Decreased core muscle size is associated with worse patient survival following esophagectomy for cancer

Preoperative risk assessment, particularly for patient frailty, remains largely subjective. This study evaluated the relationship between core muscle size and patient outcomes following esophagectomy for malignancy. Using preoperative computed tomography scans in 230 subjects who had undergone transhiatal esophagectomy for cancer between 2001 and 2010, lean psoas area (LPA), measured at the fourth lumbar vertebra, was determined. Cox proportional hazards regression was employed to analyze overall survival (OS) and disease‐free survival (DFS) adjusted for age, gender, and stage, and the Akaike information criterion was used to determine each covariate contribution to OS and DFS. Univariate analysis demonstrated that increasing LPA correlated with both OS (P = 0.017) and DFS (P = 0.038). In multivariate analysis controlling for patient and tumor characteristics, LPA correlated with OS and DFS in patients who had not received neoadjuvant treatment (n = 64), with higher LPA associated with improved OS and DFS. Moreover, LPA was of equivalent, or slightly higher importance than pathologic stage. These measures were not predictive among patients (n = 166) receiving neoadjuvant chemoradiation. Core muscle size appears to be an independent predictor of both OS and DFS, as significant as tumor stage, in patients following transhiatal esophagectomy. Changes in muscle mass related to preoperative treatment may confound this effect. Assessment of core muscle size may provide an additional objective measure for risk stratification prior to undergoing esophagectomy.     

Preoperative level of serum amyloid A is superior to C‐reactive protein in the prognosis of esophageal squamous cell carcinoma

Preoperative elevations in the levels of serum amyloid A (SAA) or C‐reactive protein (CRP) have been reported to be prognostic indicators in several malignancies. The aim of this study is to evaluate the serum levels of SAA and CRP in the prognosis of esophageal squamous cell carcinoma (ESCC). In total, 252 patients with ESCC who had undergone surgery with curative‐intent were retrospectively recruited. The specificity, sensitivity, and prognostic value of SAA or CRP levels were measured as the area under the receiver operating characteristic (ROC) curve (AUC). The clinical value of SAA and CRP levels as prognostic indicators was evaluated using Cox's proportional hazards model. The 1‐, 3‐, and 5‐year overall survival (OS) rates for the entire cohort of patients with ESCC were 71.0%, 61.0%, and 43.0%, respectively. The correlation between the levels of SAA and CRP was significant (r² = 0. 685, P < 0.001). The ROC analysis showed that the levels of CRP were associated with a significantly lower overall accuracy than were the SAA levels (AUC, 0.615 vs. 0.880; P < 0.001). For the complete cohort, the median OS was 52.0 months longer in patients with low preoperative serum levels of SAA (72.0 months) compared with patients who had high SAA levels (20.0 months, P < 0.001). The median OS among patients with low CRP levels was also longer compared with the patients who had high CRP levels (72.0 vs. 51.0 months, respectively; P < 0.001). Subgroup analyses showed that the preoperative elevated levels of SAA could find significant differences in OS for stage I, stage II, and stage III (P < 0.001, P = 0.001, and P < 0.001, respectively), whereas the increased levels of CRP could only find a difference in OS for stage II cancers. After a multivariate analysis, preoperative elevated level of SAA was found to be an independently and significant prognostic factor (P < 0.001). Our study indicates that the preoperative levels of SAA and CRP can act as prognostic factors, and that elevated levels of these proteins are associated with negative effects on the survival of patients with ESCC. SAA showed a higher prognostic value than CRP in both cohort and subgroup analysis.     

Association between the thoroughness of the histopathological examination and survival in patients with esophageal squamous cell carcinoma who achieve pathological complete response after chemoradiotherapy

The College of American Pathologists guidelines recommend examining at least four representative tumor blocks for determining pathological T stage in patients with primarily resected esophageal cancer. Whether the same pathological requirements are adequate in patients undergoing esophagectomy following neoadjuvant chemoradiotherapy (nCRT) remains unclear. We hypothesized that current examination protocols may underestimate the presence of microscopical residual disease after nCRT, potentially leading to under‐staging. We retrospectively reviewed the records of patients with esophageal squamous cancer (ESCC) who were diagnosed as having pathological complete response (pCR) following nCRT. The thoroughness of the pathological examination in pCR patients was examined using (i) the number of blocks examined in suspicious tumor area (≤4 vs. >4), and (ii) the block quotient (calculated as the pretreatment tumor length divided by the number of blocks examined in suspicious tumor area). A total of 91 patients were enrolled. The mean number of blocks used to confirm pCR was 4.8 (range: 2–14). The 5‐year overall survival (OS) and disease‐free survival (DFS) in the entire cohort were 55% and 65%, respectively. Multivariate analyses identified the block quotient as the only independent predictor of OS and DFS. Receiver operating characteristic curve analysis indicated an optimal cutoff value of 1.4 for the block quotient. Among the patients who achieved pCR, the 5‐year DFS differed significantly between subjects with a low (≤1.4) or high (>1.4) block quotient (76% vs. 47%, respectively, P = 0.03). The block quotient (calculated by the pretreatment tumor length divided by the number of blocks) – which reflects the meticulousness of the histopathological examination for confirming pCR – is associated with survival in ESCC patients.     

