The Feasibility of Early Oral Feeding After Neoadjuvant Chemotherapy Combined With "Non-Tube No Fasting"-Enhanced Recovery.

BACKGROUND: This study aimed to investigate the feasibility of early oral feeding (EOF) after neoadjuvant chemotherapy (nCT) combined with "non-tube no fasting"-enhanced recovery after minimally invasive esophagectomy (MIE). METHODS: This retrospective study investigated patients who underwent nCT combined with non-tube no fasting-enhanced recovery after MIE in the Department of Thoracic Surgery, Ward I, of the authors' hospital from January 2014 to August 2017. These patients were divided into an early oral feeding (EOF) group (n = 112) and a late oral feeding (LOF) group (n = 69). The postoperative complications were compared between the two groups. RESULTS: The study enrolled 181 patients (112 patients in the EOF group and 69 patients in the LOF group). No significant differences were found between the two groups in the incidence rates of complications such as anastomotic leakage (P = 0.961), pneumonia (P = 0.450), respiratory failure (P = 0.944), heart failure (P = 1.000), acute respiratory distress syndrome (ARDS) (P = 0.856), and unplanned reoperation (P = 0.440), whereas the time to the first postoperative flatus/bowel movement (P < 0.001) and the postoperative length of stay (P < 0.001) were significantly better in the EOF group than in the LOF group.. CONCLUSIONS: In this study, EOF after nCT combined with non-tube no fasting-enhanced recovery after MIE did not significantly increase complications, but significantly shortened the time to the first postoperative flatus/bowel movement and the postoperative length of stay.

Stratification of lymph node metastasis improves diagnostic efficiency in thoracic esophageal squamous cell carcinoma.

INTRODUCTION: Difference of the short diameter of lymph nodes in the main regions of esophageal squamous cell carcinoma (ESCC) and its value in the diagnosis of lymph nodes need to explore. METHODS: The clinical data of patients with thoracic ESCC who underwent surgical treatment in our hospital were collected. The short diameters of the largest lymph node in each region of the patient were measured by preoperative enhanced computed tomography (CT) and were compared with the postoperative pathology. RESULTS: A total of 477 patients with thoracic ESCC who did not receive neoadjuvant therapy were enrolled in this study. The receiver operating characteristic curve suggested that the short diameters of the paracardial nodes, the left gastric nodes, the right recurrent laryngeal nerve nodes, and the left recurrent laryngeal nerve nodes could well predict the postoperative pathology of the lymph nodes, with area under curve (AUC) of 0.958, 0.937, 0.931, and 0.915, the corresponding cut-off values of 5.7 mm, 5.7 mm, 5.5 mm, and 4.8 mm, the corresponding sensitivities of 94.7%, 85.4%, 88.7%, and 79.4%, and the corresponding specificities of 93.7%, 96.3%, 86.2%, and 95.0%, respectively. The AUC of the thoracic paraesophageal lymph nodes, the subcarinal nodes and all regional lymph nodes were 0.845, 0.688, and 0.776, respectively. CONCLUSION: Region-based criterion for lymph node metastasis of thoracic ESCC is beneficial to improve the diagnostic efficiency of preoperative CT.

CircRNA CircZMYM4 inhibits the growth and metastasis of lung adenocarcinoma via the miR-587/ODAM pathway.

Circular RNAs (circRNAs) are known to regulate tumorigenesis. In this study, circRNAs microarray was used to analyze the circRNA expression in lung adenocarcinoma (LUAD) tissues, and CircRNA zinc finger MYM-type containing 4(circZMYM4) was selected for further analysis. In this study, we detected circZMYM4 expression in LUAD specimens and cell lines using RT-PCR. The expression of circZMYM4 was further verified in the GEO datasets and TCGA datasets. Gain-of-function and loss-of-function experiments were used to analyze the effects of circZMYM4 on LUAD in vivo and in vitro. The relationship between miR-587 and circZMYM4 or ODAM was predicted by bioinformatics tools and confirmed using dual-luciferase reporter assays and RNA-pull down. We found that circZMYM4 was distinctly down-regulated in LUAD tissues and cell lines. Functional assays revealed that circZMYM4 overexpression suppressed LUAD cell proliferation, metastasis and suppressed apoptosis, while miR-587 overexpression could weaken these effects. Importantly, circZMYM4 upregulated ODAM expression via sponging miR-587 to suppress LUAD progression. ODAM knockdown could reverse the repressive effect of circZMYM4 overexpression on cell proliferation, migration and invasion abilities. Overall, circZMYM4 regulates the miR-587/ODAM axis to suppress LUAD progression, which may become a potential biomarker and therapeutic target.

