The incidence of pancreatic cancer is increasing year by year, but the clinical diagnosis and treatment progress is limited and the prognosis is poor. Tumor microenvironment (TME) is closely related to the invasion, metastasis and chemotherapy resistance of pancreatic cancer. Cancer-associated fibroblasts (CAFs) are fibroblasts in a state of continuous activation, which are the most prominent components in TME. CAFs can promote the malignant biological behavior of pancreatic cancer through a variety of molecule-mediated mechanisms. Moreover, several attempts targeting CAFs for the treatment of pancreatic cancer have been largely unsuccessful. It may be related to the heterogeneity of CAFs in pancreatic cancer. Therefore, in-depth study of its heterogeneity and accurate targeting of some specific phenotypes and functional CAFs subtypes in the matrix on this basis may be more promising in the clinical treatment of pancreatic cancer.

Objective:To examine the preliminary clinical efficacy of Chinese magnetic sphincter augmentation (MSA) in the treatment of gastroesophageal reflux disease (GERD).Methods:According to the enrollment criteria for the MSA developed by ShengJieKang Co. and Shanghai Chest Hospital (SS-MSA) clinical trial, a total of 19 GERD patients were treated with SS-MSA from August 2018 to January 2020 at Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University. The majority of registered cases were male patients with age of (32.2±7.3) years (range: 22 to 50 years), height of (170.7±6.2) cm (range: 160 to 179 cm) and weight of (65.2±10.3) kg (range: 47.5 to 90.0 kg). SS-MSA was implanted via laparoscopy. The major evaluation indexs of postoperative efficacy were the total time of acid exposure within 24 hours and the total number of reflux. Secondary efficacy indicators included: (1) evaluation of the average daily dose of proton pump inhibitor medications; (2) the score of GERD health related quality of life questionnaire (GERD-Q) before and after MSA implantation. Paired design t-test was used to evaluate the efficacy of the SS-MSA. Results:A total of 19 patients underwent SS-MSA surgery successfully. The history of the GERD were 19 (54) months ( M( QR)). The operation time was 63 (22) minutes and the in-hospital stay was 3 (2) days. No obvious surgical complications occurred. Postoperative adverse events included 14 cases with mild to moderate dysphagia exited after surgery, gradually eased within 1 to 3 months, 1 case with the removal of the device after 1 month of severe swallowing difficulties, 1 case of diarrhea. No corrosion, perforation, displacement occurred. The GERD-Q score (11.0(4.5) vs. 6(1.0), t=4.274, P=0.013), 24-hour acid exposure time (6.2(4.8)% vs. 0.1(0.9)%, t=5.814, P=0.004), and Demeester score (23.72(16.20) vs. 0.96(3.10), t=6.678, P=0.003) were significantly decreased 1 year after surgery( n=5). Proton pump inhibitor reuse rates were 6/18, 5/15, 3/10, and 1/5 in 1, 3, 6 and 12 months after the operation, respectively. Conclusions:SS-MSA implantation is feasible and safe with short hospital stay and rare perioperative complications. The preliminary results is good after 1 year follow-up. It could be expected to be an ideal substitutive for future GERD treatment.