Monocytosis in polycythemia vera: Clinical and molecular correlates

Monocytosis (absolute monocyte count, AMC ≥ 1 × 10⁹/L) might accompany a spectrum of myeloid neoplasms, other than chronic myelomonocytic leukemia (CMML). In the current study, we examined the prevalence, laboratory and molecular correlates, and prognostic relevance of monocytosis in polycythemia vera (PV). Among 267 consecutive patients with World Health Organization (WHO)‐defined PV, 55 (21%) patients displayed an AMC of ≥1 × 10⁹/L and 18 (7%) an AMC of ≥1.5 × 10⁹/L. In general, PV patients with monocytosis were significantly older and displayed higher frequencies of leukocytosis (81% vs. 50% at AMC ≥1 × 10⁹/L) and TET2/SRSF2 mutations (57%/29% vs. 19%/1% at AMC ≥ 1.5 × 10⁹/L). In univariate analysis, AMC ≥1.5 × 10⁹/L adversely affected overall (OS; P = .004; HR 2.6, 95% CI 1.4‐4.8) and myelofibrosis‐free (MFFS; P = .02; HR 4.4, 95% CI 1.3‐15.1) survival; during multivariable analysis, significance was borderline sustained for OS (P = .05) and MFFS (P = .06). Other independent risk factors for OS included unfavorable karyotype (P = .02, HR 3.39, 95% CI 1.17‐9.79), older age (P < .0001, HR 3.34 95% CI 1.97‐5.65), and leukocytosis ≥15 × 10⁹/L (P = .004, HR 2.04, 95% CI 1.26‐3.29). In conclusion, in the current study, we encountered a higher than expected prevalence of monocytosis in patients with PV and the mutation profile and age distribution of PV patients with monocytosis is akin to those of patients with CMML and might partly contribute to their worse prognosis.     

Original article: Upregulation of caspase‐3 expression in esophageal cancer correlates with favorable prognosis: an immunohistochemical study from a high incidence area in northern China

Caspase‐3 plays an important role as the key effector during apoptosis, but there are very few studies of caspase‐3 in esophageal squamous cell carcinoma (ESCC). The purpose of this study was to investigate the expression and prognostic significance of caspase‐3 in ESCC from Linzhou City, a high incidence area in northern China. All 64 patients underwent esophagectomy for ESCC between January 2002 and December were enrolled in this study. Caspase‐3 expression was assessed by immunohistochemistry (IHC) in primary ESCC and paired normal esophageal epithelium. The positive rate of caspase‐3 expression was higher in ESCC than in normal esophageal epithelium (79.7% vs. 50.0%, Chi‐square = 12.372, P= 0.001). Caspase‐3 expression was correlated with tumor cell differentiation (Phi = 0.717, P < 0.001), tumor infiltration depth (Phi =?0.334, P= 0.008), and pathologic TNM (pTNM) staging (rs =?0.268, P= 0.032). Patients in caspase‐3 positive group had a significantly better 5‐year overall survival than those in the negative group (77.4% vs. 35.9%, χ²= 7.344, P= 0.007). Our results showed that caspase‐3 expression was upregulated in ESCC compared with normal esophageal epithelium in population of Chinese high incidence area, and patients with caspase‐3 positive expression had better prognosis. Therefore, caspase‐3 immunostaining could be a simple and useful tool for predicting survival in ESCC patients.     

