Significant Risk Factors For Survival Research Articles

Clinical characteristics and treatment of Marjolin's ulcer at a major burn center in northwest China: a retrospective review of 126 cases.

Marjolin's ulcer (MU) is a rare, aggressive skin tumor. There are numerous case reports but large long-term studies are lacking, necessitating further exploration of its treatment. This study aimed to summarize and analyze the characteristics, treatment methods, and prognosis of MU. We retrospectively analyzed the clinical data of 126 patients with MU, treated between January 2013 and January 2023 at the burn center. Demographic data, clinical characteristics, treatment, and prognosis were statistically analyzed. Of the 126 included patients, 104 were followed up for 0.1-10.2 years. The most common cause of the primary injury was flame burn (50.8%). Lesions were commonly observed on the lower limbs (47.6%). The predominant histopathological type was squamous cell carcinoma (92.8%). Among the 126 patients, 35 (27.8%) presented with bone invasion, 37 (29.4%) presented with enlarged lymph nodes, and 9 (7.1%) had lymph node metastasis. Extensive local excision (83.3%) was the most common surgical procedure; the defect was repaired using skin grafting (41.9%), free flaps (37.1%), and local flaps (21.0%). Multivariate analysis revealed that bone invasion and lymph node involvement were risk factors for postoperative recurrence. Survival analysis showed that age, latency period, pathological type, and recurrence were significant risk factors for survival. Extensive local resection is necessary to eradicate tumors, and patient follow-up should be more frequent within 1 year postoperatively. As MU is preventable, it is essential to reach a quick diagnosis and avoid delayed management before the occurrence of deadly metastases.

Recent infection with SARS-CoV-2 in donors was associated with a higher incidence of acute graft-versus-host disease in recipients undergoing allogeneic haematopoietic stem cell transplantation.

The global pandemic has resulted in the common occurrence of SARS-CoV-2 infection in the population. In the post-pandemic era, it is imperative to understand the influence of donor SARS-CoV-2 infection on outcomes after allogeneic haematopoietic stem cell transplantation (allo-HSCT). We retrospectively analysed allo-HSCTs from donors with mild SARS-CoV-2 infection or early recovery stage (ERS) (group 1, n = 65) and late recovery stage (group 2, n = 120). Additionally, we included allo-HSCT from donors without prior SARS-CoV-2 infection as group 0 (n = 194). Transplants from donors with different SARS-CoV-2 infection status had comparable primary engraftment and survival rates. However, group 1 had higher incidences of acute graft-versus-host disease (aGvHD), grade II-IV (41.5% vs. 28.1% in group 0 [p = 0.014] and 30.6% in group 2 [p = 0.067]) and grade III-IV (22.2% vs. 9.6% [p = 0.004] in group 0 and 12.2% in group 2 [p = 0.049]). Conversely, the risk of aGvHD in group 2 was similar to that in group 0 (p > 0.5). Multivariable analysis identified group 1 associated with grade II-IV (hazard ratio [HR] 2.307, p = 0.010) and grade III-IV (HR 2.962, p = 0.001) aGvHD, which yielded no significant risk factors for survival. In conclusion, we preliminarily demonstrated donors in the active infection state or ERS of mild SARS-CoV-2 infection were associated with higher incidences of aGvHD in transplants from related donors.

