Significance of preoperative hematologic scoring in predicting death among patients with non-metastatic renal cell carcinoma undergoing nephrectomy

PurposeNeutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) are hematologic scoring and indicators of the systemic inflammatory response. The increasing use of NLR and PLR have been associated with poor outcome in various types of malignancy. We evaluated the effect of NLR and PLR on survival outcomes of nonmetastatic renal cell carcinoma (RCC).Materials and methodsWe retrospectively review 150 patients who had undergone nephrectomy for nonmetastatic RCC between 2006 and 2016. Cancer specific survival (CSS) was assessed using Kaplan–Meier method and compared using log-rank test. We applied univariate and multivariate Cox regression model to analyze the association of NLP and PLR with clinical outcome.ResultsAt median follow up of 33 months, 45 patients had died. High PLR (>100) was an independent prognostic hematologic marker for CSS (hazard ratio [HR] 2.61, 95% confidence interval [CI],1.08–6.31; P = 0.034). Univariate analysis identified elevated NLR (p = 0.005), and anemia (p = 0.023) were significantly associated with CSS.ConclusionElevated PLR is a strong hematologic prognosis factor in term of survival for patients with nonmetastatic RCC undergoing nephrectomy with curative intent. The PLR is an easily obtained biomarker which is useful for preoperative risk stratification.     

Neutrophil and platelet‐to‐lymphocyte ratio as new predictors of dropout and recurrence after liver transplantation for hepatocellular cancer

There is increasing evidence that systemic inflammation markers like neutrophil (NLR) and platelet‐to‐lymphocyte ratios (PLR) may play a role in the outcome of hepatocellular cancer (HCC). Between January 1994 and March 2012, 181 patients with HCC were registered on the transplant waiting list: 35 (19.3%) patients dropped out during the waiting period and 146 (80.7%) patients underwent liver transplantation (LT). The median follow‐up of this patient cohort was 4.2 years (IQR: 1.8–8.3). On c‐statistics, the last NLR (AUROC = 67.4; P = 0.05) was the best predictor of dropout. The last PLR had an intermediate statistical ability (AUROC = 66.1; P = 0.07) to predict post‐LT tumor recurrence. Patients with a NLR value >5.4 had poor 5‐year intention‐to‐treat (ITT) survival rates (48.2 vs. 64.5%; P = 0.02). Conversely, PLR better stratified patients in relation to tumor‐free survival (TFS) (80.7 vs. 91.6%; P = 0.02). NLR is a good predictor for the risk of dropout, while PLR is a good predictor for the risk of post‐LT recurrence. Use of these markers, which are all available before LT, may represent an additional tool to refine the selection criteria of HCC liver recipients.     

Platelet-to-lymphocyte ratio predicts mortality better than neutrophil-to-lymphocyte ratio in hemodialysis patients

Purpose

Neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) were established showing the poor prognosis in some diseases, such as cardiovascular diseases and malignancies. The risk of mortality in patients with end-stage renal disease (ESRD) was higher than normal population. In this study, we aimed to investigate the relationship between NLR, PLR, and all-cause mortality in prevalent hemodialysis (HD) patients.

Methods

Eighty patients were enrolled in study. NLR and PLR obtained by dividing absolute neutrophil to absolute lymphocyte count and absolute platelet count to absolute lymphocyte count, respectively. The patients were followed prospectively for 24 months. The primary end point was all-cause mortality.

Results

Mean levels of neutrophil, lymphocyte, and platelet were 3904 ± 1543/mm³, 1442 ± 494/mm³, 174 ± 56 × 10³/mm³, respectively. Twenty-one patients died before the follow-up at 24 months. Median NLR and PLR were 2.52 and 130.4, respectively. All-cause mortality was higher in patients with high NLR group compared to the patients with low NLR group (18.8 vs. 7.5 %, p = 0.031) and in patients with higher PLR group compared to patients with lower PLR group (18.8 vs. 7.5 %, p = 0.022). Following adjusted Cox regression analysis, the association of mortality and high NLR was lost (p = 0.54), but the significance of the association of high PLR and mortality increased (p = 0.013).

