Right gastroepiploic artery length determined anastomotic leakage after minimally invasive esophagectomy for esophageal cancer: a prospective cohort study.

BACKGROUND: This prospective cohort study, conducted at a high-volume esophageal cancer center from July 2019 to July 2022, aimed to investigate the link between the right gastroepiploic artery (RGEA) length and anastomotic leakage (AL) rates following minimally invasive esophagectomy (MIE). Real-world data on stomach blood supply in the Chinese population were examined. MATERIALS AND METHODS: A total of 516 cases were enrolled, categorized into two groups based on the Youden index-determined optimal cut-off value for the relative length of RGEA (length of RGEA/length of gastric conduit, 64.69%) through ROC analysis: Group SR (short RGEA) and Group LR (long RGEA). The primary observation parameter was the relationship between AL incidence and the ratio of direct blood supply from RGEA. Secondary parameters included the mean length of the right gastroepiploic artery, greater curvature, and the connection type between right and left gastroepiploic vessels. Patient data were prospectively recorded in electronic case report forms. RESULTS: The study revealed median lengths of 43.60 cm for greater curvature, 43.16 cm for the gastric conduit, and 26.75 cm for RGEA. AL, the most common postoperative complication, showed a significant difference between groups (16.88 vs. 8.84%, P =0.01). Multivariable binary logistic regression identified Group SR and LR (odds ratio: 2.651, 95% CI: 1.124-6.250, P =0.03) and Neoadjuvant therapy (odds ratio: 2.479, 95% CI: 1.374-4.473, P =0.00) as independent predictors of AL. CONCLUSIONS: The study emphasizes the crucial role of RGEA length in determining AL incidence in MIE for esophageal cancer. Preserving RGEA and fostering capillary arches between RGEA and LGEA are recommended strategies to mitigate AL risk.

Learning curve in relation to health-related quality of life in long-term, disease free survivors after McKeown minimally invasive esophagectomy.

BACKGROUND: The potential impact of learning curve on long-term health-related quality of life (QoL) after esophagectomy for cancer has not been investigated. The aim of this article is to investigate the relationship between learning curve for McKeown minimally invasive esophagectomy (MIE) and health-related quality of life (QoL) in long-term, disease free survivors up to 10 years after esophageal cancer resection. METHODS: Esophageal cancer patients who underwent McKeown MIE between 2009 and 2019 were identified in which 280 who were free of disease at the time of survey and completed health-related QoL and symptom questionnaires, including EORTC QLQ-C30, EORTC QLQ-OES18, and Digestive Symptom Questionnaire. Patients were assessed in 3 cohorts according to the learning phases of expertise reported by our previous study: initial phase; plateau phase, and; experienced phase. RESULTS: Median time from operation to survey was 5.8 years (interquartile range 4.6-8.2). The QLQ-C30 mean scores of functional scales, and symptom scales of respiratory and digestive systems including dyspnea (P = 0.006), shortness of breath (P = 0.003), and dysphagia (P = 0.031) were significantly better in experienced phase group. Furthermore, in the subgroup analyses for patients without postoperative major complications, patients in the initial learning phase remained suffering from more symptoms of dyspnea (P = 0.040) and shortness of breath (P = 0.001). CONCLUSION: Esophageal cancer patients undergoing McKeown MIE in initial learning phase tend to suffer from a deterioration in long-term health-related QoL and higher symptomatic burden as compared to experienced learning phase, which did not improved over time and warranted more attention.

Comparison of two different methods for lymphadenectomy along the left recurrent laryngeal nerve by minimally invasive esophagectomy in patients with esophageal squamous cell carcinoma: a prospective randomized trial.