Allogeneic hematopoietic stem cell transplantation could improve survival of cytogenetically normal adult acute myeloid leukemia patients with DNMT3A mutations

DNMT3A mutations are frequent in cytogenetically normal acute myeloid leukemia (cn‐AML) patients and associated with poor survival. The role of allogeneic hematopoietic stem cell transplantation (allo‐HSCT) in DNMT3A^mut cn‐AML patients remains unclear. In this study, we retrospectively analyzed the prognostic impact of DNMT3A mutations and explored the role of allo‐HSCT in 308 cn‐AML patients who received consolidation of intensive chemotherapy or allo‐HSCT in our center from March 2005 to May 2014. In the whole cohort, 63 patients (20.5%) were identified with DNMT3A exon 23 mutations and R882H was the most frequent variant. DNMT3A^mut patients had shorter overall survival (3‐year OS: 31.9% vs. 52.0%, P = 0.009) and disease‐free survival (3‐year DFS: 21.8% vs. 40.1%, P = 0.004) compared with DNMT3A^wt patients. Based on FLT3/NPM1/CEBPA mutations, 308 cn‐AML patients were divided into favorable/intermediate group (n = 262) and unfavorable group (n = 46). There were no significant differences in 3‐year OS and 3‐year DFS between DNMT3A^mut and DNMT3A^wt patients in both favorable/intermediate and unfavorable groups. Additionally, in multivariate analysis, DNMT3A mutation remained an independent adverse prognostic factor for the survival. In the DNMT3A^mut cohort, 23 complete remission (CR) patients received allo‐HSCT consolidation and 32 CR patients received chemotherapy consolidation, dramatic differences were observed in 3‐year OS (51.7% vs. 28.9%, P = 0.048) and 3‐year DFS (41.6% vs. 14.9%, P = 0.024) between allo‐HSCT group and chemotherapy group. Collectively, DNMT3A mutation is a poor prognostic factor for cn‐AML patients and allo‐HSCT could improve survival of cn‐AML patients with DNMT3A mutations. Am. J. Hematol. 90:992–997, 2015. © 2015 Wiley Periodicals, Inc.     

Absolute monocyte and lymphocyte count prognostic score for patients with gastric cancer

AIM:To measure the prognostic significance of absolute monocyte count/absolute lymphocyte count prognostic score(AMLPS) in patients with gastric cancer.METHODS:We retrospectively examined the combination of absolute monocyte count(AMC) and absolute lymphocyte count(ALC) as prognostic variables in a cohort of 299 gastric cancer patients who underwent surgical resection between 2006 and 2013 and were followed at a single institution.Both AMC and ALC were dichotomized into two groups using cut-off points determined by receiving operator characteristic curve analysis.An AMLPS was generated,which stratified patients into three risk groups:low risk(both low AMC and high ALC),intermediate risk(either high AMC or low ALC),and high risk(both high AMC and low ALC).The primary objective of the study was to validate the impact of AMLPS on both disease-free survival(DFS) and overall survival(OS),and the second objective was to assess the AMLPS as an independent prognostic factor for survival in comparison with known prognostic factors.RESULTS:Using data from the entire cohort,the most discriminative cut-off values of AMC and ALC selected on the receiver operating characteristic curve were 672.4/μL and 1734/μL for DFS and OS.AMLPS risk groups included 158(52.8%) patients in the lowrisk,128(42.8%) in the intermediate-risk,and 13(4.3%) in the high-risk group.With a median followup of 37.2 mo(range:1.7-91.4 mo),five-year DFS rates in the low-,intermediate-,and high-risk groups were 83.4%,78.7%,and 19.8%,respectively.And fiveyear OS rates in the low-,intermediate-,and high-risk groups were 89.3%,81.1%,and 14.4%,respectively.On multivariate analysis performed with patient- and tumor-related factors,we identified AMLPS,age,and pathologic tumor-node-metastasis stage as the most valuable prognostic factors impacting DFS and OS.CONCLUSION:AMLPS identified patients with a poor DFS and OS,and it was independent of age,pathologic stage,and various inflammatory markers.     

The duration of systemic inflammatory response syndrome is a reliable indicator of long-term survival after curative esophagectomy for esophageal squamous cell carcinoma

Background

We focused on the Systemic Inflammatory Response Syndrome (SIRS) duration after surgery for esophageal squamous cell carcinoma (ESCC) as the prognostic marker.

Methods

We enrolled a total of 222 patients with local ESCC, who underwent curative esophagectomy between 2005 and 2015. SIRS was diagnosed according to the criteria as a condition involving two or more of the following factors after surgery: (a) body temperature of?>?38 °C or?<?36 °C; (b) heart rate?>?90 beats/min; (c) respiratory rate?>?20 breaths/min (d) WBC count?>?12,000 or?<?4000 cells/mm³. We defined SIRS duration as the total sum of the days defined as SIRS conditions during 7 days after surgery. The SIRS duration was analyzed by Cox hazards modeling to determine the independent prognostic factors for overall survival (OS) and Cancer-specific survival (CSS).

