Prognostic significance of SUVmax and serum carbohydrate antigen 19-9 in pancreatic cancer

AIM:To investigate the prognostic significance of pretreatment standardized maximum uptake value(SUVmax)and serum carbohydrate antigen(CA)19-9 in pancreatic cancer.METHODS:From January 2007 to October 2011,80 consecutive patients with pancreatic cancer who received positron emission/computed tomography before any treatment were enrolled in this study.The pretreatment SUVmax and CA19-9 level of the primary pancreatic tumor were obtained and compared with clinicopathological and prognostic factors.Student’s t test for unpaired data was used to analyze the differences between two groups.Univariate analysis and Cox proportional hazards regression were used to examine the independent effects of each significant variable.Survival was analyzed by the Kaplan-Meier method.RESULTS:There was a significant correlation between both the SUVmax and serum CA19-9 of pancreatic cancer and R0 surgical resection(P=0.043 and P=0.007).Lymph node metastasis was associated with SUVmax(P=0.017),but not serum CA19-9(P=0.172).On the contrary,the tumor stage was significantly related to serum CA19-9(P=0.035),but not SUVmax(P=0.110).The univariate analysis showed that survival time was significantly related to tumor stage(P<0.001),lymph node metastasis(P=0.043),R0 surgical resection(P<0.001),serum CA19-9(P=0.001),SUVmax(P<0.001)and SUVmax plus CA19-9(P=0.002).Multivariate analysis clearly showed that only tumor stage(hazard ratio=0.452;P=0.020)was an independent prognostic factor for overall survival in pancreatic cancer.Higher SUVmax or CA19-9showed worse prognosis.We found that high serum CA19-9 plus SUVmax was the most significant variable.CONCLUSION:Higher pretreatment SUVmax and serum CA19-9 indicates poor prognosis.SUVmax plus serum CA19-9 is the most significant variable in predicting survival.     

Differentiation of Tuberculous Peritonitis from Peritonitis Carcinomatosa without Surgical Intervention

Background/Aim:

Ascites of tuberculous peritonitis (TBP) is an exudative type and may well be misdiagnosed as carcinomatous peritonitis, especially in the elderly. The aim of this study was to identify independent predictors that can differentiate TBP from peritonitis carcinomatosa without surgical intervention.

Patients and Methods:

This prospective cohort study was performed on 75 subjects in the following groups: TBP (n=27) (TBP group), ovarian cancer complicated with ascites (n=24) (Ov Ca group), and gastric cancer complicated with ascites (n=24) (Ga Ca group). The frequency of clinical symptoms, laboratory parameters, and serum tumor markers levels were compared.

Results:

In univariate analysis; fever, night sweats, and abdominal pain were significantly more frequent in the TBP group compared to those in the Ov Ca group (P < 0.001, P < 0.001, and P = 0.035, respectively) and the Ga Ca group (P < 0.001, P < 0.001, and P = 0.015, respectively). Serum CA 19-9 and carcino embryonic antigen (CEA) levels were significantly lower in the TBP and Ov Ca group compared to the Ga Ca group (P < 0.001 and P < 0.001, respectively). Elevated serum CA 125 level was found in all patients with TBP and Ov Ca and in 86.6% of patients with Ga Ca. In the multivariate analysis, presence of fever (P < 0.001), night sweats (P < 0.001), age under 40 years (P = 0.008), and normal serum CA 19-9 level (P = 0.044) were independent predictor of diagnosis of TBP.

Conclusion:

The presence of fever, elevated serum CA 125 level, normal serum CA 19-9, and CEA associated with lymphocyte predominant benign ascites may establish the diagnosis of TBP.     