Minimally Invasive Versus Open McKeown for Patients with Esophageal Cancer: A Retrospective Study.

INTRODUCTION: McKeown minimally invasive esophagectomy (McKeown-MIE) offers advantages in short-term outcomes compared with McKeown open esophagectomy (McKeown-OE); however, debate as to whether MIE is equivalent or better than OE regarding survival outcomes is ongoing. OBJECTIVE: The aim of this study was to compare long-term survival between McKeown-MIE and McKeown-OE in a large cohort of esophageal cancer (EC) patients. METHODS: We used a prospective database (independently managed by LinkDoc company) of the Thoracic Surgery Department at Henan Cancer Hospital and included patients who underwent McKeown-MIE and McKeown-OE for EC from 1 January 2015 to 6 January 2018. The perioperative data and overall survival (OS) rate in the two groups were retrospectively compared. RESULTS: We included 502 patients who underwent McKeown-MIE (n = 306) or McKeown-OE (n = 196) for EC. The median age in the total patient population was 63 years. All baseline characteristics were well-balanced between the two groups. There was a significantly shorter mean operative time (269.76 min vs. 321.14 min, p < 0.001) in the OE group. The 30-day and in-hospital mortality rates were 0, and there was no difference in 90-day mortality (p = 0.053) between the groups. The postoperative stay was shorter in the MIE group and was 14 days and 18 days in the MIE and OE groups, respectively (p < 0.001). The OS at 60 months was 58.8% and 41.6% in the MIE and OE groups, respectively (p < 0.001) [hazard ratio 1.783, 95% confidence interval 1.347-2.359]. CONCLUSIONS: These results showed that McKeown-MIE was associated with better long-term survival than McKeown-OE for patients with resectable EC.

Neoadjuvant chemotherapy versus neoadjuvant chemoradiotherapy for locally advanced oesophageal squamous cell carcinoma: a single-Centre, open-label, randomized, controlled, clinical trial (HCHTOG1903).

BACKGROUND: Neoadjuvant therapy plus oesophagectomy has been accepted as the standard treatment for patients with potentially curable locally advanced oesophageal cancer. No completed randomized controlled trial (RCT) has directly compared neoadjuvant chemotherapy and neoadjuvant chemoradiation in patients with oesophageal squamous cell carcinoma (ESCC). The aim of the current RCT is to investigate the impact of neoadjuvant chemotherapy plus surgery and neoadjuvant chemoradiotherapy plus surgery on overall survival for patients with resectable locally advanced ESCC. METHODS: This open label, single-centre, phase III RCT randomized patients (cT2-T4aN + M0 and cT3-4aN0M0) in a 1:1 fashion to receive either the CROSS regimen (paclitaxel 50 mg/m2; carboplatin (area under the curve = 2), q1w, 5 cycles; and concurrent radiotherapy, 41.4 Gy/23 F, over 5 weeks) or neoadjuvant chemotherapy (paclitaxel 175 mg/m2; and cisplatin 75 mg/m2, q21d, 2 cycles). Assuming a 12% 5-year overall survival difference in favour of the CROSS regimen, 80% power with a two-sided alpha level of 0.05 and a 5% dropout each year for an estimated 3 years enrolment, the power calculation requires 456 patients to be recruited (228 in each group). The primary endpoint is 5-year overall survival, with a minimum 5-year follow-up. The secondary endpoints include 5-year disease-free survival, toxicity, pathological complete response rate, postoperative complications, postoperative mortality and quality of life. A biobank of pre-treatment and resected tumour tissue will be built for translational research in the future. DISCUSSION: This RCT directly compares a neoadjuvant chemotherapy regimen with a standard CROSS regimen in terms of overall survival for patients with locally advanced ESCC. The results of this RCT will provide an answer for the controversy regarding the survival benefits between the two treatment strategies. TRIAL REGISTRATION: NCT04138212, date of registration: October 24, 2019.

Early Oral Feeding Following McKeown Minimally Invasive Esophagectomy: An Open-label, Randomized, Controlled, Noninferiority Trial.

