Fully robotic side-to-side stapled anastomosis provides less anastomotic leakage than conventional minimally invasive approach in Ivor Lewis esophagectomy.

INTRODUCTION: This study evaluates surgical outcomes of minimally invasive Ivor Lewis esophagectomy (ILE) for esophageal and esophagogastric cancer, with the comparison of the robotic approach (RA) and the conventional minimally invasive approach (CA). METHODS: Selected patients who underwent minimally invasive ILE for esophageal cancer were included between January 2017 and December 2023. We retrospectively investigated the patients' background characteristics and the short-term surgical outcomes. RESULTS: In this period, among a total of 840 esophagectomies, 81 patients (9.6%) underwent minimally invasive ILE, consisting of 24 cases with RA and 57 with CA. The major indications for ILE were adenocarcinoma of the distal esophagus or esophagogastric junction and patients with prior head and neck cancer treatment. Among these thoracic approaches, there were no significant differences in the patients' indications and characteristics, including age, histology, tumor location, clinical TNM stage, and preoperative therapy. Compared with the CA group, no anastomotic leakage was observed in the RA group (17.5% vs. 0, p = .035). Rates of total postoperative complications and length of hospital stay also tended to be reduced in the RA group but did not reach significance. CONCLUSION: In the Ivor Lewis esophagectomy with a side-to-side linear-stapled anastomosis, the fully robotic approach has the potential to powerfully reduce anastomotic leakage compared to the conventional minimally invasive approach.

Minimally Invasive Esophagectomy Provides Better Short- and Long-Term Outcomes Than Open Esophagectomy in Locally Advanced Esophageal Cancer.

BACKGROUND: Minimally invasive esophagectomy (MIE) has been increasingly performed for locally advanced esophageal cancer in place of open transthoracic esophagectomy (OE). This study explored the significance of MIE for esophageal squamous cell carcinoma (ESCC), focusing mainly on the depth of primary esophageal tumors. METHODS: This study retrospectively assessed short- and long-term outcomes of patients who underwent esophagectomy for ESCC from 2005 through 2021. The inverse probability of the treatment-weighting (IPTW) method was used to compare the outcomes between OE and MIE. The outcomes also were evaluated in the subgroups stratified by cT category. RESULTS: Among 1117 patients, 447 (40%) underwent OE and 670 (60%) underwent MIE. After IPTW adjustment, the incidence of any postoperative complications was significantly higher in the OE group than in the MIE group (60.8% vs 53.7%; p = 0.032), whereas the R0 resection rate was significantly higher in the MIE group (98.6% vs 92.7%; p < 0.001). The MIE group showed better 3 year overall and cancer-specific survival than the OE group (p < 0.001). The incidence of locoregional recurrence within the surgical field was significantly more frequent in the OE group (p < 0.001). In the subgroup analysis stratified by cT category, the R0 resection rate was significantly higher and the incidence of locoregional recurrence was lower in the MIE group among the patients with cT3-4 tumors. In the patients with cT1-2 tumors, MIE showed no significant benefit over OE. CONCLUSIONS: For the patients with cT3-4 tumors, MIE showed fewer postoperative complications, better locoregional control, and better prognosis than OE. Compared with OE, MIE is beneficial, especially for locally advanced ESCC.

Anatomical factor associated with thoracic procedural difficulty in robot-assisted minimally invasive esophagectomy.

BACKGROUND: Robotic surgical systems with full articulation of instruments, tremor filtering, and motion scaling can potentially overcome the procedural difficulties in endoscopic surgeries. However, whether robot-assisted minimally invasive esophagectomy (RAMIE) can overcome anatomical difficulties during thoracoscopic esophagectomy remains unclear. This study aimed to clarify the anatomical and clinical factors that influence the difficulty of RAMIE in the thoracic region. METHODS: Forty-five patients who underwent curative-intent RAMIE with upper mediastinal lymph node dissection for esophageal cancer were included. Using preoperative computed tomography images, we calculated previously reported anatomical indices to assess the upper mediastinal narrowness and vertebral body projections in the middle thoracic region. The factors influencing thoracic operative time were then investigated. RESULTS: During the thoracic procedure, the median operative time was 215 (124-367) min and the median blood loss was 20 (5-190) mL. Postoperatively, pneumonia, anastomotic leakage, and recurrent laryngeal nerve palsy occurred in 17.8%, 2.2%, and 6.7% of the patients, respectively. The multiple linear regression model revealed that a narrow upper mediastinum and greater blood loss during the thoracic procedure were significant factors associated with a prolonged thoracic operative time (P = 0.025 and P < 0.001, respectively). Upper mediastinal narrowing was not associated with postoperative complications. CONCLUSIONS: A narrow upper mediastinum was significantly associated with a prolonged thoracic operative time in patients with RAMIE.