Proton Beam Therapy for HCC Exceeding up-to-Seven Criteria

Whilst standard treatment for intermediate-stage hepatocellular carcinoma (HCC) is transcatheter arterial chemoembolization (TACE), those exceeding "up-to-seven" criteria don't respond as such as those within, and systemic therapy is suggested to be more beneficial. This is sought to be both because of the limited efficacy of TACE and its hepatic toxicity. Proton beam therapy (PBT) offers high local control and low toxicity rates, and we hypothesize that the same can be said in this patient group also. We here present the outcome of PBT for primary HCC exceeding "up-to-seven" criteria. Primary HCC treated with PBT between 2010 and 2018 were extracted from an all-in treatment database and retrospectively reviewed. (Maximum diameter of the largest tumor in centimeters) + (tumor count) > 7 was considered as exceeding "up-to-seven" criteria. Local recurrence was defined as tumor re-enlargement or the appearance of arterial phase hyperenhancement. Adverse events were evaluated by CTCAE v5.0. Overall survival and recurrence-free survival were determined by the Kaplan-Meier method, and local recurrence was analyzed as cumulative incidence with death as a competing risk. All statistical analyses were done using R. Out of 202 primary cases, 79 exceeded the "up-to-seven" criteria. The median tumor diameter was 8.0 cm (range 3.1 - 20 cm) and macroscopic vascular invasion (MVI) was observed in 26 cases. For tumor count, 36 were solitary, 28 were between 2 - 3, and 15 had 4 or more. According to the modified ALBI grade, 38 were grade 1, 18 were grade 2a and 23 were 2b. The prescribed dose was 66 Gy / 10 Fr for 6, 72.6 Gy / 22 Fr for 60, 74 Gy / 37 Fr for 12 and 60 Gy / 15 Fr for one case after relative biological effect weighting of 1.1. With a median follow-up period of 33 months (IQR 15 - 57 months), 2-year overall survival was 62% (95% C.I. 50 - 72%) and median survival time was 37 months (95% C.I. 30 - 52 months). 2-year recurrence-free survival and local recurrence rate were 42% (95% C.I. 30 - 53%) and 8% (95% C.I. 3 - 15%) respectively. Cox regression analysis revealed modified ALBI grade as the only significant risk factor for survival (hazard ratio 1.80, 95% C.I. 1.27 - 2.55, p = 0.0010) among age, sex, alpha-fetoprotein level, MVI, tumor count, and size. Other than one case of early death (2 weeks after treatment) with an unknown causal relationship, there were no adverse events of grade 4 or higher observed. PBT for primary HCC exceeding "up-to-seven" criteria appears to be safe and effective. Local control of intrahepatic lesions may be beneficial even in intermediate-stage cases, while results of this study suggests that suppression of out-of-field recurrence is required for further survival prolongment.

Acute kidney injury is common in dogs with septic peritonitis and is associated with increased mortality.

To identify the frequency of and risk factors for acute kidney injury (AKI) in dogs undergoing abdominal surgery for septic peritonitis, and to evaluate outcome and kidney-related risk factors for survival to discharge in those dogs. 77 dogs that underwent abdominal surgery for septic peritonitis. Medical records of dogs that underwent surgery for septic peritonitis from 2012 through 2022 were reviewed. Data regarding signalment, clinical and biochemical findings at presentation, blood creatinine concentration throughout hospitalization, surgery characteristics, postoperative monitoring, and outcome were collected. Dogs were classified based on occurrence of AKI and whether they presented with or developed AKI in-hospital. Perioperative risk factors were evaluated, and outcomes were compared with univariable logistic regression. 31 dogs (40.3%) had AKI diagnosed; 18/77 (23.4%) dogs presented with AKI, 11 (61.1%) of which had it postoperatively, and 13/77 (16.9%) dogs developed AKI postoperatively. Significant factors for presenting with AKI included increasing baseline respiratory rate (OR 2.5 for every 10 beats per minute higher), decreasing systolic blood pressure (OR 0.8 for every 10 mm Hg higher), and increasing body condition score (OR 2.2 for every score greater). No significant factors for developing AKI postoperatively were identified after multiple comparisons adjustment. Sixteen dogs (20.8%) did not survive to discharge; 12 (75.0%) had AKI and 4 (25.0%) did not. Dogs with AKI had decreased odds of survival to discharge (OR 0.2). AKI was common in dogs with septic peritonitis and was a significant risk factor for survival to discharge. Clinical surveillance of AKI is critical in this population.

A nomogram for predicting overall survival of patients with squamous cell carcinoma of the floor of the mouth: a population-based study.

Floor of mouth squamous cell carcinoma (SCCFOM) is a rare but aggressive malignancy with 5-year overall survival (OS) rates below 40% in published studies. However, the clinicopathological predictors of the prognosis of SCCFOM remain undefined. We aimed to establish a model to predict the survival outcomes of SCCFOM. We searched the Surveillance, Epidemiology, and End Results (SEER) database for patients diagnosed with SCCFOM between 2000 and 2017. Data on patient demographics, treatment modalities, and survival outcomes were retrieved. Risk factors for OS were evaluated by survival and Cox regression analyses. A nomogram for OS was developed based on the multivariate model and split the patients into high- and low-risk cohorts based on cutoff values. Overall, 2014 SCCFOM patients were included in this population-based study. Multivariate Cox regression showed that age, married status, grade, American Joint Committee on Cancer stage, radiotherapy, chemotherapy, and surgery were significant risk factors for survival. A nomogram was established using the regression model. The C-indices, areas under the receiver operating characteristic curves, and calibration plots demonstrated the reliable performance of the nomogram. Patients assigned to the high-risk group had a significantly lower survival rate. The nomogram predicting survival outcomes of SCCFOM patients based on clinical information showed good discriminative ability and prognostic accuracy. Our nomogram could be used to predict the survival probabilities for SCCFOM patients at different timepoints.

