Gamma-glutamyl transpeptidase-to-platelet ratio as a biomarker of liver disease and hepatic fibrosis severity in paediatric Cystic Fibrosis

BackgroundCystic fibrosis (CF)-associated liver disease (CFLD) causes significant morbidity and mortality in children with CF. Diagnosis of liver disease prior to development of cirrhosis or portal hypertension (PHT) is challenging. While imaging modalities using Elastography show great promise they are still not widely available to all clinicians. This study investigated gamma-glutamyl transpeptidase-to-platelet ratio (GPR) as a non-invasive biomarker to detect liver disease and stage fibrosis severity in children with CF.Methods237 children were enroled including 76 with CFLD and 161 with CF and no detectable liver disease (CFnoLD). CFLD was diagnosed using standard clinical, biochemical and imaging practice guidelines. Hepatic fibrosis was staged on liver biopsies available from 54 children with CFLD. Serum liver biochemistry was used to calculate GPR (median, [IQR]) and receiver operating characteristics (ROC) analysis assessed utility to detect liver disease and stage fibrosis severity.ResultsGPR was significantly increased in CFLD versus CFnoLD (0.33 [0.19–0.96] vs. 0.15 [0.11–0.21], P<0.0001). GPR demonstrated good diagnostic utility for detecting CFLD with an area under the curve (AUC) of 0.81 (95% confidence Interval [CI] [0.75–0.87]; P<0.0001), with sensitivity of 74% and specificity of 73%, using a cut-off of 0.20. GPR increased with increasing hepatic fibrosis stage. GPR discriminated both moderate-advanced (F2-F4) fibrosis vs. F0-F1 (AUC=0.82; 95%CI [0.71–0.94]; P<0.0001) and advanced (F3-F4) fibrosis vs. F0-F2 (AUC=0.77; 95%CI [0.64–0.90]; P = 0.004), with a cut-off 0.32 and 0.61, respectively. An elevated GPR of >0.84 was predictive of PHT at diagnosis of CFLD (AUC=0.81; 95%CI [0.67–0.95]; P = 0.0003).ConclusionsGPR demonstrates good diagnostic utility for assessing the presence of liver disease, PHT and hepatic fibrosis severity in children with CF. These findings will aid in better identification of patients at risk for CF-related liver involvement and the potential for more targeted and timely follow-up and treatment.     

Smoking and survival of breast cancer patients: A meta-analysis of cohort studies

ObjectivesPublished articles reported controversial results about the association of breast cancer survival with smoking. Hence, a meta-analysis was performed to investigate this association.MethodsA comprehensive search was performed to identify relevant cohort studies (up to May 31st, 2016). In the current smoking and former smoking v. never smoking analyses, the fixed- or random-effect model was selected based on the heterogeneity test among studies. And the heterogeneity was measured using Q test and I² statistic. Publication bias was estimated using Egger's regression asymmetry test.ResultsThirteen articles with 44 studies were included. Compared with never smokers, current smokers have a higher breast cancer-specific mortality and all-cause mortality, with pooled hazard ratio (HR) (HR = 1.30 95%CI: 1.16–1.45; I² = 52.4%) and (HR = 1.59, 95%CI: 1.41–1.78; I² = 87.1%), respectively. While former smokers tend to have a moderately increased all-cause mortality (HR = 1.10, 95%CI: 1.07–1.12; I² = 0.0%), but there was no significant association between former smoking and breast cancer-specific mortality (HR = 0.95, 95%CI: 0.90–1.02; I² = 0.0%).ConclusionThe present evidence indicates that current smoking leads to higher breast cancer-specific mortality and all-cause mortality than never smoking in breast cancer patients. However former smoking just causes a mild increase in all-cause morality, but not breast cancer-specific mortality.     