Objective:To examine the preliminary clinical efficacy of Chinese magnetic sphincter augmentation (MSA) in the treatment of gastroesophageal reflux disease (GERD).Methods:According to the enrollment criteria for the MSA developed by ShengJieKang Co. and Shanghai Chest Hospital (SS-MSA) clinical trial, a total of 19 GERD patients were treated with SS-MSA from August 2018 to January 2020 at Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University. The majority of registered cases were male patients with age of (32.2±7.3) years (range: 22 to 50 years), height of (170.7±6.2) cm (range: 160 to 179 cm) and weight of (65.2±10.3) kg (range: 47.5 to 90.0 kg). SS-MSA was implanted via laparoscopy. The major evaluation indexs of postoperative efficacy were the total time of acid exposure within 24 hours and the total number of reflux. Secondary efficacy indicators included: (1) evaluation of the average daily dose of proton pump inhibitor medications; (2) the score of GERD health related quality of life questionnaire (GERD-Q) before and after MSA implantation. Paired design t-test was used to evaluate the efficacy of the SS-MSA. Results:A total of 19 patients underwent SS-MSA surgery successfully. The history of the GERD were 19 (54) months ( M( QR)). The operation time was 63 (22) minutes and the in-hospital stay was 3 (2) days. No obvious surgical complications occurred. Postoperative adverse events included 14 cases with mild to moderate dysphagia exited after surgery, gradually eased within 1 to 3 months, 1 case with the removal of the device after 1 month of severe swallowing difficulties, 1 case of diarrhea. No corrosion, perforation, displacement occurred. The GERD-Q score (11.0(4.5) vs. 6(1.0), t=4.274, P=0.013), 24-hour acid exposure time (6.2(4.8)% vs. 0.1(0.9)%, t=5.814, P=0.004), and Demeester score (23.72(16.20) vs. 0.96(3.10), t=6.678, P=0.003) were significantly decreased 1 year after surgery( n=5). Proton pump inhibitor reuse rates were 6/18, 5/15, 3/10, and 1/5 in 1, 3, 6 and 12 months after the operation, respectively. Conclusions:SS-MSA implantation is feasible and safe with short hospital stay and rare perioperative complications. The preliminary results is good after 1 year follow-up. It could be expected to be an ideal substitutive for future GERD treatment.

Objective: To evaluate the safety and effectiveness of esophageal replacement with ileocolon graft. Methods: Totally 34 cases of esophageal replacement with ileocolon graft from July 2015 to November 2017 at Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiaotong University were analyzed retrospectively, including 24 male and 10 female, aging from 7 to 72 years old. Esophageal replacement with ileocolon graft by right and/or middle colic artery as a blood supply using retrosternal route except one subcutaneous route. The primary esophageal disease, postoperative complication rate and quality of life were analyzed. Results: The overall postoperative complication rate was 23.5% (8/34), cervical anastomotic leakage rate of 5.9% (2/34), necrosis of colon graft of 5.9% (2/34). There were 3 patients experienced re-operation including 2 patients with colon graft necrosis and 1 patient with intestinal obstruction after ERC. One patient with colon graft necrosis died of septic shock after reoperation. Six cases of cervical esophago-jejunal anastomosis stenosis and 1 case of diarrhea occurred in the later time. All patients were followed up for a median time of 9 months (range: 1 to 28 months), 32 cases survived but 1 patient died until last follow-up by the end of December 2017. Conclusion Esophageal replacement with ileocolon graft by right and/or middle colic artery as a blood supply using retrosternal route was safe and effective.

Objective To investigate the safety and efficacy of definitive chemoradiotherapy(dCRT) in esophageal cancer.Methods A retrospective analysis of 18 consecutive cases ofsalvage esophagectomy after dCRT by the single operation groupin department of Thoracic surgery,Shanghai chest hospital affiliated to Shanghai Jiaotong University from December 2014 to March 2017.Results 16 males and 2 females.There were 6 cases and 12 cases of recurrent and persistent tumor after dCRT respectively.All the patients were treated with McKeown operation stytle combing thoracic and abdominal lymph nodes dissection.Esophagus was replaced by stomach of 15 cases and colon of 3 cases respectively.Radical resection (R0) was performed in 12 cases,palliative resection (R2) in 6 cases.There were 4 cases of pathological complete response (pCR).The incidence of postoperative complications was 11 cases,including 6 cases of pulmonary infection,4 cases of anastomotic leak,2 cases of incision infection,one case of respiratory insufficiency,one case of recurrent laryngeal nerve paralysis,one case of chylothorax,one case of aortic bleeding caused by empyema.One patient died in perioperative period because of aortic bleeding due to empyema.The follow-up period was from 2 to 26 months,and the median follow-up time was 9 months.There were 13 patients survived and 5 patients died at the last follow-up date including one death in perioperative period,2 cases died of local-regional recurrence and metastasis respectively.Conclusion Salvage esophagectomy is a treatment option for the recurrent or persistent disease after dCRT,but the incidence of postoperative complications is high.Accurate clinical staging is especially important after dCRT and ycT4,ycN + patientsshould be avoided.R0 resection and recurrence after long disease free period are favorable prognostic factors.