OBJECTIVE: Our objective was to evaluate the impact of early oral feeding (EOF) on postoperative cardiac, respiratory, and gastrointestinal (CRG) complications after McKeown minimally invasive esophagectomy for esophageal cancer. SUMMARY BACKGROUND DATA: Nil-by-mouth with enteral tube feeding is routinely practiced after esophagectomy. METHODS: Patients were randomly allocated to receive oral feeding on the first postoperative day (EOF group) or late oral feeding (LOF group) 7 days after surgery. The primary endpoint was the occurrence of postoperative CRG complications, and the secondary outcomes included bowel function recovery and short-term quality of life (QOL). RESULTS: Between February 2014 and October 2015, 280 patients were enrolled in this study. There were 140 patients in the EOF group and 140 patients in the LOF group. EOF was noninferior to LOF for CRG complications (30.0% in the EOF group vs. 32.9% in the LOF group; 95% confidence interval of the difference: -13.8% to 8.0%). Compared with the LOF group, the EOF group showed significantly shorter time to first flatus (median of 2 days vs. 3 days, P = 0.001) and bowel movement (median of 3 vs. 4 days, P < 0.001). Two weeks after the operation, patients in the EOF group reported higher global QOL and function scores and lower symptom scores than patients in the LOF group. CONCLUSIONS: In patients after McKeown minimally invasive esophagectomy is noninferior to the standard of care with regard to postoperative CRG complications. In addition, patients in the EOF group had a quicker recovery of bowel function and improved short-term QOL.

FA01.03: USE OF 'NON-TUBE NO FASTING' ERAS PROTOCOL IN PATIENTS AFTER MIE WITH LI'S ANASTOMOSIS: OUTCOMES IN THE FIRST 113 PATIENTS PERFORMED BY A SURGEON AFTER TRAINING COURSE.

BACKGROUND: Use of enhanced recovery after surgery(ERAS) protocol in the patients after esophagectomy is reported to be feasible and safe in recent studies. And in Prof. Yin Li's research, patients after minimally invasive esophagectomy(MIE) with Li's anastomosis took oral feeding on the 1st day after operation (POD1). However, all the esophagectomy-procedures were proceeded by experienced experts. There was no report regarding whether ERAS protocol after MIE with Li's anastomosis could be safely proceeded by a young surgeon after training course. The aim of this study was to evaluate the feasibility and safety of 'Non-Tube No Fasting' ERAS Protocol in patients after MIE with Li's Anastomosis proceeded by a surgeon after the training course. METHODS: We retrospectively reviewed the clinical data of patients who underwent MIE for cancer from December 2015 to September 2017 by a new surgical team finished MIE training course in our department. During the study period, the new team performed Mckeown MIE with Li's anastomosis for 127 esophageal cancer patients. We analyzed the data of 113 patients who followed the protocol of 'Non-tube No Fasting' ERAS. The primary end-points were the incidence of anastomotic fistula, the injury of recurrent laryngeal nerve, pneumonia, and postoperative length of hospital-stay. RESULTS: All the 113 patients began oral feeding on POD1. Two patients exited the ERAS protocol on account of bucking caused by recurrent laryngeal nerve injury on POD3. The incidence of anastomotic fistula, recurrent laryngeal nerve injury and pneumonia were 3.5% (4/113), 12.4%(14/113) and 18.5%(21/113). The average length of postoperative hospital-stay was 8.6 ± 6.9 days. Both of the in-hospital mortality and 30-day mortality were 0. CONCLUSION: Our date indicated that it was feasible and safe for a selected surgeon after 'Non-tube no fasting' ERAS and MIE training courses to proceed the protocol. Of course, more clinical researches are needed to confirm this result. DISCLOSURE: All authors have declared no conflicts of interest.

[Patterns of lymphatic spread in thoracic esophageal squamous cell carcinoma: a study of 313 cases].