Trends in endocrine therapy prescription and survival in patients with non-metastatic hormone receptor positive breast cancer treated with endocrine therapy: A population based-study

PurposeTo identify prognostic factors of invasive–disease free survival (iDFS) in women with non-metastatic hormone receptor positive (HR+) breast cancer (BC) in daily routine practice.MethodsWe performed a retrospective study using data from the Côte d’Or breast and gynecological cancer registry in France. All women diagnosed with primary invasive non-metastatic HR + BC from 1998 to 2015 and treated by endocrine therapy (ET) were included. Women with bilateral tumors or who received ET for either metastasis or relapse were excluded. We performed adjusted survival analysis and Cox regression to identify prognostic factors of iDFS.ResultsA total of 3976 women were included. Age at diagnosis, ET class, SBR grade, treatment, stage and comorbidity were independently associated with iDFS. Women who had neither surgery nor radiotherapy had the highest risk of recurrence (HR = 3.75, 95%CI [2.65–5.32], p < 0.0001). Receiving aromatase inhibitors (AI) was associated with a lower risk of recurrence (HR = 0.70, 95%CI [0.54–0.90], p = 0.055) compared to tamoxifen. Compared to women with no comorbidities, women with 1 or 2 comorbidities were more likely to receive AI (OR = 1.63, 95%CI [1.22–2.17], p = 0.0009).ConclusionsComorbidities, age at diagnosis and previous treatment were associated with iDFS in non-metastatic HR + BC patients. This study also showed that women who received tamoxifen for their cancer experienced worse iDFS compared to women treated with AI.     

Risk factors for renal allograft survival with China novel donation category: Donation after brain death followed by cardiac arrest

IntroductionTo meet the need for transplantable organs, a new donation program was initiated by the Chinese government. This novel policy created three categories for deceased organ donations: donation after circulatory death cardiac death (DCD), donation after brain death (DBD), and donation after brain death followed by circulatory death (DBCD) meaning complete cardiac arrest. In fact, the DBCD method is a combination of both DBD and DCD methods. A DBCD donor meets the criteria of for brain death, but the organ procurement begins after the withdrawal of life support and the subsequent cardiac arrest death. The purpose of this study was to evaluate the long-term outcomes of kidney transplantation in our center with the DBCD policy. Potential risk factors for affecting the renal allograft survival were also analyzed based on our data.MethodA retrospective study, involving 421 kidney transplants derived from 214 donors, was conducted between December 2011 and October 2019. In particular, 373 (88.6%) transplanted organs met the criteria for DBCD, and 48 (11.4%) for DCD. The log-rank test was used to compare the difference in survival. The Cox regression analysis was used for risk factor screening.ResultAnalysis showed that the DBCD group was better than the DCD group in terms of overall (p = 0.031) as well as death-censored (p = 0.026) allograft survival using the log-rank test. A Cox regression analysis revealed that increasing donor age (p = 0.002, HR = 1.820/10 years incremental older), increasing recipient age (p = 0.028, HR = 1.521/10 years increment older), prolonged dialysis duration (p = 0.007, HR = 1.018), occurrence episodes of acute rejection (p = 0.016, HR = 2.697), delayed graft function (p = 0.012, HR = 2.962), mismatch ≥4 HLA loci (p = 0.038, HR = 3.606), and warm ischemia time > 15 min (p = 0.022, HR = 2.915), were all independent risk factors affecting the graft survival.ConclusionThe new DBCD policy of donation produced acceptable results similar or even better than the DCD practice. Based on our analysis, the graft survival of DBCD transplants may be better than DCD transplants. The main risk factors for allograft loss included an increasing donor age, recipient age, warm ischemia time > 15 min, prolonged dialysis duration, acute rejection, delayed graft function, and HLA mismatch ≥4 HLA loci.     

Outcome beyond third-line chemotherapy for metastatic triple-negative breast cancer in the French ESME program

