Correlation of tumor-associated macrophage density and proportion of M2 subtypes with the pathological stage of colorectal cancer

BACKGROUND Colorectal cancer(CRC)is a prevalent global malignancy with complex prognostic factors.Tumor-associated macrophages(TAMs)have shown paradoxical associations with CRC survival,particularly concerning the M2 subset.AIM We aimed to establish a simplified protocol for quantifying M2-like TAMs and explore their correlation with clinicopathological factors.METHODS A cross-sectional study included histopathological assessment of paraffinembedded tissue blocks obtained from 43 CRC patients.Using CD68 and CD163 immunohistochemistry,we quantified TAMs in tumor stroma and front,focusing on M2 proportion.Demographic,histopathological,and clinical parameters were collected.RESULTS TAM density was significantly higher at the tumor front,with the M2 proportion three times greater in both zones.The tumor front had a higher M2 proportion,which correlated significantly with advanced tumor stage(P=0.04),pathological nodal involvement(P=0.04),and lymphovascular invasion(LVI,P=0.01).However,no significant association was found between the M2 proportion in the tumor stroma and clinicopathological factors.CONCLUSION Our study introduces a simplified protocol for quantifying M2-like TAMs in CRC tissue samples.We demonstrated a significant correlation between an increased M2 proportion at the tumor front and advanced tumor stage,nodal involvement,and LVI.This suggests that M2-like TAMs might serve as potential indicators of disease progression in CRC,warranting further investigation and potential clinical application.

Radiomics approach for preoperative identification of stages Ⅰ-Ⅱand Ⅲ-Ⅳ of esophageal cancer

Objective： To predict preoperative staging using a radiomics approach based on computed tomography （CT）images of patients with esophageal squamous cell carcinoma （ESCC）.Methods： This retrospective study included 154 patients （primary cohort： n： t 14; validation cohort： n：40） withpathologically confirmed ESCC. All patients underwent a preoperative CT scan from the neck to abdomen. Highthroughput and quantitative radiomics features were extracted from the CT images for each patient. A radiomicssignature was constructed using the least absolute shrinkage and selection operator （Lasso）. Associations betweenradiomics signature, tumor volume and ESCC staging were explored. Diagnostic performance of radiomicsapproach and tumor volume for discriminating between stages Ⅰ-Ⅱand Ⅲ-Ⅳ was evaluated and compared usingthe receiver operating characteristics （ROC） curves and net reclassification improvement （NRI）.Results= A total of 9,790 radiomics features were extracted. Ten features were selected to build a radiomicssignature after feature dimension reduction. The radiomics signature was significantly associated with ESCCstaging （P〈0.001）, and yielded a better performance for discrimination of early and advanced stage ESCC comparedto tumor volume in both the primary [area under the receiver operating characteristic curve （AUC）： 0.795 vs. 0.694,P=0.003; NRI=0.424）] and validation cohorts （AUC： 0.762 vs. 0.624, P=0.035; NRI=0.834）.Conclusions： The quantitative approach has the potential to identify stage Ⅰ-Ⅱand Ⅲ-Ⅳ ESCC beforetreatment.

High plasma levels of COL10A1 are associated with advanced tumor stage in gastric cancer patients