Results

The cutoff point of SIRS duration was determined to be set at 5.0 days according to the receiver operating characteristic (ROC) curve, which was plotted using 5-year OS as the endpoint. Of the 222 patients, 165 (74.4%) and 57 (25.6%) were classified as having short (<?5.0) and long (≥?5.0) SIRS, respectively. The long SIRS was significantly associated with postoperative pneumonia (Hazard Ratio (HR):9.07; P?<?0.01), great amount of blood loss during surgery (HR: 2.20: P?=?0.04), preoperative high CRP value (HR: 2.45: P?=?0.04) and preoperative low albumin (HR: 2.79: P?=?0.03) by logistic-regression multivariate analysis. Cox Hazard Multivariate analyses revealed that long SIRS was a worse prognostic factor for OS (HR: 2.36; 95% Confidence Interval (CI):1.34–4.20, P?<?0.01) and CSS (HR: 2.07; 95% CI:1.06–4.06, P?=?0.03), while postoperative pneumonia and postoperative high CRP value were not worse prognostic factors for OS and CSS.

Conclusion

SIRS duration is a more reliable prognostic marker than the development of pneumonia and high postoperative CRP value after surgery for ESCC. The surgeons should aim to reduce the SIRS duration to improve the prognosis of ESCC patients.

     

Prognostic impact of immune status and hematopoietic recovery before and after fludarabine,IV busulfan,and antithymocyte globulins (FB2 regimen) reduced‐intensity conditioning regimen (RIC) allogeneic stem cell transplantation (allo‐SCT)

This retrospective analysis aimed to assess hematopoietic and immune recovery in a cohort of 53 patients [males: n = 33; median age: 59 yr (range: 22–70)] who received a FB2 (fludarabine 120–150 mg/m² + IV busulfan 6.4 mg/kg + antithymocyte globulin thymoglobulin 5 mg/kg) reduced‐intensity conditioning (RIC) allo‐stem cells transplantations (SCT). With a median follow‐up of 19 months (range: 2–53), the 2‐yr overall survival, disease‐free survival (DFS), relapse incidence, and non‐relapse mortality were 63%, 59.5%, 35%, and 6%, respectively. In univariate analysis, the factors correlated with a significantly higher 2‐yr OS and DFS were a higher total circulating lymphocytes count at transplant (>730/mm³; OS: 81% vs. 43%, P = 0.02; DFS: 73% vs. 45.5%, P = 0.03) and a higher recovery of leukocytes (>5300/mm³) (2‐yr OS: 81% vs. 44%, P = 0.007; 2‐yr DFS: 72% vs. 46%, P = 0.08), neutrophils (>3200/mm³) (2‐yr OS: 76% vs. 50%, P = 0.03; 2‐yr DFS: 67% vs. 52.0%, P = 0.1), and monocytes (>590/mm³; 2‐yr OS: 80% vs. 45%, P = 0.004; 2‐yr DFS: 76% vs. 42%, P = 0.01) at day +30 post‐transplant. In multivariate analysis, the only independent factors associated with a significantly higher OS and DFS were a better immune status at transplant (lymphocytes count >730/mm³) and a higher monocytes count (>590/mm³) at day +30 post‐transplant. These results suggest that immune status and hematopoietic recovery before and after FB2 RIC allo‐SCT can be significant predictors of outcome. This paves the way for future studies aiming to closely monitor the kinetics of immune recovery after RIC allo‐SCT and to evaluate the impact of growth factors and other immunostimulatory cytokines in the setting of RIC allo‐SCT.     

Impact of body mass index on postoperative complications and long‐term survival in patients with esophageal squamous cell cancer

Undernutrition and cachexia have been suggested to be risk factors for postoperative complications and survival in cancer patients. The aim of this study was to investigate whether body mass index (BMI) is related to the short‐term and long‐term outcomes in patients who undergo an esophagectomy for the resection of esophageal squamous cell cancer (ESCC). Three hundred forty patients who underwent an esophagectomy for the resection of ESCC between 2003 and 2008 were retrospectively reviewed. The patients were divided into two groups: an L‐BMI group characterized by a BMI < 18.5 kg/m² and an N‐BMI group characterized by a BMI ≥ 18.5 kg/m². Clinical and pathological outcome were compared between groups. The study included 40 patients in the L‐BMI group and 300 patients in the N‐BMI group. A clinicopathological assessment showed that nodal involvement was seen more frequently in the L‐BMI group (P = 0.016). Pulmonary complications seemed to occur more frequently in the L‐BMI group (P = 0.006). The 5‐year overall survival rate was higher in the N‐BMI group (63.6%) than in the L‐BMI group (32.3%) (P < 0.001). The 5‐year disease‐free survival rate was also higher in the N‐BMI group (58.0%) than in the L‐BMI group (33.6%) (P = 0.001). In multivariate analysis, the BMI (hazard ratio, 2.154; 95% CI, 1.349–3.440, P = 0.001) was found to be an independent prognostic factor for overall survival. Our data suggested that a lower BMI not only increased pulmonary complications but also impaired overall and disease‐free survival after an esophagectomy for the resection of ESCC.     