PurposeAmong metastatic breast cancer (MBC) patients, those with a triple-negative breast cancer phenotype (mTNBC) have the worst prognosis, but the benefit of chemotherapy beyond second line on outcome remains uncertain. The purpose of this study was to identify predictive factors of outcome after third- or fourth-line chemotherapy.MethodsThe ESME-MBC database is a French prospective real-life cohort with homogeneous data collection, including patients who initiated first-line treatment for MBC (2008–2016) in 18 cancer centers. After selection of mTNBC cases, we searched for independent predictive factors (Cox proportional-hazards regression models) for overall survival (OS) on third- and fourth-line chemotherapy (OS3, OS4). We built prognostic nomograms based on the main prognostic factors identified.ResultsOf the 22,266 MBC cases in the ESME cohort, 2903 were mTNBC, 1074 (37%) and 598 (20%) of which had received at least 3 or 4 lines of chemotherapy. PFS after first- and second-line chemotherapy (PFS1, PFS2) and number of metastatic sites ≥3 at baseline were identified by multivariate analysis as prognostic factors for both OS3 (HR = 0.76 95%CI[0.66–0.88], HR = 0.55 95%CI[0.46–0.65], HR = 1.36 95%CI[1.14–1.62], respectively), and OS4 (HR = 0.76 95%CI[0.63–0.91], HR = 0.56 95%CI[0.45–0.7], HR = 1.37 95%CI[1.07–1.74]), respectively. In addition, metastasis-free interval was identified as a prognostic factor for OS3 (p = 0.01), while PFS3 influenced OS4 (HR = 0.75 95%CI[0.57–0.98]). Nomograms predicting OS3 and OS4 achieved a C-index of 0.62 and 0.61, respectively.ConclusionThe duration of each previous PFS is a major prognostic factor for OS in mTNBC patients receiving third- or fourth-line chemotherapy. The clinical utility of nomograms including this information was not demonstrated.     

High Rate of Re-Revision in Patients Less Than 55 Years of Age Undergoing Aseptic Revision Total Knee Arthroplasty

BackgroundThere are limited data on the outcomes of revision total knee arthroplasty in young patients. We sought to characterize the re-revision-free survival and risk factors for re-revision in patients less than 55 years who underwent aseptic revision TKA.MethodsWe retrospectively reviewed 197 revision TKAs at a mean follow-up of 5 years. Mean age was 49 years; mean body mass index was 31 kg/m². Twenty-seven (14%) patients had at least 1 prior revision TKA. The most common indications for revision included instability (29%), arthrofibrosis (26%), and aseptic loosening (24%). Constraint included the following: 59 posterior-stabilized (30%), 123 varus-valgus constrained (62%), and 15 hinged (8%). Components revised included the following: 93 femur/tibia (47%), 68 polyethylene-only (35%), 19 femur-only (10%), and 17 other (9%). Survivorship free from re-revision was calculated via the Kaplan-Meier method and a multivariate Cox proportional regression was utilized to identify risk factors for re-revision.ResultsSurvivorship free from any re-revision at 5 years was 80%. In the multivariate analysis, patients with a prior revision (hazard ratio [HR] = 2.78, P = .02), an isolated polyethylene exchange (HR = 3.0, P = .004), and a hinged prosthesis (HR = 3.47, P = .05) were significant risk factors for lower revision-free survival. Forty-two patients (21%) underwent re-revision, most commonly for periprosthetic joint infection (7%), instability (6%), and aseptic loosening (5%). Re-revision occurred in 18/68 (26%) patients undergoing an isolated polyethylene exchange.ConclusionPatients less than 55 years undergoing revision TKA have a modest 5-year revision-free survival of 80%. Patients with prior revision TKAs (HR = 2.78), hinge type prostheses (HR = 3.47), and polyethylene-only revisions (HR = 3.0) had higher revision rates.     

Predictive role of the overexpression for CXCR4, C-Met,and VEGF-C among breast cancer patients: A meta-analysis