Novel immunological and nutritional-based prognostic index for gastric cancer

AIM: To assess the prognostic significance of immunological and nutritional-based indices, including the prognostic nutritional index(PNI), neutrophillymphocyte ratio(NLR), and platelet-lymphocyte ratio in gastric cancer.METHODS: We retrospectively reviewed 632 gastric cancer patients who underwent gastrectomy between1998 and 2008. Areas under the receiver operating characteristic curve were calculated to compare the predictive ability of the indices, together with estimating the sensitivity, specificity and agreement rate.Univariate and multivariate analyses were performed to identify risk factors for overall survival(OS). Propensity score analysis was performed to adjust variables to control for selection bias.RESULTS: Each index could predict OS in gastric cancer patients in univariate analysis, but only PNI had independent prognostic significance in multivariate analysis before and after adjustment with propensity scoring(hazard ratio, 1.668; 95% confidence interval:1.368-2.035). In subgroup analysis, a low PNI predicted a significantly shorter OS in patients with stage Ⅱ-Ⅲ disease(P = 0.019, P 0.001), T3-T4 tumors(P 0.001), or lymph node metastasis(P 0.001). Canton score, a combination of PNI, NLR, and platelet, was a better indicator for OS than PNI, with the largest area under the curve for 12-, 36-, 60-mo OS and overall OS(P = 0.022, P = 0.030, P 0.001, and P = 0.024,respectively). The maximum sensitivity, specificity, and agreement rate of Canton score for predicting prognosis were 84.6%, 34.9%, and 70.1%, respectively.CONCLUSION: PNI is an independent prognostic factor for OS in gastric cancer. Canton score can be a novel preoperative prognostic index in gastric cancer.     

Elevated CA19-9 as the Most Significant Prognostic Factor in Locally Advanced Rectal Cancer Following Neoadjuvant Chemoradiotherapy

It remains controversial regarding the prognostic significance of carbohydrate antigen 19-9 (CA19-9) for locally advanced rectal cancer (LARC) (T3–4/N+) patients with neoadjuvant chemoradiotherapy (neo-CRT). And it is unknown whether CA19-9 can identify patients who may benefit from adjuvant chemotherapy.Overall, 303 LARC patients with neo-CRT between 2004 and 2010 were recruited. Overall survival (OS), disease-free survival (DFS), distant metastasis-free survival (DMFS), and local recurrence-free survival across pretreatment CA19-9 were estimated by Kaplan–Meier method and Cox regression model.In univariate analysis, elevated CA19-9 (>35 U/mL) was significantly correlated with poor OS (P = 0.003), DFS (P = 0.001), and DMFS (P = 0.039). Adjusting for the known covariates, CA19-9 was significantly associated with OS (HR = 1.86, 95% CI 1.03–3.34, P = 0.039) and DFS (HR = 1.74, 95% CI 1.08–2.80, P = 0.024). In the elevated CA19-9 subgroup, patients with adjuvant chemotherapy got much better OS (P < 0.001) and DFS (P = 0.016) than those without. In consideration of both CA19-9 and carcinoembryonic antigen (CEA), we found that patients with both elevated CA19-9 and CEA (>5 ng/mL) got the worst OS (P = 0.021) and DFS (P = 0.006), and significantly benefited from adjuvant chemotherapy in OS (P < 0.001) and DFS (P = 0.026).Pretreatment CA19-9 level is a significant prognostic indicator in patients with LARC following neo-CRT. The addition of CA19-9 to CEA is valuable to discriminate the appropriate patients for adjuvant chemotherapy.     

Prognostic factors and long-term outcomes of hilar cholangiocarcinoma:A single-institution experience in China

AIM: To evaluate the prognostic factors of hilar cholangiocarcinoma in a large series of patients in a single institution.METHODS: Eight hundred and fourteen patients with a diagnosis of hilar cholangiocarcinoma that were evaluated and treated between 1990 and 2014, of which 381 patients underwent curative surgery, were included in this study. Potential factors associated with overall survival(OS) and disease-free survival(DFS) were evaluated by univariate and multivariate analyses.RESULTS: Curative surgery provided the best long-term survival with a median OS of 26.3 mo. The median DFS was 18.1 mo. Multivariate analysis showed that patients with tumor size > 3 cm [hazard ratio(HR) = 1.482, 95%CI: 1.127-1.949; P = 0.005], positive nodal disease(HR = 1.701, 95%CI: 1.346-2.149; P < 0.001), poor differentiation(HR = 2.535, 95%CI: 1.839-3.493; P < 0.001), vascular invasion(HR = 1.542, 95%CI: 1.082-2.197; P = 0.017), and positive margins(HR = 1.798, 95%CI: 1.314-2.461; P < 0.001) had poor OS outcome. The independent factors for DFS were positive nodal disease(HR = 3.383, 95%CI: 2.633-4.348; P < 0.001), poor differentiation(HR = 2.774, 95%CI: 2.012-3.823; P < 0.001), vascular invasion(HR = 2.136, 95%CI: 1.658-3.236; P < 0.001), and positive margins(HR = 1.835, 95%CI: 1.256-2.679; P < 0.001). Multiple logistic regression analysis showed that caudate lobectomy [odds ratio(OR) = 9.771, 95%CI: 4.672-20.433; P < 0.001], tumor diameter(OR = 3.772, 95%CI: 1.914-7.434; P < 0.001), surgical procedures(OR = 10.236, 95%CI: 4.738-22.116; P < 0.001), American Joint Committee On Cancer T stage(OR = 2.010, 95%CI: 1.043-3.870; P = 0.037), and vascular invasion(OR = 2.278, 95%CI: 0.997-5.207; P = 0.051) were independently associated with tumorfree margin, and surgical procedures could indirectly affect survival outcome by influencing the tumor resection margin. CONCLUSION: Tumor margin, tumor differentiation, vascular invasion, and lymph node status were independent factors for OS and DFS. Surgical procedures can indirectly affect survival outcome by influencing the tumor resection margin.     