Preoperative hemoglobin levels, extended resections and the body mass index influence survival after pancreaticoduodenectomy

The negative influence of perioperative transfusion of packed red blood cells on the prognosis of various malignancies is the focus of recent research interest. The development of a propensity score for the prediction of perioperative transfusion of packed red blood cells (pRBCs) and the identification of independent risk factors for survival, that can either be known prior to or during surgery in patients undergoing pancreaticoduodenectomy for pancreatic head cancer are the two objectives of this study. Logistic regression analyses and Cox regression modeling were used to identify independent risk factors for perioperative transfusion of pRBCs and to determine individual risk factors for patient survival. A total of 101 adult patients who underwent surgery between 01/01/2016 and 12/31/2020 were investigated in a single-center retrospective analysis. Preoperative hemoglobin levels (OR: 0.472, 95%-CI: 0.312-0.663, p < 0.001) and extended resections (OR: 4.720, 95%-CI: 1.819-13.296, p = 0.001) were identified as independent risk factors for perioperative transfusion of pRBCs, enabling the prediction of pRBC transfusion with high sensitivity and specificity (AUROC: 0.790). The logit of the derived propensity model for the transfusion of pRBCs (HR: 9.231, 95%CI: 3.083-28.118, p < 0.001) and preoperative Body Mass Index (BMI) (HR, 0.925; 95%-CI: 0.870-0.981, p = 0.008) were independent risk factors for survival. Low preoperative hemoglobin levels, low BMI values, and extended resections are significant risk factors for survival that can be known and thus potentially be influenced prior to or during surgery. Patient blood management programs and prehabilitation programs should strive to increase preoperative hemoglobin levels and improve preoperative malnutrition.

Efficacy and Safety of East Asian Herbal Medicine for Brain Metastases in Non-small Cell Lung Cancer: A Systematic Review and Meta-analysis Protocol to Identify Specific Herbs.

Brain metastasis (BM) is a significant risk factor for survival and prognosis in non-small cell lung cancer (NSCLC). While surgical resection and radiotherapy are the primary treatment modalities, the overall prognosis in NSCLC patients with BM remains poor, and all therapies lead to adverse events. East Asian herbal medicine (EAHM) has broad prospects as an adjuvant treatment, but its efficacy and safety remain controversial. We propose to conduct a systematic review and meta-analysis to summarize the clinical efficacy and safety of EAHM for the treatment of NSCLC with BMs and to identify specific herbs that can improve the prognosis. The PubMed, EMBASE, CENTRAL, Web of Science, CBM, CNKI, Wanfang, VIP, Evidence Reports on Kampo Treatment, ICHUSHI, and Oriental Medicine Advanced Searching Integrated System databases will be searched from their inception to October 2022. Randomized controlled trials will be included. Two authors will evaluate the eligibility and quality of the included trials. The methodological quality will be assessed using the RoB 2 tool, and Stata 16 will be used for data synthesis. Publication bias will be assessed using funnel plots and Egger tests. The GRADE (Grading of Recommendations Assessment, Development, and Evaluation) system will evaluate the quality of the synthesized evidence. Further sensitivity analyses will be performed to determine the efficacies of specific herbs in EAHM. Given there are currently no systematic reviews and meta-analyses of the efficacy of EAHM as a treatment for NSCLC with BMs, a compilation and analysis of the available high-quality clinical research evidence are essential. The results will help establish guidelines for the application of specific herbs as a complementary alternative therapy for BMs in NSCLC. The findings will be published in a peer-reviewed journal. CRD42022300527.

GPX4 Regulates Tumor Cell Proliferation via Suppressing Ferroptosis and Exhibits Prognostic Significance in Gastric Cancer.

Gastric cancer (GC) is the fourth leading cause of cancer-related death worldwide. Glutathione peroxidase 4 (GPX4) is a glutathione-dependent antioxidant enzyme known to regulate ferroptosis, which is a non-apoptotic form of cell death accompanied by iron-dependent accumulation of reactive oxygen species (ROS). This study evaluated the expression and function of GPX4 in GC. The expression of GPX4 was examined in five human GC cell lines (KATO-III, MKN-1, MKN-28, MKN-45, and MKN-74) using real-time quantitative PCR and western blotting. The role of GPX4 in GC was examined using small interference RNA and cell proliferation and ROS assays. Finally, we analyzed GPX4 expression in tumor tissues from 106 patients who underwent GC surgery using immunohistochemistry and evaluated the relationship between GPX4 levels and clinical outcomes of GC. GPX4 was expressed in all GC cell lines at various levels. GPX4 silencing and inhibition significantly reduced cell proliferation and increased ROS generation. Furthermore, the mRNA levels of prostaglandin-endoperoxide synthase 2, a known biomarker of ferroptosis, were increased after GPX4 silencing. GPX4 expression was found to be an independent prognostic factor for overall and disease-specific survival in GC patients. GPX4 can regulate cancer cell death via ferroptosis in GC cell lines and represents a significant risk factor for survival in patients with GC.