BackgroundThe overexpression of CXCR4, C-Met and VEGF-C present widely in breast tumors, they may be markers of resistance to treatment. However, the studies are still controversial. Thus, this meta-analysis aims to research the relationship between the overexpression of CXCR4, C-Met, VEGF-C and clinical prognosis among breast cancer patients.MethodsPubMed and EMBASE databases were searched for eligible literature. The outcomes of interest were progression-free survival (PFS), relapse-free survival (RFS) and overall survival (OS). All tests of statistical significance were two sided.ResultsA total of 7830 patients from 28 eligible studies were assessed. The overexpression of the CXCR4 and C-Met both implied significantly worse PFS compared with normal expression [HR = 2.56, 95% CI = 1.34–4.91, P = 0.005; and HR = 1.63 95% CI = 1.20–2.22, P = 0.002]. Meanwhile, if patients had high expression of CXCR4, they would have worse OS [HR = 2.56 95% CI = 1.52–4.31, P = 0.000]. However, the overexpression of C-Met did not relate to OS for breast cancer patients [HR = 1.16, 95% CI = 0.69–1.95, P = 0.570]. Meanwhile, no statistically significant different was observed with respect to PFS and OS between VEGF-C overexpression and normal expression [HR = 0.99, 95% CI = 0.64–1.52, P = 0.968; and HR = 0.76, 95% CI = 0.43–1.33, P = 0.333].ConclusionsOur meta-analysis showed that CXCR4 and C-Met were efficient prognostic factors for breast cancer. Nevertheless, highly expressing VEGF-C was not related to progression-free survival and overall survival. Due to the small samples and insufficient date, further studies should be conducted to clarify the association between the overexpression of CXCR4 or C-Met or VEGF-C and the prognosis about breast cancer patients.     

Supersonic shear-wave elastography and APRI for the detection and staging of liver disease in pediatric cystic fibrosis

BackgroundCurrent diagnostic methods for the diagnosis of Cystic fibrosis (CF)-associated liver disease (CFLD) are non-specific and assessment of disease progression is difficult prior to the advent of advanced disease with portal hypertension. This study investigated the potential of Supersonic shear-wave elastography (SSWE) to non-invasively detect CFLD and assess hepatic fibrosis severity in children with CF.Methods125 children were enrolled in this study including CFLD (n = 55), CF patients with no evidence of liver disease (CFnoLD = 41) and controls (n = 29). CFLD was diagnosed using clinical, biochemical and imaging best-practice guidelines. Advanced CFLD was established by the presence of portal hypertension and/or macronodular cirrhosis on ultrasound. Liver stiffness measurements (LSM) were acquired using SSWE and diagnostic performance for CFLD detection was evaluated alone or combined with aspartate aminotransferase-to-platelet ratio index (APRI).ResultsLSM was significantly higher in CFLD (8.1 kPa, IQR = 6.7–11.9) versus CFnoLD (6.2 kPa, IQR = 5.6–7.0; P < 0.0001) and Controls (5.3 kPa, IQR = 4.9–5.8; P < 0.0001). LSM was also increased in CFnoLD versus Controls (P = 0.0192). Receiver Operating Characteristic (ROC) curve analysis demonstrated good diagnostic accuracy for LSM in detecting CFLD using a cut-off = 6.85 kPa with an AUC = 0.79 (Sensitivity = 75%, Specificity = 71%, P < 0.0001). APRI also discriminated CFLD (AUC = 0.74, P = 0.004). Classification and regression tree modelling combining LSM + APRI showed 14.8 times greater odds of accurately predicting CFLD (AUC = 0.84). The diagnostic accuracy of SSWE for discriminating advanced disease was excellent with a cut-off = 9.05 kPa (AUC = 0.95; P < 0.0001).ConclusionsSSWE-determined LSM shows good diagnostic accuracy in detecting CFLD in children, which was improved when combined with APRI. SSWE alone discriminates advanced CFLD.     

Pilot study on the use of acoustic radiation force impulse imaging in the staging of cystic fibrosis associated liver disease

BackgroundAcoustic radiation force impulse (ARFI) is a novel technique for the measurement of hepatic stiffness, which could be valuable in clinical follow-up of patients affected by cystic fibrosis liver disease (CFLD).MethodsSeventy-five patients with suspected CFLD (35 males) underwent clinical and ultrasonographic evaluations, liver and pulmonary function tests, ARFI investigation, and upper gastrointestinal endoscopy. Ten ARFI measurements were taken at the deep right hepatic lobe to compute median values of Shear Wave Velocity (SWV) for each individual.ResultsSWV increased progressively from 1.02 m/s (95%, Confidence Interval, CI, 0.92–1.126) in patients with no evidence of CFLD at ultrasonography (N = 16), to 1.12 (95%CI 1.049–1.19) in patients with CFLD and no signs of portal hypertension (PHT, N = 23), and to 1.25 (95%CI 1.14–1.358) in those with CFLD and signs of PHT (N = 28). SWV was 1.63 (95%CI 1.26–1.99) in patients with oesophageal varices (N = 8) (p < 0.0001).ConclusionsARFI may represent an easy, fast and non-invasive tool for the clinical follow-up of patients with cystic fibrosis associated liver disease.     

