[The value of minimal residual disease and IKZF1 deletion for predicting prognosis in adult patients with B-cell acute lymphoblastic leukemia].

Objective: To reassess the prognostic value of minimal residual disease (MRD) and IKZF1 gene deletions in adults with B-cell acute lymphoblastic leukemia (B-ALL) who received pediatric-specific chemotherapy regimens during the Nanfang Hospital PDT-ALL-2016 trial. Methods: We retrospectively analyzed the prognosis of 149 adult patients with B-ALL who were admitted to Nanfang Hospital from January 2016 to September 2020. Prognostic factors were identified using Cox regression models. Results: The complete remission rate was 93.2% in 149 patients, with a 5-year overall survival (OS) rate of (54.3±5.0) % and a cumulative incidence of relapse (CIR) of (47.5±5.2) %. The Cox regression analysis revealed that MRD positivity at day 45 (MRD(3)) after induction therapy was independently associated with relapse risk (HR=2.535, 95%CI 1.122-5.728, P=0.025). Deletion of IKZF1 gene was independently associated with mortality risk (HR=1.869, 95%CI 1.034-3.379, P=0.039). Based on MRD(3) and IKZF1 gene status, we categorized adult patients with B-ALL into the low-risk (MRD(3)-negative and IKZF1 gene deletion-negative) and high-risk (MRD(3)-positive and/or IKZF1 gene wild type) groups. The 5-year OS and CIR rates were (45.5±6.0) % vs (69.4±8.6) % (P<0.001) and (61.6±8.3) % vs (25.5±6.5) % (P<0.001), respectively, in the high-risk and low-risk groups, respectively. The multivariate analysis showed that the high-risk group was an independent risk factor for OS (HR=3.937, 95%CI 1.975-7.850, P<0.001) and CIR (HR=4.037, 95%CI 2.095-7.778, P<0.001) . Conclusion: The combined use of MRD and IKZF1 gene in prognostic stratification can improve clinical outcome prediction in adult patients with B-ALL, helping to guide their treatment.

[Efficacy and prognostic factors of allogeneic hematopoietic stem cell transplantation in the treatment of secondary acute myeloid leukemia].

Objective: To evaluate the efficacy and prognostic factors of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with secondary acute myeloid leukemia (sAML) . Methods: In this multicenter, retrospective clinical study, adult patients aged ≥18 years who underwent allo-HSCT for sAML at four centers of the Zhejiang Hematopoietic Stem Cell Transplantation Collaborative Group from January 2014 to November 2022 were included, and the efficacy and prognostic factors of allo-HSCT were analyzed. Results: A total of 95 patients were enrolled; 66 (69.5%) had myelodysplastic syndrome-acute myeloid leukemia (MDS-AML) , 4 (4.2%) had MDS/MPN-AML, and 25 (26.3%) had therapy-related AML (tAML) . The 3-year CIR, LFS, and overall survival (OS) rates were 18.6% (95% CI 10.2%-27.0%) , 70.6% (95% CI 60.8%-80.4%) , and 73.3% (95% CI 63.9%-82.7%) , respectively. The 3-year CIRs of the M-AML group (including MDS-AML and MDS/MPN-AML) and the tAML group were 20.0% and 16.4%, respectively (P=0.430) . The 3-year LFSs were 68.3% and 75.4%, respectively (P=0.176) . The 3-year OS rates were 69.7% and 75.4%, respectively (P=0.233) . The 3-year CIRs of the groups with and without TP53 mutations were 60.0% and 13.7%, respectively (P=0.003) ; the 3-year LFSs were 20.0% and 76.5%, respectively (P=0.002) ; and the 3-year OS rates were 40.0% and 77.6%, respectively (P=0.002) . According to European LeukmiaNet 2022 (ELN2022) risk stratification, the 3-year CIRs of patients in the low-, intermediate-, and high-risk groups were 8.3%, 17.8%, and 22.6%, respectively (P=0.639) . The three-year LFSs were 91.7%, 69.5%, and 65.6%, respectively (P=0.268) . The 3-year OS rates were 91.7%, 71.4%, and 70.1%, respectively (P=0.314) . Multivariate analysis revealed that advanced disease at allo-HSCT and TP53 mutations were independent risk factors for CIR, LFS, and OS. Conclusion: There was no significant difference in the prognosis of patients who underwent allo-HSCT among the MDS-AML, MDS/MPN-AML, and tAML groups. Advanced disease at transplantation and TP53 mutations were poor prognostic factors. ELN2022 risk stratification had limited value for predicting the prognosis of patients with sAML following allo-HSCT.

