PFKFB4 as a promising biomarker to predict a poor prognosis in patients with gastric cancer

Gastric cancer (GC) is one of the most common types of cancer worldwide. Previous studies have reported that phosphofructo-2-kinase/fructose-2,6-biphosphatase 4 (PFKFB4) functions as an oncoprotein in various types of cancer. However, the association between PFKFB4 and GC remains unclear. The present study analyzed the expression levels of PFKFB4 in 148 GC tissue samples, including 46 tumor tissues with matched adjacent normal tissues, using immunohistochemistry, compared the expression levels of PFKFB4 between GC and adjacent normal tissues, and determined the association between PFKFB4 expression levels and patient clinicopathological characteristics. In addition, survival curves were generated using the Kaplan-Meier (KM) plotter database to evaluate the association between PFKFB4 expression and GC prognosis. The results revealed that PFKFB4 expression was upregulated in GC tissues compared with in adjacent normal tissues. PFKFB4 expression was associated with patient age, tumor size, pathological tumor (pT) stage and tumor-node-metastasis (pTNM) stage, and upregulated expression levels of PFKFB4 were observed in tumor tissues from patients <65 years old (compared with that in patients ≥65 years old), as well as patients with a larger tumor size and an advanced stage (pT and pTNM stage) disease. In addition, KM survival analysis demonstrated that patients with low PFKFB4 expression had a significantly improved overall survival (OS), first progression survival and post-progression survival times compared with those with high PFKFB4 expression. Furthermore, PFKFB4 expression was negatively associated with OS time in patients with late pT and pTNM stage disease. In conclusion, the results of the present study indicated that the upregulated PFKFB4 expression in GC tissues may serve as a biomarker for a more advanced disease and a poor prognosis in patients with GC.     

Decreased albumin-to-alkaline phosphatase ratio predicted poor survival of resectable gastric cancer patients

BackgroundThe albumin-to-alkaline phosphatase ratio (AAPR) is an innovative prognostic index for various cancer patients, the clinical significance of the AAPR in patients with GC is unknown.MethodsWe retrospectively reviewed 227 resectable GC patients in our center. The Kaplan–Meier method and the Cox proportional hazards model were used to analyze the disease-free survival (DFS) and overall survival (OS). The Likelihood Ratio Test (LRT) and Akaike information criterion (AIC) were used to compare the prognostic abilities of the TNM and AAPR-TNM staging systems in DFS and OS predictionResultsThe AAPR was significantly decreased in GC patients, and the optimal cut-off value for resectable and benign gastric disease was 0.437 as determined by the receiver operating characteristic (ROC) curve. The correlation analysis revealed that decreased AAPR in GC was associated with T stage (P=0.004) and TNM stage (P=0.013). Decreased preoperative AAPR correlated with both unfavorable disease-free survival (DFS) and overall survival (OS). Cox regression analysis showed that the TNM stage (DFS: P=0.001, OS: P=0.002) and differential levels of AAPR (DFS: P<0.001, OS: P<0.001) were independent risk factors of DFS and OS. ROC analysis showed that the AAPR-TNM system was more superior than the TNM staging system for DFS (z=1.91, P=0.028) and OS (z=1.937, P=0.026) prediction. The likelihood ratio test (LRT) analysis indicated that the AAPR-TNM system had a significantly larger χ² for both DFS (35.58 vs. 34.51, P<0.001) and OS (32.92 vs. 30.07, P<0.001), and a lower Akaike information criterion (AIC) value both for DFS (1,032 vs. 1,065, P<0.001) and OS (869 vs. 898, P<0.001) compared to the TNM system.ConclusionsThe AAPR level significantly decreased in patients with GC, and impacted the prognosis of patients.     

Preoperative carcinoembryonic antigen is related to tumour stage and long-term survival in colorectal cancer.

Evidence as to the value of preoperative carcinoembryonic antigen (CEA) in guiding treatment for patients with colorectal cancer is conflicting. The aim of this prospective study was to investigate the value of preoperative CEA in predicting tumour factors of proven prognostic value and long-term survival in patients undergoing surgery for colorectal cancer. Preoperative serum CEA, tumour ploidy, stage and grade were ascertained in 277 patients undergoing colorectal cancer surgery. This cohort of patients were followed up for a minimum of 5 years, or until death, in a dedicated colorectal clinic. Patients with an elevated CEA had a 5 year survival of 39%. This increased to 57% if the CEA was normal (P=0.001). The proportion of patients with a raised CEA increased with a more advanced tumour stage (P < 0.000001) and a poorly differentiated tumour grade (P < 0.005). Once stage had been controlled for, CEA was not a predictor of survival. No relationship between tumour ploidy and CEA was found. In conclusion, a raised preoperative serum CEA is likely to be associated with advanced tumour stage and poor long-term survival, compared with patients with a normal value.     