History of Transcatheter Arterial Chemoembolization Predicts the Efficacy of Hepatic Arterial Infusion Chemotherapy in Hepatocellular Carcinoma Patients.

This study sought to identify factors that are predictive of a therapeutic response to hepatic arterial infusion chemotherapy (HAIC) by focusing on the number of prior transcatheter arterial chemoembolization (TACE) sessions. To determine the parameters predicting a good response to HAIC, we retrospectively analyzed 170 patients with hepatocellular carcinoma (HCC) who received HAIC regimens comprising low-dose cisplatin combined with 5-fluorouracil (LFP) or cisplatin (CDDP) for the first time. In both the LFP and CDDP regimens, the response rates were significantly lower in patients with three or more prior TACE sessions than in those with two or fewer prior TACE sessions (LFP 57% versus 28%; p=0.01, CDDP 27% versus 6%; p=0.01). Multivariable logistic regression analysis revealed that the number of prior TACE sessions (≥ 3) was significantly associated with non-responder status (odds ratio 4.17, 95% Confidence Interval (CI) 1.76-9.86) in addition to the HAIC regimen. Multivariable analysis using the Cox proportional hazards model revealed that a larger number of prior TACE sessions (≥ 3) was a significant risk factor for survival (hazard ratio 1.60, 95% CI 1.12-2.29) in addition to Child-Pugh class, serum alpha-fetoprotein concentration, and maximum diameter of HCC. HCC patients who receive fewer prior TACE sessions (≤ 2) were found to be better responders to HAIC.

A nomogram for predicting overall survival of patients with sinonasal melanoma: A population-based study.

Sinonasal melanoma (SMM) is a rare but aggressive malignancy with 5-year overall survival (OS) rates below 40% in published studies. However, the clinicopathological predictors of the prognosis of SMM remain undefined. We aimed to establish a model to predict the survival outcomes of SMM. We searched the Surveillance, Epidemiology, and End Results (SEER) database for patients diagnosed with SMM between 1975 and 2016. Data on patient demographics, treatment modalities, and survival outcomes were retrieved. Risk factors for OS were evaluated by survival and Cox regression analyses. We also developed and validated a nomogram for OS, and compared its performance with that of conventional staging systems. Overall, 305 SMM patients were included in this population-based study. Multivariate Cox regression showed that primary site, American Joint Committee on Cancer stage, radiotherapy, and surgery were significant risk factors for survival. A nomogram was established using the regression model. The C-indices, areas under the receiver operating characteristic curves, calibration plots, and decision curve analysis demonstrated reliable performance of the nomogram. The nomogram predicting survival outcomes of SMM patients based on clinical information showed good discriminative ability and prognostic accuracy compared with conventional stage classifications. Our nomogram could be used to predict the survival probabilities for SMM patients at different timepoints. 2b.

CLL-224 Coronavirus Disease Mortality and Outcome in Macedonian Patients With Chronic Lymphocytic Leukemia: Single-Center Experience

Context: Patients with chronic lymphocytic leukemia (CLL) may be more predisposed to coronavirus disease 2019 (COVID-19) due to age, the nature of the disease, and treatment-related immunosuppression. Objective: The aim of the study was to assess risk factors of the outcome and course of COVID-19 for CLL patients in Macedonia. Design: Retrospective study of patients with CLL and COVID-19 infection in the period of time from the beginning of the pandemic to March 2022. Setting: Individual patient data from 55 CLL patients with COVID-19 infection were analyzed. The risk factors of COVID-19 disease severity and outcomes were investigated. Interventions: The outcome was the analysis of patients with COVID-19 infection in line with host risk factors and biological heterogeneity of the disease with previous therapy for CLL. Results: Our evaluation has shown that 80% of patients were male and 20% were female. The average age was 65 years. The average CIRS score was 2 and BMI was 23.6. Most of the patients (67.2%) have unmutated Ig genes. Ninety-one percent (91%) from that subgroup of patients have a severe form of COVID-19, 82% of patients were treated with chemotherapy, and 48% had a fatal outcome. Conclusions: CLL-directed treatment and unmutated Ig genes were significant risk factors for survival. Untreated patients and patients with mutated IGHV had a better chance of survival than those on treatment or who were recently treated.