OBJECTIVE: We analyzed the lymph node (MLNs) metastasis of thoracic esophageal squamous cell carcinoma (ESCC) to explore the patterns of lymphatic spread and the rational surgical procedure and extent of lymph node dissection for ESCC. METHODS: We retrospectively evaluated 313 consecutive patients treated in our hospital between January 2010 and May 2014 who underwent minimally invasive esophagectomy (MIE) for ESCC. The information of lymph node status was obtained and the features of lymph node metastasis were analyzed. RESULTS: Of the 313 cases, 122 (39.0%) were found to have lymph node metastasis. In the 4461 dissected lymph nodes, metastasis was identified in 294 (6.6%) lymph nodes. The recurrent laryngeal nerve lymph nodes were the most frequent metastatic nodes with a metastasis rate of 25.2%, followed by the paracardiac and left gastric artery lymph nodes (18.2%). Chi-square test showed that the lymph node metastasis is associated with tumor invasion and tumor differentiation (P<0.001 for both). Metastases were more frequently found in the recurrent laryngeal nerve lymph nodes in patients with tumors in the upper third esophagus and with histologically poor differentiation (P<0.05 for both). The metastasis rate of para-cardiac and left gastric artery lymph nodes was associated with tumor in the lower third of esophagus, T stage and differentiation (all P<0.05). Logistic regression analysis showed that tumor differentiation and location are independent factors affecting the metastasis of recurrent laryngeal nerve lymph nodes (P<0.05 for all). T stage, tumor differentiation and location were independent factors associated with metastasis of para-cardiac and left gastric artery lymph nodes (P<0.05 for all). CONCLUSIONS: (1) Metastases of thoracic esophageal carcinoma are often found in the recurrent laryngeal nerve lymph nodes, para-cardiac and left gastric artery lymph nodes. (2) Extensive lymph node dissection should be performed for ESCC with poor differentiation and deep tumor invasion.

[Clinical implications of the concentration and EGFR/KRAS mutations of plasma cell free DNA of patients with lung cancer and esophageal cancer].

OBJECTIVE: To analyze the correlation between the concentration of plasma cell free DNA (cfDNA) of patients with lung cancer or esophageal cancer and clinical features, and to assess the coincidence rate of the EGFR/KRAS mutations between the cfDNA and tumor tissue DNA. METHODS: A total of 30 cases lung cancer and esophageal cancer (including 15 lung cancer, 15 esophageal cancer) were enrolled in this study. The tumor tissue and plasma sample of patients were collected. The tumor tissue DNA and plasma cfDNA were extracted. The EGFR/KRAS mutations of the tumor tissue DNA and plasma cfDNA were detected by fluorescence PCR. RESULTS: The concentration of cfDNA of patients with lung cancer (5.0 ± 1.4) µg/L and esophageal cancer (7.0 ± 0.8) µg/L were positively correlated with tumor size (r = 0.574, P = 0.01). There was no significant correlation between the concentration of cfDNA and TNM stage of tumor, gender, and age of patients. There was no EGFR/KRAS gene mutations in tumor tissue DNA and plasma cfDNA of esophageal cancer. A total of 6 tumor tissue samples of lung cancer patients were detected EGFR mutation, and 1 tumor tissue sample was detected KRAS mutation. Meanwhile, 4 plasma cfDNA samples of lung cancer patients were detected EGFR mutation, and 1 plasma cfDNA sample was detected KRAS mutation. CONCLUSION: The concentration of cfDNA of patients with lung cancer and esophageal cancer was positively correlated with tumor burden. There was high coincidence rate of the EGFR/KRAS mutations between the cfDNA and tumor tissue DNA.

A practical molecular assay to predict survival in resected non-squamous, non-small-cell lung cancer: development and international validation studies.