BACKGROUND Gastric cancer(GC)remains an aggressive malignancy with a high rate of mortality,being the third leading cause of cancer-related death.More than one million newly diagnosed cases and 782685 deaths due to GC were reported in 2018.GC is characterized by limited effective treatment options and the lack of consistent biomarkers for the diagnosis and prognosis of these patients.The discovery of new biomarkers useful in the early diagnosis of GC is mandatory.AIM To evaluate the potential of COL10A1 as a circulating biomarker for the diagnosis and prognosis of gastric adenocarcinoma patients.METHODS Plasma and tissue obtained from 49 patients with gastric adenocarcinoma have been used in exploring the expression of COL10A1.Real-time PCR and western blot techniques were used to evaluate COL10A1 level in gastric tumor tissue compared to normal adjacent tissue.The circulating level of COL10A1 was also evaluated by ELISA in plasma of gastric adenocarcinoma patients.Survival analysis was made in order to evaluate the potential of COL10A1 as a biomarker for the diagnosis and prognosis of gastric adenocarcinoma patients.RESULTS Our results showed a significant increase in COL10A1 gene expression and protein levels in gastric tumor tissue compared to adjacent normal tissue(P<0.05).COL10A1 seems to show an elevated expression from the beginning of carcinogenesis,in the early stages,and its increased level remains elevated during cancer progression.A significant increase of COL10A1 plasma level in gastric adenocarcinoma patients was also identified.Moreover,increased COL10A1 plasma level was associated with poor survival of the patients.Plasma COL10A1 performed a diagnostic value in GC with area under the receiver operating characteristic curve(AUC)of 0.9171(P=0.0002),sensitivity of 87.76%,and specificity of 100.0%.Furthermore,this study demonstrated the potential role of plasma COL10A1 in the early detection of GC,as in the early stage,we obtained an AUC of 0.8789(P=0.0030),sensitivity of 81.25%,and specificity of 100.0%.CONCLUSION Circulating expression level of COL10A1 is significantly increased in gastric adenocarcinoma patients being associated with poor survival and is a potential biomarker for early detection of GC.

Pancreatic Neuroendocrine Neoplasms: Correlation between MR Features and Pathological Tumor Grades

This study investigated the accuracy of MRI features in differentiating the pathological grades of pancreatic neuroendocrine neoplasms（PNENs）. A total of 31 PNENs patients were retrospectively evaluated, including 19 cases in grade 1, 5 in grade 2, and 7 in grade 3. Plain and contrastenhanced MRI was performed on all patients. MRI features including tumor size, margin, signal intensity, enhancement patterns, degenerative changes, duct dilatation and metastasis were analyzed. Chi square tests, Fisher＇s exact tests, one-way ANOVA and ROC analysis were conducted to assess the associations between MRI features and different tumor grades. It was found that patients with older age, tumors with higher TNM stage and without hormonal syndrome had higher grade of PNETs（all P〈0.05）. Tumor size, shape, margin and growth pattern, tumor pattern, pancreatic and bile duct dilatation and presence of lymphatic and distant metastasis as well as MR enhancement pattern and tumor-topancreas contrast during arterial phase were the key features differentiating tumors of all grades（all P〈0.05）. ROC analysis revealed that the tumor size with threshold of 2.8 cm, irregular shape, pancreatic duct dilatation and lymphadenopathy showed satisfactory sensitivity and specificity in distinguishing grade 3 from grade 1 and grade 2 tumors. Features of peripancreatic tissue or vascular invasion, and distant metastasis showed high specificity but relatively low sensitivity. In conclusion, larger size, poorlydefined margin, heterogeneous enhanced pattern during arterial phase, duct dilatation and the presence of metastases are common features of higher grade PNENs. Plain and contrast-enhanced MRI provides the ability to differentiate tumors with different pathological grades.

Clinical Utility of Tumor Markers

Tumor markers comprise a wide spectrum of biomacromolecules excessively synthesized by a variety of neoplastic cells. These markers can be endogenous products of highly active metabolites from malignant neoplastic cells or the products of newly activated genes. Ideally, tumor markers should be highly sensitive, specific, and reliable with a high prognostic value and organ specificity. In addition, they should reflect the tumor stage. However, no tumor markers identified thus far have all of these characteristics. Nevertheless, most tumor markers show excellent clinical relevance for monitoring the efficacy of a variety of therapies. We herein review how to use the recommended tumor markers to diagnose malignancies, such as gastrointestinal carcinoma, liver cancer, bile duct/pancreatic cancer, lung cancer, breast cancer, gynecologic cancer, and urologic cancer.