Development and Validation Study of the Prognostic Impact of Deep Learning-Determined Myxoid Stroma After Neoadjuvant Chemotherapy in Patients with Esophageal Squamous Cell Carcinoma.

PURPOSE: This study was designed to investigate the prognostic significance of artificial intelligence (AI)-based quantification of myxoid stroma in patients undergoing esophageal squamous cell carcinoma (ESCC) surgery after neoadjuvant chemotherapy (NAC) and to verify its significance in an independent validation cohort from another hospital. METHODS: We evaluated two datasets of patients with pathological stage II or III ESCC who underwent surgery after NAC. Cohort 1 consisted of 85 patients who underwent R0 surgery for the primary tumor after NAC. Cohort 2, the validation cohort, consisted of 80 patients who received same treatments in another hospital. AI-based myxoid stroma was evaluated in resected specimens, and its area was categorized by using the receiver operating characteristic curve for overall survival (OS) of cohort 1. RESULTS: The F1 scores, which are the degree of agreement between the automatically detected myxoid stroma and manual annotations, were 0.83 and 0.79 for cohorts 1 and 2. The myxoid stroma-high group had a significantly poorer prognosis than the myxoid stroma-low group in terms of OS, disease-specific survival (DSS), and recurrence-free survival (RFS) in cohort 1. Comparable results were observed in cohort 2, where OS, DSS, and RFS were significantly affected by myxoid stroma. Multivariate analysis for RFS revealed that AI-determined myxoid stroma-high was one of the independent prognostic factors in cohort 1 (hazard ratio [HR] 1.97, p = 0.037) and cohort 2 (HR 4.45, p < 0.001). CONCLUSIONS: AI-determined myxoid stroma may be a novel and useful prognostic factor for patients with pathological stage II or III ESCC after NAC.

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.

Uptake and accumulation mechanisms of hexachloroplatinate(IV) ions in the unicellular alga, Pseudococcomyxa simplex.

Platinum uptake was examined by adding hexachloroplatinate(IV) solution to the unicellular alga Pseudococcomyxa simplex. After the addition of platinum solution ([Pt] = 100 mg/kg, pH 3.2-3.2) for a certain time, the cells were quickly frozen and subjected to µ-XRF (X-ray fluorescence) analysis using synchrotron X-rays. The beam size of approximately 1 micrometer allowed visualization of the platinum distribution within a single cell. On the other hand, we examined platinum uptake in enzyme-treated protoplasts and lyophilized cells and found that the platinum uptake concentrations in these samples were higher than in living in-vivo cells. Cell wall and cell metabolism were presumed to interfere with the uptake of hexachloroplatinate(IV) ions. All platinum ions taken up by the cells were reduced to divalent form. The effect of light on platinum addition was also investigated. When platinum was added under light conditions, some samples showed higher platinum accumulation than under shade conditions.

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.

Genomic signatures of past and present chromosomal instability in Barrett's esophagus and early esophageal adenocarcinoma.

The progression of precancerous lesions to malignancy is often accompanied by increasing complexity of chromosomal alterations but how these alterations arise is poorly understood. Here we perform haplotype-specific analysis of chromosomal copy-number evolution in the progression of Barrett's esophagus (BE) to esophageal adenocarcinoma (EAC) on multiregional whole-genome sequencing data of BE with dysplasia and microscopic EAC foci. We identify distinct patterns of copy-number evolution indicating multigenerational chromosomal instability that is initiated by cell division errors but propagated only after p53 loss. While abnormal mitosis, including whole-genome duplication, underlies chromosomal copy-number changes, segmental alterations display signatures of successive breakage-fusion-bridge cycles and chromothripsis of unstable dicentric chromosomes. Our analysis elucidates how multigenerational chromosomal instability generates copy-number variation in BE cells, precipitates complex alterations including DNA amplifications, and promotes their independent clonal expansion and transformation. In particular, we suggest sloping copy-number variation as a signature of ongoing chromosomal instability that precedes copy-number complexity. These findings suggest copy-number heterogeneity in advanced cancers originates from chromosomal instability in precancerous cells and such instability may be identified from the presence of sloping copy-number variation in bulk sequencing data.