BACKGROUND: Lymph nodes along the left recurrent laryngeal nerve (LRLN) is thought to be highly involved in esophageal cancer. Given the unique anatomical positioning of the nerve, performing lymphadenectomy in this region requires advanced techniques within limited working space. Meanwhile, high incidence of morbidity and mortality is associated with lymphadenectomy. Although several methods have been applied to reduce the technical requirement and the incidence of postoperative complication, the optimal method remains controversial. METHODS: This study was a single-center, prospective, randomized trial to investigate the utility of lymphadenectomy along the LRLN during the minimally invasive esophagectomy in esophageal squamous cell carcinoma patients by comparing the surgical outcome, postoperative complication, survival rate, and quality of life (QoL) between the retraction method (RM) and the suspension method (SM) in patients with esophageal cancer from June 2018 to November 2020. QoL was assessed according to questionnaire: EQ-5D-5L. RESULTS: Of 94 patients were enrolled and randomized allocated to RM and SM group equally. Characteristics did not differ between groups. The duration of lymph node dissection along LRLN was significant longer in SM group ( P <0.001). No difference was observed about postoperative complications. One of in-hospital death was occurred in each group ( P >0.999). Patients in neither of groups exhibiting difference about 3-year disease-free survival rate ( P =0.180) and overall survival rate ( P =0.430). No difference was observed in postoperative QoL between groups at different time points (all, P >0.05). CONCLUSION: Both methods of lymph node dissection along the LRLN during minimally invasive esophagectomy in esophageal squamous cell carcinoma patients are technically feasible and safe. The RM appears more favorable in terms of reducing surgical duration compared to the SM.

Impact of perioperative decreased serum albumin level on anastomotic leakage in esophageal squamous cell carcinoma patients treated with neoadjuvant chemotherapy followed by minimally invasive esophagectomy.

BACKGROUND: Anastomotic leakage (AL) is a severe complication following esophagectomy with high mortality. Perioperative decreased serum albumin level is considered a predictive of AL, however, its impact on AL incidence in patients treated with neoadjuvant chemotherapy (NCT) followed by minimally invasive esophagectomy (MIE) is not well defined. METHODS: The data of 318 consecutive esophageal cancer patients who underwent MIE were collected retrospectively from January 2021 to December 2021. The perioperative level of albumin was detected and the baseline of altering levels for albumin was established. The incidence of postoperative complications and survival rate were analyzed between groups. RESULTS: After exclusion, 137 patients were enrolled and assigned to more decreased albumin (MA) and less decreased albumin (LA) groups. The levels of albumin descended significantly after MIE (p < 0.0001). There was no significant difference in the clinicopathologic characteristics or surgical outcomes between groups. The incidence of postoperative AL was 10.2% in MA group and 1.4% in LA group (p = 0.033). Three patients died due to AL in MA group, while no mortality was observed in LA group (p = 0.120). The rate of other postoperative complications was similar between groups. Progression-free survival (PFS) in LA group was a little higher than that in MA group, but it was no significant difference (p = 0.853). Similarly, no difference was observed in overall survival (OS) between groups (p = 0.277). CONCLUSIONS: Severely deficient serum albumin after MIE was an indicator of AL in esophageal cancer patients treated with NCT. TRIAL REGISTRATION: Chinese clinical trial registry: ChiCTR2200066694, registered December14th,2022. https://www.chictr.org.cn/edit.aspx?pid=185067&htm=4 .

Concurrent radiotherapy cannot provide superiority of surgical oncological outcome and long-term survival rate in locally advanced esophageal squamous cell carcinoma patients receiving neoadjuvant chemotherapy followed by minimally invasive esophagectomy.