Intraosseous schwannoma of the mandible: new case series, literature update, and proposal of a classification.

Intraosseous schwannoma of the mandible is rare, with diagnostic and therapeutic challenges. The aims of this study were to report new cases of intraosseous schwannoma of the mandible and to propose a clinical classification, providing suggestions for treatment methods. The cases of 13 patients treated at the authors' hospital and 86 cases reported previously in the literature were reviewed. The most common clinical feature was facial swelling (60/93). The rate of cortical thinning or expansion was 44.8% (43/96); widening of the inferior alveolar nerve canal on radiographs was observed in 15 patients.

Effects of personalized oral exercises on swallowing function among patients with oral cancer after free flap transplantation: a cluster randomized controlled trial.

Dysphagia is a common complication in patients with oral cancer who have undergone free flap transplantation. The aim of this cluster randomized controlled trial was to evaluate the effect of personalized oral exercises on swallowing function in this group of patients. Eligible patients were randomly assigned to the intervention (n = 34) or control (n = 34) group. Intervention group patients received personalized oral exercises starting on day 6 after surgery. Swallowing function was evaluated on days 6 and 15, and at 1 month postoperative using the Mann Assessment of Swallowing Ability-Oral Cancer tool (MASA-OC). On day 15 and at 1 month after surgery, the total MASA-OC score (P = 0.003, P < 0.001) and the mouth opening (P = 0.001, P < 0.001) and lip seal (both P < 0.001) item scores showed a significantly greater improvement in the intervention group than in the control group. Moreover, the changes in salivation (P < 0.001) and tongue movement (P = 0.025) scores at 1 month after surgery were significantly greater in the intervention group than in the control group. There was no significant difference between the groups in the change in tongue strength scores on day 15 or at 1 month postoperative (P = 0.476, P = 0.223). Personalized oral exercises can improve swallowing function in patients with oral cancer after free flap transplantation.

[Circular RNA hsa_circ_0006834 is a potential prognostic biomarker for hepatocellular carcinoma].

OBJECTIVE: To explore the differentially expressed circular RNAs (circRNAs) in hepatocellular carcinoma (HCC) and their association with clinical features and prognosis of HCC patients. METHODS: RNA sequencing was performed on 56 pairs of HCC and adjacent tissues to identify the differentially expressed circRNAs in HCC, whose expressions were validated by RT-qPCR in another 15 pairs of HCC and adjacent tissues. The correlation of the selected circRNAs with the clinical features and prognosis of the patients was analyzed using Chi-square test, Cox proportional hazards regression model and Kaplan-Meier analysis. The predictive value of the identified circRNA for recurrence-free survival and overall survival of HCC patients was assessed using ROC curves. RESULTS: We identified 17 significantly up-regulated and 45 down-regulated circRNAs in HCC tissues using RNA sequencing (P < 0.05). Among these circRNAs, hsa_circ_0006834 was found to be significantly down-regulated in HCC tissues, and its expression level was negatively correlated with vascular invasion and Barcelona Clinic Liver Cancer (BCLC) stage and positively with recurrence-free survival and overall survival of the patients (P < 0.05). As an independent prognostic factor for HCC, hsa_circ_0006834 had an AUC of 0.750 and 0.7601 for predicting 2-year recurrence-free survival and overall survival of HCC patients, respectively. CONCLUSION: hsa_circ_0006834 is a new potential biomarker for evaluating the prognosis of HCC patients.

[Comparison of risk factors for hemorrhagic stroke and ischemic stroke, a prospective long-term follow-up cohort study].