BACKGROUND: The frequent recurrence of early-stage non-small-cell lung cancer (NSCLC) is generally attributable to metastatic disease undetected at complete resection. Management of such patients depends on prognostic staging to identify the individuals most likely to have occult disease. We aimed to develop and validate a practical, reliable assay that improves risk stratification compared with conventional staging. METHODS: A 14-gene expression assay that uses quantitative PCR, runs on formalin-fixed paraffin-embedded tissue samples, and differentiates patients with heterogeneous statistical prognoses was developed in a cohort of 361 patients with non-squamous NSCLC resected at the University of California, San Francisco. The assay was then independently validated by the Kaiser Permanente Division of Research in a masked cohort of 433 patients with stage I non-squamous NSCLC resected at Kaiser Permanente Northern California hospitals, and on a cohort of 1006 patients with stage I-III non-squamous NSCLC resected in several leading Chinese cancer centres that are part of the China Clinical Trials Consortium (CCTC). FINDINGS: Kaplan-Meier analysis of the Kaiser validation cohort showed 5 year overall survival of 71·4% (95% CI 60·5-80·0) in low-risk, 58·3% (48·9-66·6) in intermediate-risk, and 49·2% (42·2-55·8) in high-risk patients (p(trend)=0·0003). Similar analysis of the CCTC cohort indicated 5 year overall survivals of 74·1% (66·0-80·6) in low-risk, 57·4% (48·3-65·5) in intermediate-risk, and 44·6% (40·2-48·9) in high-risk patients (p(trend)<0·0001). Multivariate analysis in both cohorts indicated that no standard clinical risk factors could account for, or provide, the prognostic information derived from tumour gene expression. The assay improved prognostic accuracy beyond National Comprehensive Cancer Network criteria for stage I high-risk tumours (p<0·0001), and differentiated low-risk, intermediate-risk, and high-risk patients within all disease stages. INTERPRETATION: Our practical, quantitative-PCR-based assay reliably identified patients with early-stage non-squamous NSCLC at high risk for mortality after surgical resection. FUNDING: UCSF Thoracic Oncology Laboratory and Pinpoint Genomics.

Neoadjuvant Chemotherapy Compared with Surgery for Oesophageal Carcinoma: A Retrospective Study and Missing Evidence.

Background: Negative evidence for the use of neoadjuvant chemotherapy (NAC) to treat oesophageal squamous cell carcinoma (ESCC) has been reported in Western countries in the past century. However, in China, most ESCC patients underwent paclitaxel and platinum-based NAC without evidence from local RCTs. Empiricism or a lack of evidence does not necessarily mean that the evidence is negative. However, there was no way to compensate for the missing evidence. The only way to obtain evidence is by conducting a retrospective study using propensity score matching (PSM) to compare the effects of NAC and primary surgery on overall survival (OS) and disease-free survival (DFS) among ESCC patients in China, which is the country with the highest prevalence of ESCC patients. Methods: From January 1, 2015, to December 31, 2018, a total of 5443 patients with oesophageal cancer/oesophagogastric junction carcinoma who underwent oesophagectomy were retrospectively identified at Henan Cancer Hospital. After PSM, 826 patients were selected for the retrospective study and divided into the NAC and primary surgery groups. The median follow-up period was 54.08 months. Toxicity and tumour responses to NAC, intraoperative and postoperative outcomes, recurrence, DFS and OS were analysed. Results: The postoperative complication rates were not significantly different between the two groups. The 5-year DFS rates were 57.48% (95% CI, 52.05% to 62.53%) for the NAC group and 49.93% (95% CI, 44.56% to 55.05%) for the primary surgery group (P=0.0129). The 5-year OS rates were 62.95% (95% CI, 57.63% to 67.79%) for the NAC group and 56.29% (95% CI, 50.99% to 61.25%) for the primary surgery group (P=0.0397). Conclusion: Compared with primary surgery, NAC with paclitaxel and platinum-based chemotherapy and two-field extensive mediastinal lymphadenectomy might be associated with long-term survival benefits among ESCC patients.

Relationship between postoperative complications of esophageal cancer surgery and season: a retrospective study.

Background: Esophageal cancer in China accounts for nearly half of the global esophageal cancer cases. The relationship between the occurrence of postoperative complications of esophageal cancer surgery and seasonal changes is not clear. Our purpose is to clarify the relationship between postoperative complications of esophageal cancer and season, so as to reduce the incidence of complications. Methods: We retrospectively analyzed the medical records of patients undergoing esophageal cancer surgery in our hospital between January 2013 and December 2014. Patients were divided into the summer group (March-August) and the non-summer group (September-February) according to the seasonal climate. Pulmonary, cardiac, and other complications were recorded. Differences in postoperative complications were compared between the two groups by the chi-squared test. Results: In the 251 patients enrolled, the total postoperative complication rate was 37.8%. The occurrence of incision complications in the summer group was significantly higher than that in the non-summer group (10.1% vs. 3.5%, P=0.044). Pulmonary and cardiac complications in summer group were significantly rarer than those in the non-summer group (16.7% vs. 27.4%, P=0.039; and 8.0% vs. 16.8%, P=0.032, respectively). Conclusions: During the warm months of the year, clinicians should focus on preventing postoperative incision complications, and they should focus on preventing pulmonary and cardiac complications during the cold months.

Preemptive analgesia in the "non-tube no fasting" fast track program for resectable esophageal carcinoma.