Prechemotherapy neutrophil : lymphocyte ratio is superior to the platelet : lymphocyte ratio as a prognostic indicator for locally advanced esophageal squamous cell cancer treated with neoadjuvant chemotherapy

The study aimed to evaluate the prognostic significance of prechemotherapy neutrophil to lymphocyte ratio and platelet to lymphocyte ratio, and preoperative neutrophil to lymphocyte ratio and platelet to lymphocyte ratio in locally advanced esophageal squamous cell cancer. We analyzed retrospectively locally advanced esophageal squamous cell cancer patients who had received neoadjuvant chemotherapy before undergoing a radical esophagectomy between 2009 and 2012. Neutrophil to lymphocyte ratio and platelet to lymphocyte ratio before chemotherapy and before the surgery were calculated. Univariate analyses showed that prechemotherapy neutrophil to lymphocyte ratio >5 (P = 0.048, hazard ratio = 2.86; 95% confidence interval: 1.01–8.12) and prechemotherapy platelet to lymphocyte ratio >130 (P = 0.025, hazard ratio = 5.50; 95% confidence interval: 1.23–24.55) were associated significantly with overall survival (OS), and prechemotherapy platelet to lymphocyte ratio >130 (P = 0.026, hazard ratio = 3.18; 95% confidence interval: 1.15–8.85) was associated significantly with progression‐free survival. However, only prechemotherapy neutrophil to lymphocyte ratio >5 (P = 0.024, hazard ratio = 3.50; 95% confidence interval: 1.18–10.40) remained significantly associated with OS in multivariate analyses. Neither preoperative neutrophil to lymphocyte ratio nor platelet to lymphocyte ratio was associated with OS or progression‐free survival. The prechemotherapy neutrophil to lymphocyte ratio >5 to preoperative neutrophil to lymphocyte ratio ≤5 group showed significantly worse OS than the prechemotherapy neutrophil to lymphocyte ratio ≤5 to preoperative neutrophil to lymphocyte ratio ≤5 group (P = 0.050). The prechemotherapy platelet to lymphocyte ratio >130 to preoperative platelet to lymphocyte ratio ≤130 group (P = 0.016) and platelet to lymphocyte ratio >130 to preoperative platelet to lymphocyte ratio >130 group (P = 0.042) showed significantly worse OS than the prechemotherapy platelet to lymphocyte ratio ≤30 to preoperative platelet to lymphocyte ratio ≤130 group. In conclusions, prechemotherapy neutrophil to lymphocyte ratio is an independent prognostic factor for OS in patients with advanced esophageal squamous cell cancer treated with neoadjuvant chemotherapy, and, as an adverse prognostic predictor, increased prechemotherapy neutrophil to lymphocyte ratio is superior to platelet to lymphocyte ratio. Maintaining a low neutrophil to lymphocyte ratio and platelet to lymphocyte ratio throughout treatment is a predictor of better OS.     

Relationship between obesity and clinical outcome in adults with acute myeloid leukemia: A pooled analysis from four CALGB (alliance) clinical trials

Obesity has been previously suggested as an adverse prognostic marker in patients with acute leukemia. To evaluate the relationship between obesity and clinical outcome, disease‐free survival (DFS) and overall survival (OS), in patients with acute myelogenous leukemia (AML), including acute promyelocytic leukemia (APL), we performed a pooled analysis of four CALGB (Alliance) clinical trials. Our study included 446 patients with APL from CALGB 9710, and 1,648 patients between 18 and 60 years of age with non‐APL AML from CALGB 9621, 10503, and 19808. Obesity was defined as BMI ≥30 kg/m². Multivariate Cox proportional‐hazard regression models were fitted for DFS and OS. Obesity was seen in 50% and 38% of APL and non‐APL AML patients, respectively. In APL patients, obesity was associated with worse DFS (HR 1.53, 95% CI 1.03–2.27; P = 0.04) and OS (HR 1.72, 95% CI 1.15–2.58; P = 0.01) after adjusting for age, sex, performance status, race, ethnicity, treatment arm and baseline white blood cell count. Obesity was not significantly associated with DFS or OS in the non‐APL AML patients. In conclusion, our study indicates that obesity has significant prognostic value for DFS and OS in APL patients, but not for non‐APL AML patients. Am. J. Hematol. 91:199–204, 2016. © 2015 Wiley Periodicals, Inc.     