An AAS Dependent Method for Quantitative Analysis of Essential Trace Elements from Blood Samples of Pakistani Female Breast Cancer Patients

Breast cancer is the second leading cancer in the world. The long-term exposure of some metallic compounds induces different forms of cancer, including breast cancer. Trace elements are essential metals for the physiological functions of the cell on a molecular level and also contribute in treatment of many diseases. The aim of study was to compare the level of essential trace elements, sodium, potassium, calcium, iron, and zinc in breast cancer patients with normal healthy adult women. Total forty-five patients (age range from 25 - 73 years) were included in this study and divided into three groups according to three different stages of breast cancer including tumor-II, tumor-III and tumor-IV. Blood was collected from all participants after taking history, clinical data and taking consent. However, about fifteen non-cancer healthy women in age range from 26 - 69 years were subjected to this study. The elemental concentrations were determined through atomic absorption spectrophotometer subsequent to microwave-induced acid digestion. The results of Na, K, Zn, Fe, Ca, were observed to decrease in blood samples of breast cancer patients as compared to non-cancer subjects. The results are reliable with other numerous literature reported studies, the efficiency, and deficiency of these trace metals may contribute an important role in the progress of breast cancer.

Prognostic factors and failure patterns in non-metastatic nasopharyngeal carcinoma after intensity-modulated radiotherapy

Background: The prognostic values of staging parameters require continual re?assessment amid changes in diag?nostic and therapeutic methods. This study aimed to identify the prognostic factors and failure patterns of non?meta?static nasopharyngeal carcinoma(NPC) in the intensity?modulated radiotherapy(IMRT) era.Methods: We reviewed the data from 749 patients with newly diagnosed, biopsy?proven, non?metastatic NPC in our cancer center(South China, an NPC endemic area) between January 2003 and December 2007. All patients under?went magnetic resonance imaging(MRI) before receiving IMRT. The actuarial survival rates were estimated using the Kaplan–Meier method, and survival curves were compared using the log?rank test. Multivariate analyses with the Cox proportional hazards model were used to test for the independent prognostic factors by backward eliminating insigniicant explanatory variables.Results: The 5?year occurrence rates of local failure, regional failure, locoregional failure, and distant failure were 5.4, 3.0, 7.4, and 17.4%, respectively. The 5?year survival rates were as follows: local relapse?free survival, 94.6%; nodal relapse?free survival, 97.0%; distant metastasis?free survival, 82.6%; disease?free survival, 75.1%; and overall survival, 82.0%. Multivariate Cox regression analysis revealed that orbit involvement was the only signiicant prognostic fac?tor for local failure(P = 0.011). Parapharyngeal tumor extension, retropharyngeal lymph node involvement, and the laterality, longest diameter, and Ho's location of the cervical lymph nodes were signiicant prognostic factors for both distant failure and disease failure(all P < 0.05). Intracranial extension had signiicant prognostic value for distant failure(P = 0.040).Conclusions: The key failure pattern for NPC was distant metastasis in the IMRT era. With changes in diagnostic and therapeutic technologies as well as treatment modalities, the signiicant prognostic parameters for local control have also been altered substantially.

Staging systems for predicting survival of patients with hepatocellular carcinoma after surgery

AIM: To compare the staging systems for stratifying and predicting the prognosis of patients with hepatocel-lular carcinoma (HCC) after partial hepatectomy (PH). METHODS: Clinical data about 438 HCC patients who underwent PH from January 1991 to December 2004 at our hospital were retrospectively analyzed. Tumor stage was evaluated following the Chinese tumor node me-tastasis (TNM) and barcelona clinic liver cancer (BCLC) staging systems, respectively. Survival curves for the HCC patients were plotted using the Kaplan-Meier method and differences were compared by the log-rank test. The accuracy of each system for predicting death of HCC patients was evaluated by calculating the area under the receiver operating characteristic curve. RESULTS: The HCC patients were classified into stag-es Ⅰ-Ⅲ, stages Ⅰ-Ⅳ and stages A-C, according to the 3 staging systems, respectively. Log-rank test showed that the cumulative survival rate was significantly dif-ferent for the HCC patients at 3 Chinese system stag-es, TNM stages Ⅰ and Ⅱ, TNM stages Ⅲ and Ⅳ, and 3 BCLC stages (P < 0.05). However, no significant differ-ence was found in the HCC patients at TNM stages Ⅱ and Ⅲ. The accuracy of the Chinese and BCLC staging systems was higher than that of the TNM staging sys-tem for predicting the survival rate of HCC patients. CONCLUSION: The Chinese and BCLC staging systems are better for stratifying and predicting the prognosis of HCC patients after PH than the TNM staging system.