BACKGROUND: To evaluate effectiveness of concurrent radiotherapy in esophageal cancer patient treated with neoadjuvant therapy. METHODS: The data of 1026 consecutive esophageal squamous cell carcinoma (ESCC) patients who underwent minimally invasive esophagectomy (MIE) were retrospectively collected. The main inclusion criteria were patients with locally advanced (cT2-4N0-3M0) ESCC who underwent neoadjuvant chemoradiotherapy (NCRT) or neoadjuvant chemotherapy (NCT) followed by MIE, and divided into two groups according to different neoadjuvant strategies. Propensity score matching was performed to improve the comparability between the two groups. RESULTS: After exclusion and matching, 141 patients were enrolled retrospectively: 92 received NCT, and 49 received NCRT. No difference in clinicopathologic characteristics or incidence of adverse events between groups. A shorter operation time (215.7 ± 35.5 min) (p < 0.001), less blood loss (111.2 ± 67.7 ml) (p = 0.0007) and a greater number of lymph nodes retrieved (33.8 ± 11.7) (p = 0.002) were observed in NCT group than in NCRT group. The incidence of postoperative complications was similar between groups. Although patients in NCRT group had better pathological complete response (16, 32.7%) (p = 0.0026) and ypT0N0 (10, 20.4%) (p = 0.0002) rates, there was no significant difference in 5-year progression-free survival (p = 0.1378) or disease-specific survival (p = 0.1258) between groups. CONCLUSIONS: Compared with NCRT, NCT has certain advantages in that it can simplify the surgical procedure and decrease the surgical technique required without compromising the surgical oncological outcomes and long-term survival of patients.

Safety and feasibility of three-dimensional McKeown minimally invasive esophagectomy.

BACKGROUND: To compare the perioperative outcomes from McKeown minimally invasive esophagectomy (MIE) when performed in three-dimensional versus two-dimensional visualization system, and investigate the learning curve of a single surgeon who implemented three-dimensional McKeown MIE. METHODS: A total of 335 consecutive cases (three-dimensional or two-dimensional) were identified. Perioperative clinical parameters were compared and cumulative sum learning curve was plotted. Propensity score matching was used to reduce selection bias from confounding factors. RESULTS: Patients in three-dimensional group were associated with more chronic obstructive pulmonary disease (23.9% vs 3.0%, p < 0.01). After propensity score matching (108 matched patients in each groups), this finding was no longer statistically significant. Comparing to two-dimensional group, significant improvement in total retrieved lymph nodes (28 vs 33, p = 0.003) was observed in three-dimensional group. In addition, more lymph nodes around the right recurrent laryngeal nerve were harvested in three-dimensional group than that in two-dimensional group (p = 0.045). However, there were no significantly differences were found between the two groups in terms of other intraoperative parameters (e.g., operative time) and postoperative relevant outcomes (e.g., lung infection). Furthermore, the change point in the cumulative sum learning curves for intraoperative blood loss and thoracic procedure time was 33 procedures, respectively. CONCLUSION: Three-dimensional visualization system appears to be superior in performing lymphadenectomy during McKeown MIE to that of a two-dimensional technique. For surgeons proficient in performing two-dimensional McKeown MIE, the learning curve for a three-dimensional procedure appears to begin near proficiency after more than 33 cases.

Neoadjuvant Anlotinib and chemotherapy followed by minimally invasive esophagectomy in patients with locally advanced esophageal squamous cell carcinoma: Short-term results of an open-label, randomized, phase II trial.

Background: Clinical benefits of neoadjuvant Anlotinib for locally advanced esophageal squamous cell carcinoma (ESCC) remains unclear. This study evaluated the efficacy and safety of neoadjuvant Anlotinib plus chemotherapy followed by minimally invasive esophagectomy (MIE) for the treatment of patients with locally advanced ESCC. Methods: Patients with locally advanced ESCC were randomly assigned to neoadjuvant Anlotinib combined with chemotherapy (Anlotinib group) or neoadjuvant chemoradiotherapy alone (nCRT group) with an allocation ratio of 1:1. The primary endpoint was the R0 surgical resection rate. Secondary endpoints included postoperative pathologic stage, complete response (CR) rate, and safety. Safety was assessed by adverse events (AEs) and postoperative complications. Results: From August 2019 to August 2021, 93 patients were assigned to the nCRT or Anlotinib group. Of the 93 patients, 79 underwent MIE and were finally included in the per-protocol set (nCRT group: n=39; Anlotinib group: n=40). The R0 resection rate was 97.4% for nCRT versus 100.0% for Anlotinib group (p>0.05). Compared with the nCRT group, patients in the Anlotinib group had shorter total operation duration (262.2 ± 39.0 vs. 200.7 ± 25.5 min, p=0.010) and less blood loss (161.3 ± 126.7 vs. 52.4 ± 39.3 mL, p<0.001). No significant differences were found in the postoperative pathologic stage between the Anlotinib group and nCRT group (all p>0.05). Besides, the incidences of AEs (80.0% vs. 92.3%) and postoperative complications (22.5% vs. 30.8%) were similar between the two groups (all p>0.05). Conclusions: Neoadjuvant Anlotinib plus chemotherapy had a similar safety profile and pathologic response, but better surgical outcomes than nCRT for locally advanced ESCC.