Combination of preoperative red cell distribution width and neutrophil to lymphocyte ratio as a prognostic marker for gastric cancer patients

BackgroundThe neutrophil to lymphocyte ratio (NLR) and red blood cell distribution width (RDW) play an important role in the prognosis of several cancers, but their prognostic value in patients with stage II–III gastric cancer (GC) is unclear. We aimed to evaluate the prognostic value of the RDW-NLR (R-NLR) score based on RDW and NLR in stage II–III GC patients after radical surgery.MethodsPreoperative RDW and NLR clinicopathological data were retrospectively reviewed and analyzed from stage II–III GC patients who underwent radical gastrectomy. The optimal cut-off values for pre-RDW-variation coefficient (pre-RDW-cv) and pre-NLR were defined as 14.10% and 2.015, respectively. The R-NLR score was defined as 2 (both elevated RDW and NLR), 1 (one of these was elevated), or 0 (neither were elevated). Prognostic factors were identified by univariate and multivariate analyses.ResultsA total of 151 patients were included in this study, and 65 (43.05%), 54 (35.76%), and 32 (21.19%) patients had an R-NLR score of 0, 1 and 2, respectively. The preoperative R-NLR score was significantly correlated with tumor size and gender (all P<0.05). The 5-year overall survival (OS) in the R-NLR 0, 1, and 2 groups was 52.30%, 44.40%, and 31.20%, respectively (P=0.031), while the 5-year DFS was 47.70%, 13.30%, and 18.80%, respectively (P<0.001). Further, while the 5-year disease-free survival (DFS) rate was significantly improved in low RDW-cv and NLR patients compared with those with high RDW-cv and NLR (all P<0.05), but not OS (all P>0.05). Multivariate analysis demonstrated that the R-NLR score was independently correlated with OS [hazard ratio (HR), 1.527; P=0.007] and DFS (HR, 1.939; P=0.001).ConclusionsWe validated the preoperative R-NLR score to be a promising predictor for stage II–III GC patients who have undergone radical gastrectomy.     

Relevance of age on survival of 341 patients with multiple myeloma treated with conventional chemotherapy: updated results of the MM87 prospective randomized protocol. Cooperative Group of Study and Treatment of Multiple Myeloma.

Age could influence the prognosis of multiple myeloma patients treated with conventional chemotherapy. Between January 1987 and March 1990, 341 consecutive previously untreated patients with multiple myeloma received chemotherapy within the prospective, multicentre, randomized Protocol MM87. Survival was evaluated in patients aged > or < or = 66 years (the median age for the whole series) and in a subgroup of patients aged < 55 years. These groups were similar for main clinical characteristics, including results of cytostatic treatment. As of May 1996, 271 (79%) of the 341 patients had died, and median follow-up of the 70 (21%) living patients was 82 months. Overall, younger patients survived longer than older ones. In fact, in patients > and < or = 66 years, median survival was 31 and 44 months (P < 0.00095) and the percentage of patients surviving over 72 months was 17% and 32% (P = 0.0018) respectively; in patients < 55 years, these figures were 57 months and 35% respectively (P = 0.02 and 0.01, with respect to patients aged > 55 years). In all groups, about 50% of the patients surviving over 72 months had stage I disease. For multiple myeloma patients treated with chemotherapy, survival is favourably affected by relatively young age and early stage of disease.     