Objective: To analyze and compare the risk factors for hemorrhagic stroke and ischemic stroke and understand the exposure levels in population. Methods: A cohort study of risk factors of stroke was conducted in a rural community in Fengxian District of Shanghai in 2003, and the common risk factors of stroke were investigated at baseline survey, the cerebrovascular hemodynamics indexes were detected, the cerebrovascular function score was calculated according to the unified integral rule, and the incidence of stroke was observed in follow up. The risk factors for hemorrhagic stroke and ischemic stroke were analyzed by cohort study. The risk factors for two subtypes of stroke were compared. Result: A total of 10 565 participants were included in the study, with a mean follow-up period of (11.15±2.26) years, and 103 hemorrhagic stroke cases and 268 ischemic stroke cases were observed during follow-up period. The independent risk factors of hemorrhagic stroke included decreased cerebrovascular function score [hazard ratio (HR)=1.56, 95%CI: 1.23-1.98], history of alcohol consumption (HR=2.46, 95%CI: 1.39-4.34), hypertension (HR=1.75, 95%CI: 1.00-3.07) and older age (HR=1.07, 95%CI: 1.04-1.10). The independent risk factors of ischemic stroke included decreased cerebrovascular function score (HR=1.43, 95%CI: 1.25-1.65), smoking history (HR=1.52, 95%CI: 1.13-2.05), hypertension (HR=1.51, 95%CI: 1.10-2.07), family history of stroke (HR=1.89, 95%CI: 1.13-3.15), left ventricular hypertrophy (HR=1.74, 95%CI: 1.07-2.81) and older age (HR=1.07, 95%CI: 1.05-1.08). Conclusions: Decreased cerebrovascular function score, hypertension, and older age were common independent risk factors of both types of stroke, alcohol consumption history was an independent risk factor of hemorrhagic stroke, and smoking history, and family history of stroke and left ventricular hypertrophy were independent risk factors of ischemic stroke.

[Application of methylene blue near-infrared fluorescence imaging for oral sentinel lymph node mapping in rats].

OBJECTIVE: To explore the concentration range and penetration depth of methylene blue near-infrared fluorescence imaging, and to clarify the role of methylene blue in oral lymphatic drainage and sentinel lymph node localization, so as to lay a foundation for the potential research and application of sentinel lymph node in oral cancer. METHODS: 10% (mass fraction) methylene blue injection was diluted into 29 different concentrations with 0.9% (mass fraction) normal saline, and the concentration range of methylene blue near-infrared fluorescence imaging was determined by near-infrared fluorescence imager. The maximum penetration depth of methylene blue near-infrared fluorescence was determined by covering pigskin with different thicknesses (1, 2, 3, 4 and 5 mm) in methylene blue solution. 0.2 mL methylene blue solution was injected into the submucosal 0.5 cm at the lateral margin of tongue on one side of the rats. The near-infrared fluorescence imager was used for continuously monitoring for 3 hours. The first near-infrared fluorescence hotspot was identified as sentinel lymph node and labeled by percutaneous observation. The rats were then sacrificed and dissected in the head and neck. Near-infrared fluorescence imaging was performed again to observe whether the fluorescent tissue was consistent with the labeled fluorescent hotspot in vitro, and the presence of lymphoid tissue was confirmed by pathological examination after resection. RESULTS: Except that no fluorescence signals were detected in the blank control groups, the fluorescence intensity of methylene blue increased first and then decreased with its solution concentration decreased. When the concentration of methylene blue was diluted to the picomole level, the fluorescence signal could still be detected. The maximum penetration depth of methylene blue fluorescence was 4 mm. Methylene blue near-infrared fluorescence could be localized in oral lymphatic drainage and sentinel lymph node. The fluorescence was sustained for more than 3 hours after methylene blue injection. Methylene blue solution concentrations of 3.34 mmol/L, 6.68 mmol/L, 13.37 mmol/L and 26.74 mmol/L were selected in the rats to map sentinel lymph node by near-infrared fluorescence. CONCLUSION: Methylene blue near-infrared fluorescence has a certain penetrating ability and can transcuta-neously map the sentinel lymph node and their associated lymphatic vessels in rats, which is expected to be further applied in the study of sentinel lymph node in oral cancer.

