[Efficacy and safety of neoadjuvant chemotherapy combined with PD-1 antibody for esophageal squamous cell carcinoma in the real world].

Objective: To evaluate the efficacy and safety of neoadjuvant chemotherapy combined with programmed death-1 (PD-1) antibody in operable, borderline or potentially resectable locally advanced esophageal squamous cell carcinoma(ESCC) in the real world. Methods: The study retrospectively analyzed 28 patients with operable or potentially resectable locally advanced ESCC patients treated with preoperative chemotherapy combined with PD-1 inhibitor in Nanjing Drum Tower Hospital, Affiliated Hospital of Nanjing University Medical School from April 2020 to March 2021. According to the clinical TNM staging system of the 8th edition of the American Joint Committee on Cancer, there were 1, 15, 10, 1 and 1 case of stage Ⅱ, Ⅲ, ⅣA, ⅣB and unknown stage respectively. The treatment was two cycle of dual drug chemotherapy regimen including taxane plus platinum or fluorouracil combined with PD-1 antibody followed by tumor response assessment and surgery if the patient was eligible for resection. Results: Of the 28 patients, 1, 2, 3 and 4 cycles of chemotherapy combined with PD-1 antibody treatment completed in 1, 21, 5, and 1 patient, respectively. Objective response rate (ORR) was 71.4% (20/28), and disease control rate (DCR) was 100% (28/28). The incidence of adverse events exceeding grade 3 levels was 21.4% (6/28), including 3 neutropenia, 1 leukopenia, 1 thrombocytopenia and 1 immune hepatitis. There was no treatment-related death. Of the 23 patients underwent surgery, R0 resection rate was 87.0% (20/23), 13 patients had down staged to the T1-2N0M0 I stage, the pCR rate was 17.3% (4/23), and the pCR rate of primary tumor was 21.7% (5/23). Four patients received definitive chemoradiotherapy. One patient rejected surgery and other treatment after achieved PR response. Conclusion: Neoadjuvant chemotherapy combined PD-1 inhibitor is safe and has high efficacy in operable, borderline or potentially resectable locally advanced ESCC, and it is a promising regimen.

[Establishment of a nomogram predicting risk factors of postoperative perineal wound complications after abdominoperineal resection for rectal cancer].

Objective: To investigate the risk factors of perineal incision complications after abdominoperineal resection (APR) for rectal cancer, and to establish a nomogram model to predict the complications of perineal incision. Methods: A case-control study was conducted to retrospectively collect the medical records of 213 patients with colorectal cancer who underwent APR at the First Affiliated Hospital of Nanjing Medical University from January 2010 to December 2016. The complications of perineal incision after APR were classified according to the modified Clavien-Dindo classification of surgical complications (Version 2019), and the complications of grade II and above were defined as "clinically significant complications" .Twenty-two factors related to complication of perineal incision, such as gender, age, surgical procedure, surgical approach, perineal repair, placement of drainage tube, skin position of drainage tube, operation time, intraoperative blood loss, preoperative radiotherapy and chemotherapy, intraoperative local perfusion chemotherapy, tumor classification, pathological grade, tumor T stage, tumor TNM stage and so on, were analyzed by chi-square test for univariate risk factor of complication in all variables, and variables with P<0.2 in univariate analysis were further included in multivariate analysis. Logistic regression analysis was used to screen out independent risk factors. R software (R 3.3.2) was introduced. The rms software package was used to construct a nomogram prediction model. The C-index was calculated (higher meaning better consistency with actual risk) to evaluate the discriminant degree of the model. The Bootstrap method was used to repeat the sampling for internal verification. A total of 42 patients with colorectal cancer who underwent APR from January 2017 to December 2017 at the First Affiliated Hospital of Nanjing Medical University were externally validated, and the corrected C-index was calculated. The model conformity was determined by comparing the C-index calibration difference between the predicted and actual risks. Results: Of the 213 patients with colorectal cancer, 131 were male and 82 were female, with mean age of (59.6±11.6) years. The incidence of postoperative perineal incision complications was 20.2% (43/213), including 27 cases of Clavien-Dindo II and above complications. Univariate analysis showed that the Eastern Cancer Cooperative Group (ECOG) score, preoperative albumin, skin position of drainage tube, intraoperative blood loss, preoperative radiotherapy and chemotherapy were associated with complications of postoperative perineal incision (All P<0.05) . Multivariate analysis showed that preoperative albumin levels ≤38 g/L (OR=105.261, 95% CI: 7.781 to 1423.998, P<0.001), perinead drainage (OR=11.493, 95% CI: 1.379 to 95.767, P=0.024), intraoperative blood loss >110 ml (OR=6.476, 95% CI: 1.505 to 27.863, P=0.012) and preoperative radiotherapy and chemotherapy (OR=7.479, 95% CI: 1.887 to 29.640, P=0.004) were postoperative clinically significant independent risk factors for perineal incision complications. The nomogram model was established. Preoperative albumin level <38 g/L was for 100 points, the preoperative chemoradiotherapy was for 52.5 points, the intraoperative blood loss >110 ml was for 28.5 points, and the perineal drainage was for 17.5 points. Adding all the points was the total score, and the complication rate corresponding to the total score was the predicted rate of the model. The model had a C-index of 0.863. After internal verification, the C-index dropped by 0.005. External verification showed a C-index of 0.841. Conclusions: Preoperative nutritional status, skin position of drainage tube, intraoperative blood loss and preoperative radiotherapy and chemotherapy may affect the occurrence of perineal wound complications after APR for rectal cancer. The nomogram model constructed in this study is helpful for predicting the probability of clinically significant complications after APR.