Clinical significance of CA19-9 in diagnosis of digestive tract tumors

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Effect of complication grade on survival following curative gastrectomy for carcinoma

AIM: To elucidate the potential impact of the grade of complications on long-term survival of gastric cancer patients after curative surgery.METHODS: A total of 751 gastric cancer patients who underwent curative gastrectomy between January 2002 and December 2006 in our center were enrolled in this study. Patients were divided into four groups: no complications, Grade I, Grade II and Grade III complications, according to the following classification systems: T92 (Toronto 1992 or Clavien), Accordion Classification, and Revised Accordion Classification. Clinicopathological features were compared among the four groups and potential prognostic factors were analyzed. The Log-rank test was used to assess statistical differences between the groups. Independent prognostic factors were identified using the Cox proportional hazards regression model. Stratified analysis was used to investigate the impact of complications of each grade on survival.RESULTS: Significant differences were found among the four groups in age, sex, other diseases (including hypertension, diabetes and chronic obstructive pulmonary disease), body mass index (BMI), intraoperative blood loss, tumor location, extranodal metastasis, lymph node metastasis, tumor-node-metastasis (TNM) stage, and chemotherapy. Overall survival (OS) was significantly influenced by the complication grade. The 5-year OS rates were 43.0%, 42.5%, 25.5% and 9.6% for no complications, and Grade I, Grade II and Grade III complications, respectively (P < 0.001). Age, tumor size, intraoperative blood loss, lymph node metastasis, TNM stage and complication grade were independent prognostic factors in multivariate analysis. With stratified analysis, lymph node metastasis, tumor size, and intraoperative blood loss were independent prognostic factors for Grade I complications (P < 0.001, P = 0.031, P = 0.030). Age and lymph node metastasis were found to be independent prognostic factors for OS of gastric cancer patients with Grade II complications (P = 0.034, P = 0.001). Intraoperative blood loss, TNM stage, and chemotherapy were independent prognostic factors for OS of gastric cancer patients with Grade III complications (P = 0.003, P = 0.005, P < 0.001). There were significant differences among patients with Grade I, Grade II and Grade III complications in TNM stage II and III cancer (P < 0.001, P = 0.001).CONCLUSION: Complication grade may be an independent prognostic factor for gastric cancer following curative resection. Treatment of complications can improve the long-term outcome of gastric cancer patients.     

Postoperative serum CA19-9, CEA and CA125 predicts the response to adjuvant chemoradiotherapy following radical resection in pancreatic adenocarcinoma

Objective

To evaluate the prediction of benefits from adjuvant chemoradiotherapy by postoperative serum CA19-9, CA125 and CEA.

Yield of clinical and radiographic surveillance in patients with resected pancreatic adenocarcinoma following multimodal therapy

Background

Following potentially curative resection at this centre, patients with pancreatic adenocarcinoma (PAC) are routinely enrolled in a programme of clinical and radiographic surveillance. This study sought to evaluate its diagnostic yield.

Methods

All patients who underwent pancreaticoduodenectomy for PAC at this institution during 1998–2008 were identified. Patients with asymptomatic recurrence were compared with those with symptomatic recurrence. Factors associated with survival following the detection of recurrence were compared.