Conclusion

Although both NLR and PLR were associated with all-cause mortality in prevalent HD patients, only PLR could independently predict all-cause mortality in these populations.

     

Correlation of preoperative neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio with metabolic parameters in patients undergoing sleeve gastrectomy

BackgroundObesity and its related diseases, type 2 diabetes (T2D) and overall metabolic syndrome, often show a low-grade of chronic inflammation due to loss of balance between pro- and anti-inflammatory signals. Neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are considered cost-effective markers for the detection of this subclinical inflammation.ObjectivesTo evaluate the potential prognostic factor of NLR and PLR as inflammatory biomarkers on weight loss and T2D remission after sleeve gastrectomy (SG).SettingUniversity Medical Institutions.MethodsPatients who underwent SG as primary treatment for severe obesity were included. Anthropometric and blood parameters were measured at baseline and postoperatively (1, 2, and 5 yr after surgery). The prognostic ability of NLR and PLR was evaluated by a receiver operator characteristic curve and a cutoff point was calculated. A value of P < .05 was considered significant.ResultsA total of 182 patients were analyzed. Preoperative NLR showed an inverse correlation with excess weight loss (Spearman −.525; P = .033) and units of body mass index lost (Spearman −.502; P = .039) 5 years after surgery. Preoperative NLR also showed a direct correlation with fasting glucose (Spearman .685; P = .002) and Homeostasis Model Assessment of Insulin Resistance (Spearman .764; P < .001). Lower preoperative NLR is also associated with a complete remission of T2D at 5 years. Preoperative PLR did not show any correlation with the variables studied.ConclusionThe preoperative NLR is a potential prognostic factor of long-term weight loss and T2D remission in patients undergoing SG. PLR does not correlate with metabolic parameters in these patients.     

Evaluation of the platelet-to-lymphocyte ratio as a prognostic indicator in a European cohort of patients with prostate cancer treated with radiotherapy

ObjectivesRecent evidence suggests that the presence of a systemic inflammatory response plays an important role in the progression of several solid tumors. The platelet-to-lymphocyte ratio (PLR) has been proposed as an easily assessable marker of systemic inflammation and has been shown to represent a prognostic marker in different cancer entities. To evaluate the prognostic value of the PLR in prostate cancer, we performed the present study.Methods and materialsData from 374 consecutive patients with prostate cancer, treated with 3D conformal radiotherapy from 1999 to 2007, were analyzed. Distant metastases–free survival (MFS), cancer-specific survival (CSS), overall survival (OS), biochemical disease–free survival, and time to salvage systemic therapy were assessed using the Kaplan-Meier method. Cox proportional hazards analysis was performed to calculate hazard ratio (HR) and 95% CI. Multivariate Cox regression analysis was performed to adjust for other covariates.ResultsUsing receiver operating characteristics analysis, the optimal cutoff level for the PLR was 190. Kaplan-Meier analyses revealed that PLR≥190 was a prognostic factor for decreased MFS (P = 0.004), CSS (P = 0.004), and OS (P = 0.024) whereas a significant association of an elevated PLR with biochemical disease–free survival (P = 0.740) and time to salvage systemic therapy (P = 0.063) was not detected. In multivariate analysis, an increased PLR remained a significant prognostic factor for poor MFS (HR = 2.24, 95% CI: 1.06–4.76, P = 0.036), CSS (HR = 3.99, 95% CI: 1.19–13.4, P = 0.025), and OS (HR = 1.87, 95% CI: 1.02–3.42, P = 0.044).ConclusionsOur findings indicate that the PLR may predict prognosis in patients with prostate cancer and may contribute to future individual risk assessment in them.     