P-P13 Long-term outcome after portal vein resection during pancreaticoduodenectomy for pancreatic ductal adenocarcinoma: a propensity score matched analysis

Abstract Background Portal vein resection (PVR) with pancreaticoduodenectomy (PD) is often performed to achieve clear margins for patients with vascular involvement in pancreatic ductal adenocarcinoma (PDAC). However, there is evidence to suggest that patients undergoing PVR often have more advanced cancers, therefore the impact of PVR on survival and recurrence remains unclear. The aim of this study is to assess overall (OS) and recurrence free (RFS) survival in patients who underwent PVR during PD, with particular attention to margin positivity. Methods A retrospective analysis was performed on 638 patients who underwent PD during a 12-year period. Exclusion criteria included PD for non-PDAC tumours, neoadjuvant chemotherapy or intra-operative radiotherapy. 374 patients were included in the study (90 PVR and 284 non-PVR). Patient characteristics and histopathological factors associated with OS and RFS were then evaluated using univariate and multivariate Cox regression analyses. 270 patients (90 PVR and 180 non-PVR), were matched by propensity score based on perineural invasion, pT and pN staging. The Kaplan-Meier method was used to calculate survival and log-rank tests. Results Resection margin positivity was associated with shorter OS and RFS (p &amp;lt; 0.0001), and the superior mesenteric vein (SMV) margin was the most significant risk factor for survival on competing risks analysis. Absent adjuvant chemotherapy, nodal metastasis and margin positivity were independent risk factors for OS and RFS on multivariate analysis. PVR was associated with higher intra-operative blood loss (p = 0.009), but was not associated with increased length of stay, complications or readmissions. PVR patients had increased pT staging, nodal metastasis and perineural invasion, however, there was no difference in OS (p = 0.551) or RFS (p = 0.256) between PVR and non-PVR after propensity matching. Conclusions Positive resection margins are associated with shorter survival times, and the SMV margin is the most significant prognostic indicator for overall survival and recurrence compared to other margins. PVR is a relatively safe procedure, however, it does not achieve the intended survival benefits of complete margin clearance. The impact on survival for margin positivity, particularly the SMV margin, and nodal metastasis should be considered when making decisions with regards to vein resection and adjuvant treatments.

Effect of Therapeutic Modification on Outcomes in Heart Transplantation Over the Past Two Decades - A Single-Center Experience in Japan.

During these 2 decades (1999-2019), many therapeutic strategies have been developed in the field of heart transplant (HTx) to improve post-HTx outcomes. In the present study, 116 consecutive HTx adults between 1999 and 2019 were retrospectively reviewed to evaluate the influences of a therapeutic modification on post HTx outcomes.Methods and Results:Patient survival, functional status and hemodynamics after HTx and modification of therapeutic strategies were reviewed. The overall cumulative survival rate at 10 and 20 years post-HTx was 96.4 and 76.7%, respectively. There were no significant differences in survival rate or exercise tolerance after HTx between extracorporeal and implantable continuous flow-LVAD. Post-HTx patient survival in patients, irrespective of the donor risk factors such as donor age, low LVEF, history of cardiac arrest, was equivalent across cohorts, while longer TIT and higher inotrope dosage prior to procurement surgery were significant risk factors for survival. In 21 patients given everolimus (EVL) due to renal dysfunction, serum creatinine significantly decreased 1 year after initiation. In 22 patients given EVL due to transplant coronary vasculopathy (TCAV), maximum intimal thickness significantly decreased 3 years after initiation. The analysis of a 20-year single-center experience with HTx in Japan shows encouraging improved results when several therapeutic modifications were made; for example, proactive use of donor hearts declined by other centers and the use of EVL in patients with renal dysfunction and TCAV.

Retrospective Multicenter Long-Term Follow-up Analysis of Prognostic Risk Factors for Recurrence-Free, Metastasis-Free, Cancer-Specific, and Overall Survival After Curative Nephrectomy in Non-metastatic Renal Cell Carcinoma.

