scholarly journals Trans-bronchial lung cryobiopsy in patients at high-risk of complications

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Benjamin Bondue ◽  
Pascal Schlossmacher ◽  
Nathalie Allou ◽  
Virgile Gazaille ◽  
Olivier Taton ◽  
...  

Abstract Background The surgical lung biopsy (SLB) is the recommended sampling technique when the pathological analysis of the lung is required in the work-up of an interstitial lung disease (ILD) but trans-bronchial lung cryobiopsy (TBLC) is increasingly recognized as an alternative approach. As TBLCs have lower mortality and morbidity risks than SLB, this study aimed to investigate the safety of TBLCs in patients at higher risk of complications and for whom SLB was not considered as an alternative. Method This prospective study was conducted in two hospitals in which TBLCs were performed in patients with body mass index (BMI) > 35, and/or older than 75 years, and/or with severely impaired lung function (FVC < 50% or DLCO < 30%), and/or systolic pulmonary artery pressure > 45 mmHg, and/or a clinically significant cardiac disease. Patients with any of these risk factors constituted the high-risk group. Clinical outcomes were compared with those obtained in patients without these risk factors (low-risk group). Results Ninety-six patients were included between April 2015 and April 2020, respectively 38 and 58 in the high-risk or the low-risk group. No statistically significant difference was observed between both groups in terms of severity and rate of bleeding, pneumothorax, or duration of hospital stay (p value ranging from 0.419 to 0.914). Conclusion This preliminary study on a limited number of patients suggests that TBLC appears safe in those in whom lung biopsy is at high-risk of complications according to their age, BMI, lung impairment, and cardiac comorbidities.

2017 ◽  
Vol 27 (7) ◽  
pp. 1387-1392 ◽  
Author(s):  
Jinhong Jung ◽  
Young Seok Kim ◽  
Ji Hyeon Joo ◽  
Won Park ◽  
Jong-Hoon Lee ◽  
...  

ObjectiveThe aim of this study was to investigate the survival, patterns of failure, and prognostic factors in patients with stage II endometrial carcinoma treated with adjuvant radiotherapy.MethodsWe reviewed the medical records of patients who underwent total hysterectomy, bilateral salpingo-oophorectomy, and pelvic lymph node dissection followed by adjuvant radiotherapy in 10 participating hospitals of the Korean Radiation Oncology Group. Most patients received adjuvant external beam radiation therapy, with a median dose of 50.4 Gy; approximately 50% of these patients received an additional brachytherapy boost, with a median dose of 18 Gy. Adjuvant chemotherapy was administered to 19 patients.ResultsA total of 122 patients were examined. Over a median follow-up period of 62.7 months (range, 1.9–158.8 months), the 5-year overall survival (OS) and disease-free survival rates were found to be 91.1% and 85.1%, respectively. Recurrence was observed in 14 patients (11.5%), including 3 with local recurrence and 11 with distant metastases as the first site of recurrence. Univariate analysis indicated that lymphovascular invasion was related to an unfavorable OS. An age of 60 years or above, histologic grade 3, and lymphovascular invasion were identified as risk factors for OS. Because there were several risk factors related to OS, we assigned patients to a high-risk group (defined as cases with ≥1 risk factors) and a low-risk group. The 5-year OS rate of the high-risk group was significantly inferior to that of the low-risk group (82.9% vs 100%, P = 0.003).ConclusionsThe high-risk group had a significantly poorer survival rate than the low-risk group, and distant metastasis was the main pattern of recurrence, thus indicating that further adjuvant chemotherapy should be considered in high-risk patients.


Author(s):  
Xinshuang Yu ◽  
Peng Dong ◽  
Yu Yan ◽  
Fengjun Liu ◽  
Hui Wang ◽  
...  