Solitary Celiac Lymph Node Metastasis Has a Better Long-Term Survival Compared With Solitary Mediastinal Lymph Node Metastasis in Esophagectomy of Esophageal Squamous Cell Cancer: A Propensity Score Matching Analysis.

Background: The prognostic benefit of extensive lymphadenectomy remains controversial in esophageal squamous cell carcinoma (ESCC). The purpose of this retrospective study was to investigate the potential effect of solitary mediastinal (SM) lymph node metastasis and solitary celiac (SC) lymph node metastasis on the short- and long-term outcomes for patients who underwent minimally invasive McKeown esophagectomy. Methods: From September 2009 to December 2020, a total of 934 cases were diagnosed with ESCC and underwent minimally invasive McKeown esophagectomy in our department; 223 cases met the inclusion and exclusion criteria. Propensity score matching (PSM) was utilized to contrast the postoperative results and long-term survival of Group 1 (SM) and Group 2 (SC). Univariate and multivariate Cox proportional hazards regression analyses were used on possible predictors of survival. Results: One hundred forty-seven patients were available for outcome comparison after PSM. The postoperative results were not significantly different between the two groups. In terms of long-term survival, the 5-year disease-free survival (DFS) was 37.6% and 57.3% (p = 0.191) and 5-year disease-specific survival (DSS) was 39.7% and 68.4% (p = 0.028) for Group 1 (SM) and Group 2 (SC), respectively. Univariate and multivariate Cox proportional hazards regression analyses showed that body mass index (BMI), pathologic stage (pStage), and SC/SM grouping had significant hazard ratios (HRs), which suggested that SC is associated with better DSS. Conclusion: This cohort study showed that SC lymph node metastasis has a better long-term survival compared with SM lymph node metastasis in esophagectomy of ESCC. The results challenge the current understanding and need confirmation in further research.

Spinal astrocytic FGFR3 activation leads to mechanical hypersensitivity by increased TNF-α in spared nerve injury.

BACKGROUND: Accumulated studies indicated a crucial role of astrocytes in neuropathic pain (NPP) development, spread and potentiation by a communication with the nervous system. Increased GFAP expression in dorsal horn of the spinal cord indicated the participation of astrocyte in NPP. However, the underlying mechanism is still in need of further investigations. METHODS: In our study, the spared nerve injury (SNI) model was established with partial sciatic nerve ligation. The expression status of FGFR3 was studied in spinal dorsal horn of SNI models. The molecular mechanism of spinal astrocytic FGFR3 activation in mechanical hypersensitivity was investigated. RESULTS: SNI rats showed with hind paw mechanical hypersensitivity and increased GFAP expression in their spinal cords. Increased FGFR3 expression was observed in spinal dorsal horn of SNI models, which was consistent with increased GFAP expression. Elevated FGFR3 upregulates GFAP and TNF-α expression in astrocytes in vivo and in vitro. FGFR3 inhibition by PD173074 lead to downregulation of GFAP and TNF-α and increased withdrawal threshold of SNI models. Mechanically, FGFR3-TBX3 axis activation enhanced TNF-α expression in cultured primary spinal astrocytes. Spinal TNF-α synthesis induced mechanical hypersensitivity in SNI rat models. CONCLUSION: FGFR3 is involved in NPP maintenance via FGFR3-TBX3 axis activation induced TNF-α synthesis. FGFR3 and correlated signaling pathways of astrocytes are potential molecular targets for NPP administration.