We evaluated prognostic risk factors of recurrence-free survival (RFS), metastasis-free survival (MFS), cancer-specific survival (CSS), and overall survival (OS) outcomes in patients with non-metastatic renal cell carcinoma (nmRCC) after curative nephrectomy during long-term follow-up. The medical records of 4,260 patients with nmRCC who underwent curative nephrectomy between 2000 and 2012 from five Korean institutions and follow-up after postoperative 1 month until December 2017 were retrospectively analyzed for RFS, MFS, OS, and CSS. During the median 43.86 months of follow-up, 342 recurrences, 127 metastases, and 361 deaths, including 222 cancer-specific deaths, were reported. In addition to the unreached median survival of RFS and MFS, the median OS and CSS times were 176.75 and 227.47 months, respectively. Multivariable analyses showed that nephrectomy type (laparoscopy vs. open), pathological T stages, and nuclear grade were common significant risk factors for survival, and the baseline ASA, hemoglobin, and pathological N stage were common factors only for RFS, OS, and CSS (p < 0.05). Further, tumor necrosis for MFS; platelet count, extent (partial vs. radical) of surgery, and lymphovascular invasion for RFS; baseline diabetes, hypertension, age, body mass index, extent of surgery, and pathological sarcomatoid differentiation for OS; and baseline diabetes, hypertension, body mass index, and pathological sarcomatoid differentiation for CSS were additionally significant risk factors (p < 0.05). RFS, MFS, OS, and CSS were significantly different depending on the pathological T stages (p < 0.05). In conclusion, this large-numbered, long-term follow-up study revealed significant factors affecting the survival of patients with nephrectomized nmRCC.

PF179 DIFFERENT IMPACT OF BCR BREAKPOINT ON THE OUTCOME OF ALLOGENEIC HEMATOPOIETIC CELL TRANSPLANTATION FROM DIFFERENT GRAFT SOURCE FOR PH+ALL IN THE ERA OF TKI

Background:Prognostic significance of different BCR breakpoints in Philadelphia chromosome‐positive acute lymphoblastic leukemia (Ph+ALL) has not been established. BCR‐ABL1–positive cells outside the B‐lineage compartment was reported in 40% of adult patients with Ph+ALL and the frequency was different between patients with minor BCR (mi‐bcr) and those with Major BCR (Ma‐bcr). This could suggest the possibility of biological differences in Ph+ALL according to BCR breakpoint. In the era of tyrosine kinase inhibitors (TKIs), allogeneic hematopoietic cell transplantation (allo‐HCT) is still considered to be a choice to cure Ph+ALL. Different effect of unrelated graft source was reported on the outcome of allo‐HCT with positive minimal residual disease (MRD) in a recent study.Aims:We aimed to clarify the impact of BCR breakpoint as well as MRD status and graft source on the outcome of allo‐HCT for Ph+ALL in the era of TKI.Methods:We analyzed data from a registry database for 803 adult Ph+ALL patients who underwent unrelated allo‐HCT in the first complete remission. BCR breakpoint was mi‐bcr in 627 patients (78%), and Ma‐bcr in 154 (19%).Results:Overall survival (OS) rates at 4 years were 64% in mi‐bcr and 61% in Ma‐bcr among patients who underwent unrelated bone marrow or peripheral blood transplantation (UBMT) (P = 0.43), and 65% in mi‐bcr and 67% in Ma‐bcr among patients who underwent unrelated cord blood transplantation (UCBT) (P = 0.53). Similarly, the cumulative incidence of relapse or non‐relapse mortality (NRM) was not significantly different between patients with mi‐bcr and those with Ma‐bcr in either UBMT or UCBT (Relapse: UBMT, 20% in mi‐bcr and 18% in Ma‐bcr at 4 years, P = 0.73; UCBT, 20% in mi‐bcr and 15% in Ma‐bcr at 4 years, P = 0.35; NRM: UBMT, 25% in mi‐bcr and 30% in Ma‐bcr at 4 years, P = 0.31; UCBT, 23% in mi‐bcr and 26% in Ma‐bcr at 4 years, P = 0.98). BCR breakpoint was not a significant prognostic factor in multivariate analyses, regardless of graft source. However, in subanalyses, Ma‐bcr was a significant risk factor for survival and NRM in multivariate analyses among patients with MRD(+) at UBMT [Ma‐bcr (vs. mi‐bcr): OS: Hazard ratio (HR) 2.29, 95%CI 1.38 to 3.80, P = 0.001; NRM: HR 3.29, 95%CI 1.72 to 6.27, P &lt; 0.001]. NRM was higher in patients with Ma‐bcr than in those with mi‐bcr among patients with MRD(+) at UBMT (44 % in Ma‐bcr vs. 14% in mi‐bcr at 4 years, P &lt; 0.001), which led to lower survival rate in patients with Ma‐bcr.Summary/Conclusion:BCR breakpoint was a significant prognostic factor in Ph+ALL patients with MRD(+) at UBMT. This is the first study reporting the possibility of significant impact of BCR breakpoint on MRD‐based transplant outcome in Ph+ALL in the era of TKI.