[Application value of whole exon sequencing and immune related indicators in the precision treatment of oral squamous cell carcinoma].

OBJECTIVE: To explore the significance and feasibility of whole exon sequencing and immune related indexes in personalized precision treatment of oral squamous cell carcinoma (OSCC). METHODS: We retrospectively screened the patients who underwent surgery for oral cancer in Peking University Hospital of Stomatology and underwent genetic and immune biomarkers tests between January 2021 and June 2022. Combined with the clinicopathological characteristics of patients, potential targeted drugs and immunotherapy drugs were screened to evaluate the possibility of gene testing benefiting OSCC. The main evaluation indicators included the number of gene mutations, combined positive score (CPS), tumor mutation burden (TMB), microsatellite sequence status and human leukocyte antigen B (HLA-B) locus. Excel was used for statistical analysis. RESULTS: A total of 10 patients were enrolled and 9 were included in this study, including 6 males and 3 females, with an average age of (55.44±9.59) years. The tumor location was buccal (5 cases), tongue (3 cases) and gingival (1 case). The results of genetic testing showed that 3 (33.3%) patients had no gene mutations in the tumor tissue, 5 (55.6%) patients had unique TP53 gene mutations, and 1 (11.1%) patient had TP53 and CHEK1 mutations. However, no drugs were available for targeted therapy of the mutated genes. The genetic tumor gene testing results showed that no genetic tumor gene was found in all the patients, suggesting that OSCC had a low possibi-lity of hereditary tumor. In terms of immune efficacy related markers, CPS test results showed that 8 patients had CPS≥1. TMB detection results showed that the median value of TMB value was 0.72 mutations/Mb, and the range was 0 to 4.32 mutations/Mb. The negative and positive control results of microsatellite sequence status were consistent, indicating that all the tumor tissues detected were microsatellite stability. The results of HLA-B detection showed that only one patient had B62 gene mutation, suggesting that the B44 and B62 related genotypes of HLA-B in OSCC tissue samples were low. CONCLUSION: The present results do not support the wide application and promotion of genetic testing and immune related indexes in OSCC.

[Category of facial symmetry perception after maxillary reconstruction using anterolateral thigh flap].

OBJECTIVE: To preliminarily establish a category of facial symmetry perception after maxillary reconstruction using anterolateral thigh flap (ALTF) by the methods of stereophotogrammetry and subjective assessment. METHODS: The patients underwent maxillectomy due to neoplasms invasion, and all the maxillary defects were reconstructed using ALTF.Three-dimensional (3D) photographs were captured from the patients with a stereophotogrammatrical camera set-up.In the Geomagic software, the mirror image was created by reflecting along an arbitrary plane outside of the face.After the registration, the postoperative side on the original 3D photograph was segmented into 6 areas.The 3D change of the facial soft-tissue was measured using surface-based color map.Twenty laypeople took part in the study as observers, and they were asked to rate the 3D photographs using 5 point Likert-type scale according to their own aesthetic standard.The soft tissue asymmetry was graded according to the score.The collected data were subjected to statistical analysis using the SPSS 24.0 software. RESULTS: In the study, 44 subjects were recruited (21 males and 23 females, age range from 19 to 79 years).The soft-tissue symmetry was graded into three levels according to the subjective scores.The grade Ⅰ was basically symmetrical.The grade Ⅱ was slightly asymmetrical.The grade Ⅲ was obviously asymmetrical.Statistically significant differences were found in the suborbital (P < 0.05) and zygomatic (P < 0.05) areas when comparing all grades of soft-tissue asymmetry, and in the buccal (P < 0.05) and superiolabial (P < 0.05) areas when comparing grades Ⅰ and Ⅲ.The extent of maxillary defect had significant impact on the symmetry of the midface soft-tissue after maxillary reconstruction. CONCLUSION: Varying extent maxillectomy would result in varying degrees of asymmetry, and cause different grades of symmetry perception even if they had been reconstructed using ALTF.The higher the grade, the worse the symmetry of facial soft-tissue.Suborbital and zygomatic areas were important aesthetic units that affected the facial symmetry perception, followed by buccal and superiolabial areas.The clinicians should pay attention to the soft-tissue support in these areas when reconstructing the maxillary defect, especially large defect with orbital floor involved.