Pancreatic cancer is a highly aggressive disease with poor prognosis. N6-methyladenosine (m6A) is critical for post-transcriptional modification of messenger RNA (mRNA) and long non-coding RNA (lncRNA). However, the m6A-associated lncRNAs (m6A-lncRNA) and their values in predicting clinical outcomes and immune microenvironmental status in pancreatic cancer patients remain largely unexplored. This study aimed to evaluate the importance of m6A-lncRNA and established a m6A-lncRNA signature for predicting immunotherapeutic response and prognosis of pancreatic cancer. The m6A-lncRNA co-expression networks were constructed using data from the TCGA and GTEx database. Based on the least absolute shrinkage and selection operator (LASSO) analysis, we constructed an 8 m6A-lncRNA signature risk model, and selection operator (LASSO) analysis, and stratified patients into the high- and low-risk groups with significant difference in overall survival (OS) (HR = 2.68, 95% CI = 1.74–4.14, P &lt; 0.0001). Patients in the high-risk group showed significantly reduced OS compared to patients in the low-risk group (P &lt; 0.001). The clinical characteristics and m6A-lncRNA risk scores were used to construct a nomogram which accurately predicted the OS in pancreatic cancer. TIMER 2.0 were used to investigate tumor immune infiltrating cells and its relationship with pancreatic cancer. CIBERSORT analysis revealed increased higher infiltration proportions of M0 and M2 macrophages, and lower infiltration of naive B cell, CD8+ T cell and Treg cells in the high-risk group. Compared to the low-risk group, functional annotation using ssGSEA showed that T cell infiltration and the differential immune-related check-point genes are expressed at low level in the high-risk group (P &lt; 0.05). In summary, our study constructed a novel m6A-associated lncRNAs signature to predict immunotherapeutic responses and provided a novel nomogram for the prognosis prediction of pancreatic cancer.


2021 ◽  
Vol 12 ◽  
Author(s):  
Qian Zhang ◽  
Liping Lv ◽  
Ping Ma ◽  
Yangyang Zhang ◽  
Jiang Deng ◽  
...  

BackgroundPancreatic adenocarcinoma (PAAD) spreads quickly and has a poor prognosis. Autophagy research on PAAD could reveal new biomarkers and targets for diagnosis and treatment.MethodsAutophagy-related genes were translated into autophagy-related gene pairs, and univariate Cox regression was performed to obtain overall survival (OS)-related IRGPs (P&lt;0.001). LASSO Cox regression analyses were performed to construct an autophagy-related gene pair (ARGP) model for predicting OS. The Cancer Genome Atlas (TCGA)-PAAD cohort was set as the training group for model construction. The model predictive value was validated in multiple external datasets. Receiver operating characteristic (ROC) curves were used to evaluate model performance. Tumor microenvironments and immune infiltration were compared between low- and high-risk groups with ESTIMATE and CIBERSORT. Differentially expressed genes (DEGs) between the groups were further analyzed by Gene Ontology biological process (GO-BP) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses and used to identify potential small-molecule compounds in L1000FWD.ResultsRisk scores were calculated as follows: ATG4B|CHMP4C×(-0.31) + CHMP2B|MAP1LC3B×(0.30) + CHMP6|RIPK2 ×(-0.33) + LRSAM1|TRIM5×(-0.26) + MAP1LC3A|PAFAH1B2×(-0.15) + MAP1LC3A|TRIM21×(-0.08) + MET|MFN2×(0.38) + MET|MTDH×(0.47) + RASIP1|TRIM5×(-0.23) + RB1CC1|TPCN1×(0.22). OS was significantly shorter in the high-risk group than the low-risk group in each PAAD cohort. The ESTIMATE analysis showed no difference in stromal scores but a significant difference in immune scores (p=0.0045) and ESTIMATE scores (p=0.014) between the groups. CIBERSORT analysis showed higher naive B cell, Treg cell, CD8 T cell, and plasma cell levels in the low-risk group and higher M1 and M2 macrophage levels in the high-risk group. In addition, the results showed that naive B cells (r=-0.32, p&lt;0.001), Treg cells (r=-0.31, p&lt;0.001), CD8 T cells (r=-0.24, p=0.0092), and plasma cells (r=-0.2, p&lt;0.026) were statistically correlated with the ARGP risk score. The top 3 enriched GO-BPs were signal release, regulation of transsynaptic signaling, and modulation of chemical synaptic transmission, and the top 3 enriched KEGG pathways were the insulin secretion, dopaminergic synapse, and NF-kappa B signaling pathways. Several potential small-molecule compounds targeting ARGs were also identified.ConclusionOur results demonstrate that the ARGP-based model may be a promising prognostic indicator for identifying drug targets in patients with PAAD.


2019 ◽  
Vol 5 (suppl) ◽  
pp. 98-98
Author(s):  
Sushma Agrawal ◽  
Prabhakar Mishra ◽  
Punita Lal ◽  
Gaurav Agarwal ◽  
Amit Agarwal ◽  
...  