Proximal aortic repair in dialysis patients: A national database analysis

ObjectivesDialysis is a well-established risk factor for morbidity and mortality after cardiovascular procedures. However, little is known regarding the outcomes of proximal aortic surgery in this high-risk cohort.MethodsPerioperative (in-hospital or 30-day mortality) and 10-year outcomes were analyzed for all the patients who underwent open proximal aortic repair with the diagnosis of nonruptured thoracic aortic aneurysm (aneurysm, n = 325) or type A aortic dissection (dissection, n = 461) from 1987 to 2015 using the US Renal Data System database.ResultsIn patients with aneurysm, perioperative mortality was 12.6%. The 10-year mortality was 81% ± 3%. Age 65 years or more (hazard ratio [HR], 1.35; 95% confidence interval [CI], 1.03 to 1.78; P = .03), chronic obstructive pulmonary disease (HR, 1.68; 95% CI, 1.01-2.82; P = .047), and Black race (HR, 1.46; 95% CI, 1.09-1.97; P = .01) were independently associated with worse 10-year mortality. In patients with dissection, perioperative mortality was 24.3% and 10-year mortality was 87.9% ± 2.2%. Age 65 years or more (HR, 1.49; 95% CI, 1.19-1.86; P < .001), congestive heart failure (HR, 1.39; 95% CI, 1.11-2.57; P = .004), and diabetes mellitus as the cause of dialysis (HR, 1.75; 95% CI, 1.2-2.57; P = .004) were independently associated with worse 10-year mortality. Black race (HR, 0.74; 95% CI, 0.6-0.92; P = .008) was associated with a better outcome.ConclusionsWe described challenging perioperative and 10-year outcomes for dialysis patients undergoing proximal aortic repair. The present study suggests the need for careful patient selection in the elective repair of proximal aortic aneurysm for dialysis-dependent patients, whereas it affirms the feasibility of emergency surgery for acute type A aortic dissections.     

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.     

Neutrophil to lymphocyte ratio changes predict small hepatocellular carcinoma survival

Background

There is limited information available concerning the delta neutrophil to lymphocyte ratio (ΔNLR) in hepatocellular carcinoma (HCC). The present study was designed to evaluate the predictive value of dynamic change of NLR in patients who undergo curative resection for small HCC.

Methods

A retrospective cohort study was performed to analyze 189 patients with small HCC who underwent curative resection between February 2007 and March 2012. Patient data were retrieved from our prospectively maintained database. Patients were divided into two groups: group A (NLR increased, n = 80) and group B (NLR decreased, n = 109). Demographic and clinical data, overall survival (OS), and recurrence-free survival (RFS) were statistically compared and a multivariate analysis was used to identify prognostic factors.

Results

The 1, 3, and 5-y OS in group A was 92.7, 70.0, and 53.0%, respectively, and 96.2, 87.5, and 75.9%, respectively, for group B (P = 0.003); The corresponding 1, 3, and 5-y RFS was 58.7, 37.9, 21.8, and 81.2%, 58.5% and 53.8% for groups A and B, respectively (P <0.001). Multivariate analysis suggested that ΔNLR was an independent prognostic factor for both OS (P = 0.004, Hazard Ratio (HR) = 2.637, 95% confidence interval (CI) 1.356–5.128) and RFS (P <0.001, HR = 2.372, 95% CI 1.563–3.601).

Conclusions

Increased NLR, but not high preoperative NLR or postoperative NLR, helps to predict worse OS and RFS in patients with small HCC who underwent curative resection.     

Comparison of the Nottingham Prognostic Index and OncotypeDX© recurrence score in predicting outcome in estrogen receptor positive breast cancer