Accurate occlusion-driven maxillary reconstruction with deep circumflex iliac artery flap using computer-assisted techniques and intraoral anastomosis: a case series.

The aim of this study was to evaluate the feasibility and accuracy of occlusion-driven maxillary reconstruction with the deep circumflex iliac artery (DCIA) flap, using computer-assisted design and manufacturing (CAD/CAM) technology and intraoral anastomosis. The data of 11 patients who underwent occlusion-driven maxillary reconstruction with this method between December 2018 and December 2020 in the Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology were reviewed retrospectively. Postoperative complications and functional and aesthetic outcomes were recorded. The accuracy of the postoperative restoration was assessed using Geomagic Control 2014. Reconstruction was successful in nine patients; all were satisfied with their aesthetic and functional outcomes. One patient underwent extraoral anastomosis after failure of intraoral anastomosis. In another patient, the DCIA flap had to be removed after the operation because of flap failure. Among the 10 patients with DCIA flap success, colour map analysis showed a mean deviation of 0.40 ± 0.08 mm between the preoperative and postoperative craniomaxillary models. Thus, occlusion-driven maxillary reconstruction with the DCIA flap, using CAD/CAM technology and intraoral anastomosis, appears to be a feasible and accurate method for the repair of maxillary defects.

Bone resorption after maxillary reconstruction with the vascularized free iliac flap.

The aim of this study was to evaluate the resorption of the iliac bone after maxillary reconstruction with a vascularized free iliac flap. Twenty-seven patients with maxillary defects who underwent maxillary reconstruction with the vascularized free iliac flap between January 2017 and January 2021 were included. Computed tomography (CT) images taken at 1 week, approximately 6 months, and 1 year after the surgery were used for evaluation. The total iliac bone thickness and height, cortical bone thickness, and cancellous bone density were measured in the CT images. Compared with 1 week after the surgery, the total thickness and height of the iliac bone were reduced significantly 1 year after the surgery, and the cortical bone thickness and cancellous bone density were reduced significantly at 6 months and 1 year after the surgery. Compared with 6 months after the surgery, cancellous bone density was reduced significantly 1 year after the surgery. In conclusion, during the first year after maxillary reconstruction with a vascularized free iliac flap, there was significant resorption of iliac bone, including the total iliac bone thickness and height, the cortical bone thickness, and the cancellous bone density.

[Preliminary analysis of the promotion effect of laparoscopic standardized surgical treatment for gastric cancer in regional medical centers in Shanghai].