Impact of age on sorafenib outcomes in hepatocellular carcinoma: an international cohort study

Background There is no consensus on the effect of sorafenib dosing on efficacy and toxicity in elderly patients with hepatocellular carcinoma (HCC). Older patients are often empirically started on low-dose therapy with the aim to avoid toxicities while maximising clinical efficacy. We aimed to verify whether age impacts on overall survival (OS) and whether a reduced starting dose impacts on OS or toxicity experienced by the elderly.Methods In an international, multicentre cohort study, outcomes for those aged <75 or ≥75 years were determined while accounting for common prognostic factors and demographic characteristics in univariable and multivariable models.Results Five thousand five hundred and ninety-eight patients were recruited; 792 (14.1%) were aged ≥75 years. The elderly were more likely to have larger tumours (>7 cm) (39 vs 33%, p < 0.01) with preserved liver function (67 vs 57.7%) (p < 0.01). No difference in the median OS of those aged ≥75 years and <75 was noted (7.3 months vs 7.2 months; HR 1.00 (95% CI 0.93–1.08), p = 0.97). There was no relationship between starting dose of sorafenib 800 mg vs 400 mg/200 mg and OS between those <75 and ≥75 years. The elderly experienced a similar overall incidence of grade 2–4 sorafenib-related toxicity compared to <75 years (63.5 vs 56.7%, p = 0.11). However, the elderly were more likely to discontinue sorafenib due to toxicity (27.0 vs 21.6%, p < 0.01). This did not vary between different starting doses of sorafenib.Conclusions Clinical outcomes in the elderly is equivalent to patients aged <75 years, independent of dose of sorafenib prescribed.Subject terms: Targeted therapies, Hepatocellular carcinoma     

Clinicopathological and prognostic significance of programmed death ligant-1 expression in gastric cancer: a meta-analysis

BackgroundGastric cancer (GC) is a common malignant tumor with a high incidence in China. The use of immune checkpoint inhibitors has become the focus of tumor immunotherapy in recent years. This study was to investigate the clinicopathological and prognostic significance of programmed death ligant-1 (PD-L1) expression in GC.MethodsWe searched the PubMed, ScienceNet, EMbase, CNKI, and Wanfang databases for retrospective cohort studies on the clinicopathology and prognosis of PD-L1 expression in GC published between January 2010 and April 2020. The literature was first selected to extract data according to the inclusion and exclusion criteria, then a meta-analysis performed using Stata15.0 software. Publication bias and sensitivity analysis were carried out for the included studies.ResultsA total of 3,218 patients in 15 studies were included in the meta-analysis. The positive expression of PD-L1 was related to a decrease in the 3-year survival rate (HR =1.32, 95% CI: 1.02–1.49, P=0.028) and 5-year survival rate (HR =1.39, 95% CI: 1.14–1.69, P=0.001). The difference in PD-L1 expression was related to lymph node metastasis (OR =1.73, 95% CI: 1.18–2.54, P<0.001), but not to tumor stage (OR =1.28, 95% CI: 0.81–2.02, P=0.292).ConclusionsThe results show that PD-L1 is related to the prognosis of GC. Its high expression decreases the 3- and 5-year survival rates and promotes lymph node metastasis, but does not reflect tumor stage. The results may provide a theoretical basis for the choice of clinical immunotherapy in GC patients.     

Comparison of anal cancer outcomes in public and private hospital patients treated at a single radiation oncology center

Objective

To compare clinical and treatment characteristics and outcomes in locally advanced anal cancer, a potentially curable disease, in patients referred from a public or private hospital.

Methods

We retrospectively reviewed 112 anal cancer patients from a public and a private hospital who received definitive chemoradiotherapy at the same cancer center between 2004 and 2013. Tumor stage, radiotherapy delay, radiotherapy duration, and unplanned treatment breaks ≥10 days were compared using t-test and χ² test. Overall survival (OS), disease free survival (DFS), and colostomy free survival (CFS) were examined using the Kaplan-Meier method and compared with the log-rank test. Cox proportional hazard models for OS and DFS were developed.

Results

The follow-up was 14.9 months (range, 0.7-94.8 months). Public hospital patients presented with significantly higher clinical T stage (P<0.05) and clinical stage group (P<0.05), had significantly longer radiotherapy delays (P<0.05) and radiotherapy duration (P<0.05), and had more frequent radiation therapy (RT) breaks ≥10 days (P<0.05). Three-year OS showed a marked trend in favor of private hospital patients for 3-year OS (72.8% vs. 48.9%; P=0.171), 3-year DFS (66.3% vs. 42.7%, P=0.352), and 3-year CFS (86.4% vs. 68.9%, P=0.299). Referral hospital was not predictive of OS or DFS on multivariate analysis.

Conclusions

Public hospital patients presented at later stage and experienced more delays in initiating and completing radiotherapy, which may contribute to the trend in poorer DFS and OS. These findings emphasize the need for identifying clinical and treatment factors that contribute to decreased survival in low socioeconomic status (SES) populations.     