No Difference in the Rate of Periprosthetic Joint Infection in Patients Undergoing the Posterolateral Compared to the Direct Anterior Approach

BackgroundThere remains inconsistent data about the association of surgical approach and periprosthetic joint infection (PJI). We sought to evaluate the risk of reoperation for superficial infection and PJI after primary total hip arthroplasty (THA) in a multivariate model.MethodsWe reviewed 16,500 primary THAs, collecting data on surgical approach and all reoperations within 1 year for superficial infection (n = 36) or PJI (n = 70). Considering superficial infection and PJI separately, we used Kaplan–Meier survivorship to assess survival free from reoperation and a Cox Proportional Hazards multivariate models to assess risk factors for reoperation.ResultsBetween direct anterior approach (DAA) (N = 3,351) and PLA (N = 13,149) cohorts, rates of superficial infection (0.4 versus 0.2%) and PJI (0.3 versus 0.5%) were low and survivorship free from reoperation for superficial infection (99.6 versus 99.8%) and PJI (99.4 versus 99.7%) were excellent at both 1 and 2 years. The risk of developing superficial infection increased with high body mass index (BMI) (hazard ratio [HR] = 1.1 per unit increase, P = .003), DAA (HR = 2.7, P = .01), and smoking status (HR = 2.9, P = .03). The risk of developing PJI increased with the high BMI (HR = 1.04, P = .03), but not surgical approach (HR = 0.68, P = .3).ConclusionIn this study of 16,500 primary THAs, DAA was independently associated with an elevated risk of superficial infection reoperation compared to the PLA, but there was no association between surgical approach and PJI. An elevated patient BMI was the strongest risk factor for superficial infection and PJI in our cohort.Level of EvidenceIII, retrospective cohort study.     

Local treatment options for young women with ductal carcinoma in situ: A systematic review and meta-analysis comparing breast conserving surgery with or without adjuvant radiotherapy,and mastectomy

PurposeYoung age is associated with poor prognosis in ductal carcinoma in situ (DCIS) of female breast and controversy exists regarding the optimal treatment modality for young patients. We aimed to compare treatment outcomes among breast conserving surgery (BCS), BCS with adjuvant radiotherapy (BCS + RT), and total mastectomy (MT) for young DCIS women.MethodsPubMed, Cochrane, and Embase were searched for studies reporting comparative results among BCS, BCS + RT, or MT in ≤50 years old (y/o) DCIS females. Study quality was assessed and meta-analysis with subgroup analysis was performed to pool the effect sizes of the outcomes-of-interest.ResultsWe included 3 randomized control trials and 18 observational studies. For DCIS women ≤50 y/o, RT following BCS significantly reduced the risk for ipsilateral breast tumor recurrence (IBTR) (HR = 0.66, 95% CI 0.50–0.87). However, the benefit was less robust in extremely young patients and with long follow-ups. RT revealed no statistically significant preventive effect on ipsilateral invasive recurrence (HR = 1.38, 95% CI 0.98–1.94). On the other hand, MT yielded the lowest IBTR (BCS + RT vs MT: HR = 4.4, 95% CI 2.06–9.40), both in ipsilateral DCIS recurrence and ipsilateral invasive recurrence. There was great heterogeneity and could not reach an evident conclusion concerning survival outcomes.ConclusionThis study highlighted the varying effect of RT for young DCIS females. The local control benefit of MT was definite without survival differences observed. Our study provided a moderate certainty of evidence to guide the treatment for young DCIS women. Further age-specific prospective trial is warranted.     