Role of dynamic perfusion magnetic resonance imaging in patients with local advanced rectal cancer

BACKGROUND The management of rectal cancer patients is mainly based on the use of the magnetic resonance imaging(MRI)technique as a diagnostic tool for both staging and restaging.After treatment,to date,the evaluation of complete response is based on the histopathology assessment by using different tumor regression grade(TRG)features(e.g.,Dworak or Mandard classifications).While from the radiological point of view,the main attention for the prediction of a complete response after chemotherapy treatment focuses on MRI and the potential role of diffusion-weighted images and perfusion imaging represented by dynamiccontrast enhanced MRI.The main aim is to find a reliable tool to predict tumor response in comparison to histopathologic findings.AIM To investigate the value of dynamic contrast-enhanced perfusion-MRI parameters in the evaluation of the healthy rectal wall and tumor response to chemo-radiation therapy in patients with local advanced rectal cancer with histopathologic correlation.METHODS Twenty-eight patients with biopsy-proven rectal adenocarcinoma who underwent a dynamic contrast-enhanced MR study performed on a 1.5 T MRI system(Achieva,Philips),before(MR1)and after chemoradiation therapy(MR2),were enrolled in this study.The protocol included T1 gadolinium enhanced THRIVE sequences acquired on axial planes.A dedicated workstation was used to generate color permeability maps.Region of interest was manually drawn on tumor tissue and normal rectal wall,hence the following parameters were calculated and statistically analyzed:Relative arterial enhancement(RAE),relative venous enhancement(RVE),relative late enhancement(RLE),maximum enhancement(ME),time to peak and area under the curve(AUC).Perfusion parameters were related to pathologic TRG(Mandard’s criteria;TRG1=complete regression,TRG5=no regression).RESULTS Ten tumors(36%)showed complete or subtotal regression(TRG1-2)at histology and classified as responders;18 tumors(64%)were classified as non-responders(TRG3-5).Perfusion MRI parameters were significantly higher in the tumor tissue than in the healthy tissue in MR1(P<0.05).At baseline(MR1),no significant difference in perfusion parameters was found between responders and nonresponders.After chemo-radiation therapy,at MR2,responders showed significantly(P<0.05)lower perfusion values[RAE(%)54±20;RVE(%)73±24;RLE(%):82±29;ME(%):904±429]compared to non-responders[RAE(%):129±45;RVE(%):154±39;RLE(%):164±35;ME(%):1714±427].Moreover,in responders group perfusion values decreased significantly at MR2[RAE(%):54±20;RVE(%):73±24;RLE(%):82±29;ME(%):904±429]compared to the corresponding perfusion values at MR1[RAE(%):115±21;RVE(%):119±21;RLE(%):111±74;ME(%):1060±325];(P<0.05).Concerning the time-intensity curves,the AUC at MR2 showed significant difference(P=0.03)between responders and non-responders[AUC(mm2×10-3)121±50 vs 258±86],with lower AUC values of the tumor tissue in responders compared to nonresponders.In non-responders,there were no significant differences between perfusion values at MR1 and MR2.CONCLUSION Dynamic contrast perfusion-MRI analysis represents a complementary diagnostic tool for identifying vascularity characteristics of tumor tissue in local advanced rectal cancer,useful in the assessment of treatment response.

Do the existing staging systems for primary liver cancer apply to combined hepatocellular carcinoma-intrahepatic cholangiocarcinoma?