IntroductionTraditionally, Nottingham prognostic index (NPI) informed prognosis in patients with estrogen receptor positive, human epidermal growth factor receptor-2 negative, node negative (ER+/HER2-/LN-) breast cancer. At present, OncotypeDX© Recurrence Score (RS) predicts prognosis and response to adjuvant chemotherapy (AC).AimsTo compare NPI and RS for estimating prognosis in ER + breast cancer.MethodsConsecutive patients with ER+/HER2-/LN- disease were included. Disease-free (DFS) and overall survival (OS) were determined using Kaplan-Meier and Cox regression analyses.Results1471 patients met inclusion criteria. The mean follow-up was 110.7months. NPI was calculable for 1382 patients: 19.8% had NPI≤2.4 (291/1471), 33.0% had NPI 2.41–3.4 (486/1471), 30.0% had NPI 3.41–4.4 (441/1471), 10.9% had NPI 4.41–5.4 (160/1471), and 0.3% had NPI>5.4 (4/1471). In total, 329 patients underwent RS (mean RS: 18.7) and 82.1% had RS < 25 (270/329) and 17.9% had RS ≥ 25 (59/329). Using multivariable Cox regression analyses (n = 1382), NPI independently predicted DFS (Hazard ratio (HR): 1.357, 95% confidence interval (CI): 1.140–1.616, P < 0.001) and OS (HR: 1.003, 95% CI: 1.001–1.006, P = 0.024). When performing a focused analysis of those who underwent both NPI and RS (n = 329), neither biomarker predicted DFS or OS. Using Kaplan Meier analyses, NPI category predicted DFS (P = 0.008) and (P = 0.026) OS. Conversely, 21-gene RS group failed to predict DFS (P = 0.187) and OS (P = 0.296).ConclusionIn our focused analysis, neither NPI nor RS predicted survival outcomes. However, in the entire series, NPI independently predicted both DFS and OS. On the 40th anniversary since its derivation, NPI continues to provide accurate prognostication in breast cancer, outperforming RS in the current study.     

Development and validation of a novel nomogram for predicting systemic inflammatory response syndrome’s occurrence in patients undertaking flexible ureteroscopy

BackgroundThe occurrence of systemic inflammatory response syndrome (SIRS) is an early alert for sepsis after flexible ureteroscopy (fURS). Once sepsis occurs, it often leads to severe or fatal consequences. We aimed to identify SIRS patients preoperatively by developing and validating a feasible prognostic nomogram model based on retrospective cohort analysis.MethodsA total of 311 patients who underwent fURS in Dongguan Kanghua Hospital (Dongguan, China) between 2016 and 2020 were included and randomly divided into a primary cohort (n=219) and validation cohort (n=92). Single factor regression analysis was used to identify the primary cohort’s meaningful characters between SIRS and non-SIRS groups. Factors of the primary cohort were then identified by least absolute shrinkage and selection operator (LASSO) regression analysis, and a nomogram was built to execute the subsequent analysis using these factors. Finally, we analyzed and drew the calibration curve, receiver operating characteristic (ROC) curve, and decision curve analysis (DCA) curve to validate the prognostic value of the nomogram in calibration and discrimination.ResultsReview of the single regression analysis of characters in the primary cohort showed gender, stone burden, diabetes, neutrophil (N), lymphocyte (L), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocytes ratio (LMR), urine-WBC, nitrite (Nit), urine culture, and surgery time as significant factors between the SIRS and non-SIRS groups (P<0.05). The LASSO regression analysis suggested NLR, PLR, and urine culture were substantial factors in predicting SIRS postoperatively, lambda.min and lambda.1se (standard error, SE) were 0.01491 and 0.0796. A nomogram built with the three factors showed good calibration and discrimination, with the Brier values 0.064 and 0.034 and the area under curve (AUC) values 0.897 (95% CI: 0.837–0.957) and 0.976 (95% CI: 0.947–1.000) in the primary and validation cohort, respectively. DCA demonstrated the nomogram was clinically useful, and the predict probability of SIRS’s occurrence was very close to the actual rate as the risk threshold increased by higher than 60% in clinical impact curve analysis.ConclusionsNLR, PLR, and urine culture were significantly related to the occurrence of SIRS’s after fURS. The nomogram with these three factors showed excellent calibration, discrimination, and clinical usefulness.     

Preoperative hematologic markers as independent predictors of prognosis in resected pancreatic ductal adenocarcinoma: neutrophil-lymphocyte versus platelet-lymphocyte ratio

Background

The objective of this study was to investigate whether the preoperative hematologic markers, the platelet-lymphocyte ratio (PLR), or the neutrophil-lymphocyte ratio (NLR) ratio are significant prognostic indicators in resected pancreatic ductal adenocarcinoma.

Methods

A total of 84 patients undergoing pancreatoduodenectomy for pancreatic ductal adenocarcinoma over a 10-year period were identified from a retrospectively maintained database.