High levels of phosphorylated MAP kinase are associated with poor survival among patients with glioblastoma during the temozolomide era

We investigated whether high levels of activated mitogen-activated protein kinase (p-MAPK) were associated with poor survival among patients with newly diagnosed glioblastoma during the temozolomide era. Nuclear p-MAPK expression of 108 patients with GBM was quantified and categorized in the following levels: low (0%–10%), medium (11%–40%), and high (41%–100%). Independent predictors of overall survival were determined using a multivariate Cox proportional hazards model. Our study included 108 patients with newly diagnosed GBM. Median age was 65 years, and 74% had high Karnofsky performance status (KPS ≥ 80). Median overall survival among all patients was 19.5 months. Activated MAPK expression levels of <10%, 11%–40%, and ≥41% were observed in 33 (30.6%), 37 (34.3%), and 38 (35.2%) patients, respectively. Median survival for low, medium, and high p-MAPK expression was 32.4, 18.2, and 12.5 months, respectively. Multivariate analysis showed 2.4-times hazard of death among patients with intermediate p-MAPK than low p-MAPK expression (hazard ratio [HR], 2.4; P = .02); high-expression patients were 3.9 times more likely to die, compared with patients with low p-MAPK (HR, 3.9; P = .007). Patients aged ≥65 years (HR, 2.8; P = .002) with KPS < 80 (HR, 3.1; P = .0003) and biopsy or partial resection (HR, 1.9; P = .02) had higher hazard of death. MGMT and PTEN expression were not associated with survival differences. This study provides quantitative means of evaluating p-MAPK in patients with GBM. It confirms the significant and independent prognostic relevance of p-MAPK in predicting survival of patients with GBM treated in the temozolomide era and highlights the need for therapies targeting the p-MAPK oncogenic pathway.     

The prognostic value of morphometry in advanced epithelial ovarian cancers.

The relationship between morphometric and clinical data was assessed in a series of 60 advanced ovarian carcinomas. Morphometric parameters included nuclear area, nuclear perimeter, shortest and longest nuclear axis, roundness coefficient, volume percentage of epithelium (VPE) and mitotic index. All patients had at least 5 years of follow-up. Univariate survival analysis showed that FIGO stage (P < 0.001), VPE (P < 0.001), mean nuclear area (P < 0.001) and size of residual tumour (P < 0.001) are significantly associated with survival. When the response rate of these patients to cisplatin combination chemotherapy was evaluated, variables with good prognostic outcome were residual tumour size (P = 0.01), mean nuclear area (P = 0.0006) and s.d. of nuclear area (P = 0.0019). We conclude that morphometric parameters are able to support diagnostic and therapeutic decisions.     

Clinical significance of circulating exosomal PD-L1 and soluble PD-L1 in extranodal NK/T-cell lymphoma,nasal-type

Exosomal PD-L1 (exoPD-L1) is reported to be associated with immunosuppression in various cancers. However, its clinical value in extranodal NK/T cell lymphoma (ENKTL) has not been defined yet. We retrospectively evaluated the prognostic value of pretreatment circulating soluble PD-L1 (sPD-L1) and exosomal PD-L1 (exoPD-L1) in ENKTL patients treated with VIPD-containing chemotherapy. A total of 107 ENKTL patients, including 101 early stage and 6 advanced stage patients were enrolled in our study. ExoPD-L1 and sPD-L1 in the blood were measured by single molecule array (Simoa) and enzyme-linked immunosorbent assay (ELISA), respectively. Compared with the healthy individuals (n=16), the patients with ENKTL (n=107) exhibited significantly elevated exoPD-L1 and sPD-L1 levels in the blood. High pretreatment plasma exoPD-L1 concentration was associated with higher SUVmax level and recurrence rate. Similarly, high sPD-L1 group was also associated with some adverse clinical parameters, including advanced stage, elevated LDH levels, B symptoms, high IPI score and PINK score. The 5-year progression-free survival (PFS) rate and overall survival (OS) rates were 65.2% and 85.7% for the whole cohort, respectively. Patients with a low pretreatment exoPD-L1 level (simoa signal < 1.2) had 5-year OS and PFS rates of 88.1% and 86.1%, respectively, compared with 56.0%. (P=0.012) and 35.7% (P=0.007) in patients with high exoPD-L1 level (simoa signal > 1.2). The 5-year OS and PFS rates for patients with low sPD-L1 group (< 219 pg/mL) was significantly higher than high sPD-L1 group (≥ 219 pg/mL) (OS, 91.3% vs. 55.5%, P < 0.001; PFS, 68.9% vs. 34.6%, P=0.003). However, no correlation was found between circulating exoPD-L1 and sPD-L1 levels. This is the first study to measure plasma exoPD-L1 level on the Quanterix Simoa platform. Our results proved that circulating exoPD-L1 and sPD-L1 levels were significantly elevated in ENKTL and might be potential biomarkers for predicting the survival outcomes of ENKTL patients.     