Prediction of lymph node status in completely resected IIIa/N2 small cell lung cancer: importance of subcarinal station metastases

BackgroundThe aim of this study was to determine the prognostic value of lymph node status in patients with pathologic N2 (pN2) stage IIIA small cell lung cancer (SCLC).MethodsA total of 163 consecutive pN2 stage IIIA SCLC patients who underwent pulmonary resections and systematic lymphadenectomies at Shanghai Chest Hospital between January 2006 and June 2014 were enrolled. We retrospectively analyzed the potential clinicopathologic factors that influenced survival, including the node levels (single or multiple-station) and the node-spreading patterns (skip N2 or non-skip N2). The prognostic significance was examined by Cox regression analysis.ResultsThe median overall survival (OS) was 23.7 months. Multiple-station lymph node metastasis indicated a poorer prognosis than single-station involvement (p = 0.003). Skip metastasis did not appear to influence survival (p = 0.099). With respect to the station of lymph node metastasis, the OS was only related to the involvement of the subcarinal node, regardless of tumor location (p < 0.05). Multivariate analysis showed two statistically significant risk factors for survival, including multiple-station lymph node and subcarinal node metastasis (hazard ratio [HR] = 1.76, 95% confidence interval [CI]:1.11–2.78, p = 0.015; HR = 1.61, 95% CI: 1.03–2.50, p = 0.036, respectively).ConclusionsMultiple-station N2 metastasis and involvement of the subcarinal node predicted poor prognosis in pN2 stage IIIA SCLC patients, which may profoundly influence therapeutic decisions.

PRMT9 promotes hepatocellular carcinoma invasion and metastasis via activating PI3K/Akt/GSK-3β/Snail signaling.

Protein arginine methyltransferases (PRMT) catalyze protein arginine methylation and play an important role in many biological processes. Aberrant PRMT expression in tumor cells has been documented in several common cancer types; however, its precise contribution to hepatocellular carcinoma (HCC) cell invasion and metastasis is not fully understood. In this study, we identified a new oncogene, PRMT9, whose overexpression strongly promotes HCC invasion and metastasis. PRMT9 expression was detected more frequently in HCC tissues than in adjacent noncancerous tissues. PRMT9 overexpression was significantly correlated with hepatitis B virus antigen (HBsAg) status, vascular invasion, poor tumor differentiation and advanced TNM stage. Patients with higher PRMT9 expression had a shorter survival time and higher recurrence rate. PRMT9 expression was an independent and significant risk factor for survival after curative resection. Functional studies demonstrated that PRMT9 increased HCC cell invasion and lung metastasis. Knocking down PRMT9 with short hairpin RNA (shRNA) inhibited HCC cell invasion. Further investigations found that PRMT9 increased cell migration and invasion through epithelial‐mesenchymal transition (EMT) by regulating Snail expression via activation of the PI3K/Akt/GSK‐3β/Snail signaling pathway. In clinical HCC samples, PRMT9 expression was positively associated with Snail expression and was negatively associated with E‐cadherin expression. In conclusion, our study demonstrated that PRMT9 is an oncogene that plays an important role in HCC invasion and metastasis through EMT by regulating Snail expression via activation of the PI3K/Akt/GSK‐3β/Snail signaling pathway. Thus, PRMT9 may serve as a candidate prognostic biomarker and a potential therapeutic target.

RETRACTED ARTICLE: Sorcin Predicts Poor Prognosis and Promotes Metastasis by Facilitating Epithelial-mesenchymal Transition in Hepatocellular Carcinoma

Metastasis-associated recurrence is the main cause for the poor prognosis of hepatocellular carcinoma (HCC). However, the detailed molecular mechanisms underlying HCC metastasis remain elusive. Though some data indicated the oncogenic role of Sorcin in tumors, the prognostic value and biological role of Sorcin in HCC is still unknown. In this study, it demonstrated that Sorcin expression levels were significantly upregulated in HCC tumor tissues compared with matched adjacent nontumorous liver tissues and normal liver tissues, and such expression level correlated with HCC metastasis. High Sorcin expression was significantly correlated with aggressive clinicopathological characteristics such as multiple tumor nodules, high Edmondson-Steiner grade, microvascular invasion, advanced TNM stage and advanced BCLC stage (all P < 0.05). HCC patients with high Sorcin expression had both shorter survival and higher recurrence than those with low Sorcin expression (all P < 0.05). Sorcin expression was an independent and significant risk factor for survival and recurrence of HCC patients. Results of functional experiments showed that Sorcin could promote HCC cell proliferation, migration, and invasion in vitro, and facilitate HCC growth and metastasis in vivo. Mechanistically, Sorcin exerted its role by activating extracellular signal-regulated kinase (ERK) pathway and promoted metastasis by facilitating epithelial-mesenchymal transition (EMT) in HCC.