Membrane PKC-beta 2 protein expression predicts for poor response to chemotherapy and survival in patients with diffuse large B-cell lymphoma

The protein kinase C (PKC) plays an important role in the activation and survival of B cells. The purpose of this study was to analyze the clinical significance of PKC-beta 2 protein expression in patients with diffuse large B-cell lymphoma (DLBCL). Tumors from 76 patients with DLBCL who received anthracycline-containing chemotherapy were examined for PKC-beta 2 protein expression by immunohistochemistry. Twenty-six cases (34%) were positive for PKC-beta 2 protein, and 50 (66%) were negative. Patients with PKC-beta-2-positive tumors showed a lower complete remission rate (31 vs 62%; P=0.015) and a lower 5-year disease-free survival (DFS) (30 vs 60%; P=0.03) than the PKC-beta-2-negative group. Overall survival (OS) was significantly lower in patients with the membranous staining pattern of PKC-beta 2 protein when compared to those with PKC-beta-2-negative tumors (14 vs 64%; P=0.005). In patients with low international prognostic index (IPI), those with tumors showing membrane expression of PKC-beta 2 had a significantly inferior DFS and OS (0 vs 79%, P=0.003; 25 vs 80%; P=0.01) compared to PKC-beta-2-negative tumors. In multivariate analysis for OS, the membrane staining of PKC-beta 2 is the strongest independent adverse prognostic factor (OR=3.4, P=0.011). Our results suggest that membrane expression of PKC-beta 2 protein on DLBCL predicts for poor survival, especially in patients with low IPI.     

Long-term survival after induction therapy with idarubicin and cytosine arabinoside for de novo acute myeloid leukemia

 We treated 153 patients with de novo acute myeloid leukemia (AML) with two induction courses of conventional-dose cytosine arabinoside (ara-C) and idarubicin (AIDA) followed by either a third course of AIDA, high-dose ara-C or bone-marrow transplantation. The complete remission (CR) rate for all patients was 63.4%, with a higher CR rate for patients with a normal (versus unfavorable) karyotype (73.2% vs 52.5%;P=0.038). The probability of overall survival (OS) was 30.7% after 5 years (26.3% after 7 years). Improved OS at 5 years could be observed for patients up to 50 years old versus patients older than 50 years of age (37.6% vs 19.9%;P=0.001) and patients with a normal (versus unfavorable) karyotype (42.9% vs 14.1%;P=0.0016). Disease-free survival (DFS) after 5 years was 33.2% for all 97 CR patients and was significantly better for patients with a normal (versus unfavorable) karyotype (44.3% vs 12.3%;P=0.003). Multivariate analysis revealed that the age for OS (P<0.02) and the karyotype for both OS (P<0.03) and DFS (P<0.05) were independent prognostic factors. In conclusion, AIDA is an effective and well-tolerated induction regimen (even in elderly patients) with a 5-year survival of more than 30% when combined with ara-C-containing postremission therapy. The karyotype is the most powerful prognostic factor for predicting the outcome of patients treated with this protocol. Received: 10 December 1999 / Accepted: 25 February 2000     

Prognostic value of preoperative platelet–lymphocyte and neutrophil–lymphocyte ratio in patients undergoing surgery for esophageal squamous cell cancer

Increasing evidence has suggested that the host inflammatory status is associated with prognosis of several solid tumors. Preoperative platelet–lymphocyte ratio (PLR) and neutrophil–lymphocyte ratio (NLR), both acquired from routine blood tests, can reflect the status of systematic inflammation. However, whether they are correlated with clinical outcomes of esophageal carcinoma is still unknown. The purpose of this study was to determine the prognostic value of preoperative PLR and NLR in patients with resected esophageal squamous cell carcinoma (ESCC). Preoperative PLR and NLR were evaluated in 317 eligible ESCC patients from September 2008 to December 2010. Receiver operating characteristic curves were applied to establish optimal cutoff points. The prognostic values of PLR and NLR were determined by both univariate and multivariate analyses. The optimal cutoff value of preoperative PLR and NLR were 103.0 and 2.1, respectively. One hundred and ninety‐seven (62.1%) patients showed high level of preoperative PLR, while 148 (46.7%) patients showed high level of preoperative NLR. Both elevated PLR (P < 0.001) and NLR (P = 0.009) were correlated with poor disease‐specific survival in univariate analysis. However, only preoperative PLR (P = 0.003) had a significant correlation with prognosis in multivariate analysis. In subgroup analyses, the predictive value of PLR was significant for stage I (P = 0.008) and stage II (P = 0.044) patients, but not for stage III patients (P = 0.100). Preoperative PLR is easily obtained from a routine blood test and may provide additional prognostic information for ESCC patients, especially in the early stage.     