Prognostic significance of the combination of preoperative hemoglobin,albumin, lymphocyte and platelet in patients with gastric carcinoma: a retrospective cohort study

Nutritional and immune status is important to the prognosis of patients with gastric carcinoma (GC). Here, we evaluated the prognostic significance of the combination of preoperative hemoglobin, albumin, lymphocyte and platelet (HALP) in patients with GC. From January 2005 to December 2011, 1332 patients with GC who underwent gastrectomy were randomly divided into the training (n = 888) and the validation sets (n = 444) by X-tile according to the sample size ratio 2:1. The cut-point of HALP was 56.8 and the patients were subsequently subdivided into HALP < 56.8 and HALP ≥ 56.8 groups in both two sets. Multivariate analysis revealed that gender (p < 0.001, p < 0.001), tumor size (p = 0.003, p = 0.035) and T stage (p < 0.001, p = 0.044) were independently related to HALP both in the training and the validation sets. Kaplan-Meier (p < 0.001, p = 0.003) and Cox regression (p = 0.043, p = 0.042) showed that the prognosis of HALP ≥ 56.8 group was significantly better than that of HALP < 56.8 group both in two sets (p < 0.001, p < 0.001). Nomograms of these two sets based on HALP was more accurate in prognostic prediction than TNM stage alone. Our findings suggested that HALP was closely associated with clinicopathological features and was an independent prognostic factor in GC patients. Nomogram based on HALP could accurately predict the prognosis of GC patients.     

Outcomes of resected pancreatic cancer in patients age ≥70

Objective

To determine outcomes of patients ≥70 years with resected pancreatic cancer.

Methods

A study was conducted to identify pancreatic cancer patients ≥70 years who underwent surgery for pancreatic carcinoma from 2000 to 2012. Patients were excluded if they had neoadjuvant therapy. The primary endpoint was overall survival (OS).

Results

We identified 112 patients with a median follow-up of surviving patients of 36 months. The median patient age was 77 years. The median and 5 year OS was 20.5 months and 19%, respectively. Univariate analysis (UVA) showed a significant correlation for increased mortality with N1 (P=0.03) as well as post-op CA19-9 >90 (P<0.001), with a trend towards decreased mortality with adjuvant chemoradiation (P=0.08). Multivariate analysis (MVA) showed a statistically significant increased mortality associated with N1 (P=0.008), post-op CA19-9 >90 (P=0.002), while adjuvant chemoradiation (P=0.04) was associated with decreased mortality.

Conclusions

These data show that in patients ≥70, nodal status, post-op CA19-9, and adjuvant chemoradiation, were associated with OS. The data suggests that outcomes of patients ≥70 years who undergo upfront surgical resection are not inferior to younger patients.     

Peripheral Blood Lymphocyte Percentage May Predict Chemotolerance and Survival in Patients with Advanced Pancreatic Cancer. Association between Adaptive Immunity and Nutritional State

