one of the independent predictive factors for AL (odds ratio, 2.75; 95% confidence interval, 1.10-6.92; p = 0.03) on multivariate analysis. Further, the diseases in the lower third of the conduit were associated with AL. CONCLUSIONS: Presence of DS can predict AL in patients who underwent cervical esophagogastrostomy after esophagectomy.