Background: Surgery is the main treatment for esophageal cancer, but postoperative incision pain seriously reduces patients' quality of life. The aim of this study was to investigate the feasibility and effectiveness of preemptive analgesia of the upper abdomen with ropivacaine in the "non-tube no fasting" fast track recovery program for esophageal carcinoma. Methods: We retrospectively analyzed the medical records of patients who underwent minimally invasive esophagectomy (MIE) from February 2014 to August 2014. Patients in the study group underwent a conventional analgesia program together with local infiltration injection of ropivacaine in the upper abdominal incision 30 min before the operation, while patients in the control group underwent the conventional analgesia program alone. Ropivacaine was injected locally around the planned surgical incision, including intradermally, subcutaneously, in the fascial muscles, and in the parietal peritoneum layers. Li's anastomosis method was performed in the neck after MIE. No indwelling chest tube or abdominal cavity tube was placed in any patients. The use of analgesic pumps in the two groups of patients was recorded. Results: A total of 102 patients were enrolled in the study, with 52 patients in the study group and 50 patients in the control group. Patients in both groups completed the surgery successfully as planned, and the anesthesia methods and drugs used during the operation were the same. The surgical duration, blood loss, and the number of resected lymph nodes did not differ significantly between the two groups. Three patients in the study group and 10 patients in the control group used analgesia pumps (P=0.031). The visual analog scale (VAS) score at 30 days after surgery in the group with preemptive analgesia was significantly better than that in the control group (P=0.048). Conclusions: Preemptive analgesia for the upper abdomen with ropivacaine in the "non-tube no fasting" fast track recovery program for esophageal carcinoma is feasible and worthy of promotion.

The safety of neoadjuvant chemotherapy combined with non-tube nofasting fast-track surgery for esophageal carcinoma.

Our non-tube no fasting (early oral feeding and no nasogastric tube) fast-track surgery (FTS) was safe and effective to combine with neoadjuvant chemotherapy for McKeown minimally invasive esophagectomy. In addition, the two groups were similar in terms of the recovery time, hospital discharge day, and early resumption of oral feeding. Objectives: To evaluate the safety of early oral feeding (EOF) combined with neoadjuvant chemotherapy (NAC) of esophagectomy. Summary Background Data: Our non-tube no fasting (early oral feeding and no nasogastric tube) fast-track surgery (FTS) was safe and effective for primary surgery esophageal cancer patients. Methods: We retrospectively evaluated consecutive patients who underwent non-tube no fasting and McKeown minimally invasive (MIE). They were divided into two groups: one received NAC, and the other received primary surgery. Complications after the operation, postoperative CRG complications, operative time, operative bleeding, and length of stay were evaluated. Results: Between 01/2014 and 12/2017, there hundred and eighty two consecutive patients underwent MIE with total two-field lymphadenectomy under the non-tube no fasting fast-track surgery program. A total of 137 patients received NAC, and 245 accepted primary surgery. Propensity score matching was used to compare NAC patients with 62 matched patients from each group. The NAC group had a similar number of total complications as the primary surgery group (32.26% in the primary surgery group vs. 25.81% in the NAC group; p=0.429) and had the same median postoperative hospitalization duration (8 days, p=0.723). Conclusions: After McKeown MIE, the patients receiving NAC combined with "non-tube no fasting" FTS had a similar incidence of postoperative complications outcomes as those without NAC. In addition, the two groups were similar in terms of the recovery time, hospital discharge day, and early resumption of oral feeding.

Predictive model of postoperative pneumonia after neoadjuvant immunochemotherapy for esophageal cancer.