[Clinical trial of simplified drilling method for dental implant site preparation].

Objective: To investigate the clinical effect of simplified drilling method and conventional drilling method in implants. Methods: A total of 46 patients (62 implants) were enrolled in this study that with dentition defect from May 2015 to May 2016 in the Implant department of Xi'an Jiao Tong University. The experimental group and the control group were randomly assigned according to the random number method, 23 cases in each group. The experimental group used the simplified drilling method (guided drill+ final drill), the control group using the conventional drilling method (step by step drill). The operation time, implant stability, marginal bone resorption rate and implant retention rate were compared between the two drilling methods. Results: The retention of the experiment group was 97% (31/32), the the control group was 100% (30/30). The operative time in the experiment group [(4.9±0.5) min] was significantly lower from the control group [(8.9±2.0) min] (P=0.000). There was no significant difference between the two methods in bone resorption (P=0.197), implant stability (P>0.05) and implant survival rate (P=0.492). Conclusions: The simplified drilling method can significantly reduce the operation time without compromising the clinical outcomes, and the osseointegration is well. The simplified drilling method should be used when sufficient bone mass, careful use in class II bone, forbidden in class I bone.

Extracellular signal-regulated kinase activation in the spinal cord contributes to visceral hypersensitivity induced by craniofacial injury followed by stress.

BACKGROUND: We previously developed an animal model to examine mechanisms that underlie the emergence of visceral hypersensitivity modeling pain characteristics of temporomandibular disorder (TMD) patients with comorbid irritable bowel syndrome (IBS). In ovariectomized (OVx) rats with estradiol (E2) replacement, visceral hypersensitivity developed subsequent to masseter muscle inflammation followed by repeated forced swim (FS) stress. The purpose of this study was to investigate whether activation of extracellular signal-regulated kinase (ERK) in the spinal cord contributes to visceral hypersensitivity in this overlapping pain model. METHODS: In OVx with E2 replacement rats masseter muscle inflammation was followed by 3 day FS (comorbid condition). Depression-like behaviors were assessed by sucrose preference and in the elevated plus maze, and visceral sensitivity was measured by the visceromotor response (VMR) to colorectal distention. The protein level of ERK1/2 and phosphorylated ERK1/2 (p-ERK1/2) in the L6-S2 dorsal spinal cord was analyzed by western blot. KEY RESULTS: FS stress decreased sucrose consumption in E2 replaced rats in sucrose preference test. The expression of p-ERK1/2 in the L6-S2 dorsal spinal cord increased significantly in E2 with comorbid rats. Intrathecal injection of mitogen-activated protein kinase (MAPK) kinase (MEK) inhibitor PD98059 blocked the visceral hypersensitivity induced by masseter muscle inflammation combined with FS stress. CONCLUSIONS & INFERENCES: These data indicate that ERK1/2 activation contributes to the visceral hypersensitivity evoked by craniofacial inflammation pain combined with stress. The results may provide a new therapeutic avenue for alleviating overlapping pain conditions.

Segregation of VIPergic-nitric oxidergic and cholinergic-nitric oxidergic innervation in porcine middle cerebral arteries.

The distribution of nitric oxide synthase (NOS)-, choline acetyltransferase (ChAT)-, and vasoactive intestinal polypeptide (VIP)-immunoreactivities, and nicotinamide adenine dinucleotide phosphate diaphorase (NADPHd)-reactivities in the sphenopalatine ganglia (SPG), and perivascular nerves in middle cerebral arteries of the pig was investigated by double-staining techniques using combined immunofluorescence and histochemistry methods. In the SPG, almost all ganglionic cells were NOS-immunoreactive (I) and NADPHd-positive, and both NOS immunoreactivities and NADPHd reactivities were completely co-localized. ChAT-I ganglionic cells accounted for 75%, while VIP-I ganglionic cells represented 42% of all ganglionic cells. Almost all VIP immunoreactivities were co-localized with ChAT immunoreactivities, and all ganglionic cells that were VIP-I and/or ChAT-I were NOS-I and NADPHd-reactive. None of the ganglionic cells in the SPG were immunoreactive to calcitonin gene-related peptide (CGRP). CGRP immunoreactivities, however, were found to surround some ganglionic cells. In middle cerebral arteries, all adventitial NOS-I bundles and fine fibers were coincident with NADPHd fibers. Almost all adventitial ChAT-I bundles and thin fibers, and VIP-I mesh-like fibers stained positively for NADPHd, while the mesh-like NADPHd fine fibers were not ChAT-I. Simultaneous labeling using antibodies against VIP and ChAT further indicated that VIP-I fibers were closer than ChAT-I fibers to the smooth muscle. In rare occasions, perivascular fibers were found to be stained for both ChAT and VIP, showing that most ChAT-I and VIP-I fibers were not coincident. These results suggest that ChAT and VIP are rarely co-localized in perivascular nerves in middle cerebral arteries, and point out that the neurotransmitter and the modulator that are co-localized within the same nerve cell body may distribute totally independently and differently at the terminal level. The present results also indicate that in cerebral perivascular nerves, the combination of nitric oxide (NO) and acetylcholine (ACh), as well as the combination of NO and VIP, are localized in the same nerve with different axons containing either NO plus ACh, or NO plus VIP. These findings support the hypothesis that ACh and VIP may act as modulators in regulating presynaptic release of NO, and therefore, cerebral neurogenic vasodilation, from their respective perivascular cholinergic-nitric oxidergic and VIPergic-nitric oxidergic nerves.