Survival outcomes after breast-conserving therapy compared with mastectomy for patients with early-stage metaplastic breast cancer: a population-based study of 2412 patients

BackgroundPrevious studies revealed that patients with early-stage metaplastic breast cancer (MBC) underwent mastectomy more often than breast-conserving therapy (BCT) mainly due to the larger tumor size. This study was performed to compare the survival outcomes following BCT versus mastectomy for patients with early-stage MBC.MethodsSurveillance, Epidemiology, and End Results (SEER) database was used to identify women diagnosed with early-stage MBC (T1-3N0-3M0) between 2001 and 2016, who were treated with either BCT or mastectomy. We assessed overall survival (OS) and breast cancer-specific survival (BCSS) using the Kaplan-Meier method and hazard ratios using Cox proportional hazards models.ResultsA total of 2412 MBC patients were identified, 881 (36.5%) of whom underwent BCT and 1531(63.5%) underwent mastectomy. The median follow-up time was 73 months. Most of patients had older age (≥50 years old), larger tumor size, higher American Joint Committee on Cancer (AJCC) stage and hormone receptor negativity. After adjustment for confounding variables, patients who underwent BCT had significantly improved OS (5-year OS: 84.3% vs 62.5%; 10-year OS: 73.0% vs 52.1%; adjusted HR = 0.76, 95%CI: 0.59–0.97, p = 0.028) and BCSS (5-year BCSS: 89.1% vs 70.8%; 10-year BCSS: 83.9% vs 67.5%; adjusted HR = 0.72, 95%CI: 0.53–0.96, p = 0.026) than those who underwent mastectomy, and this improvement remained significant for all T and N stages of MBC except for N2-3 stage.ConclusionBCT conferred improved OS and BCSS compared with mastectomy for patients with early-stage MBC, and the improvement persisted in almost all of the subgroups of different T and N stages.     

Non-invasive liver elastography (Fibroscan) for detection of cystic fibrosis-associated liver disease

BackgroundCystic fibrosis-associated liver disease (CFLD) is the second cause of mortality in CF. The prevalence is estimated to be 26–45%, but sensitive diagnostic tools are lacking.We investigated whether non-invasive liver elastography (Fibroscan) could serve as a screening tool.MethodsFibroscan measurements were performed in 66 CF patients. Age-specific cutoff values were determined in a control population (n = 59). The measurements were compared to clinical data, biyearly biochemistry and ultrasound.ResultsFibroscan was easy to perform in this patient population. There were 14 patients (21%) with abnormal liver stiffness measurements.Liver stiffness was significantly increased in patients with clinical CFLD (11.2 kPa versus 5.1 kPa), biochemical CFLD (7.4 kPa versus 5.4 kPa) or ultrasonographical CFLD (8.2 versus 4.3 kPa) (p < 0.02 for all).ConclusionsFibroscan is an objective measure and is easy to perform in CF patients, even in children and could provide a valuable tool to detect, and quantify CFLD.     

Identification of intermediate risk breast cancer patients with1–3 positive lymph nodes and excellent survival after tamoxifen as only systemic adjuvant therapy by use of markers of proliferation and apoptosis

BackgroundAccording to current guidelines, patients with primary breast cancer and 1–3 lymph node metastases will in general be offered adjuvant chemotherapy.AimOur objective was to investigate the relationship between markers of proliferation and apoptosis with survival for patients subjected to adjuvant tamoxifen solely.Material and methodsTumour cytosol samples from 409 consecutive patients with operable oestrogen receptor positive BC, stage I–III and treated with tamoxifen for 2 or 5 years were assessed for levels of caspase-cleaved cytokeratin-18 (ccCK18), an indicator of apoptosis, by use of an ELISA assay. Data on S-phase fraction (SPF) were available for 370 patients. Survival analyses were performed according to levels of ccCK18 and SPF separately, as well as combined.ResultsA wide range of ccCK18 protein levels was found, median 9.97, range 0.0–87.3 pg/μgDNA. Increasing SPFs were significantly associated with a lower distant recurrence-free survival (DRFS) (p = 0.025) and breast cancer survival (BCS) (p = 0.046). In the group with low SPF (below mean), low amounts of ccCK/18 correlated with a shorter DRFS (p = 0.0028) and BCS (p = 0.0027). A Proliferation Index (PI); a quotient of ccCK18/SPF was constructed. Low PI (high ccCK18/SPF ratios) were significantly correlated with an improved survival both when analysed as continuous variables; DRFS (p = 0.021), BCS (p = 0.038) and when divided into quartiles; DRFS (p < 0.001) and BCS (p = 0.0012). A similar correlation was found in patients with 1–3 lymph node metastases; DRFS (p = 0.089) and BCS (p = 0.019). A Cox's proportional hazard model including age, tumour size, lymph node status, PgR and ccCK18/SPF was used for multivariate analysis. High ccCK18/SPF ratios correlated with improved survival; DRFS (HR = 0.47 (0.22–0.98), p = 0.043), and BCS (HR = 0.39 (0.16–1.00), p = 0.049), respectively.ConclusionBy use of a proliferation index based on markers of proliferation and apoptosis, a group of patients with 1–3 lymph node metastases with good outcome following adjuvant tamoxifen was identified; this group could possibly be spared adjuvant chemotherapy.     