Objective: To explore the promotion effect of laparoscopic standardized surgery for gastric cancer observational in some regional medical centers in Shanghai. Methods: A retrospective cohort study was carried out. Eleven regional medical centers in Shanghai received the promotion program of laparoscopic standardized surgery for gastric cancer, which was led by Ruijin Hospital, Shanghai Jiaotong University School of Medicine (Shanghai Minimally Invasive Surgery Center) from January to December 2020. Clinicopathological data of gastric cancer patients treated at these 11 regional medical centers before and after the promotion program were collected. Inclusion criteria were as follows: patients undergoing laparoscopic distal gastrectomy or total gastrectomy; gastric cancer confirmed by pathology; without distant metastasis or peritoneal metastasis. Patients who did not undergo laparoscopic D2 radical resection, or received neoadjuvant chemotherapy before surgery, or without complete clinical data were excluded. Patients undergoing laparoscopic surgery from January to December 2019 were included in the pre-promotion group (46 cases). Patients undergoing laparoscopic surgery from January to December 2021 were included in the post-promotion group (102 cases). In addition, patients undergoing laparoscopic surgery at Ruijin Hospital from January 2021 to December were included in the control group (138 cases). The baseline data, perioperative measurements postoperative complications, and pathological results of the three groups were analyzed and compared. Results: There were no significant differences in baseline characteristics among the three groups (all P>0.05). Compared with the pre-promotion group, the operation time in post-promotion group was significantly shorter [(207.3±36.0) minutes vs. (254.2±47.1) minutes, t=7.038,P<0.001], and the number of harvested lymph node was significantly more (24.4±12.2 vs. 18.9±5.5, t=2.900, P=0.004). However, there were no significant differences in the extent of resection, time to fluid intake, and postoperative hospital stay between the two groups (all P>0.05). Compared with the control group, the operation time [(207.3±36.0) minutes vs (172.6±26.0) minutes, t=8.281, P<0.001], time to fluid intake [(6.3±3.2) days than (5.5±3.0) days, t=2.029, P=0.044], and the postoperative hospital stay [(14.3±5.6) days vs. (10.1±4.8) days, t=6.036, P<0.001] in the post- promotion group were still longer. Total gastrectomy was less common in the post-promotion group compared with the control group [18 cases (17.6%) vs. 41 cases (29.7%), χ2=7.380, P=0.007]. However, there was no significant difference in the number of harvested lymph node between the two groups (P>0.05). The morbidity of postoperative complication in the post-promotion group (9.8%, 10/102) was significantly lower than that in the pre-promotion group (23.9%, 11/46) (χ2=5.183, P=0.023), while above morbidity was not significantly different between the post-promotion group and the control group [9.8% vs. 6.5% (9/138), χ2=0.867, P=0.352]. Conclusion: After the promotion of laparoscopic standardized surgery for gastric cancer in regional medical centers, the standardization degree of surgery has been improved, and the morbidity of postoperative complication decreases. Laparoscopic standardized surgery for gastric cancer can be promoted to more regional medical centers.

[Prognostic significance of IKZF1 gene deletions in patients with B-cell acute lymphoblastic leukemia].

Objective: This study aimed to investigate the prognostic significance of IKZF1 gene deletion in patients with acute B lymphoblastic leukemia (B-ALL) . Methods: The clinical data of 142 patients with B-ALL diagnosed in Nanfang Hospital between March 2016 and September 2019 were analyzed. Results: IKZF1 deletion was found in 36.0% of the 142 patients with B-ALL, whereas exon 4-7 deletion was found in 44.0% . White blood cell counts were higher in patients with the IKZF1 deletion (52.0% and 28.3% , P=0.005) ; these patients also experienced worse effects of mid-term induction therapy (40.0% and 70.7% , P<0.001) and had a higher proportion of Philadelphia chromosome-positive (52.0% and 21.7% , respectively, P<0.001) . Univariate analysis revealed that the 3-year overall survival rate (OS) and event-free survival rate (EFS) in the IKZF1 deletion group were significantly lower than the IKZF1 wild-type group [ (37.1±7.3) % vs (54.7±5.4) % , (51.8±7.9) % vs (73.9±4.7) % ; P=0.025, 0.013, respectively]. Multivariable analysis showed that harboring IKZF1 deletion was an adverse factor of EFS and OS (HR=1.744, 2.036; P=0.022, 0.020, respectively) . Furthermore, the IKZF1 deletion/chemotherapy group had significantly lower 3-year OS, EFS, and disease-free survival rates than other subgroups. In the IKZF1 deletion cohort, allo-hematopoietic stem cell transplantation (HSCT) significantly improved OS and EFS compared to non-allo-HSCT[ (67.9±10.4) % vs (31.9±11.0) % , (46.6±10.5) % vs (26.7±9.7) % ; P=0.005, 0.026, respectively]. Conclusion: Pediatric-inspired chemotherapy was unable to completely reverse the negative effect of IKZF1 deletion on prognosis. Pediatric-inspired regimen therapy combined with allo-HSCT, in contrast, significantly improved the overall prognosis of IKZF1 deletion B-ALL.

Preoperative oral carbohydrates in elderly patients undergoing free flap surgery for oral cancer: randomized controlled trial.