bjective    To evaluate the safety and efficacy of neoadjuvant therapy followed by minimally invasive esophagectomy (MIE) for locally advanced esophageal cancer. Methods    We retrospectively analyzed clinical data of 56 consecutive patients with locally advanced esophageal cancer treated by neoadjuvant therapy followed by surgery in our hospital between January 2015 and December 2016. There were 51 males and 5 females. The patients were divided into 2 groups. Neoadjuvant therapy followed by open surgery esophagectomy group was as an OE group with 25 patients aged 61 (50-73) years. And neoadjuvant therapy followed by MIE was as a MIE group with 31 patients aged 60 (55-79) years. Results    The pathologic complete response (pCR) rate of 28 patients with neoadjuvant concurrent chemoradiotherapy was significantly higher than that of 28 patients with neoadjuvant chemotherapy (21.4% vs. 10.7%, P<0.05). The operation time, intraoperative blood loss, R2 rate and the number of lymph nodes dissection in the MIE group were obviously better than those of the OE group with statistical differences (P<0.05). However, there was no significant difference in the number of resected lymph nodes along the bilateral recurrent laryngeal nerves and lymph node metastasis rate (P>0.05) between the two groups. The incidence of postoperative respiratory complications in the MIE group was lower than that of the OE group (P=0.041). There was no significant difference between the two groups in the incidence of other complications, re-operation, re-entry to ICU, median length of stay or perioperative deaths (P>0.05). There was only one patient with neoadjuvant concurrent chemoradiotherapy in the OE group died due to gastric fluid asphyxia caused by  trachea-esophageal fistula. Conclusion    Neoadjuvant therapy followed by MIE for locally advanced esophageal cancer is safe and feasible. The oncological outcomes seem comparable regardless of OE.

Objective     To compare short-term quality of life and postoperative complications in esophageal squamous cell carcinoma patients with different routes reconstruction after McKeown esophagectomy. Methods     The clinical data of 144 patients with esophageal squamous cell carcinoma who received McKeown esophagectomy in Shanghai Chest Hospital from January 2016 to October 2016 were retrospectively reviewed. Among them 93 patients accepted retrosternal approach (a RR group, 71 males and 22 females at an average age of 63.5±7.7 years) and 51 patients accepted posterior mediastinal approach (a PR group, 39 males and 12 females at an average age of 62.3±8.0 years). Short-term surgical outcomes were compared and a Quality of Life Questionnaire of Patients Underwent Esophagectomy 1.0   was performed at postoperative 1st and 3rd month. Results     There was no difference in two groups in sex, age, Body Mass Index (BMI), and location and clinical stage of tumors (P>0.05). The neoadjuvant therapy was more performed in the RR group (16.1% vs. 5.9%, P=0.075). There were more robot-assisted esophagecctomy operations performed in the PR group (52.9% vs. 45.2%, P=0.020). No significant difference was noted in operation duration, intraoperative blood loss or length of ICU stay between the RR and PR groups (251.3±59.1 min vs. 253.1±27.7 min, P=0.862; 223.7±75.1 ml vs. 240.0±75.1 ml, P=0.276; 3.7±6.6 d vs. 2.3±2.1 d, P=0.139). The patients in the PR group had more lymph nodes dissected and shorter hospital stay (P<0.001). Rate of R1/2 resection was higher in the RR group (12.9% vs. 5.9%, P=0.187). No surgery-related mortality was observed in both groups. The anastomotic leak and the anastomotic stricture was higher in the RR group than that in the PR group (25.8% vs. 5.9%, P=0.003). No significant difference was found between the two groups in the quality of life at postoperative 1st and 3rd month. However, the quality of life at postoperative 3rd month significantly improved in both groups (P<0.001). Compared with the PR group, the dysphagia was more severe in the RR group at postoperative 1st month (3.3±1.5 vs. 2.6±1.1, P=0.007), while the reflux symptom was lighter at postoperative 3rd month (3.0±1.8 vs. 3.6±1.6, P=0.045). Conclusion     The two different routes reconstruction after McKeown esophagectomy are both safe and feasible. The anterior mediastinal approach increases the risk of anastomotic leak, but with low incidence of reflux symptom.