Results

A total of 216 of 327 (66.1%) resected patients developed recurrence. Asymptomatic recurrence was detected in 118 (54.6%) patients. Symptomatic recurrence was associated with multifocal disease or carcinomatosis, poor performance status and less frequent subsequent therapy. Median time to recurrence did not differ between groups, but survival after detection was shorter in symptomatic patients (5.1 months vs. 13.0 months; P < 0.001). Treatment was administered more frequently to asymptomatic patients (91.2% vs. 61.4%; P < 0.001). At recurrence, a preserved performance status score of ≤1, further therapy, low CA 19-9, and an isolated site of recurrence were independently associated with longer post-recurrence survival (P < 0.001).

Conclusions

Overall, 54.6% of cases of recurrent PAC were detected prior to the onset of symptoms using a standardized clinical and radiographic surveillance strategy. Although this retrospective analysis limits definitive conclusions associating this strategy with survival, these results suggest the need for further studies of postoperative surveillance.     

Neutrophil-lymphocyte ratio predicts the prognosis of patients with hepatocellular carcinoma after liver transplantation

AIM:To determine whether an elevated neutrophillymphocyte ratio(NLR)is negatively associated with tumor recurrence in patients with hepatitis B virus(HBV)-related hepatocellular carcinoma(HCC)after liver transplantation(LT),and to determine the optimal predictive NLR cut-off value.METHODS:The data of HCC patients who had undergone LT came from the China Liver Transplant Registry database.We collected data from 326 liver cancer patients who had undergone LT at our medical center.We divided the patients into groups based on their NLRs(3,4 or 5).We then compared the clinicopathological data and long-time survival between these groups.Meanwhile,we used receiver operating characteristic analysis to determine the optimal NLR cut-off.RESULTS:Of 280 HCC patients included in this study,263 were HBV positive.Patients with an NLR<3 and patients with an NLR≥3 but<4 showed no significant differences in overall survival(OS)(P=0.212)or disease-free survival(DFS)(P=0.601).Patients with an NLR≥4 but<5 and patients with an NLR≥5also showed no significant differences in OS(P=0.208)or DFS(P=0.618).The 1-,3-and 5-year OS rates of patients with an NLR<4 vs an NLR≥4 were 87.8%,63.8%and 61.5%vs 73.9%,36.7%and 30.3%,respectively(P<0.001).The 1-,3-and 5-year DFS rates of patients with an NLR<4 vs NLR≥4 were 83.9%,62.9%and 60.7%vs 64.9%,30.1%and 30.1%,respectively(P<0.001).Univariate and multivariate analyses demonstrated that three factors,including NLR≥4(P=0.002),were significant predictors of tumor recurrence in HCC patients after LT.CONCLUSION:A preoperative elevated NLR significantly increased the risk for tumor recurrence in HCC patients after LT.     

Serum carbohydrate antigen 19-9 represents a marker of response to neoadjuvant therapy in patients with borderline resectable pancreatic cancer

Objectives

The purpose of this study was to determine the relationship between carbohydrate antigen (CA) 19-9 levels and outcome in patients with borderline resectable pancreatic cancer treated with neoadjuvant therapy (NT).

Methods

This study included all patients with borderline resectable pancreatic cancer, a serum CA 19-9 level of ≥40 U/ml and bilirubin of ≤2 mg/dl, in whom NT was initiated at one institution between 2001 and 2010. The study evaluated the associations between pre- and post-NT CA 19-9, resection and overall survival.

Results

Among 141 eligible patients, CA 19-9 declined during NT in 116. Following NT, 84 of 141 (60%) patients underwent resection. For post-NT resection, the positive predictive value of a decline and the negative predictive value of an increase in CA 19-9 were 70% and 88%, respectively. The normalization of CA 19-9 (post-NT <40 U/ml) was associated with longer median overall survival among both non-resected (15 months versus 11 months; P = 0.022) and resected (38 months versus 26 months; P = 0.020) patients. Factors independently associated with shorter overall survival were no resection [hazard ratio (HR) 3.86, P < 0.001] and failure to normalize CA 19-9 (HR 2.13, P = 0.001).

Conclusions

The serum CA 19-9 level represents a dynamic preoperative marker of tumour biology and response to NT, and provides prognostic information in both non-resected and resected patients with borderline resectable pancreatic cancer.     