Application of radiofrequency ablation for the treatment of intermediate-stage hepatocellular carcinoma.

Transcatheter arterial chemoembolization (TACE) is a standard therapy for the treatment of intermediate-stage hepatocellular carcinoma (HCC). In this study, we tried to elucidate the possibility of using radiofrequency ablation (RFA) as an alternative treatment of intermediate-stage HCC. Among 246 patients who were initially diagnosed with intermediate-stage HCC, 76 who were treated with TACE (TACE group) and 91 who were treated with RFA (RFA group) were enrolled in this study. The risk for survival was analyzed with the Cox Proportional Hazard Model, and the survival rates were compared using propensity score matching. About half (50.6%) of the intermediate-stage HCC patients in the RFA group were diagnosed with Barcelona Clinic Liver Cancer substage-B1 (BCLC-B1) compared with only 19.7% of the patients in the TACE group. Survival of the RFA group was longer than that of TACE group in patients with BCLC-B1 and BCLC-B2. In contrast, no difference between groups was observed in patients with BCLC-B3/4. Multivariate analysis revealed that large tumor size (>30 mm, hazard ratio = 1.685, P = 0.043), high des-γ-carboxyprothrombin (>100 mAU/mL, hazard ratio = 1.920, P = 0.012), and TACE group (hazard ratio = 1.896, P = 0.016) were significant risk factors for survival. Overall 3-year survival of the patients in the RFA group (69.5%) was significantly longer than that of patients in the TACE group (51.5%) after propensity score matching (P = 0.032). No significant adverse events were observed in either group. RFA was useful for the treatment of less advanced intermediate-stage HCC and could be an alternative to TACE in selected cases.

The importance of age and weight on cavopulmonary shunt (stage II) outcomes after the Norwood procedure: Planned versus unplanned surgery

ObjectiveThe study objective was to evaluate the outcomes of the cavopulmonary shunt after the Norwood procedure with a particular focus on age, weight, and whether surgery was planned or expedited by clinical findings. MethodsWe studied 297 consecutive patients with hypoplastic left heart syndrome undergoing the cavopulmonary shunt operation between 2002 and 2014. All patients underwent the Norwood procedure with a right ventricle to pulmonary artery conduit. Unplanned surgery was any situation in which surgery was expedited because of refractory desaturation, angiographic findings, or failure to discharge. ResultsThere were 222 planned and 75 unplanned procedures. Planned surgery was performed at median of 5.4 (4.6-6.3) months compared with 3.9 (3.3-5.0) months for the unplanned group (P < .001). Early mortality was 1.3% in the planned group compared with 5.3% in the unplanned group (P = .07). At 5 and 10 years, survival was significantly worse in the unplanned group (73% vs 85%, P = .03). On multivariable analysis, atrioventricular valve regurgitation, the need for atrioventricular valve repair, and impaired ventricular function (graded composite variable) were the predominant risk factors (hazard ratio [HR], 7.49), with an incremental risk within these 3 variables. The planned versus unplanned nature of the surgery was less significant (HR, 1.75) because it was eclipsed by ventricular function and tricuspid intervention. Additional factors were aortic atresia/mitral atresia subgroup (HR, 2.07) and somatic growth (z-score weight) at the time of surgery (HR, 0.60 for z-score change from −2.54 to −1.16). Age and weight at surgery were not significant risk factors for survival. Interstage interventions on the aortic arch or right ventricle to pulmonary artery conduit did not adversely influence outcomes. ConclusionsThe ventricular function, atrioventricular valve regurgitation, and need for tricuspid intervention were the primary risk factors for survival after the cavopulmonary shunt operation. Although unplanned surgery is associated with poor outcomes, this is related to the primary risk factors and not the timing or age of the patient. Somatic growth also has a significant influence on survival. Thus, an earlier cavopulmonary shunt operation is safe in infants who are thriving, but those with poor weight gain are at higher risk.