The aim of this study was to evaluate the safety of carbohydrate intake 2 hours before surgery in elderly patients undergoing free flap surgery for oral cancer. Elderly patients undergoing free flap surgery between September 2019 and January 2021 were randomly divided into control (n = 43) and intervention (n = 43) groups. Control group patients fasted for 6 hours and were forbidden from drinking water for 4 hours before surgery. Intervention group patients fasted for 6 hours and were forbidden from drinking after the oral administration of 5 ml/kg carbohydrate (≤400 ml) 2 hours before surgery. The main outcome measures were aspiration, fasting blood glucose level, insulin concentration, insulin resistance index (fasting at admission, prior to anaesthesia induction, immediately after surgery, and at 6 a.m. on postoperative days 1 and 2), and comfort before and after surgery. No aspiration occurred in any of the patients during anaesthesia. There were significant differences in fasting blood glucose, insulin concentration, and insulin resistance index between the control and intervention groups prior to anaesthesia induction, immediately after surgery, and on day 1 after surgery (P < 0.01). Thirst (P = 0.001) and hunger (P = 0.003) differed significantly between the two groups prior to anaesthesia induction. The intake of oral carbohydrate 2 hours before surgery was both safe and effective for elderly patients with oral cancer undergoing free flap surgery and could relieve the physiological stress response.

[Impact of adjuvant chemotherapy on prognosis in intrahepatic cholangiocarcinoma patients underwent radical resection].

Objectives: To investigate the clinical value of adjuvant chemotherapy(ACT) in patients with intrahepatic cholangiocarcinoma(ICC) who underwent radical resection and to explore the optimal population that can benefit from ACT. Methods: A retrospective cohort study method was adopted. The clinical and pathological data of 685 patients with ICC who underwent curative intent resection in 10 Chinese hepatobiliary surgery centers from January 2010 to December 2018 were collected;There were 355 males and 330 females. The age(M(IQR)) was 58(14) years (range: 22 to 83 years). Propensity score matching(PSM) was applied to balance the differences between the adjuvant and non-adjuvant chemotherapy groups. Log-rank test was used to compare the prognosis of the two groups of patients. A Bayesian network recurrence-free survival(RFS) prediction model was constructed using the median RFS time (14 months) as the target variable, and the importance of the relevant prognostic factors was ranked according to the multistate Birnbaum importance calculation. A survival prognostic prediction table was established to analyze the population benefiting from adjuvant chemotherapy. Results: Among 685 patients,214 received ACT and 471 did not receive ACT. A total of 124 pairs of patients were included after PSM, and patients in the ACT group had better overall survival (OS) and RFS than those in the non-ACT group(OS: 32.2 months vs. 18.0 months,P=0.003;RFS:18.0 months vs. 10.0 months,P=0.001). The area under the curve of the Bayesian network RFS prediction model was 0.7124. The results of the prognostic factors in order of importance were microvascular invasion (0.158 2),perineural invasion (0.158 2),N stage (0.155 8),T stage (0.120 9), hepatic envelope invasion (0.090 3),adjuvant chemotherapy (0.072 1), tumor location (0.057 5), age (0.042 3), pathological differentiation (0.034 0), sex (0.029 3), alpha-fetoprotein (0.028 9) and preoperative jaundice (0.008 5). A survival prediction table based on the variables with importance greater than 0.1 (microvascular invasion,perineural invasion,N stage,T staging) and ACT showed that all patients benefited from ACT (increase in the probability of RFS≥14 months from 2.21% to 7.68%), with a more significant increase in the probability of RFS≥14 months after ACT in early-stage patients. Conclusion: ACT after radical resection in patients with ICC significantly prolongs the OS and RFS of patients, and the benefit of ACT is greater in early patients.

Potential biomarkers in the fibrosis progression of nonalcoholic steatohepatitis (NASH).