Predicting the survival benefit of local surgery in patients aged 70 years or older with stage IV breast cancer: A population-based analysis

PurposeThe aim of this study was to establish individualized nomograms to predict survival outcomes in older female patients with stage IV breast cancer who did or did not undergo local surgery, and to determine which patients could benefit from surgery.MethodsA total of 3,129 female patients with stage IV breast cancer aged ≥70 years between 2010 and 2015 were included in the Surveillance, Epidemiology, and End Results program. Multivariate Cox regression analysis was used to identify risk factors for overall survival (OS) and breast cancer-specific survival (BCSS). Survival analysis was performed using the Kaplan–Meier plot and log-rank test. Nomograms and risk stratification models were constructed.ResultsPatients who underwent surgery had better OS (HR = 0.751, 95% CI [0.668–0.843], P < 0.001) and BCSS (HR = 0.713, 95% CI [0.627–0.810], P < 0.001) than patients who did not undergo surgery. Patients with human epidermal growth factor receptor 2-positive, lung or liver metastases may not benefit from surgery. In the stratification model, low-risk patients benefited from surgery (OS, HR = 0.688, 95% CI [0.568–0.833], P < 0.001; BCSS, HR = 0.632, 95% CI [0.509–0.784], P < 0.001), while patients in the high-risk group had similar outcomes (OS, HR = 0.920, 95% CI [0.709–1.193], P = 0.509; BCSS, HR = 0.953, 95% CI [0.713–1.275], P = 0.737).ConclusionOlder female patients with stage IV breast cancer who underwent surgery had better OS and BCSS than those who did not in each specific subgroup. Patients in low- or intermediate-risk group benefit from surgery while those in the high-risk group do not.     

Predictive and prognostic values of tumor infiltrating lymphocytes in breast cancers treated with neoadjuvant chemotherapy: A meta-analysis

BackgroundThis meta-analysis assessed the predictive and prognostic value of tumor infiltrating lymphocytes (TILs) in neoadjuvant chemotherapy (NACT) treated breast cancer and an optimal threshold for predicting pathologic complete response (pCR).MethodsA systematic search of PubMed, EMBASE and Web of Science electronic databases was conducted to identify eligible studies published before April 2022. Either a fixed or random effects model was applied to estimate the pooled hazard ratio (HR) and odds ratio (OR) for prognosis and predictive values of TILs in breast cancer patients treated with NACT. The study is registered with PROSPERO (CRD42020221521).ResultsA total of 29 published studies were eligible. Increased levels of TILs predicted response to NACT in HER2 positive breast cancer (OR = 2.54 95%CI, 1.50–4.29) and triple negative breast cancer (TNBC) (OR = 3.67, 95%CI, 1.93–6.97), but not for hormone receptor (HR) positive breast cancer (OR = 1.68, 95 %CI, 0.67–4.25). A threshold of 20% of H & E-stained TILs was associated with prediction of pCR in both HER2 positive breast cancer (P = 0.035) and TNBC (P = 0.001). Moreover, increased levels of TILs (either iTILs or sTILs) were associated with survival benefit in HER2-positive breast cancer and TNBC. However, an increased level of TILs was not a prognostic factor for survival in HR positive breast cancer (pooled HR = 0.64, 95%CI: 0.03–14.1, P = 0.78).ConclusionsIncreased levels of TILs were associated with increased rates of response to NACT and improved prognosis for the molecular subtypes of TNBC and HER2-positive breast cancer, but not for patients with HR positive breast cancer. A threshold of 20% TILs was the most powerful outcome prognosticator of pCR.     

