Immunotherapy plus chemotherapy have been confirmed to be effective in treating advanced or metastatic gastric cancer (GC). Anti- programmed death-1 (PD-1) plus antiangiogenic agents have shown promising activity and tolerant toxicity in subsequent therapy of late-stage gastric cancer. The aim of this study was to assess the efficacy and safety of anti-PD-1 plus anti-angiogenic agents and chemotherapy in advanced or metastatic GC and to explore the potential biomarkers associated with response.We retrospectively reviewed thirty human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic GC patients who received PD-1 plus anti-angiogenic drugs and chemotherapy. Conversion therapy was defined when the patients could undergo resection post combination therapy. Clinical data were retrieved from medical records. We conducted exploratory biomarker analysis of baseline gene mutations and tumor mutation burden (TMB) using the next-generation sequencing (NGS), PD-L1 by immunohistochemistry (IHC), and the tumor immune microenvironment (TIME) by multiplex immunofluorescence.A total of 30 patients received anti-PD-1plus anti-angiogenic drugs and chemotherapy during the study period. The objective response rate (ORR) was 76.7% [95% confidence interval (CI): 57.7-90.1%] and disease control rate (DCR) was 86.7% (95% CI: 69.3-96.2%). A total of 11 patients (36.7%) achieved conversion therapy and underwent surgery. The R0 resection rate was 90.9%. Of the 11 patients, 9 (81.8%) responded to the treatment, 1 with a pathological complete response (pCR) and 8 with a major pathological response (MPR). No adverse events of grade 3 or higher occurred. Neither PD-L1 expression nor TMB was significantly correlated with treatment response. Analysis of TIME revealed that the fraction of CD8+ T cell in the invasive margin was higher in responders than non-responders before treatment. TAM2 in the tumor center and CD8+ T cell in the invasive margin was significantly increased after combination therapy, which suggested that combination therapy promoted infiltration of CD8+ T cells, thereby exerting an antitumor effect.Immunotherapy plus anti-angiogenic drugs and chemotherapy is a promising treatment strategy for advanced or metastatic GC patients. Tumor infiltration CD8+ T cells may serve as potential predictive biomarker.
OBJECTIVE To investigate the advantages of a structural nutritional care management model (hereafter referred to as structural management) in severe acute pancreatitis (SAP) patients undergoing early enteral nutrition via nasal jejunal nutrition tubes. METHODS A total of 88 patients with SAP diagnosed and treated in our hospital were recruited as the study cohort and underwent enteral nutrition treatment. A random number table was used for the random grouping. The control group was routinely managed, and the study group was also administered structural management. In the study, we observed and compared the differences and changes in the relevant nutritional indexes (albumin (ALB), prealbumin (PA), and transferrin (TRF)) and the gastrointestinal hormone indexes (gastrin (MTL), vasoactive peptide (VIP), and 5-hydroxytryptamine (5-HT)) before and after the treatment. Between the two groups, we also compared the times required for the recovery of the relevant gastrointestinal physiological function indexes, the mechanical ventilation times, the hospitalization durations in the ICU, the complications, the satisfaction indexes and the satisfaction rates. RESULTS After the treatment, the relevant nutritional indicators, including ALB (35.26±3.35 g/L), PA (25.19±5.64 g/L), and TRF (2.82±0.54 g/L) in the study group were higher than the ALB (28.19±2.74 g/L), PA (21.29±4.32 g/L), and TRF (2.26±0.32 g/L) in the control group (all P<0.05). After the treatment, the relevant gastrointestinal hormone indicators, including MTL (269.72±37.18 pg/mL) and 5-HT (2214.61±432.95 ng/mL) in the study group were higher than the MTL (231.25±32.63 pg/mL) and 5-HT (1914.26±391.53 ng/mL) in the control group (all P<0.05). Moreover, the VIP in the study group was 53.13±6.17 pg/mL, which was significantly lower than the VIP in the control group (65.29±9.35 pg/mL, P<0.05). The time required for the recovery of the gastrointestinal function indexes in the study group was less than it was in the control group (P<0.05). The duration of the mechanical ventilation (8.16±1.93 days) and the hospitalization durations in the ICU (9.24±0.77 days) in the study group were significantly shorter than the duration of the mechanical ventilation (12.24±1.65 days) and the hospitalization durations in the ICU (13.23±0.88 days) in the control group (all P<0.05). The overall complication rate in the study group was significantly lower than it was in the control group (P<0.05), and the satisfaction rate in the study group was significantly higher than it was in the control group (P<0.05). CONCLUSION The combined use of structural management in SAP patients undergoing enteral nutrition treatment significantly improved the relevant nutritional indicator and gastrointestinal hormone indicator levels. It also contributed to the recovery of the gastrointestinal function indicators in the SAP patients, reduced the durations of their mechanical ventilation, their hospitalization durations in the ICU, and their complications and contributed to a significant increase in their satisfaction with the nursing.