Background: Postoperative pneumonia (PP) is the most common pulmonary complication of esophagectomy. It is of great importance to identify any high-risk factors and prevent pulmonary complications to improve the prognosis of patients with esophageal cancer undergoing esophagectomy. Thus, we established a predictive model of PP in patients with neoadjuvant immunochemotherapy for resectable esophageal squamous cell carcinoma (ESCC), and provide suggestions for the best strategy for the perioperative period of the patients. Method: We retrospectively analyzed 78 patients who underwent esophagectomy for squamous cell carcinoma after neoadjuvant immunochemotherapy between September 2019 and August 2021.We used the "glmnet" language package in R to perform least absolute shrinkage and selection operator (LASSO) regression to screen the best predictors of PP, and nomograms predicting PP were constructed utilizing screened factors. The performance of nomograms was internally validated by calibration curves, concordance index (C-index), and the Brier score for overall performance. Results: Twenty-six patients (33.3%) had postoperative pneumonia. After LASSO regression, the factors that were independently associated with PP were diffusing capacity of the lungs for carbon monoxide (DLCO) (P=0.0002), white blood cell (WBC) difference before vs. after neoadjuvant immunochemotherapy (P=0.0133). We constructed a prediction model, plotted the nomogram, and verified its accuracy. Its Brier score was 0.147, its calibration slope was 0.98, and its C-index was 0.85 (95% CI: 0.75-0.95). Internal validation demonstrated a good discrimination power that the actual probability corresponds closely with the predicted probability. Conclusions: Our prediction model can predict the possibility of PP in patients with neoadjuvant immunochemotherapy for resectable esophageal squamous cell carcinoma and may facilitate physicians' efforts to reduce the incidence of postoperative pneumonia.

The Improved Mediastinal Drainage Strategy for the Enhanced Recovery System After Esophagectomy.

BACKGROUND: The improved drainage strategy was the transperitoneal placement of a single mediastinal drainage tube after esophagectomy. This study aimed to explore its effect on the incidence of postoperative complications, pain scores, and hospital stay. METHODS: Data from 108 patients who underwent minimally invasive esophagectomy were retrospectively analyzed. Patients were divided into 2 groups: those in group A were treated with transthoracic placement of mediastinal drain and those in group B were treated with transperitoneal placement. The incidence of postoperative complications, pain scores, and postoperative hospital stay were compared. RESULTS: The maximum pain scores in group B were significantly lower than those in group A from the first to the fourth postoperative days (PODs): POD1, 3.9 ± 0.7 vs 2.3 ± 0.7; POD2, 3.5 ± 0.8 vs 2.1 ± 0.7; POD3, 3.3 ± 0.8 vs 1.7 ± 0.8; and POD4, 3.1 ± 0.7 vs 1.7 ± 0.8 (all P < .001). Compared with group A, there were fewer postoperative analgesic drug users in group B (44.6% vs 17.9%; P = .005), fewer cases of pleural effusion (10.7% vs 0%; P = .045), and fewer cases of closed thoracic drainage due to pleural effusion or pneumothorax (14.3% vs 0%; P = .014). There were no significant differences in the incidence of anastomotic leakage, mediastinitis, major pulmonary complications, major abdominal complications, surgical site infection, and total postoperative complications, without statistical differences in postoperative hospital stay and 30-d mortality (all P > .05). CONCLUSIONS: The transperitoneal placement of a single mediastinal drain can reduce postoperative pain and the incidence of pleural effusion, without increasing the incidence of other major postoperative complications and postoperative hospital stay.

A phase III study on neoadjuvant chemotherapy versus neoadjuvant toripalimab plus chemotherapy for locally advanced esophageal squamous cell carcinoma: Henan Cancer Hospital Thoracic Oncology Group 1909 (HCHTOG1909).

BACKGROUND: Neoadjuvant chemotherapy (NAC) and neoadjuvant chemoradiotherapy (NACR) are the standard treatments for esophageal squamous cell carcinoma (ESCC). However, the 5-year overall survival (OS) rate is still far from satisfactory. In recent years, immune checkpoint inhibitors (ICIs) have shown promising results in the treatment of ESCC. More than 20 phase II clinical trials have been launched to explore combinations of ICIs in the neoadjuvant setting for ESCC. Based on our phase II clinical trial, a two-arm phase III trial was launched in Henan Cancer Hospital. ICIs combined with NAC may usher in a new era and may benefit locally advanced, resectable ESCC patients. METHODS: A two-arm phase III trial was launched in April 2020 in Henan Cancer Hospital. Patient recruitment will be completed within 18 months. The primary endpoint is event-free survival (EFS). The secondary endpoints include pathologic complete response (pCR), disease-free survival (DFS) rate, overall response rate (ORR), R0 resection rate, major pathologic response (MPR), adverse events (AEs), complication rate and quality of life (QOL). A biobank of pretreatment, resected tumor tissue and paired blood samples will be built for translational research in the future. DISCUSSION: This RCT directly compares NAC with neoadjuvant toripalimab plus chemotherapy in terms of EFS for locally advanced ESCC. The results may usher in a new era of resectable ESCC treatment. TRIAL REGISTRATION: NCT04280822 (https://www.clinicaltrials.gov/ct2/show/NCT04280822). Registered title: "A Phase III, Randomized Controlled Study of Neo-adjuvant Toripalimab (JS001) in Combination with Chemotherapy versus Neo-adjuvant Chemotherapy for Resectable Esophageal Squamous Cell Carcinoma". Version 1.0/Nov. 21, 2019.