Results

The preoperative NLR was found to be a significant prognostic marker (P = .023), whereas PLR had no significant relationship with survival (P = .642) using univariate Cox survival analysis. The median overall survival in patients with an NLR of ≤3.0 (n = 55) was 13.7, 17.0 months in those with an NLR of 3.0 to 4.0 (n = 17) and 5.9 months in patients with a value of >4.0 (n = 12) (log rank, P = .016). The NLR retained its significance on multivariate analysis (P = .039) along with resection margin status (P = .001).

Conclusion

The preoperative NLR represents a significant independent prognostic indicator in patients with resected pancreatic ductal adenocarcinoma, whereas PLR does not.     

A retrospective validation of CanAssist Breast in European early-stage breast cancer patient cohort

CanAssist Breast (CAB), a prognostic test uses immunohistochemistry (IHC) approach coupled with artificial intelligence-based machine learning algorithm for prognosis of early-stage hormone-receptor positive, HER2/neu negative breast cancer patients. It was developed and validated in an Indian cohort. Here we report the first blinded validation of CAB in a multi-country European patient cohort. FFPE tumor samples from 864 patients were obtained from-Spain, Italy, Austria, and Germany. IHC was performed on these samples, followed by recurrence risk score prediction. The outcomes were obtained from medical records. The performance of CAB was analyzed by hazard ratios (HR) and Kaplan Meier curves. CAB stratified European cohort (n = 864) into distinct low- and high-risk groups for recurrence (P < 0.0001) with HR of 3.32 (1.85–5.93) like that of mixed (India, USA, and Europe) (n = 1974), 3.43 (2.34–4.93) and Indian cohort (n = 925), 3.09 (1.83–5.21). CAB provided significant prognostic information (P < 0.0001) in women aged ≤ 50 (HR: 4.42 (1.58–12.3), P < 0.0001) and >50 years (HR: 2.93 (1.44–5.96), P = 0.0002). CAB had an HR of 2.57 (1.26–5.26), P = 0.01) in women with N1 disease. CAB stratified significantly higher proportions (77%) as low-risk over IHC4 (55%) (P < 0.0001). Additionally, 82% of IHC4 intermediate-risk patients were stratified as low-risk by CAB. Accurate risk stratification of European patients by CAB coupled with its similar performance inIndian patients shows that CAB is robust and functions independent of ethnic differences. CAB can potentially prevent overtreatment in a greater number of patients compared to IHC4 demonstrating its usefulness for adjuvant systemic therapy planning in European breast cancer patients.     

Neutrophil to lymphocyte ratio and platelet to lymphocyte ratio reflect disease activity and flares in patients with systemic lupus erythematosus – A prospective study

ObjectivesTo determine the association between neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) with disease activity and flares in an inception cohort of patients with systemic lupus erythematosus (SLE) using a prospective study design.MethodsConsecutive adult patients (age ≥ 21) who fulfilled the 1997 American College of Rheumatology (ACR) or the 2012 Systemic Lupus International Collaboration Clinic Classification (SLICC) Criteria for SLE were followed every 3 months, with SLE disease activity assessed by using SLEDAI-2K, and disease flares defined and captured by the SELENA-SLEDAI Flare Index (SFI). NLR and PLR were computed from the automated machine-counted blood count differentials. Linear mixed model and generalized estimating equation model were constructed to analyze the associations between NLR/PLR and SLEDAI-2K and disease flares, with multivariate adjustments.ResultsOf 290 patients recruited, the median (IQR) duration of follow-up and baseline SLEDAI-2K were 4.7 (3.2–6.1) years and 2 (0.5–3.5), respectively. On multivariable analyses, NLR was shown to be positively and significantly associated with SLEDAI-2K (estimate of coefficient (β) = 0.05, P < 0.01) and severe disease flares (odds ratio [OR] 1.05, P < 0.05), but not with overall disease flares [OR 1.02, non-significant]. While PLR was shown to be positively associated with SLEDAI-2K [β = 0.09, P < 0.05], no statistically significant association between PLR and overall or severe disease flares was found [OR 1.00 and OR 1.06 respectively, non-significant].ConclusionDerived readily from automated blood count differentials, the NLR potentially serves as a surrogate prospective marker of disease activity and severe disease flares in SLE patients.     

