Molecular and immunological characteristics of postoperative relapse in lymph node-positive esophageal squamous cell cancer.

BACKGROUND: The molecular and immunological characteristics of primary tumors and positive lymph nodes in esophageal squamous cell carcinoma (ESCC) are unknown and the relationship with recurrence is unclear, which this study attempted to explore. METHODS: A total of 30 ESCC patients with lymph node positive (IIB-IVA) were enrolled. Among them, primary tumor and lymph node specimens were collected from each patient, and subjected to 551-tumor-targeted DNA sequencing and 289-immuno-oncology RNA panel sequencing to identify the different molecular basis and immunological features, respectively. RESULTS: The primary tumors exhibited a higher mutation burden than lymph nodes (p < 0.001). One-year recurrent ESCC exhibited a higher Mucin16 (MUC16) mutation rate (p = 0.038), as well as univariate and multivariate analysis revealed that MUC16 mutation is independent genetic factor associated with reduced relapse-free survival (univariate, HR: 5.39, 95% CI: 1.67-17.4, p = 0.005; multivariate, HR: 7.36, 95% CI: 1.79-30.23, p = 0.006). Transcriptomic results showed non-relapse group had higher cytolytic activity (CYT) score (p = 0.025), and was enriched in the IFN-α pathway (p = 0.036), while those in the relapsed group were enriched in the TNF-α/NF-κB (p = 0.001) and PI3K/Akt pathway (p = 0.014). CONCLUSION: The difference in molecular characteristics between primary lesions and lymph nodes may be the cause of the inconsistent clinical outcomes. Mutations of MUC16 and poor immune infiltration are associated with rapid relapse of nodes-positive ESCC.

Reciprocal inhibition between TP63 and STAT1 regulates anti-tumor immune response through interferon-γ signaling in squamous cancer.

Squamous cell carcinomas (SCCs) are common and aggressive malignancies. Immune check point blockade (ICB) therapy using PD-1/PD-L1 antibodies has been approved in several types of advanced SCCs. However, low response rate and treatment resistance are common. Improving the efficacy of ICB therapy requires better understanding of the mechanism of immune evasion. Here, we identify that the SCC-master transcription factor TP63 suppresses interferon-γ (IFNγ) signaling. TP63 inhibition leads to increased CD8+ T cell infiltration and heighten tumor killing in in vivo syngeneic mouse model and ex vivo co-culture system, respectively. Moreover, expression of TP63 is negatively correlated with CD8+ T cell infiltration and activation in patients with SCC. Silencing of TP63 enhances the anti-tumor efficacy of PD-1 blockade by promoting CD8+ T cell infiltration and functionality. Mechanistically, TP63 and STAT1 mutually suppress each other to regulate the IFNγ signaling by co-occupying and co-regulating their own promoters and enhancers. Together, our findings elucidate a tumor-extrinsic function of TP63 in promoting immune evasion of SCC cells. Over-expression of TP63 may serve as a biomarker predicting the outcome of SCC patients treated with ICB therapy, and targeting TP63/STAT/IFNγ axis may enhance the efficacy of ICB therapy for this deadly cancer.

Laparoscopic gastric dissociation using a two-port approach in minimally invasive esophagectomy.

BACKGROUND: A new approach for laparoscopic gastric dissociation in minimally invasive esophagectomy (MIE) was attempted. This study aimed to evaluate the short-term outcomes, safety, and efficacy of two-port laparoscopy using the McKeown procedure. METHODS: This retrospective study included 206 consecutive patients with esophageal cancer who underwent a modified two-port laparoscopic or the traditional five-port McKeown procedure at our institution from August 2019 to August 2021. Surgical outcomes of the two methods were compared. RESULTS: Of the 206 patients, 106 (51.46%) underwent the modified two-port procedure, whereas 100 (48.54%) underwent the traditional five-port procedure. Subsequently, 182 propensity score-matched patients were compared. No significant differences were observed in laparoscopic operative time, blood loss during laparoscopic surgery, number of dissected lymph nodes, and pain score on postoperative day 1 between the two groups. The rate of complication and postoperative length of hospital stay did not differ significantly between the two groups. The total hospitalization cost also did not differ significantly between the two groups (p = 0.325). No postoperative deaths occurred in either group. CONCLUSIONS: Our findings demonstrate that laparoscopic gastric dissociation using the two-port approach in MIE is a safe and effective procedure, with short-term outcomes comparable to those of the traditional five-port procedure in patients with esophageal cancer. Larger studies with longer follow-up duration are warranted.

DAB2IP predicts treatment response and prognosis of ESCC patients and modulates its radiosensitivity through enhancing IR-induced activation of the ASK1-JNK pathway.

BACKGROUND: Disabled homolog 2 interacting protein (DAB2IP) plays a tumor-suppressive role in several types of human cancers. However, the molecular status and function of the DAB2IP gene in esophageal squamous cell carcinoma (ESCC) patients who received definitive chemoradiotherapy is rarely reported. METHODS: We examined the expression dynamics of DAB2IP by immunohistochemistry (IHC) in 140 ESCC patients treated with definitive chemoradiotherapy. A series of in vivo and in vitro experiments were performed to elucidate the effect of DAB2IP on the chemoradiotherapy (CRT) response and its underlying mechanisms in ESCC. RESULTS: Decreased expression of DAB2IP in ESCCs correlated positively with ESCC resistance to CRT and was a strong and independent predictor for short disease-specific survival (DSS) of ESCC patients. Furthermore, the therapeutic sensitivity of CRT was substantially increased by ectopic overexpression of DAB2IP in ESCC cells. In addition, knockdown of DAB2IP dramatically enhanced resistance to CRT in ESCC. Finally, we demonstrated that DAB2IP regulates ESCC cell radiosensitivity through enhancing ionizing radiation (IR)-induced activation of the ASK1-JNK signaling pathway. CONCLUSIONS: Our data highlight the molecular etiology and clinical significance of DAB2IP in ESCC, which may represent a new therapeutic strategy to improve therapy and survival for ESCC patients.