Simple SummaryAlterations of the immune system that consist of induced inflammation and reduction in blood lymphocytes are a major factor contributing to cancer progression in patients with pancreatic carcinoma (PC). Identification of the percentage of lymphocytes in the Total number of White Blood Cells (L% TWBC) that could be associated with chemotolerance and survival time may be important for predicting treatment efficacy. The aim of this retrospective study was to highlight the best value of L% for predicting chemotolerance (n° of cycles tolerated) and survival beyond 12 months from diagnosis. The study found that L ≥ 29.7% TWBC compared to L < 29.7% predicted chemotolerance (p < 0.0001) and survival at every time point of follow-up: 6 (p = 0.04), 12 (p = 0.0003) and 18 months (p = 0.004) after diagnosis. Simple, rapid, routine laboratory data can be useful to predict treatment tolerance and efficacy in PC patients.AbstractPancreatic Carcinoma (PC) cells have the ability to induce patient immunosuppression and to escape immunosurveillance. Low circulating lymphocytes are associated with an advanced stage of PC and reduced survival. Blood lymphocytes expressed as a percentage of Total White Blood Cells (L% TWBC) could predict chemotolerance (n° of tolerated cycles), survival time and Body Weight (BW) more effectively than lymphocytes expressed as an absolute value (L_AB > 1500 n°/mm³) or lymphocytes >22%, which is the lowest limit of normal values in our laboratory. Forty-one patients with advanced PC, treated with chemotherapy, were selected for this observational retrospective study. Patients were evaluated at baseline (pre-chemotherapy), and at 6, 12 and 18 months, respectively, after diagnosis of PC. The study found L ≥ 29.7% to be a better predictor of survival (COX model, using age, sex, BW, serum creatinine, bilirubin and lymphocytes as covariates), chemotolerance (r = +0.50, p = 0.001) and BW (r = +0.35, p = 0.027) than L_AB > 1500 or L > 22%. BW did not significantly correlate with chemotolerance or survival. The preliminary results of this study suggest that L ≥ 29.7% is more effective than L_AB > 1500 or L > 22% at predicting chemotolerance, survival time and nutritional status. A possible impact of nutritional status on chemotherapy and survival seems to be lymphocyte-mediated given the association between BW and L%. This study may serve as the basis for future research to explore whether nutritional interventions can improve lymphopenia, and if so, how this may be possible.     

Second-line treatment efficacy and toxicity in older vs. non-older patients with advanced gastric cancer: A multicentre real-world study

ObjectivesAlthough gastric cancer (GC) incidence rises with age, older patients are poorly represented in clinical trials, whose results are therefore difficult to translate into standard management of older patients. Purpose of this study was to compare clinico-pathological features and survival outcomes between older and non-older patients with advanced GC treated with at least two chemotherapy lines.Materials and MethodsClinico-pathological characteristics, basal values, and treatment data of older (≥70 years at second-line start) and non-older patients were compared using chi-square test or 2-tailed Fisher exact test. The Kaplan-Meier estimation was used to calculate progression-free survival (PFS) and overall survival (OS), which were examined by log-rank test.ResultsOlder patients represented 31.8% of the population (N = 868). Intestinal type was more frequent in older patients (P = .02). Poorly differentiated tumours were more often observed in non-older patients (P = .009). At stage IV diagnosis, the rate of liver metastases was higher in older patients (P = .02), while peritoneal spread was more represented in non-older patients (P = .002). Although older patients were more often treated with monotherapy (P = .001), they had similar PFS (HR 0.86, 95%CI 0.71–1.03, P = .102) and OS (HR 0.82, 95%CI 0.65–1.02, P = .08) compared to the non-older counterpart. No statistical differences were observed in treatment-related adverse events, hospital admissions, or further treatment lines between age groups.ConclusionIn our large cohort study, despite some differences in tumour characteristics and treatment intensity, no survival difference was found between older and non-older patients with advanced GC treated with at least two chemotherapy lines. Incidence of adverse events was similar between age groups.     

Survival and Prognostic Factors for Breast Cancer Patients with Regional Oligo-Recurrence

PurposeThis study aimed to evaluate survival outcomes and identify prognostic factors for regional oligo-recurrence in breast cancer patients who received salvage local treatment.MethodsIn the breast cancer registry of our institution, 18,790 patients received curative surgery for stage I–III breast cancer between January 1995 and June 2016. Of those patients, only 87 (0.5%)underwent salvage local treatment for isolated nodal recurrence on the axillary lymph nodes (ALNs) (n = 58), supraclavicular lymph nodes (SCNs) (n = 17), or internal mammary lymph nodes (IMNs) (n = 12).ResultsThe median follow-up duration after regional oligo-recurrence was 49 months (range: 6–194 months). For patients with recurrence of ALN, SCN, or IMN, the 5-year progression-free survival (PFS) and overall survival (OS) rates were 40.0%, 32.1%, and 25.0%, respectively (p = 0.3) and 62.7%, 70.0%, and 58.3%, respectively(p = 0.97). In the multivariable analysis for PFS, age at recurrence ≥ 65 years, disease-free interval < 24 months, non-luminal A subtype, and in-field failure (marginally significant) were found to be risk factors (RFs). However, the location of the tumor was not a significant factor for PFS (p = 0.71). When we stratified patients by the number of RFs, the 5-year PFS rates were 67.5% for patients with ≤ 1 RF and 7.3% for those with > 1 RF (p < 0.01). For patients with ≤ 1 RF, the 5-year PFS rates were 73.5% in the ALN group and 51.1% in the SCN/IMN group (p = 0.09). For patients with > 1 RF, the 5-year PFS rates were 7.3% in the ALN group and 7.1% in the SCN/IMN group (p = 1.00).ConclusionIn breast cancer patients with regional oligo-recurrence, clinical outcomes after salvage treatment were favorable in patients with ≤ 1 RF, while patients with > 1 RF had poor prognoses irrespective of the location of recurrence.     