Background:The incidence of combined hepatocellular carcinoma-intrahepatic cholangiocarcinoma(cHCC-ICC)is relatively low,and the knowledge about the prognosis of cHCC-ICC remains obscure.In the study,we aimed to screen existing primary liver cancer staging systems and shed light on the prognosis and risk factors for cHCC-ICC.Methods:We retrospectively reviewed 206 cHCC-ICC patients who received curative surgical resection from April 1999 to March 2017.The correlation of survival measures with the histological types or with tumor staging systems was determined and predictive values of tumor staging systems with cHCC-ICC prognosis were compared.Results:The histological type was not associated with overall survival(OS)(P=0.338)or disease-free survival(DFS)(P=0.843)of patients after curative surgical resection.BCLC,TNM for HCC,and TNM for ICC stages correlated with both OS and DFS in cHCC-ICC(all P<0.05).The predictive values of TNM for HCC and TNM for ICC stages were similar in terms of predicting postoperative OS(P=0.798)and DFS(P=0.191)in cHCC-ICC.TNM for HCC was superior to BCLC for predicting postoperative OS(P=0.022)in cHCC-ICC.Conclusion:The TNM for HCC staging system should be prioritized for clinical applications in predicting cHCC-ICC prognosis.

Elevated pretreatment plasma fibrinogen level is associated with metastasis of non-small cell lung cancer(NSCLC)

Objective The aim of this study was to investigate the correlation between pretreatment fibrinogen levels and metastasis in non-small cell lung cancer(NSCLC).Methods The study included 503 NSCLC patients with a clear pathological diagnosis and 168 patients diagnosed with benign lung diseases by histological examination.Pretreatment plasma fibrinogen values were quantified,and the relationship between plasma fibrinogen level and clinical variables comprising tumor size,metastasis,and clinical stage was examined using Kruskal-Wallis test,Wilcoxon rank sum test,and Chi-square test.Results The median plasma fibrinogen values were statistically higher in NSCLC patients with metastasis than patients with benign lung diseases and NSCLC patients without metastasis(Kruskal-Wallis test;P<0.001).Plasma fibrinogen values were also significantly higher in advanced clinical stages(Wilcoxon rank sum test;P<0.001).A significant relationship was observed between elevated fibrinogen(>2.974 g/L)and metastasis,clinical stage,and tumor size(Chi-square test;P<0.001).Conclusion This correlation suggests that elevated pretreatment plasma fibrinogen levels can predict metastasis and advanced tumor stage in NSCLC patients.

POST-OPERATIVE STAGING AND SURVIVAL BASED ON THE REVISED TNM STAGING SYSTEM FOR NON-SMALL CELL LUNG CANCER

Objective: To study the factors affecting post-operative staging and survival in non-small cell lung cancer (NSCLC) patients based on the revised TNM staging system adopted by the UICC in 1977. Methods: Data were collected from 1757 consecutively operated NSCLC patients, including those receiving complete tumor excision, tumor debulking and exploratory thoractomy from April 1969 through Dec. 1993. the end point of follow-up was Nov. 30, 1998. Cumulative survival and its influencing factors were analyzed by Kaplan-Meier and Cox model of SPSS software. Results: In this series, 30 patients (1.7%) were lost from follow-up. The 5-year cumulative survival was 88.0% for patients in stage I A, and 53.9% in stage IB, 33.5% in stage II, 14.7% in stage III A, 5.5% in stage IIIB and 7.0% in stage IV. The overall 5-year survival rate was 28.2%. The 5-year survivals were 39.8%, 14.4% and 4.2% in patients treated with completely tumor resection, tumor debulking and explorative thoractomy, respectively. The 10-year survival rate was 31.4%, 9.5% and 0, respectively. Factors affecting long-term cumulative survival, in the order of decreasing significance, were the type of operation, lymph node status, staging, size and pathological type of the primary tumor. Conclusion: the revised staging system for NSCLC is superior to that used since 1986 as far as the end results of treatment in patients in different stage and the staging specificity are concerned. The T3N1M0 classification and the definition of Ml need to be further studied.

Clinical Study on Effect of Kang'aibao Oral Liquid(抗癌宝口服液) in Treating 103 Patients of Malignant Tumor

Objective: To observe the clinical efficacy of Kang'aibao oral liquid (KABL), a Chinese herbal preparation in treating malignant tumor of middle or advanced stage. Methods: A comparative study was done by observing the effect of 103 patients treated with KABL, and another 90 patients treated with chemotherapy at the same time were taken as the control group.Results: The immunologic function, short term effective rate (complete relieved rate and partial relieved rate), survival quality, 1 , 2 and 3 year survival rate, median survival time, and carcinoembryonic antigen (CEA) declining rate of the KABL group were significantly higher than those of the control group. Conclusion: KABL has the effects of inhibiting tumor growth, prolonging survival time and improving survival quality of tumor patients.