Prognostic significance of baseline nutritional index for patients with esophageal squamous cell carcinoma after radical esophagectomy

Background

Radical esophagectomy is the cornerstone of curative treatment for patients with resectable esophageal squamous cell carcinoma (ESCC). Patient survival after surgery for ESCC is mainly associated with pathological tumor progression. Recently, the impact of baseline immune-nutritional status of various types of patients with cancer on survival has been highlighted. The purpose of the present study was to investigate the association between the baseline prognostic nutritional index (PNI) and postoperative short- and long-term results after esophagectomy for patients with ESCC.

Methods

In total, 202 patients with ESCC who underwent radical esophagectomy at our institution between 2002 and 2010 were enrolled. PNI was calculated as 10× serum albumin (g/dL) + 0.005 × total lymphocyte counts (per mm³). Receiver operating characteristic (ROC) curves were generated for multiple logistic regression analysis using 5-year overall survival as the endpoint to determine an optimal PNI cutoff value, in which patients were classified into two groups: high PNI and low PNI. We evaluated the significance of PNI on postoperative morbidity and long-term survival using univariate and multivariate analyses.

Results

The mean PNI was 48.9 ± 4.6 (range 37.2–64.0). The area under the ROC curve in multiple logistic regression analysis was 0.5367. The projected 5-year survival rate was optimal at a PNI of 44.1. Hence, the PNI cutoff point was set at 44, with subjects classified by PNI level into the low (PNI <44) or high (PNI ≥44) PNI groups. Of 202 patients, 173 (85.7 %) and 29 (14.3 %) were classified as having high and low PNI, respectively. No significant differences were noted between the two groups regarding patient background, including age, sex, pT, pN, and pStage, or postoperative complications. However, overall survival (OS) and relapse-free survival (RFS) were significantly worse in the low PNI group than in the high PNI group. The 5-year OS and RFS rates in the high PNI vs. low PNI groups were 67.2 vs. 41.2 % (P = 0.007) and 61.5 vs. 38.8 % (P = 0.008), respectively. Multivariate analysis revealed that PNI was a significant prognostic factor for both OS (hazard ratio, 1.826; 95 % confidence interval, 1.015–3.285; P = 0.044) and RFS (hazard ratio, 1.862; 95 % confidence interval, 1.121–3.095; P = 0.016).

Conclusion

Preoperative PNI is an independent prognostic marker of both OS and RFS for patients with potentially curative ESCC. A careful follow-up for tumor recurrence after surgery is required for ESCC patients with low PNI.

     

Prognostic Significance of Preoperative Circulating Monocyte Count in Patients With Breast Cancer: Based on a Large Cohort Study

Growing evidence showed that inflammation response plays an important role in cancer development and progression, and absolute lymphocyte count (ALC), absolute monocyte count (AMC), and lymphocyte to monocyte ratio (LMR) have been used as parameters of systemic inflammation in several tumors. In this study, we evaluated the prognostic significance of preoperative ALC, AMC and LMR in breast cancer and 2000 patients between January 2002 and December 2008 at Sun Yat-Sen University Cancer Center were enrolled. Patients were grouped by the cut-off value according to the receiver operating characteristics (ROC) curve analysis. Kaplan–Meier analysis showed that patients with elevated AMC levels (>0.48 × 10⁹/L) had shorter overall survival (OS, P < 0.001). In multivariate analysis, preoperative AMC was identified as an independent prognostic parameter for OS in breast cancer patients (hazard ratio = 1.374, 95% confidence interval: 1.045–1.807). Subgroup analyses revealed that AMC was an unfavorable prognostic factor in stage II–III breast cancer patients and Luminal B, human epithelial growth factor receptor-2 overexpressing subtype, and triple-negative breast cancer (all P < 0.05). Additionally, the prognostic value of ALC and LMR could not be proven in the current study. Preoperative AMC may serve as an easily available and low-priced parameter to predict the outcomes of breast cancer.     