98 Background: Complete response (CR) to NACT portends favorable long term outcomes in LABC. There is a need for a tool to risk categorise patients for recurrence risk (RR), so that intensification of treatment can be offered to women with high risk of recurrence. Methods: A prospectively maintained database of LABC (between January 2007 to December 2012), who received NACT followed by definitive surgery, radiotherapy and endocrine therapy in endocrine sensitive disease was retrospectively analyzed for clinico-pathological and treatment factors affecting disease free survival (DFS). A risk scoring model was developed on the basis of beta coefficients of identified independent risk factors for DFS. Results: The incidence of loco-regional relapse was 8% and that of distant metastases was 32% in a dataset of 206 patients at a median follow-up of 47 months (IQR 24-62 mo). The independent risk factors for recurrence were index T stage [HR 1.8 (0.9-3.6)], N stage [HR 1.7 (0.4 – 4.7)], grade [HR 1.8 (0.8-4.2)], age less than and more than 40 years [HR 1.6 (0.4-0.9)], pathologic CR [HR 4.3 (1.7- 10.7)], intrinsic subtype [HR 2.2 (1.3-3.7)], and type of surgery (BCS vs MRM) [HR 2.2 (1.3-3.6)]. The ROC of the model for the prediction of recurrence was 0.67 (95 % CI: 0.61-0.75). The results of this model were validated by dividing the population into 3 risk groups: low risk (score less than 12), intermediate risk group (score between 13-15), high risk group (score 16 or more). The chances of recurrence are 16% versus 34% versus 57% in low, intermediate and high risk group respectively. Presence of three risk factors implies low risk, five intermediate and more than five high risk. Conclusions: The risk scoring model developed by us predicts RR and can be used for selecting patients for treatment intensification in high risk category.


2022 ◽  
Vol 12 ◽  
Author(s):  
Xitao Wang ◽  
Xiaolin Dou ◽  
Xinxin Ren ◽  
Zhuoxian Rong ◽  
Lunquan Sun ◽  
...  

Pancreatic ductal adenocarcinoma (PDAC) is a highly heterogeneous malignancy. Single-cell sequencing (scRNA-seq) technology enables quantitative gene expression measurements that underlie the phenotypic diversity of cells within a tumor. By integrating PDAC scRNA-seq and bulk sequencing data, we aim to extract relevant biological insights into the ductal cell features that lead to different prognoses. Firstly, differentially expressed genes (DEGs) of ductal cells between normal and tumor tissues were identified through scRNA-seq data analysis. The effect of DEGs on PDAC survival was then assessed in the bulk sequencing data. Based on these DEGs (LY6D, EPS8, DDIT4, TNFSF10, RBP4, NPY1R, MYADM, SLC12A2, SPCS3, NBPF15) affecting PDAC survival, a risk score model was developed to classify patients into high-risk and low-risk groups. The results showed that the overall survival was significantly longer in the low-risk group (p &lt; 0.05). The model also revealed reliable predictive power in different subgroups of patients. The high-risk group had a higher tumor mutational burden (TMB) (p &lt; 0.05), with significantly higher mutation frequencies in KRAS and ADAMTS12 (p &lt; 0.05). Meanwhile, the high-risk group had a higher tumor stemness score (p &lt; 0.05). However, there was no significant difference in the immune cell infiltration scores between the two groups. Lastly, drug candidates targeting risk model genes were identified, and seven compounds might act against PDAC through different mechanisms. In conclusion, we have developed a validated survival assessment model, which acted as an independent risk factor for PDAC.


Blood ◽  
1979 ◽  
Vol 54 (6) ◽  
pp. 1249-1257 ◽  
Author(s):  
JP Litam ◽  
F Cabanillas ◽  
TL Smith ◽  
GP Bodey ◽  
EJ Freireich

Abstract The records of 292 patients with malignant lymphoma other than Hodgkin's disease, registered in our protocols from 1967 to 1977, were reviewed to identify those with central nervous system (CNS) involvement. Thirty-one patients were encountered with this complication, an incidence of 11%. Patients with a diffuse histology had a higher frequency of CNS recurences (27/174 = 16%) in contrast to only 4/118 (3%) for those with nodular types. However, if only patients with diffuse histology in CR are considered, the frequency of CNS relapse is 13.5% (13/98). The risk factors that predict for the development of this complication were studied using multivariate analysis. Diffuse poorly differentiated lymphocytic and diffuse undifferentiated lymphomas were found to be associated with a high risk of CNS relapse. Prior chemotherapy, bone marrow involvement, age less than 35, and extranodal disease were also identified as high-risk factors. Using the information generated by a logistic regression model, patients with malignant lymphoma of diffuse type can be classified into three categories when first seen: low-risk group, intermediate, and high-risk group. CNS prophylaxis is recommended for the intermediate and high-risk group, while only close follow-up is advised for the low-risk group patients who have one adverse characteristic.