Outcomes of colorectal cancer surgery in nonagenarian patients: a multicenter retrospective study

BackgroundThe use of surgery in patients with colorectal cancer (CRC) aged ≥90 years remains controversial. This study aimed to evaluate the short-term postoperative and long-term oncologic outcomes of CRC surgery in patients within this age group.MethodsA total of 151 consecutive nonagenarian patients who underwent CRC surgery were included from 3 different hospitals. The Comprehensive Complication Index (CCI) was used to grade postoperative complications. Univariate and multivariate analyses were conducted to identify factors associated with CCI and overall survival (OS).ResultsThe patients had a mean age of 92.8 years (standard deviation ±1.9 years). Forty-six patients (30.5%) underwent emergency surgery, and 105 patients (69.5%) underwent elective surgery. The postoperative complications rate was 66.2% (100/151), and the mean CCI was 26.3 (±30.8). Twenty-three patients (15.2%) died postoperatively, and the perioperative mortality rates for elective surgery and emergency surgery were 7.6% (8/105) and 32.6% (15/46), respectively (P<0.001). The 1-, 3-, and 5-year survival rates were 77.5%, 53.9%, and 38.6%, respectively. Multivariate analysis revealed emergency surgery and American Society of Anesthesiologists (ASA) score to be predictors of postoperative complications. Advanced tumor stage, palliative surgery, ASA score ≥4, and CCI >17 were associated with poor OS.ConclusionsCRC surgery should not be denied to nonagenarian patients. Surgical treatment can be performed with acceptable morbidity and mortality, and achieves long-term survival in a select group.     

Prognostic value of systemic immune-inflammatory index in survival outcome in gastric cancer: a meta-analysis

BackgroundIn recent years, many studies have reported that the systemic immune-inflammatory index (SII) can be used to predict the prognosis of cancer patients; however, this finding remains controversial in gastric cancer (GC). Therefore, the purpose of this study was to systematically and comprehensively probe the prognostic role of SII in GC.MethodsRelevant publications were extracted from PubMed, EMBASE, Cochrane Library databases, and WANFANG DATA (Chinese database). The included studies had patients with pathologically confirmed GC and long-term follow-up data. The patient''s outcome was death, recurrence, or status at the end of follow-up. The studies included randomized controlled tests, case-control studies, or cohort studies using a multivariate proportional hazard model adjusted for survival outcomes. Cochran’s Q test and Higgins’ I-squared statistic were performed to assess heterogeneity. Publication bias was assessed by visual inspection of a Begg’s funnel plot.ResultsA total of 6,925 patients in 11 studies were included. The pooled hazard ratio (HR) indicated that a higher SII value was significantly associated with worse overall survival (OS) [HR: 1.53, 95% confidence interval (CI): 1.27–1.83] and worse disease-free survival (DFS) (HR: 1.57, 95% CI: 1.24–1.97) in GC patients. In the subgroup analysis, the HR was 1.72 (95% CI: 1.51–1.95) and 1.27 (95% CI: 0.96–1.67) in the group of patients aged <59 and ≥59 years, respectively.ConclusionsThe pooled HR indicates that a higher SII in younger patients with GC predicts a poor prognosis. In elderly patients with GC, the prognostic role of SII needs further research.     