Prognosis of HER2 over-expressing gastric cancer patients with liver metastasis

AIM: To study the risk factors for liver metastasis and the prognosis in patients with human epidermal growth factor receptor 2 (HER2) over-expressing gastric cancer (GC).METHODS: A total of 84 GC patients recruited from the General Hospital of the People’s Liberation Army (PLA) between 2003 and 2010 were randomly enrolled in this study. HER2 expression was detected by immunohistochemistry in 84 GC patients with liver metastases. The study group consisted of 66 men and 18 women, with an average age of 54 years (range: 19-74 years). Liver metastasis was diagnosed by magnetic resonance imaging or computed tomography. Patients were followed-up and predictive factors of liver metastasis were evaluated.RESULTS: The median follow-up period was 47 mo (range: 6-85 mo). The characteristics of 35 (25.7%) patients with HER2 over-expression of liver metastatic GC are presented. HER2 over-expression was detected in 23 out of 49 (46.9%) patients with intestinal GC, and 9 out of 35 (25.7%) patients with diffuse GC. 29 out of 59 (49.2%) patients aged < 60 years were HER2-positive, while 8 out of 25 (32%) patients aged ≥ 60 were HER2-positive; a significant difference (P < 0.05). Univariate analysis (log-rank test) showed that HER2 over-expression, sex, Lauren classification, differentiation and disease-free interval were correlated with poor survival (P < 0.05). Survival analysis with a survival curve showed that HER2 over-expression was significantly relevant, with a reduced survival time in GC patients with liver metastases (P < 0.01). 2-year survival was not associated with the patient’s age. A disease-free survival longer than 12 mo has a significant association with extended overall survival (OS) in GC patients with liver metastases. The median survival time after the diagnosis of liver metastases was 18 mo [95% confidence interval (CI): 9.07-26.94] among HER2 positive GC patients with liver metastases. In comparison, for 49 (69.4%) out of 84 HER2 negative patients with liver metastatic GC, the median survival time was 47 mo (95% CI: 19.37-74.63). In patients with HER2 positive liver metastatic GC, the median OS was significantly shorter than in HER2 negative patients (median, 20.32 mo; 95% CI: 16.51-24.13 vs median, 50.14 mo; 95% CI: 37.83-62.45; P < 0.01).CONCLUSION: HER2 over-expressing GC patients with liver metastases have a poor prognosis. Overall survival was significantly lower in HER2 positive patients. HER2-overexpression is correlated with a lower survival rate.     

Risk factors of lymphatic metastasis complement poor radiological detection in gallbladder cancer

AIM:To explore risk factors of lymphatic metastasis(LM)in gallbladder cancer,and their potential to complement unsatisfactory radiological detection.METHODS:Radiological detection of LM by computed tomography(CT)was reported to fail in more than60%of patients with pathological LM.In order to find risk factors highly suggestive of LM other than radiological manifestations,the documents of 63 patients were analyzed statistically.Except for 4 patients having T1a disease,in whom cholecystectomy is enough for radical resection,59 patients underwent lymphadenectomy with at least 3 lymph nodes dissected.Fifty point eight percent(32/63)of patients were found to have LM during pathological examination.The median number of dissected lymph nodes was 6(range 3-20).RESULTS:Only 31.3%(10/32)of patients with LM were detected by CT.Through multivariate analysis,two risk factors of LM were discovered as age<60years(OR=6.24;P<0.01)and carbohydrate antigen(CA)19-9 elevation(OR=5.70;P<0.05).By analysis of patients with pathological LM but failed to be detected by CT,81.8%(18/22)of patients had at least one risk factor,including 31.3%(10/32)who had the risk factor of age<60 years,and 37.5%(12/32)who had the risk factor of CA 19-9 elevation.Besides,among patients with LM(n=32),those whose age were younger than 60 years(OR=3.41;P<0.05)were more likely to have 3 or more positive lymph nodes.CONCLUSION:Age<60 years and CA 19-9 elevation could complement radiological detection of LM.Patients aged<60 years are at higher risk of multiple positive nodes.     