Objective To investigate our early results of robot-assisted esophagectomy (RAE) and present our learning curve experience with the largest study from one-single institution of China.Methods Between November 2015 and April 2017,a series of consecutive patients undergoing RAE at Shanghai Chest Hospital were reviewed.The patients'demographics,operative and postoperative outcomes were demonstrated.Results A total of 154 patients underwent RAE during the study.All patients received Mckeown esophagectomy and extensive thoraco-abdominal two-field lymph node dissection.Of these,122 were male and 32 were female.The mean total operative duration was 179-445 (271.0 ±61.5) min and the operative duration of the thoracic phase was 51-142 (96.7 ± 27.0)min.The mean estimated blood loss was 100 -1 000 (230.4 ±74.4)ml.The pathological results showed that 150 had squamous cell carcinoma,2 had adenocarcinoma,and 2 had small cell carcinoma.The R0 resection was 92.2％.The mean number of lymph node dissection was 11-64 (20.4 ± 8.5) and the lymph node sampling rate along left and right recurrent laryngeal nerve (RLN) were 92.2％ and 88.3％.The morbidity was present in 64 of 154 patients (41.6％).The major complications rate was anastomotic leak (12.3％),and vocal cord paralysis (16.9％).Intensive care unit (ICU) hospital stay time was 0-27 (2.7 ± 3.6) d,the median length of hospital stay was 7-81 (15.8 ± 11.6)days.There was no 90-day mortality.Conclusions RAE is a safe and feasible alternative for treatment of esophageal cancer.RAE can improve the efficacy of lymph node dissection,especially for the lymphadenectomy along recurrent laryngeal nerve.

Objective To study the relativity between imageology and pathology during lung cancer,and estimate whether the lung cancer is preinvasive lesions,which can support evidences for the operation methods.Methods Clinical data of 624 patients who were diagnosed as lung adenocarcinoma and had solitary pulmonary nodule(diameter≤3 cm) were collected,all of them were scanned by thin layer CT scan(1 mm).The correlation between imageology and pathology data were analyzed.Results In 125 cases of GGO,the ratio of invasive lesions were 0 (0/72),6.1％ (3/49) and 100％ (4/4) in stage T1a,T1b and T1c respectively.In 285 cases of mGGO,if solid component was less than 0.5 cm,the ratio of invasive lesions were 1.7％ (1/58),6.9％ (2/29) and 50.0％ (2/4) in stage T~,T1b and Tic;but the ratio of invasive lesions were 81.3％ (13/16),94.1％ (96/102) and 97.4％ (74/76) respectively when the solid component was more than 0.5 cm.In 214 cases with solid nodules,the ratio of invasive lesions were 87.1％ (27/31),98.8％ (84/85) and 99.0％ (97/98) in stage T1 a,T1b and T1c.Conclusion The ratio of invasive lesions and solid component increased gradually along with the growing of tumor diameter in stage T1 lung cancer.CT imaging was highly correlated with the pathology diagnosis of preinvasive lesions and invasive lesions,which can be used as the guidance for operation methods.

OBJECTIVETo investigate the effects of recombinant human granulocyte macrophage colony-stimulating factor (rhGM-CSF) on wound healing and microRNA expression in diabetic rats.