Purpose: To identify risk factors of secondary cancer in nasopharyngeal carcinoma (NPC) patients after radiotherapy. Materials and methods: The data of NPC patients with secondary cancer were extracted from the Surveillance, Epidemiology, and End Results database from 2004 to 2016. Univariate and multivariate logistic regression analysis was performed to identify risk factors of secondary cancer. Risk factors selected from the multivariable logistic regression analysis were used to build a predicting model. Results: A total of 3931 patients were included: 329 (8.37%) patients developed secondary cancers and 3602 (91.63%) patients did not have secondary cancers. Univariate logistic regression analysis revealed that age, race, and the American Joint Committee on Cancer (AJCC) stage were risk factors of secondary cancer. Multivariable analysis demonstrated that age [Odds ratio (OR) = 1.03, P < 0.001], race (OR = 1.17, P = 0.010), AJCC stage (OR = 0.82, P = 0.002), and chemotherapy (OR = 1.55, P = 0.028) were independent risk factors of secondary cancer. Age, race, AJCC stage, and chemotherapy were entered into a nomogram for predicting secondary cancer. The area under the ROC curve of the nomogram was 0.645 [95% confidence interval (CI): 0.617-0.673]. The decision curve showed that if the threshold probability is between 4% and 25%, using the nomogram added more benefit than either the treat-all-patients scheme or the treat-none scheme. Conclusion: Age, race, AJCC stage, and chemotherapy were independent risk factors of secondary cancer in nasopharyngeal carcinoma patients after radiotherapy.
Objective
To explore the clinical value of balloon dilatation through flexible bronchoscope in the management of tracheobronchial stenosis of endobronchial tuberculosis.
Methods
From January 2005 to September 2009, 149 cases of tracheobronchial stenosis caused by endobronchial tuberculosis were examined by flexible bronchoscope and treated with balloon dilatation. Changes of the clinical features, atelectasis and airway diameters were observed and evaluated before and after the last treatment and in 12 months.
Results
The airway diameters were immediately enlarged (100%, 149/149) after the procedure, and the clinical symptoms were relieved. The average airway diameter changed from (2.7±1.4) mm before the procedure, to (6.8±2.0) mm, (6.4±1.7) mm and (6.3±2.3) mm immediately, 3 and 12 months after the treatments. Expansion of atelectasis was seen in 92% (34/37) of the cases, and the rate of restenosis was 3.4% (5/146) 12 months after treatment. There were significant differences before and after the treatments in the airway diameters, expansion rate of atelectasis and the general outcome (t=13.09-20.50, P<0.01), but there were no differences among measurements immediately, 3 and 12 months after the treatments. The final effective rate was 93.3% (139/149). Severe complications (4.0%, 6/149) were rare in these patients.
Conclusion
Balloon dilatation through flexible bronchoscope is a simple, effective and safe method for the management of tracheobronchial stenosis after endobronchial tuberculosis.