Adjuvant trastuzumab without chemotherapy for treating early HER2-positive breast cancer in older patients: A propensity score-adjusted analysis of a prospective cohort study

PurposeTo gauge the effects of treatment practices on prognosis for older patients with HER2-positive early breast cancer, particularly to determine whether adjuvant trastuzumab alone can offer benefit over no adjuvant therapy. This is a prospective cohort study which accompanies the RESPECT that is a randomized-controlled trial (RCT).MethodsPatients who declined the RCT were treated based on the physician's discretion. We studied the 1) trastuzumab-plus-chemotherapy group, 2) trastuzumab-monotherapy group, and 3) non-trastuzumab group (no therapy or anticancer therapy without trastuzumab). The primary endpoint was disease-free survival (DFS), which was compared using the propensity-score method. Relapse-free survival (RFS) and health-related quality of life (HRQoL) were assessed.ResultsWe enrolled 123 patients aged over 70 years (median: 74.5). Treatment categories were: trastuzumab-plus-chemotherapy group (n = 36, 30%), trastuzumab-monotherapy group (n = 52, 43%), and non-trastuzumab group (n = 32, 27%). The 3-year DFS was 96.7% in trastuzumab-plus-chemotherapy group, 89.2% in trastuzumab-monotherapy group, and 82.5% in non-trastuzumab group. DFS in non-trastuzumab group was lower than in trastuzumab-plus-chemotherapy and trastuzumab-monotherapy groups (propensity-adjusted hazard ratio; HR: 3.29; 95% CI: 1.15–9.39; P = 0.026). The RFS in non-trastuzumab group was lower than in trastuzumab-plus-chemotherapy and trastuzumab-monotherapy groups (propensity-adjusted HR = 7.80; 95% CI: 2.32–26.2, P < 0.0001). There were no significant intergroup differences in the proportions of patients showing HRQoL deterioration at 36 months (P = 0.717).ConclusionTrastuzumab-treated patients had better prognoses than patients not treated with trastuzumab without deterioration of HRQoL. Trastuzumab monotherapy could be considered for older patients who reject chemotherapy.     

Contralateral parenchymal enhancement on MRI is associated with tumor proteasome pathway gene expression and overall survival of early ER+/HER2-breast cancer patients

PurposeTo assess whether contralateral parenchymal enhancement (CPE) on MRI is associated with gene expression pathways in ER+/HER2-breast cancer, and if so, whether such pathways are related to survival.MethodsPreoperative breast MRIs were analyzed of early ER+/HER2-breast cancer patients eligible for breast-conserving surgery included in a prospective observational cohort study (MARGINS). The contralateral parenchyma was segmented and CPE was calculated as the average of the top-10% delayed enhancement. Total tumor RNA sequencing was performed and gene set enrichment analysis was used to reveal gene expression pathways associated with CPE (N = 226) and related to overall survival (OS) and invasive disease-free survival (IDFS) in multivariable survival analysis. The latter was also done for the METABRIC cohort (N = 1355).ResultsCPE was most strongly correlated with proteasome pathways (normalized enrichment statistic = 2.04, false discovery rate = .11). Patients with high CPE showed lower tumor proteasome gene expression. Proteasome gene expression had a hazard ratio (HR) of 1.40 (95% CI = 0.89, 2.16; P = .143) for OS in the MARGINS cohort and 1.53 (95% CI = 1.08, 2.14; P = .017) for IDFS, in METABRIC proteasome gene expression had an HR of 1.09 (95% CI = 1.01, 1.18; P = .020) for OS and 1.10 (95% CI = 1.02, 1.18; P = .012) for IDFS.ConclusionCPE was negatively correlated with tumor proteasome gene expression in early ER+/HER2-breast cancer patients. Low tumor proteasome gene expression was associated with improved survival in the METABRIC data.     