Comparison of Outcomes in Patients Undergoing Renal Transplantation With Impaired vs Normal Left Ventricular Ejection Fraction

BackgroundRenal transplantation improves long-term outcomes in patients with end-stage renal disease (ESRD); however, patients with impaired left ventricular ejection fraction (LVEF) are less likely to be selected for renal transplantation. We sought to evaluate the effect of renal transplantation in this population.MethodsWe retrospectively evaluated 181 patients who underwent renal transplantation between 2011 and 2016. For patients with pretransplant LVEF <50% (cohort 1) and ≥50% (cohort 2), we evaluated the effect of renal transplantation on LVEF, graft failure, and mortality.ResultsCohort 1 comprised 24 patients (mean age, 47 years; pretransplant LVEF 38%). Cohort 2 comprised 157 patients (mean age, 53 years; pretransplant LVEF 64%). Forty-six percent of cohort 1 experienced significant improvement in LVEF posttransplant, with mean LVEF improvement from 38% to 66%. There was no significant association between pretransplant LVEF and graft failure (hazard ratio [HR] = 2.7; 95% confidence interval [CI], 0.6-11.4; P = .1) or mortality (HR = 1.02; 95% CI, 0.3-3.6; P = .9). Coronary artery disease predicted mortality (HR = 3.12; 95% CI, 1.2-8.4; P = .02). Older age trended toward higher mortality (HR = 1.04; 95% CI, 1.0-1.1; P = .05). Younger age predicted graft failure (HR = 0.96; 95% CI, 0.8-0.9; P = .02).ConclusionsIn patients with ESRD undergoing renal transplantation, there was no significant association between pretransplant LVEF and mortality or graft failure, suggesting that patients with ESRD with impaired LVEF can experience positive posttransplant outcomes.     

The clinical value of regional lymphadenectomy for intrahepatic cholangiocarcinoma

ObjectiveThe aim of this study was to explore the clinical value of lymph node dissection (LND) for intrahepatic cholangiocarcinoma (ICC).MethodsClinical and pathological data were collected from 147 ICC patients who attended two tertiary centers over the past 5 years. The patients were classified into two groups: the LND group (group A) and the no-performance LND (NLND) group (group B). Clinical and pathological parameters were compared between the two groups to analyze the impact of LND on the long-term survival time of ICC patients.ResultsOf the 147 patients, 54.4% (80) received LND and 42.5% (34/80) of these were found to have lymph node metastasis (LNM). LND did not increase postoperative complications (27.5%, P = 0.354), but postoperative hospital stays were longer (12.2 ± 6.3 d, P = 0.005) in group A compared with group B (20.9%, 9.5 ± 3.5 d). The 5-year survival rates of groups A and B are almost similar (21% vs 29%, P = 0.905). The overall survival rate of cN0 (diagnosis obtained by imaging) is better than pN1 (diagnosis obtained by histopathology), but lower than pN0 (all P < 0.05). Compared with NLND, the median survival time of LND patients with T1 has not significantly improved (29.3 vs 35.1 months, P = 0.762), but the patients with T2-4 has been significantly increased (29.0 vs 17.1 months, P = 0.040). Elevated CA19-9 level (HR = 1.764, 95% CI: 1.113–2.795, P = 0.016), vascular invasion (HR = 2.697, 95% CI: 1.103–6.599, P = 0.030), and T category (HR = 1.848, 95% CI: 1.059–3.224, P = 0.031) were independent risk factors for poor long-term survival time of the ICC patients (all P values < 0.05).ConclusionICC patients with cN0 may have LNM, and the long-term survival time of LNM patients is usually poor. We suggest that patients with ICC may require routine LND, especially those with T2-4 category.