Key words:
Tuberculosis; Bronchi; Tracheal stenosis; Bronchoscopy; Balloon dilatation
Context Genistein, a soy-derived isoflavone, exhibits structural similarities with 17β-estradiol and demonstrates antioxidant, anti-inflammatory, and estrogenic properties. Despite its low bioavailability limiting its clinical application, it shows potential for breast cancer prevention and treatment.
Abstract Background Duration of antituberculosis therapy (ATT) for managing female genital tuberculosis (FGTB) is controversial with the intermittent regimen no more advocated. We therefore conducted a prospective, real-world research to compare 6 months and 9 months of ATT. Methods Between 2012 and 2018, 109 drug-susceptible patients newly diagnosed with FGTB and/or tuberculous peritonitis (genital, 13; peritoneal, 34; mixed, 62) received naïve treatment for 9–12 months and further 18-month follow-up. Data on disease features at baseline and long-term outcome (intent-to-treat) were compared between group A (aged 15–35 years) and group B (aged ≥ 36 years). Efficacy and side effects of treatment were compared within each group 6 months and 9 months from ATT initiation (per-protocol), respectively. Results In contrast to group B at baseline, group A had more clinical evidence predicting active tuberculosis ( P < 0.05), severer performance of genital lesions and pelvic adhensions ( P < 0.05), more signs of active pulmonary tuberculosis ( P < 0.01), and less performance of only TBP ( P < 0.01). Intent-to-treat analysis showed higher incidence of overall single side effects and poor compliance in group B ( P < 0.05), and similar recurrence rate between 2 groups. Per-protocol analysis showed increased complete response rate ( P < 0.01) and similar incidence of side effects ( P > 0.05) in group A, similar complete response rate ( P > 0.05) and increased incidence of overall single side effects ( P < 0.05) in group B at 9-mo duration. Conclusions Younger females with FGTB had a greater risk of systemic infection of TB compared to older ones. Nine-month ATT using daily therapy proved to be beneficial for younger patients at reproductive age. Six-month option was suitable for older patients for improving the side effects and poor compliance in the duration of treatment.
Objective
To explore the clinical efficacies of splenectomy and preserving accessory spleen for children with Gaucher's disease (GD).
Methods
Retrospective analyses were conducted for 6 type I GD post-splenectomic patients from January 2010 to September 2015.There were 4 males and 2 females with a mean age of 2.4 (1.2-4.8) years.Quality of life was impaired with bleeding tendency.There were low levels of platelet (62-143×109/L) and hemoglobin (49-110 g/L) without bone pain and neurological symptoms preoperatively.The average operative age was 6.6 years.Two received enzyme replacement therapy and another did for 6 months.
Results
Six cases underwent splenectomy.Among 3 cases with accessory spleen, two reserved accessory spleen.The size of removed spleen was 28 cm×21 cm×15 cm to 31 cm×18 cm×11 cm.And the specimen weight was 1.97-3.35 kg.Four cases had splenic infarction.Pathological examinations confirmed the diagnosis of GD and splenic infarction was present in 5 cases.The discharge levels of platelet (330-1419×109/L) and hemoglobin (87-121 g/L) improved significantly.There was no mortality during a follow-up period of 1-45 months.One patient discontinued enzyme replacement therapy after operation, one disconued enzyme replacement therapy at 6 months after operation, and the other one continued enzyme replacement therapy at a half dose.Growth & development and quality-of-life significantly improved and the levels of platelet (368-969×109/L) and hemoglobin (100-121 g/L) increased.
Conclusions
Splenectomy is efficacious for relieving the clinical symptoms of GD so that it reduces the dosage of enzyme replacement therapy.And preserving accessory spleen may decrease the complications of total or partial splenectomy.