2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 156-156
Author(s):  
Pengfei Yu

156 Background: Postoperative adjuvant chemotherapy was beneficial for some patients,however, it may increase the treatment burden and reduce the immunity of other patients. Screening appropriate patients based on molecular markers for individualized adjuvant chemotherapy was necessary. Methods: Between June 2002 to June 2004, 119 patients who underwent radical gastrectomy were retrospectively analyzed. 61 patients had adjuvant chemotherapy based on platinum and 5-FU for 4 to 6 cycles. ToPo II negative, MRP positive and GST-π positive were regarded as three risk factors which may be associated with chemotherapy resistance and poor prognosis. Patients were divided into two groups: high-risk group (≥2 risk factors) and the low-risk group (<2 risk factors), and the tumor recurrence and patients’ survival time of the two groups were analyzed. Results: The average recurrence time of the low-risk group was significantly longer than that of the high-risk group (21.29 ± 11.10 VS 15.16 ± 8.05 months ,p<0.01).The 3-year and 5-year survival rate of the high-risk group was 57.4% and 42.6%, however, it had no significant difference compared to 66.2% and 58.5% of the low-risk group (P> 0.05). In the high-risk group, the 3-year survival rate of patients with/without chemotherapy were 62.1% and 52.0%, 5-year survival rates were 44.8% and 40.0%, but the difference was not statistically significant (P> 0.05). In the low-risk group, the 3-year survival rate of patients with/without chemotherapy were 81.2% and 51.5%, 5-year survival rates were 71.9% and 45.5%, and the difference was statistically significant (p<0.05). Conclusions: Combined determination of MDR-related proteins ToPo II, MRP and GST-π may be prospectively valuable for optimizing the chemotherapy regimes, and further predicting the outcomes of gastric cancer patients.


2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 8045-8045
Author(s):  
Ralf Ulrich Trappe ◽  
Christian Koenecke ◽  
Martin H. Dreyling ◽  
Christiane Pott ◽  
Ulrich Duehrsen ◽  
...  

8045 Background: The PTLD-1 trials have established risk-stratified sequential treatment of B-cell PTLD. After rituximab induction, patients (pts) in complete remission (25 %) received rituximab consolidation, while all others received R-CHOP. The PTLD-2 trial tests modified risk-stratification including clinical risk factors. These are the results of the 2nd scheduled interim analysis (40/60 planned pts). Methods: The prospective, multicenter phase II PTLD-2 trial (NCT02042391) enrols treatment-naïve adult SOT recipients with CD20-positive PTLD. Key exclusion criteria are CNS involvement, ECOG > 2, pregnancy, and severe organ dysfunction or severe, active infection. Treatment consists of rituximab (1400 mg SC; first application 375 mg/m2 IV) on days 1, 8, 15 and 22. After restaging, pts in CR as well as those in PR with ≤ 2 IPI risk factors at diagnosis (low-risk group) continue with four three-weekly courses of rituximab. Most other pts (high-risk group) receive 4 cycles of R-CHOP-21, while thoracic SOT recipients who progress under rituximab (very-high-risk group) receive six cycles of alternating R-CHOP-21 and R-DHAOx. The primary endpoint (event-free survival in the low-risk group) is not analyzed here. Secondary endpoints presented here are response and overall response (ORR) by computed tomography, overall survival (OS), time to progression (TTP) and treatment-related mortality (TRM) overall and by risk group. Results: 40 pts were recruited at 12 centers (2015 – 2019). 21/40 were kidney, 11 lung, 4 liver, 3 heart, and 1 liver/kidney transplant recipients. Median age was 54 years. 38/40 PTLD were monomorphic and 15/40 EBV-associated. 38 pts were evaluated for response at interim staging: 13 were allocated to the low-risk, 17 to the high-risk and 8 to the very-high-risk group. ORR was 28/30 (93 %, CR: 16/30 [53 %]). With a median follow-up of 1.9 years, the 1-year/3-year Kaplan-Meier (KM) estimates of TTP and OS in the intention-to-treat population (40 pts) were 85 %/80 % and 70 %/70 %, respectively. In the low-risk group, the 2-year KM estimate of OS was 100 %. The frequency of infections (all grades) was 50 %, and TRM occurred in 3/40 pts (8 %). Conclusions: One third of enrolled pts were treated in the low-risk group and the recruitment goal for evaluation of the primary endpoint will likely be reached. Interim efficacy and toxicity data with rituximab SC and modified risk-stratification are encouraging despite the inclusion of 35 % thoracic SOT recipients. Clinical trial information: NCT02042391 .