Absolute lymphocyte count at the time of first relapse predicts survival in patients with diffuse large B‐cell lymphoma

Peripheral blood absolute lymphocyte count (ALC) is a survival prognostic factor in hematological malignancies. No reports have addressed whether ALC at the time of first relapse (ALC‐R) predicts survival. Thus, we assessed the prognostic significance of ALC‐R in diffuse large B‐cell lymphoma (DLBCL). Patients were required to have been diagnosed with first relapsed DLBCL, have ALC‐R values, and to be followed at Mayo Clinic, Rochester. From Feb 1987 until March 2006, 97 first relapsed DLBCL patients qualified for the study. The overall survival (OS) and progression‐free survival (PFS) were measured from the time of first relapse. The value of ALC‐R ≥ 1.0 × 10⁹/L was used for the analysis. Both groups (ALC‐R ≥ 1 or < 1 × 10⁹/L) were balanced for the international prognostic index at relapse (IPI‐R) (P = 0.3), and for autologous stem cell transplantation (P = 0.4). Superior OS and PFS were observed with an ALC‐R ≥ 1.0 × 10⁹/L (N = 60) versus ALC‐R < 1.0 × 10⁹/L (N = 37) [median OS: 28.7 months, 5 years OS rates of 39% versus median OS: 10.2 months, 5 years OS rates of 14%, P < 0.002; and median PFS: 14.8 months, 5 years PFS rates of 21% versus median PFS: 6.5 months, 5 years PFS rates of 8%, P < 0.004, respectively]. ALC‐R was an independent prognostic factor for OS [RR = 0.4, P < 0.01] and PFS [RR = 0.5, P < 0.005]. ALC‐R predicts survival suggesting that host immunity is an important variable predicting survival in first relapsed DLBCL. Am. J. Hematol. 2009. © 2008 Wiley‐Liss, Inc.     

Radical systematic mediastinal lymphadenectomy versus mediastinal lymph node sampling in patients with clinical stage IA and pathological stage T1 non-small cell lung cancer

Purpose  To explore the appropriate method of mediastinal lymph node dissection for selected clinical stage IA (cIA) non-small cell lung cancer (NSCLC). Methods  From 1998 through 2002, the curative-intent surgery was performed to 105 patients with cIA NSCLC who had been postoperatively identified as pathologic-stage T1. According to the method of intraoperative medistinal lymph node dissection, they were divided into radical systematic mediastinal lymphadenectomy (LA) group (n = 42) and mediastinal lymph-node sampling (LS) group (n = 63). The effects of LS and LA on morbidity, N staging, overall survival (OS) and disease-free survival (DFS) were investigated. Also, associations between clinicopathological parameters and survival were analyzed. Results  The mean numbers of dissected lymph nodes per patient in the LA group was significantly greater than that in the LS group (15.59 ± 3.08 vs. 6.46 ± 2.21, P < 0.001), and the postoperative overall morbidity rate was higher in the LA group than that in the LS group (26.2 vs. 11.1%, P = 0.045). There were no significant difference in migration of N staging, OS and DFS between two groups. However, for patients with lesions between 2 and 3 cm, the 5-year OS in LA group was significantly higher than that in LS group (81.6 vs. 55.8%, P = 0.041), and the 5-year DFS was also higher (77.9 vs. 52.5%, P = 0.038). For patients with lesions of 2 cm or less, 5-year OS and DFS were similar in both groups. Multivariate analysis showed that lymph node metastasis was the unique unfavorable prognostic factor (P < 0.001). Conclusions  After being intraoperatively identified as stage T1, patients with lesions between 2 and 3 cm in cIA NSCLC should be performed with LA to get a potentially better survival, and patients with lesions of 2 cm or less should be performed with LS to decrease invasion.     

Absolute lymphocyte count at day 28 independently predicts event-free and overall survival in adults with newly diagnosed acute lymphoblastic leukemia

We investigated the prognostic impact of absolute lymphocyte count (ALC) following induction chemotherapy in newly diagnosed adult acute lymphoblastic leukemia (ALL). Patients with ALC ≥350 cells/μL at day 28 had a median overall survival (OS) of 47.4 months when compared with 17.6 months for those with an ALC <350 cells/μL (HR = 1.98, P = 0.007). Among patients who achieved a complete remission, median event‐free survival (EFS) for those with ALC ≥350 cells/μL on day 28 was 42.1 months when compared with 13.9 months in those with ALC <350 cells/μL (HR = 2.08, P = 0.006). In multivariable analysis, the ALC on day 28 (<350 cells/μL vs. ≥350 cells/μL, P ≤ .0004 for OS and EFS) along with WBC at diagnosis (≤6.0 or >30.0 K/μL vs. >6.0–30.0 K/μL, P ≤ 0.002 for OS and EFS) and cytogenetics (abnormal vs. normal, P = 0.002 for OS and P = 0.02 for EFS) were independent prognostic factors of both OS and EFS. Combining these three factors segregates patients in three well‐defined risk groups. These data suggest that ALC can be used in combination with other prognostic features to better predict outcome and that targeting the immune system to improve ALC may be a worthwhile strategy in ALL. Am. J.Hematol. © 2012 Wiley Periodicals, Inc.