Cancer field surgery for locoregional tumor control of cervical carcinoma

As the current standard,surgery is applied to treat early-stage cervical cancer and selected post-irradiation pelvic relapses.Surgical therapy for local disease is based on a model of unlimited isotropic cancer cell propagation and dissection artifacts such as subperitoneal“ligaments”and“spaces”.For regional disease,the role of traditional surgery is diagnostic and eventually cytoreductive.However,the isotropic local tumor propagation model has to be rejected due to numerous inconsistencies with clinical facts.Likewise,the“ligament and space”approach to the subperitoneum is too crude and variable to accurately cover both local spread and intercalated lymph node metastases of cervical cancer.The ontogenetic cancer field model is fully in line with the locoregional spread patterns of carcinoma of the female genital tract.Developmentally derived(ontogenetic)anatomy enables unbiased and accurate dissection of the complex tissue structures within the subperitoneum.Cancer field surgery founded on these insights has a high potential to improve the treatment outcome of cervical carcinoma.

HER2-positive circulating tumor cells indicate poor clinical outcome in stageⅠto Ⅲ breast cancer patients

Metastases may occur in node-negative breast cancer patients. It indicates that breast cancer cells can bypass regional lymph nodes and hematogenously disseminate to distant organs. In a recent paper (Clin Cancer Res 2006, 12:1715-1720) , Wulfing et al. evaluated the prognostic value of blood-borne, HER2-positive circulating tumor cells (CTC) in the peripheral blood from 42 breast cancer patients with a median follow-up of 95 months. HER2-

A nomogramfor predicting overall survival in patients with low-grade endometrial stromal sarcoma: A population-based analysis

Background:Low-grade endometrial stromal sarcoma(LG-ESS)is a rare tumor that lacks a prognostic prediction model.Our study aimed to develop a nomogram to predict overall survival of LG-ESS patients.Methods:A total of 1172 patients confirmed to have LG-ESS between 1988 and 2015 were selected from the Surveillance,Epidemiology and End Results(SEER)database.They were further divided into a training cohort and a validation cohort.The Akaike information criterion was used to select variables for the nomogram.The discrimination and calibration of the nomogram were evaluated using concordance index(C-index),area under time-dependent receiver operating characteristic curve(time-dependent AUC),and calibration plots.The net benefits of the nomogram at different threshold probabilities were quantified and compared with those of the International Federation of Gynecology and Obstetrics(FIGO)criteria-based tumor staging using decision curve analysis(DCA).Net reclassification index(NRI)and integrated discrimination improvement(IDI)were also used to compare the nomogram’s clinical utilitywith that of the FIGO criteria-based tumor staging.The risk stratifications of the nomogram and the FIGO criteria-based tumor staging were compared.Results:Seven variables were selected to establish the nomogram for LG-ESS.The C-index(0.814 for the training cohort and 0.837 for the validation cohort)and the time-dependent AUC(>0.7)indicated satisfactory discriminative ability of the nomogram.The calibration plots showed favorable consistency between the prediction of the nomogram and actual observations in both the training and validation cohorts.The NRI values(training cohort:0.271 for 5-year and 0.433 for 10-year OS prediction;validation cohort:0.310 for 5-year and 0.383 for 10-year OS prediction)and IDI(training cohort:0.146 for 5-year and 0.185 for 10-year OS prediction;validation cohort:0.177 for 5-year and 0.191 for 10-year OS prediction)indicated that the established nomogram performed significantly better than the FIGO criteria-based tumor staging alone(P<0.05).Furthermore,DCA showed that the nomogram was clinically useful and had better discriminative ability to recognize patients at high risk than the FIGO criteria-based tumor staging.Conclusions:A prognostic nomogram was developed and validated to assist clinicians in evaluating prognosis of LG-ESS patients.