Pregnancy associated breast cancer (PABC): Report from a gestational cancer registry from a tertiary cancer care centre,India

BackgroundPregnancy associated breast cancer (PABC) is a rare entity and defined as breast cancer diagnosed during pregnancy or one-year post-partum. There is sparse data especially from low and middle-income countries (LMIC) and merits exploration.MethodsThe study (2013–2020) evaluated demographics, treatment patterns and outcomes of PABC.ResultsThere were 104 patients, median age of 31 years; 43 (41%) had triple-negative disease, 31(29.8%) had hormone-receptor (HR) positive and HER2 negative, 14 (13.5%) had HER2-positive and HR negative and 16(15.4%) had triple positive disease. 101(97%) had IDC grade III tumors and 74% had delayed diagnosis. 72% presented with early stage (24, EBC) or locally advanced breast cancer (53, LABC) and received either neoadjuvant (n = 49) or adjuvant (n = 26) chemotherapy and surgery. Trastuzumab, tamoxifen, and radiotherapy were administered post-delivery. At a median follow up of 27 (IQR:19–35) months, the estimated 3-year event-free survival (EFS) for EBC and LABC was 82% (95% CI: 65.2–100) and 56% (95% CI: 42–75.6%) and for metastatic 24% (95% CI: 10.1%–58.5%) respectively.Of the 104 patients, 34 were diagnosed antepartum (AP) and 15 had termination, 2 had preterm and 16 had full-term deliveries(FTDs). Among postpartum cohort (n = 70), 2 had termination, 1 had preterm, 67 had FTDs. 83(including 17 from AP) children from both cohorts were experiencing normal milestones.ConclusionData from the first Indian PABC registry showed that the majority had delayed diagnosis and aggressive features(TNBC, higher grade). Treatment was feasible in majority and stage matched outcomes were comparable to non-PABCs.     

The Usefulness of the Pretreatment Neutrophil/Lymphocyte Ratio as a Predictor of the 5-Year Survival in Stage 1–3 Triple Negative Breast Cancer Patients

BackgroundWe have previously shown that the neutrophil/lymphocyte ratio (NLR) is a predictor of survival among breast cancer patients. The aim of this study was to determine the predictive value of NLR among different nodal and chemotherapy subgroups of triple negative breast cancer (TNBC).MethodsPatients with stage 1–3 TNBC who underwent treatment from 2007 to 2014 and had blood counts prior to treatments were included. Patients were categorized into high (≥2) and low (<2) NLR groups. Primary outcomes were overall survival (OS) and disease-free survival (DFS).ResultsThe average follow-up time was 54 months. The high NLR group had worse OS (HR 2.8, CI 1.3–5.9, p < 0.001) and DFS (HR 2.3, CI 1.2–4.2, p < 0.001) than the low NLR group. After adjusting for confounding variables, high NLR was an independent prognostic factor for both OS (HR 5.5, CI 2.2–13.7, p < 0.0001) and DFS (HR 5.2, CI 2.3–11.6, p < 0.0001). Categorization of TNBC patients by NLR (high vs. low) and nodal status (positive vs. negative) resulted in four groups with significantly different OS and DFS (log rank p < 0.0001). Significant improvements in OS (p < 0.001) and DFS (p < 0.001) were observed for patients who received chemotherapy and had high NLR but not for patients with low NLR (p = 0.65 and p = 0.07, respectively).ConclusionHigh pretreatment NLR is an independent predictor of poor OS and DFS among TNBC patients. Combining NLR and pN provides better risk stratification for TNBC patients. Chemotherapy appears to be beneficial only in patients with high NLR. Larger prospective studies are needed to validate these findings.     