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.

Emergent endoscopic submucosal dissection for a polypoid fibroadipose tumor accidentally disgorged from the mouth: an organ-preserving minimally invasive treatment.

Video 1The yellow protruded lesion at the larynx is different from the main lesion.

KRAS mutation as a predictor of insufficient trastuzumab efficacy and poor prognosis in HER2-positive advanced gastric cancer.

PURPOSE: Although RAS and PIK3CA mutations have been associated with resistance to anti-EGFR antibody in colorectal cancer or trastuzumab in breast cancer, their implications for trastuzumab resistance in HER2-positive advanced gastric cancer (AGC) remains unclear. We aimed to assess the relationship between trastuzumab efficacy and mutation status in the HER family signaling pathway. METHODS: This study retrospectively evaluated patients with HER2-positive AGC who received first-line trastuzumab-containing chemotherapy between March 2011 and November 2015. Multiplex genotyping, including KRAS, NRAS, PIK3CA, and BRAF, was then performed using the Luminex Assay, after which KRAS amplification was measured using quantitative real-time reverse transcription-polymerase chain reaction. Thereafter, the association between genetic alterations and clinical outcomes were evaluated. RESULTS: KRAS mutation (MT) was detected in 6 of 77 patients (7.8%), whereas KRAS amplification was found in 15 of 67 patients (22%). No mutations in NRAS, PIK3CA, or BRAF were identified. The KRAS MT group showed significantly worse response rates (16.7% vs. 66.2%, P = 0.016), progression-free survival [median, 4.8 vs. 11.6 months; hazard ratio (HR), 3.95; 95% CI, 1.60-9.76; P = 0.0029], and overall survival (11.5 vs. 23.6 months; HR, 3.80; 95% CI, 1.56-9.28; P = 0.033) compared to the KRAS wild-type group. KRAS amplification had no effect on clinical outcomes. CONCLUSION: KRAS mutation was an independent prognostic factor for poor survival and might predict insufficient trastuzumab efficacy, whereas KRAS amplification showed no prognostic significance during trastuzumab treatment. Further investigations are warranted to confirm the predictive value of KRAS status in HER2-positive AGC.

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.

Omental Flap Wrapping Around the Esophagogastric Anastomosis and Association with Anastomotic Leak in Esophagectomy for Esophageal Cancer: A Propensity Score-Matching Analysis.

BACKGROUND: Anastomotic leakage after esophagectomy remains frequent and can cause surgery-related mortality. Wrapping the esophageal conduit anastomosis with a greater omental flap is a proposed method to reduce leakage. However, the usefulness of omental wrapping (OW) has not been elucidated. STUDY DESIGN: This study included 338 patients with esophageal cancer who underwent McKeown esophagectomy and reconstruction using a gastric conduit between April 2005 and August 2021. The study participants were divided into 2 groups: reconstructions with and without OW. We performed propensity score matching between the reconstructions with and without OW. The propensity score was calculated according to baseline characteristics, performance and physical statuses, presence of comorbidities, and types and details of the treatment procedures undergone. RESULTS: We included 338 patients (169 with OW and 169 without OW) in this study. After matching, all clinical and surgical features were statistically equivalent between the groups. Reconstruction and anastomosis with OW were significantly associated with decreased leakage (p = 0.016) and surgical site infection (p = 0.041). Reconstruction and anastomosis with OW also exhibited a trend toward more frequent stricture, although this was not statistically significant (p = 0.051). Independent risk factors for leakage were reconstruction without OW (odds ratio, 2.55; 95% CI, 1.234 to 5.285; p = 0.0088) and younger age (odds ratio, 1.06; 95% CI, 1.012 to 1.102; p = 0.011). CONCLUSIONS: OW can reduce leakage in the esophagogastric anastomosis. OW can be performed conveniently and may be recommended to reinforce the anastomotic site, which can improve short-term outcomes after esophagectomy for esophageal cancer.