PURPOSE: Fibrosis is the only histological feature reflecting the severity and prognosis of nonalcoholic steatohepatitis (NASH). We aim to explore novel genes associated with fibrosis progression in NASH. METHODS: Two human RNA-seq datasets were downloaded from the public database. Weighted gene co-expression network analysis (WGCNA) was used to identify their co-expressed modules and further bioinformatics analysis was performed to identify hub genes within the modules. Finally, based on two single-cell RNA-seq datasets from mice and one microarray dataset from human, we further observed the expression of hub genes in different cell clusters and liver tissues. RESULTS: 7 hub genes (SPP1, PROM1, SOX9, EPCAM, THY1, CD34 and MCAM) associated with fibrosis progression were identified. Single-cell RNA-seq analysis revealed that those hub genes were expressed by different cell clusters such as cholangiocytes, natural killer (NK) cells, and hepatic stellate cells (HSCs). We also found that SPP1 and CD34 serve as markers of different HSCs clusters, which are associated with inflammatory response and fibrogenesis, respectively. Further study suggested that SPP1, SOX9, MCAM and THY1 might be related to NASH-associated hepatocellular carcinoma (HCC). Receiver operating characteristic (ROC) analysis showed that the high expression of these genes could well predict the occurrence of HCC. At the same time, there were significant differences in metabolism-related pathway changes between different HCC subtypes, and SOX9 may be involved in these changes. CONCLUSIONS: The present study identified novel genes associated with NASH fibrosis and explored their effects on fibrosis from a single-cell perspective that might provide new ideas for the early diagnosis, monitoring, evaluation, and prediction of fibrosis progression in NASH.

[Risk factors of newly developed nonalcoholic fatty liver disease after pancreaticoduodenectomy].

Objective: To identify the risk factors of newly developed nonalcoholic fatty liver disease(NAFLD) after pancreaticoduodenectomy(PD). Methods: The clinical data of 130 patients who had undergone PD at Department of Hepatopancreatobiliary Surgery, Nanjing Drum Tower Hospital, the Affiliated Hospital of Medical School of Nanjing University from June 2018 to December 2020 were collected retrospectively. There were 74 males and 56 females, with age(M(IQR)) of 62(16) years (range: 22 to 84 years). Twenty-nine patients who developed NAFLD were divided into NAFLD group and 101 patients who did not suffer NAFLD were divided into no NAFLD group. Observation indications included:(1)preoperative demographics,intraoperative and postoperative characteristics; (2)the risk factors of newly developed NAFLD after PD. Count data were analyzed using χ2 test or Fisher's exact test. Measurement data were analyzed by student t test or Mann-Whitney U test. Multivariate analysis was performed using Logistic regression model with a stepwise forward approach. Results: All 130 patients successfully underwent PD and 29 cases(22.3%) developed NAFLD in 6 months after PD. The results of univariate analysis showed that gender,diabetic mellitus,the level of triglyceride preoperatively,and pancreatic ductal adenocarcinoma were the related factors of the development of NAFLD after PD(t=-2.655, χ²=4.563,U=-2.192,χ²=7.044;all P<0.05).Multivariate analysis revealed that gender,body mass index and pancreatic ductal adenocarcinoma were independent risk factors for the development of NAFLD after PD(OR=2.849,1.214,4.165,all P<0.05). Conclusion: Gender, body mass index and pancreatic ductal adenocarcinoma were independent risk factors for the development of NAFLD after PD.

[Study of neurotrophic factor receptor tyrosine kinase gene fusion in the precise treatment of wild-type gastrointestinal stromal tumor].

The neurotrophin receptor kinase (NTRK) gene encodes neurotrophic factor receptor tyrosine kinase (NTRK), which plays an important role in the development and function of the nervous system. NTRK gene fusion mutation results in the production of chimeric NTRK proteins, which have carcinogenic potential through constitutive activation or overexpression. NTRK gene fusion mutation can lead to a special type of wild type gastrointestinal stromal tumor (GIST), whose clinical manifestations and treatment are completely different from other types of GIST. This fusion mutation can be detected clinically by a variety of methods, including tumor DNA and RNA sequencing and immunohistochemical staining. In patients with NTRK fusion positive tumors, NTRK inhibitors such as larotrectinib and entrectinib have shown good antitumor efficacy, with clinical response rates as high as 75%. Therefore, there is a need to improve the recognition and detection of fuch patients and to improve their prognosis by individualized and precise treatment with TRK inhibitors.