Role of Systemic Inflammatory Markers in Pediatric Kidney Transplantation

BackgroundNeutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), systemic immune-inflammation index (SII = N × P/L), and neutrophil percentage-albumin ratio (NPAR) have become accepted markers of inflammation in recent years. These indices are used as indicators of disease activity, mortality, and morbidity in many diseases. This study evaluated the relationship between inflammatory indices and graft function in pediatric kidney transplant recipients.MethodsMedical records of pediatric patients who underwent kidney transplantation at Ege University between 1995 and 2020 were reviewed retrospectively. Demographic, clinical, and laboratory data were recorded during the third month, first year, and fifth year of transplantation and at the last visit.ResultsThe median age of the 119 patients (60 boys/59 girls) at the time of transplantation was 154 months, and the median follow-up period was 101 months. According to Spearman correlation analysis, patients' final creatinine levels were positively correlated with NLR (r = 0.319), PLR (r = 0.219), SII (r = 0.214), and NPAR (r = 0.347) of the last visit; final estimate glomerular filtration rate levels were negatively correlated with NLR (P = .010, r = −0.250) and NPAR (P = .004, r = −0.277). The median NPAR of the patients with chronic allograft dysfunction at the last visit was found to be statistically significantly higher than without (P = .032).ConclusionNLR, PLR, SII, and NPAR values are correlated with creatinine levels after 5 years of kidney transplantation. The NPAR and final creatinine levels had the highest correlation coefficient among these inflammatory markers. These results suggest that inflammatory markers, especially NPAR, may be a candidate to be an indicator of ongoing inflammation in the graft.     

Impact of the neutrophil-to-lymphocyte ratio as a surgical prognostic factor in renal cell carcinoma with inferior-vena-cava tumor thrombus

BackgroundThe aim of this study is to evaluate the efficacy of radical nephrectomy with thrombectomy and to identify the prognostic factors for patients with renal cell carcinoma (RCC) and inferior vena cava tumor thrombus (IVCTT). The role of the neutrophil-to-lymphocyte ratio (NLR), which has been reported to be a useful prognostic predictor for various solid cancers, was also investigated.MethodsFifty-five patients with RCC and IVCTT who underwent radical nephrectomy and thrombectomy in our hospital were retrospectively analyzed. The relationship between clinical characteristics and surgical outcome was examined using the Kaplan–Meier method. Univariate and multivariate analyses were carried out to determine the prognostic factors.ResultsThe median follow-up time after surgery was 44.2 months. Twenty-seven patients died of RCC, and 4 died of other disease at last follow-up. There were no patients with postoperative pulmonary embolism (PE) or deaths from PE. The median cancer-specific survival (CSS) and overall survival (OS) were 81.0 (95% confidence interval [CI]: 42.0–103.2) and 69.0 (95% CI: 34.3–81.5) months, respectively. Significant prognostic factors for CSS were distant metastasis (p = 0.045) and NLR ≥ 2.9 (p = 0.009). The only independent predictor for OS was the NLR ≥ 2.9 (p = 0.034).ConclusionsA high preoperative NLR level was an independent poor prognostic factor influencing CSS and OS of patients with RCC and IVCTT who underwent radical nephrectomy and thrombectomy. The NLR may be an available biomarker that helps with preoperative risk stratification.     

Prognostic implications of lobular breast cancer histology: New insights from a single hospital cross-sectional study and SEER data

BackgroundInvasive lobular breast cancer (ILC) is generally believed to have an increased risk for late relapse compared to invasive ductal breast cancer (IDC). However, the study most often referred to is a chemotherapy trial that mainly included node positive patients. We hypothesize that nodal status may influence the hazard of relapse since time of diagnosis differently in invasive ductal carcinoma (IDC) and ILC.MethodsPrimary operable breast cancer patients from our institution diagnosed between 2000 and 2009 were studied. Multivariable analysis and subgroup analyses were performed to assess whether ILC carries a different prognosis compared to IDC. SEER data were used for external validation.ResultsIn lymph node negative patients, ILC carries a better prognosis regarding distant metastasis free interval (DMFI) (HR 3.242 (1.380–7.614), p = 0.0069) with a trend towards improved breast cancer specific survival (BCSS), over the entire study frame (UZ Leuven data). In lymph node positive patients, both DMFI (HR 0.466 (0.309–0.703), p = 0.0003) and BCSS (HR 0.441 (0.247–0.788), p = 0.0057) are significantly worse for ILC, especially after longer follow-up (>4–5 years) (UZ Leuven data). Similar results were found in the SEER cohort. Results remained identical when excluding screen detected cases (data not shown).ConclusionThe prognostic impact of lobular histology not only depends on time since diagnosis but also on nodal status. The general believe that ILC have compromised late-term outcome compared to IDC seems untrue for the majority ( = node negative) of ILCs.