Prognostic nutritional index predicts postoperative complications and long-term outcomes of gastric cancer

AIM:To investigate the impact of prognostic nutritional index(PNI)on the postoperative complications and long-term outcomes in gastric cancer patients undergoing total gastrectomy.METHODS:The data for 386 patients with gastric cancer were extracted and analyzed between January2003 and December 2008 in our center.The patients were divided into two groups according to the cutoff value of the PNI:those with a PNI≥46 and those with a PNI<46.Clinicopathological features were compared between the two groups and potential prognostic factors were analyzed.The relationship between postoperative complications and PNI was analyzed by logistic regression.The univariate and multivariate hazard ratios were calculated using the Cox proportional hazard model.RESULTS:The optimal cutoff value of the PNI was set at 46,and patients with a PNI≥46 and those with a PNI<46 were classified into PNI-high and PNI-low groups,respectively.Patients in the PNI-low group were more likely to have advanced tumor(T),node(N),and TNM stages than patients in the PNI-high group.The low PNI is an independent risk factor for the incidence of postoperative complications(OR=2.223).The 5-year overall survival(OS)rates were 54.1%and21.1%for patients with a PNI≥46 and those with a PNI<46,respectively.The OS rates were significantly lower in the PNI-low group than in the PNI-high group among patients with stagesⅡ(P=0.001)andⅢ(P<0.001)disease.CONCLUSION:The PNI is a simple and useful marker not only to identify patients at increased risk for postoperative complications,but also to predict long-term survival after total gastrectomy.The PNI should be included in the routine assessment of advanced gastric cancer patients.     

Krüppel-like factor 8 overexpression is correlated with angiogenesis and poor prognosis in gastric cancer

AIM:To investigate Krüppel-like factor 8 (KLF8) expression in gastric cancer and its relationship with angiogenesis and prognosis of gastric cancer. METHODS:One hundred and fifty-four patients with gastric cancer who underwent successful curative resection were retrospectively enrolled in the study. Fifty tumor-adjacent healthy gastric tissues (≥ 5 cm from the tumor margin) obtained during the original resection were randomly selected for comparative analysis. In situ expression of KLF8 and CD34 proteins were examined by immunohistochemistry. The intratumoral microvessel density (MVD) was determined by manually counting the immunostained CD34-positive endothelial cells in three consecutive high-magnification fields (× 200). The relationship between differential KLF8 expression and MVD was assessed using Spearman’s correlation coefficient test. χ2 test was performed to evaluate the effects of differential KLF8 expression on clinicopathologic factors. Kaplan-Meier and multivariate Cox survival analyses were used to assess the prognostic value of differential KLF8 expression in gastric cancer. RESULTS:Significantly higher levels of KLF8 protein were detected in gastric cancer tissues than in the adjacent non-cancerous tissues (54.5% vs 34.0%, P < 0.05). KLF8 expression was associated with tumor size (P < 0.001), local invasion (P = 0.005), regional lymph node metastasis (P = 0.029), distant metastasis (P = 0.023), and tumor node metastasis (TNM) stage (P = 0.002), as well as the MVD (r = 0.392, P < 0.001). Patients with KLF8 positive expression had poorer overall survival (P < 0.001) and cancer-specific survival (P < 0.001) than those with negative expression. Multivariate analysis demonstrated that KLF8 expression independently affected both overall and cancer-specific survival of gastric cancer patients (P = 0.035 and 0.042, respectively). CONCLUSION:KLF8 is closely associated with gastric tumor progression, angiogenesis and poor prognosis, suggesting it may represent a novel prognostic biom     

Expression and clinical significance of CD73 and hypoxia-inducible factor-1α in gastric carcinoma

AIM: To investigate the expression of CD73 and hypoxia-inducible factor-1α (HIF-1α) in human gastric carcinoma, and explore their clinical significance and prognostic value. METHODS: CD73 and HIF-1α expressions were detected by immunohistochemistry in consecutive sections of tissue samples from 68 gastric carcinoma patients. The peritumor tissues 2 cm away from the tumor were obtained and served as controls. The presence of CD73 and HIF-1α was analyzed by immunohis-tochemistry using the Envision technique. RESULTS: CD73 and HIF-1α expressions in gastric carcinoma were significantly higher than those in gastric mucosal tissues as control (P < 0.001) and showed a close correlation (Spearman r = 0.390, P = 0.001). Overexpression of CD73 was positively correlated with differentiation of tumor (P = 0.000), histopathology (P = 0.041), depth of invasion (P < 0.001), nodal status (P = 0.003), metastasis (P = 0.013), and the American Joint Committee on Cancer (AJCC) stage (P < 0.001). High expression of HIF-1α was positively correlated with tumor diameter (P = 0.031), depth of invasion (P = 0.022), and AJCC stage (P = 0.035). The overall survival rate was low in the patients with high expression of CD73 (P < 0.001). Moreover, CD73+/HIF-1α+ patients had the worst prognosis (P < 0.001). CD73 expression was proven to be an independent predictor for patients with gastric carcinoma by both multivariate Cox regression analysis (P = 0.021) and receiver operating characteristic curves (P = 0.001).CONCLUSION: CD73 expression correlates closely with HIF-1α expression in gastric carcinoma. CD73 could be an independent prognostic indicator for gastric carcinoma.     