METHODSEighteen male SD rats of clean grade were used to reproduce diabetes model. Four weeks later, a total of 64 full-thickness skin wounds were created on the back of 16 rats with established diabetes, with 4 wounds on each rat. Two symmetrical wounds on either side of the spine were created as a pair according to paired design. Then the wounds were divided into groups A and B according to the random number table and blind method (red and blue tags on the rhGM-CSF or the gel vehicle), with 32 wounds in each group. The ointment with red tag was applied on the wounds of group A and the blue one on group B. The application was conducted once a day, with a thickness of 3 mm, up to post injury day (PID) 14. Gross observation of wound healing was conducted on PID 3, 7, 14. The wound healing rate was determined on PID 3 and 7. On PID 3, 7, 14, tissues from 2, 4, and 8 wounds were harvested from each group respectively for the observation of the histopathological changes with HE staining, and also for analyzing the expression of proliferating cell nuclear antigen (PCNA) and CD31 with immunohistochemical staining (denoted as absorbance value). On PID 7, tissues from 6 wounds in each group were harvested for microarray gene chip to screen the differentially expressed microRNAs. Enrichment analysis of Kyoto encyclopedia of genes and genomes (KEGG) signaling pathway on the differentially expressed microRNAs were performed after the microRNA screening results were validated by real-time fluorescent quantitative RT-PCR. Data were processed with paired t test or two-sample t test.

RESULTS(1) On PID 3, the wound area was significantly decreased, and the wound granulation was significantly proliferated in both groups. On PID 7, the wound area was further decreased, and the wound area was almost filled by granulation in both groups; the conditions in group A were better. On PID 14, all the wounds in group A were almost healed, while a small area of raw wound with incrustation still remained in some wounds of group B. On PID 3 and 7, the wound healing rates of group A were (41 ± 5)% and (75 ± 4)%, significantly higher than those of group B [(31 ± 9)% and (71 ± 4)%, with t values respectively 10.13 and 8.06, P values below 0.001]. (2) On PID 3, the epidermal cells, endothelial cells, and Fbs in the wounds of 2 groups were sparse, with heavy infiltration of inflammatory cells. The above condition in the wounds was better in group A than in group B. On PID 7, the epidermal cells, endothelial cells, and Fbs were gradually well arranged in group A; infiltration of inflammatory cells decreased, and the condition was better than that of group B. On PID 14, the wounds of group A were completely covered by epidermis, while infiltration of inflammatory cells still remained in some wounds of group B. (3) On PID 3, 7, 14, the positive expressions of CD31 and PCNA in group A were respectively 0.275 ± 0.018, 0.345 ± 0.034, 0.305 ± 0.023; 0.406 ± 0.063, 0.223 ± 0.011, 0.045 ± 0.022. They were significantly higher than those of group B (0.222 ± 0.020, 0.229 ± 0.018, 0.197 ± 0.015; 0.324 ± 0.039, 0.162 ± 0.012, 0.018 ± 0.020, with t values from 2.281 to 9.652, P < 0.05 or P < 0.01). (4) According to the microRNAs detection and screening, as compared with group B, 18 microRNAs were up-regulated while 13 were down-regulated in the wounds of group A. (5) The results of real-time fluorescent quantitative RT-PCR had good consistency with the results of microRNAs detection. (6) Enrichment analysis of KEGG signaling pathway showed that among the 31 differentially expressed microRNAs, 4 took part in the MAPK signaling pathway, 3 took part in the Wnt signaling pathway, 1 took part in the TGF-β signaling pathway, 3 took part in the epidermal growth factor receptor signaling pathway, 2 took part in the cell cycle pathway, 5 took part in the axon guidance signaling pathway, 6 took part in the focal adhesion pathway, 3 took part in the regulation of actin cytoskeleton pathway, 1 took part in the extracellular cell matrix receptor pathway, 3 took part in the adherens junction pathway, and 1 took part in the cell adhesion molecules pathway. After disclosing the blind, it showed that the ointment with red tag was the rhGM-CSF gel and the blue one was gel vehicle.

CONCLUSIONSThe rhGM-CSF gel can promote wound healing in diabetic rats, producing significant differential microRNA expression in wounds, and they may be the target at gene post-transcriptional level of rhGM-CSF gel in promoting wound healing.

Animals ; Bacteria ; isolation & purification ; Burns ; drug therapy ; microbiology ; pathology ; Diabetes Mellitus, Experimental ; complications ; Granulocyte-Macrophage Colony-Stimulating Factor ; pharmacology ; Humans ; Male ; MicroRNAs ; genetics ; Proliferating Cell Nuclear Antigen ; metabolism ; Rats ; Recombinant Proteins ; Signal Transduction ; Wound Healing ; drug effects