Endoscopic Management of Early Upper Gastrointestinal Bleeding After Minimally Invasive Ivor-Lewis Esophagectomy.

Minimally invasive esophagectomy is now accepted as a regular treatment modality for esophageal cancer. Upper gastrointestinal (GI) bleeding is a common postoperative adverse event of esophagectomy. However, there are very few reports in the literature on endoscopic management of early upper GI bleeding after an esophagectomy. Here, we report the successful management of such an early case of GI bleeding after thoracolaparoscopic esophagectomy by the use of endoscopic intrathoracic anastomosis.

[Study on safety and feasibility of minimally invasive esophagectomy without the use of postoperative nasogastric tube decompression].

OBJECTIVE: To investigate the safety and feasibility of forgoing postoperative nasogastric tube decompression in minimally invasive esophagectomy for patients with esophagus carcinoma. METHODS: Clinical data of 90 eligible patients who underwent elective minimally invasive esophagectomy in our department from January 2012 to May 2013 by the same surgical team were retrospectively analyzed. Among them, 45 patients did not receive the use of postoperative nasogastric tube decompression and 45 patients received nasogastric tube decompression after operation. The observation parameters included the time to first flatus, the time to intake of fluid diet, the duration of postoperative hospitalization, pharyngalgia, vomiting, and postoperative complications, as well as the need for placing or replacing the nasogastric tube. RESULTS: The incidence of pharyngalgia was significantly higher in nasogastric tube group (100% vs 44.4%, P<0.001). The time to intake of fluid diet [median 2 d(2-4 d) vs. median 9 d(7-20 d), P<0.001] and the time to first flatus [median 3 d(3-8 d) vs. median 6 d(3-9 d), P<0.001] were all significantly shorter in non-nasogastric tube group as compared to nasogastric tube group. Compared with the nasogastric tube group, the non-nasogastric tube group had shorter postoperative hospital stay (P<0.001). There were no significant differences in the incidence of postoperative complications and vomiting between two groups. CONCLUSION: Minimally invasive esophagectomy without the use of postoperative nasogastric tube decompression is safe and feasible, which can improve recovery and shorten postoperative hospital stay.

Use of a fast-track surgery protocol on patients undergoing minimally invasive oesophagectomy: preliminary results.

OBJECTIVES: The aim of this study was to evaluate the safety and effectiveness of a fast-track surgery (FTS) protocol on patients undergoing minimally invasive oesophagectomy. METHODS: We retrospectively analysed the clinical data of 80 eligible patients who underwent elective minimally invasive oesophagectomy in our department from January 2012 to April 2013 by the same surgical team. Two groups of these patients were compared. The control group comprised patients treated with traditional methods. Clinical parameters were compared. The study group was formed by patients treated with the fast-track concept, such as (i) a semi-liquid meal was administered up to 6 h before surgery and the patients were made to drink 200 ml of 10% glucose solution 3 h before surgery; (ii) no nasogastric tube, no abdominal drainage tube and no draining sinus in the neck; (iii) the chest tube and catheter were removed as early as possible; (iv) prevention of hypothermia therapy; (v) an attempt at bedside rehabilitation on postoperative day (POD) 2; and (vi) early postoperative enteral nutrition, restrictive intravenous fluids intraoperatively and postoperatively, and oral feeding initiated 48 h after surgery. RESULTS: There were no significant differences between the two groups with regard to age, sex, pathologic tumor-node-metastasis stage, tumour location, pathology, American Society of Anesthesiologists score, preoperative albumin level, 30-day readmission or complications (P >0.05). Compared with the conventional group, the FTS group had earlier first flatus [(3 (3-4) vs 6 (6-7) days], less fluid transfusion [2.1 (2.06-2.2) vs 2.8 (2.7-2.9) l] and shorter postoperative hospital stay [7 (6-9) days vs 12 (10-16.5) days] (P <0.05). There was no difference between the two groups with regard to vomiting, but patients in the conventional group suffered from/experienced pharyngitis considerably more than the FTS group (P <0.001). CONCLUSIONS: FTS on patients with oesophageal cancer receiving minimally invasive oesophagectomy is safe, feasible and efficient, and can accelerate postoperative rehabilitation. Compared with the conventional protocol, its advantages were limited to short-term follow-up.

Minimally invasive esophagectomy-left neck anastomosis.

Minimally invasive esophagectomy (MIE) is supplementary to open surgery in the thoracic surgery. A 65-year-old male was identified with middle thoracic esophageal squamous cell carcinoma by gastroscopy. In preoperative examinations, neither obvious abnormality nor distant metastasis was noted, and he could tolerate the esophagectomy according to his heart and lung function tests. Chest computed tomography (CT) and endoscopic ultrasonography showed no visible swollen lymph node in the mediastinum. The cTNM classification was T2N0M0. Therefore, MIE was performed. The patient recovered well after the surgery.