Ecological stoichiometry of plant leaves, litter and soils in a secondary forest on China's Loess Plateau.

Ecological stoichiometry can reveal nutrient cycles in soil and plant ecosystems and their interactions. However, the ecological stoichiometry characteristics of leaf-litter-soil system of dominant grasses, shrubs and trees are still unclear as are their intrinsic relationship during vegetation restoration. This study selected three dominant plant types of grasses (Imperata cylindrica (I. cylindrica) and Artemisiasacrorum (A.sacrorum)), shrubs (Sophora viciifolia (S. viciifolia) and Hippophae rhamnoides (H. rhamnoides)) and trees (Quercus liaotungensis (Q. liaotungensis) and Betula platyphylla (B. platyphylla)) in secondary forest areas of the Chinese Loess Plateau to investigate ecological stoichiometric characteristics and their intrinsic relationships in leaf-litter-soil systems. The results indicated that N concentration and N:P ratios in leaf and litter were highest in shrubland; leaf P concentration in grassland was highest and litter in forestland had the highest P concentration. Soil C, N and P concentrations were highest in forestland (P < 0.05) and declined with soil depth. Based on the theory that leaf N:P ratio indicates nutritional limitation of plant growth, this study concluded that grass and shrub growth was limited by N and P element, respectively, and forest growth was limited by both of N and P elements. The relationships between the N concentration in soil, leaf and litter was not significant (P >0.5), but the soil P concentration was significantly correlated with litter P concentration (P < 0.05). These finding enhance understanding of nutrient limitations in different plant communities during vegetation restoration and provide insights for better management of vegetation restoration.

Highlighting sarcopenia management for promoting surgical outcomes in esophageal cancers: Evidence from a prospective cohort study.

BACKGROUND: Studies have provided controversial and limited knowledge regarding the impact of sarcopenia on surgical outcomes in esophageal cancers due to retrospective study designs and single muscle-mass assessment. This prospective cohort study aimed to resolve these issues. METHODS: Bioelectrical impedance analysis, handgrip strength measurement, and the 4-m walking test were conducted before surgery. Sarcopenia was diagnosed as low appendicular skeletal muscle mass index (<7.0 kg/m2 in men and <5.7 kg/m2 in women) plus low handgrip strength (<26 kg in men and <18 kg in women) and/or low gait speed (<0.8 m/s). Presarcopenia was diagnosed as either: (1) solely low muscle mass index; or (2) solely low handgrip strength and/or gait speed. Endpoints included perioperative biochemical indicators, postoperative complications, and the recovery of postoperative quality of life (QOL). RESULTS: In total, 212 patients were enrolled, including 55 (25.9%) and 60 (28.3%) patients diagnosed with sarcopenia and presarcopenia, respectively. The presarcopenic and normal patients showed a similar risk of postoperative complications and were combined. Despite similar baseline levels, sarcopenic patients (vs. non-sarcopenic) showed decreased prealbumin on postoperative day (POD) 1, decreased albumin on PODs 1, 3, and 5, and delayed recovery of lymphocyte counts (all P < 0.05). The levels of C-reactive protein in sarcopenic patients was lower than in non-sarcopenic patients on POD 1 (P = 0.010) but higher on POD 5 (P = 0.001). Multivariate analyses demonstrated the independent predictive value of sarcopenia for overall complications (P < 0.001), major complications (Clavien-Dindo grade ≥ III, P = 0.001), and delayed hospital discharge (>12 days, P < 0.001). Sarcopenia was demonstrated as a risk factor for deteriorated global QOL (P = 0.001), physical (P = 0.001) and role functions (P = 0.006), and severe fatigue (P = 0.004) at four weeks after surgery. CONCLUSIONS: Sarcopenia was associated with poor metabolic stress and immune responses surrounding esophagectomy and was a potential target for reducing complications and promoting recovery of QOL.