Key words:
Gaucher's disease; Splenectomy; Accessory spleen
Abstract Objective: To explore the relationship between the circular clock gene NPAS2 (neural PAS domain protein 2) and the survival prognosis of gastric cancer (GC) patients and clarify its role in evaluating GC prognosis. Methods: The tumor tissues and clinical data of 101 patients with GC were collected retrospectively. Immunohistochemical staining (IHC) was used to detect the expression of NPAS2 protein in GC and adjacent tissues. Univariate and multivariate Cox regression analysis was used to determine the independent prognostic factors of GC, and a nomogram prediction model was established. The ROC curve, the ROC area under the curve (AUC), the calibration curve, and C-index were used to evaluate the predictive effectiveness of the model. Kaplan Meier analysiswas used to compare the risk stratification of subgroups according to the median score in the nomogram model of each patient. Results: Microarray IHC analysis showed that the positive rate of NPAS2 protein expression in GC tissues was 65.35%, which was significantly higher than 30.69% in adjacent tissues. The high expression of NPAS2 was correlated with TNM stage (P<0.05), pN stage (P<0.05), metastasis (P<0.05), venous invasion (P<0.05), lymphatic invasion (P<0.05), and lymph node positive (P<0.05) of GC. Kaplan Meier survival analysis showed that the 3-year overall survival (OS) of patients with high NPAS2 expression was significantly shortened (P<0.0001). Univariate and multivariate COX regression analysis showed that TNM stage (P=0.009), metastasis (P=0.009), and NPAS2 expression (P=0.020) were independent prognostic factors of OS in GC patients for 3 years. The nomogram prediction model based on independent prognostic factors has a C-Index of 0.740 (95% CI: 0.713-0.767). Furthermore, subgroup analysis showed that the 3-year OS time of the high-risk group was significantly lower than that of the low-risk group (P<0.0001). Conclusion: NPAS2 is highly expressed in GC tissues and is closely related to worse OS in patients. Therefore, the evaluation of NPAS2 expression may be a potential marker for GC prognosis evaluation. Notably, the nomogram model based on NPAS2 can improve the accuracy of GC prognosis prediction and assist clinicians in postoperative patient management and decision-making.
Abstract Background: Krebs von den Lungen-6 (KL-6) is considered a sensitive biomarker for diagnosis of interstitial lung disease (ILD). We aimed to evaluate the diagnosis value of Nanopia® KL-6 (SEKISUI MEDICAL CO., LTD., Tokyo, Japan) in a Chinese cohort of patients with ILD. Methods: Totally 451 patients were enrolled in our multicenter study, including 166 (36.8%) ILD patients, 210 (46.6%) non-ILD patients and 75 (16.6%) health controls. All ILD patients underwent high-resolution computed tomography (HRCT) followed by pulmonary function test (PFT). Serum KL-6 concentrations were measured by latex particle enhanced turbidimetric immunoassay (LTIA). Results: KL-6 serum concentrations were significantly higher in ILD patients (911 U/ml, IQR 477-1790) than in non-ILD patients (225 U/ml, IQR 166-323) and health controls (196 U/ml, IQR 153-230, p<0.0001). Serum KL-6 higher than 435.5 U/ml appeared as the optimal cut-off value associated with ILD. KL-6 concentrations were inversely correlated with forced vital capacity (FVC) (rho=-0.515, p<0.001), total lung capacity (TLC) (rho=-0.563, p<0.001) and diffuse lung capacity of carbon monoxide (DLco) (rho=-0.544, p<0.001). ILD patients with more severe characteristics of HRCT including ground glass opacity, reticular pattern or honeycombing had significantly higher serum KL-6 levels. In the subgroup of ILD patients, serum KL-6 concentrations were higher in idiopathic interstitial pneumonia (IIP) patients (1024U/ml, IQR 697-2112.25) than in other ILD patients (743U/ml, IQR 702.75-2058.25, p<10-4). ILD and retained smoking were independent factors associated with higher KL-6 levels in multivariate analysis. Conclusions: Our study confirms that KL-6 is a credible biomarker for the diagnosis of ILD in a Chinese cohort of patients. High serum KL-6 concentration should call attention to physicians to assess ILD with HRCT and PFT.
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