Prognostic value of KRAS and BRAF mutations in curatively resected colorectal cancer

AIM: To investigate the prognostic role of KRAS and BRAF mutations after adjustment for microsatellite instability(MSI) status in Japanese colorectal cancer(CRC) population.METHODS: We assessed KRAS and BRAF mutations and MSI status in 813 Japanese patients with curatively resected, stage Ⅰ-Ⅲ CRC and examined associations of these mutations with disease-free survival(DFS) and overall survival(OS) using uni- and multivariate Cox proportional hazards models.RESULTS: KRAS and BRAF mutations were detected in 312(38%) of 812 and 40(5%) of 811 tumors, respectively. KRAS mutations occurred more frequently in females than in males(P = 0.02), while the presence of BRAF mutations was significantly associated with the female gender(P = 0.006), proximal tumor location(P 0.001), mucinous or poorly differentiated histology(P 0.001), and MSI-high tumors(P 0.001). After adjusting for relevant variables, including MSI status, KRAS mutations were associated with poorer DFS(HR = 1.35; 95%CI: 1.03-1.75) and OS(HR = 1.46; 95%CI: 1.09-1.97). BRAF mutations were poor prognostic factors for DFS(HR = 2.20; 95%CI: 1.19-4.06) and OS(HR = 2.30; 95%CI: 1.15-4.71). Neither the BRAF by MSI interaction test nor the KRAS by MSI interaction test yielded statistically significant results for DFS and OS.CONCLUSION: KRAS and BRAF mutations are associated with inferior survival, independent of MSI status, inJapanese patients with curatively resected CRC.     

Preoperative predictors of short-term survival after hepatectomy for multinodular hepatocellular carcinoma

AIM: To investigate preoperative factors associated with poor short-term outcome after resection for multinodular hepatocellular carcinoma (HCC) and to assess the contraindication of patients for surgery.METHODS: We retrospectively analyzed 162 multinodular HCC patients with Child-Pugh A liver function who underwent surgical resection. The prognostic significance of preoperative factors was investigated by univariate analysis using the log-rank test and by multivariate analysis using the Cox proportional hazards model. Each independent risk factor was then assigned points to construct a scoring model to evaluate the indication for surgical intervention. A receiver operating characteristics (ROC) curve was constructed to assess the predictive ability of this system.RESULTS: The median overall survival was 38.3 mo (range: 3-80 mo), while the median disease-free survival was 18.6 mo (range: 1-79 mo). The 1-year mortality was 14%. Independent prognostic risk factors of 1-year death included prealbumin < 170 mg/L [hazard ratio (HR): 5.531, P < 0.001], alkaline phosphatase > 129 U/L (HR: 3.252, P = 0.005), α fetoprotein > 20 μg/L (HR: 7.477, P = 0.011), total tumor size > 8 cm (HR: 10.543; P < 0.001), platelet count < 100 × 10⁹/L (HR: 9.937, P < 0.001), and γ-glutamyl transpeptidase > 64 U/L (HR: 3.791, P < 0.001). The scoring model had a strong ability to predict 1-year survival (area under ROC: 0.925, P < 0.001). Patients with a score ≥ 5 had significantly poorer short-term outcome than those with a score < 5 (1-year mortality: 62% vs 5%, P < 0.001; 1-year recurrence rate: 86% vs 33%, P < 0.001). Patients with score ≥ 5 had greater possibility of microvascular invasion (P < 0.001), poor tumor differentiation (P = 0.003), liver cirrhosis with small nodules (P < 0.001), and intraoperative blood transfusion (P = 0.010).CONCLUSION: A composite preoperative scoring model can be used as an indication of prognosis of HCC patients after surgical resection. Resection should be considered with caution in patients with a score ≥ 5, which indicates a contraindication for surgery.     