Comparison of survival between adolescent and young adult vs older patients with hepatocellular carcinoma

BACKGROUNDDue to the special clinical features and biologic characteristics of adolescent and young adult (AYA) cancers, AYA cancers are different from cancers in children and elderly individuals. However, there are few reports on AYA hepatocellular carcinoma (HCC).AIMTo investigate the overall survival (OS) of AYA (15-39 years) and elderly (40-74 years) patients with HCC.METHODSThe data of all the HCC cases were extracted from the Surveillance, Epidemiology, and End Results database from 2004 to 2015 and were then divided into two groups based on age: AYA group (15-39 years) and older group (40-74 years). Kaplan-Meier curves and log-rank tests were used to compare the OS of the two groups. Propensity score matching (PSM) was employed to analyze the OS difference between the two groups. The Cox proportional hazards regression model was used to perform multivariate analysis to explore the risk factors for OS of HCC patients.RESULTSCompared to elderly cancer patients, AYA patients with HCC had a worse Surveillance, Epidemiology, and End Results stage, including the distant stage (22.1% vs 15.4%, P < 0.001), and a more advanced American Joint Committee on Cancer (AJCC) stage, including AJCC III and IV (49.2% vs 38.3%, P < 0.001), and were more likely to receive surgery (64.5% vs 47.5%, P < 0.001). Before PSM, the AYA group had a longer survival in months (median: 20.00, interquartile range [IQR]: 5.00-62.50) than the older group (median: 15.00, IQR: 4.00-40.00) (P < 0.001). After PSM, the AYA group still had a longer survival in months (median: 21.00, IQR: 5.00-64.50) than the older group (median: 18.00, IQR: 6.00-53.00) (P < 0.001). The Cox proportional hazards regression model showed that advanced age (hazard ratio [HR] = 1.405, 95%CI: 1.218-1.621, P < 0.001) was a risk factor for OS of HCC patients. In the subgroup analysis, the Cox proportional hazards regression model showed that in AJCC I/II HCC patients, advanced age (HR = 1.749, 95%CI: 1.352-2.263, P < 0.001) was a risk factor for OS, while it was not a risk factor in AJCC III/IV HCC patients (HR = 1.186, 95%CI: 0.997-1.410, P = 0.054) before PSM. After PSM, advanced age (HR = 1.891, 95%CI: 1.356-2.637, P < 0.001) was still a risk factor for OS in AJCC I/II HCC patients, but was not a risk factor for OS in AJCC III/IV HCC patients (HR = 1.192, 95%CI: 0.934-1.521, P = 0.157) after PSM.CONCLUSIONAYA patients with HCC have different clinical characteristics from older adults. In different AJCC stages, the two groups of patients have different OS: In AJCC I/II HCC patients, advanced age is a risk factor for OS, but it is not a risk factor for OS in the AJCC III/IV HCC patient group.     

Pattern of No.12a lymph node metastasis in gastric cancer

Objective:The current standard D2 lymphadenectomy for gastric cancer(GC)includes dissection of lymph nodes(LNs)along the proper hepatic artery(No.12 a),however,the survival benefit remains controversial.The purpose of this study was to evaluate the pattern of No.12 a LN metastasis(LNM)in GC and explore the indications for No.12 a LN dissection.Methods:Medical records of 413 consecutive GC patients who underwent curative surgery in Zhongshan Hospital,Fudan University between January 2015 and December 2018 were enrolled and reviewed retrospectively.The correlation between No.12 a LNM and clinicopathologic characteristics of patients was analyzed.Results:The overall incidence of No.12 a LNM was 2.67%(11/413).Tumor location(P=0.012),depth of tumor infiltration(P<0.01)and N stage(P=0.018)were significant factors associated with No.12 a LNM.All the tumors with No.12 a LNM involved the lower third of the stomach and were in T3-4 stages.Patients with No.12 a LNM had extensive LNM than those without(20.91±4.25 vs.5.0±0.54,P<0.001).For advanced GC patients(stage III/IV)with tumors involving the lower third of the stomach,the incidence of No.12 a LNM increased to 10.7%(11/103).Patients with No.12 a LNM had a significantly poorer recurrence-free survival(RFS)(P=0.005)and overall survival(OS)(P=0.017).According to the result of multivariable Cox regression,No.12 a LNM was not an independent impact factor on RFS and OS.Conclusions:The overall incidence of No.12 a LNM was low but it was much higher in GC patients who had very advanced tumors involving the lower third of the stomach.No.12 a LN dissection should be considered for these patients to improve the survival outcomes.