2020 ◽  
Vol 10 ◽  
Author(s):  
Ming Li ◽  
Jinbo Yue ◽  
Xiangbo Wan ◽  
Bin Hua ◽  
Qiuan Yang ◽  
...  

PurposeThe aim of this study was to develop a widely accepted prognostic nomogram and establish a risk-adapted PMRT strategy based on locoregional recurrence for pT1-2N1M0 breast cancer.Methods and MaterialsA total of 3,033 patients with pT1-2N1M0 breast cancer treated at 6 participating institutions between 2000 and 2016 were retrospectively reviewed. A nomogram was developed to predicted locoregional recurrence-free survival (LRFS). A propensity score-matched (PSM) analyses was performed in risk-adapted model.ResultsWith the median follow-up of 65.0 months, the 5-year overall survival (OS), disease free survival (DFS) and LRFS were 93.0, 84.8, and 93.6%, respectively. There was no significant difference between patients who received PMRT or not for the entire group. A nomogram was developed and validated to estimate the probability of 5-year LRFS based on five independent factors including age, primary tumor site, positive lymph nodes number, pathological T stage, and molecular subtype that were selected by a multivariate analysis of patients who did not receive PMRT in the primary cohort. According to the total nomogram risk scores, the entire patients were classified into low- (40.0%), moderate- (42.4%), and high-risk group (17.6%). The 5-year outcomes were significantly different among these three groups (P&lt;0.001). In low-risk group, patients who received PMRT or not both achieved a favorable OS, DFS, and LRFS. In moderate-risk group, no differences in OS, DFS, and LRFS were observed between PMRT and no PMRT patients. In high-risk group, compared with no PMRT, PMRT resulted in significantly different OS (86.8 vs 83.9%, P = 0.050), DFS (77.2 vs 70.9%, P = 0.049), and LRFS (90.8 vs. 81.6%, P = 0.003). After PSM adjustment, there were no significant differences in OS, DFS, and LRFS in low-risk and moderate-risk groups. However, in the high-risk group, PMRT still resulted in significantly better OS, DFS and improved LRFS.ConclusionsThe proposed nomogram provides an individualized risk estimate of LRFS in patients with pT1-2N1M0 breast cancer. Risk-adapted PMRT for high-risk patients is a viable effective strategy.


2016 ◽  
Vol 3 (1) ◽  
pp. 14
Author(s):  
Netty Katrina Dameria ◽  
Djaswadi Dasuki ◽  
Rukmono Siswishanto

Background: Caesarean section is a procedure to reduce maternal and perinatal mortality and morbidity. The caesarean section rate is continuously uprising in the last 3 decades. However, the increasing rate, especially in low risk women, may compromise maternal and perinatal outcome. In 1985, WHO recommended that optimal national caesarean rates should be in the range of 5% to 10% and the rate above 15% might be less benefits. Previous study conducted in DR Sardjito hospital reported caesarean section rate in 1996 was 13.38%, while in 2001 was 18.39%. In national level, based on Indonesia Basic Health Survey 2010, caesarean section rate was 10.8%. Therefore, in this study we analyzed the rate of Caesarean section performed in DR Sardjito hospital, and studied whether the operations occurred in high-risk group or low-risk group.Objective: To compare the rate of caesarean section between high-risk group and low-risk group in DR Sardjito hospitalMethod: Retrospective cohortResult and Discussion: Participants of this study were 7821 patients undergoing labor at RSUP DR Sardjito in 2009-2013. Among them, 3152 patients underwent caesarean section and 4669 patients underwent vaginal delivery. There was an increasing in the overall caesarean section rate of 38,7% in 2009 to 43% in 2013. T-test found the presence of significant differences between the caesarean section rate of high-risk group and low-risk group in 2009-2013 (p<0.05) with a mean difference was 28.5 (20.2-36.8). Caesarean section rate of high-risk group was significantly higher than the low-risk group (p<0.05).Conclusion: There was a difference in caesarean section rate of high-risk group compared to low-risk group. Caesarean section rate in high-risk group was significantly higher than in the low-risk group.Keywords: caesarean section rate, caesarean section, low-risk group, high- risk group


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