Lower serum folate is associated with development and invasiveness of gastric cancer

AIM: To evaluate the associations of serum folate level with development, invasiveness and patient survival of gastric cancer.METHODS: In this nested case-control study, patients with newly diagnosed gastric cancer undergoing gastrectomy were enrolled, and patients receiving chemotherapy prior to surgery, with other concurrent malignancy, or of the aboriginal and alien populations were excluded. In total, 155 gastric cancer patients and 149 healthy controls were enrolled for determination of serum folate levels and their correlation with gastric cancer. Using the median value of serum folate computed among the overall population as the cutoff value, the associations between serum folate and gastric cancer in all cases and different age and gender subgroups were analyzed by multivariate logistic regression analysis. In the patient cohort of gastric cancer, receiver-operating characteristic analyses were performed to calculate the best cutoff values of serum folate, and the associations between serum folate levels and clinicopathological features were further analyzed by multivariate regression analysis. Survival analyses were conducted using the Cox proportional hazards model.RESULTS: The mean serum folate level was significantly lower in gastric cancer patients than that in controls (3.71 ± 0.30 ng/mL vs 8.00 ± 0.54 ng/mL, P < 0.01), and folate levels were consistently lower in gastric cancer patients regardless of age and gender (all P < 0.01). Using the median serum folate value as the cutoff value, low serum folate was significantly associated with gastric cancer risk in the whole population (OR = 19.77, 95%CI: 10.54-37.06, P < 0.001) and all strata (age < 60 years OR = 17.39, 95%CI: 7.28-41.54, age ≥ 60 years (OR = 21.67, 95%CI: 8.27-56.80), males (OR = 17.95, 95%CI: 7.93-40.62), and females (OR = 20.95, 95%CI: 7.66-57.31); all P < 0.001. In the patient cohort of gastric cancer, the respective cutoff values showed that low serum folate levels were significantly associated with serosal invasion (OR = 2.54, 95%CI: 1.23-5.23), lymphatic invasion (OR = 2.23, 95%CI: 1.17-4.26), and liver metastasis (OR = 6.67, 95%CI: 1.28-34.91) of gastric cancer (all P < 0.05). Serum folate level below 1.90 ng/mL was associated with poor patient survival (HR = 1.84, 95%CI: 1.04-3.27, P < 0.05) in univariate analysis.CONCLUSION: Lower serum folate levels were significantly associated with gastric cancer development and invasive phenotypes. The role of folate depletion in gastric cancer invasion warrants further study.     

The predictive value of preoperative serum neutrophil-to-lymphocyte ratio and tumor markers for early breast cancer patients: A retrospective study

Peripheral blood of Neutrophil-to-Lymphocyte ratio (NLR), carcinoma embryonic antigen (CEA), cancer antigen 125 (CA125) and cancer antigen 15–3 (CA15-3) could be used as prognostic indicators for several types of tumors. The purpose of this study was to evaluate the predictive value of inflammatory cell ratio and tumor markers for postoperative breast cancer patients. Clinical data concerning 190 breast cancer patients who underwent radical surgery in Zhejiang Provincial Hospital of Chinese Medicine from 2013 and 2016 were retrospectively analyzed. The effects of NLR, CEA, CA125, and CA153 on the disease-free survival (DFS) of patients with breast cancer were analyzed by χ² test and Cox regression analyses. There were totally 32 of 190 patients had local or distant metastases within 5 years after surgery. The peripheral blood NLR, CEA, CA125, and CA15-3 areas under the curve (AUC) were 0.8272, 0.667, 0.702, and 0.715, and the optimal cutoff values were 2.65, 1.47, 10.55, and 10.55, respectively. Univariate analysis and Kaplan-Meier survival analysis revealed that the serum NLR, CEA, CA125, and CA15-3 were related to postoperative 5-year DFS (P < .05). In addition, multivariate survival analysis identified the following independent prognostic factors: NLR (P < .001), CA125 (P = .045) and ki-67 (P = .020). Preoperative serum inflammatory biomarker of NLR and tumor marker of CA125 have potential prognostic value for breast carcinoma.