Objective:Lymphovascular invasion(LVI)is a crucial step in metastasis and is closely associated with poor prognosis in patients with breast cancer.However,its clinical and molecular characteristics remain insufficient...Objective:Lymphovascular invasion(LVI)is a crucial step in metastasis and is closely associated with poor prognosis in patients with breast cancer.However,its clinical and molecular characteristics remain insufficiently defined.We aimed to identify molecular targets for LVI-positive(LVI+)breast cancer and predict patient prognosis via the analysis of genomic variations using targeted sequencing.Methods:We established a large-scale targeted sequencing cohort of 4,079 breast cancer samples,which included 3,159 early-stage and locally advanced patients with available LVI statuses.Comparisons of somatic mutation frequencies and germline pathogenic/likely pathogenic(P/LP)mutation frequencies,mutational signature analyses,and mutual exclusivity and co-occurrence analyses were performed to identify key genomic features involved in LVI+patients.Additionally,Kaplan-Meier survival analysis was conducted to further explore the prognostic value of co-mutations in LVI+cases.Results:We observed that LVI+patients with the hormone receptor-positive/human epidermal growth factor receptor 2-negative(HR+/HER2-)and triple-negative breast cancer(TNBC)subtypes exhibited worse disease-free survival.Notably,HR+/HER2-and HER2+breast cancer patients with LVI displayed distinct genomic features compared with LVI-tumors.Specifically,LVI+HR+/HER2-tumors exhibited greater frequencies of somatic mutations in TP53 and ESR1,germline BRCA2 P/LP variations,and an enrichment of clock-like single-base substitution(SBS)1 mutational signatures.In contrast,LVI+HER2+tumors demonstrated a higher incidence of somatic PIK3CA mutations and increased activity of the apolipoprotein B m RNA editing enzyme catalytic polypeptide(APOBEC)-associated SBS2 signature.Furthermore,we revealed that the co-mutation of TP53 and NF1 could serve as a potential prognostic marker for LVI+HR+/HER2-patients.Conclusions:Our findings provide a comprehensive overview of the genomic characteristics of LVI in breast cancer,thereby offering insights that may help in refining precision treatment strategies for LVI+breast cancer patients.展开更多
AIM: To investigate the meaning of lymphovascular invasion (LVI) in rectal cancer after neoadjuvant radiotherapy. METHODS: A total of 325 patients who underwent radical resection using total mesorectal excision (TME) ...AIM: To investigate the meaning of lymphovascular invasion (LVI) in rectal cancer after neoadjuvant radiotherapy. METHODS: A total of 325 patients who underwent radical resection using total mesorectal excision (TME) from January 2000 to January 2005 in Beijing cancer hospital were included retrospectively, divided into a preoperative radiotherapy (PRT) group and a control group, according to whether or not they underwent preoperative radiation. Histological assessments of tumor specimens were made and the correlation of LVI and prognosis were evaluated by univariate and multivariate analysis. RESULTS: The occurrence of LVI in the PRT and control groups was 21.4% and 26.1% respectively. In the control group, LVI was signifi cantly associated with histological differentiation and pathologic TNM stage, whereas these associations were not observed in the PRT group. LVI was closely correlated to disease progression and 5-year overall survival (OS) in both groups. Among the patients with disease progression, LVI positive patients in the PRT group had a signifi cantly longer median disease-free period (22.5 mo vs 11.5 mo, P = 0.023) and overall survival time (42.5 mo vs 26.5 mo, P = 0.035) compared to those in the control group, despite the fact that no signifi cant difference in 5-year OS rate was observed (54.4% vs 48.3%, P = 0.137). Multivariate analysis showed the distance of tumor from the anal verge, pretreatment serum carcinoembryonic antigen level, pathologic TNM stage and LVI were the major factors affecting OS. CONCLUSION: Neoadjuvant radiotherapy does not reduce LVI significantly; however, the prognostic meaning of LVI has changed. Patients with LVI may benefi t from neoadjuvant radiotherapy.展开更多
To systematically evaluate the prognostic value of lymphovascular invasion （LVI） in radical prostatectomy （RP） by a meta-analysis based on the published literature. To identify relevant studies, PubMed, Cochrane L...To systematically evaluate the prognostic value of lymphovascular invasion （LVI） in radical prostatectomy （RP） by a meta-analysis based on the published literature. To identify relevant studies, PubMed, Cochrane Library, and Web of Science database were searched from 1966 to May 2014. Finally, 25 studies （9503 patients） were included. LVI was found in 12.2% （1156/9503） of the RP specimens. LVI was found to be correlated with higher pathological tumor stages （greater than pT3 stage） （risk ratio [RR] 1.90, 95% confidence interval [CI] 1.73-2.08, P〈 0.00001）, higher Gleason scores （greater than GS = 7） （RR 1.30, 95% CI 1.23-1.38, P 〈 0.00001）, positive pathological node （pN） status （RR 5.67, 95% CI 3.14-10.24, P 〈 0.00001）, extracapsular extension （RR 1.72, 95% CI 1.46-2.02, P 〈 0.00001）, and seminal vesicle involvement （RR 3.36, 95% CI 2.41-4.70, P 〈 0.00001）. The pooled hazard ratio （HR） was statistically significant for Biochemical Recurrence-Free （BCR-free） probability （HR 2.05, 95% ／ CI 1.64-2.56; Z = 6.30, P〈 0.00001）. Sensitivity analysis showed that the pooled HR and 95% CI were not significantly altered by the omission of any single study. Begg＇s Funnel plots showed no significant publication bias （P = 0.112）. In conclusion, LVI exhibited a detrimental effect on the BCR-Free probability and clinicopathological features in RP specimens, and may prove to be an independent prognostic factor of BCR.展开更多
BACKGROUND Lymphovascular invasion(LVI)and perineural invasion(PNI)are associated with decreased survival in colorectal cancer(CRC),but its significance in N1c stage remains to be clearly defined.AIM We retrospectivel...BACKGROUND Lymphovascular invasion(LVI)and perineural invasion(PNI)are associated with decreased survival in colorectal cancer(CRC),but its significance in N1c stage remains to be clearly defined.AIM We retrospectively identified 107 consecutive patients who had CRC with N1c disease radically resected at our hospital.Tumors were reviewed for LVI and PNI by one pathologist blinded to the patients’outcomes.Disease-free survival(DFS),overall survival(OS)and cancer-specific survival(CSS)were determined using the Kaplan-Meier method,with LVI and PNI prognosis differences determined by multivariate analysis using the Cox multiple hazards model.Results were compared using log-rank test.The receiver operating characteristic(ROC)curve was used to evaluate the prognostic predictive ability.RESULTS The median follow-up time was 63.17(45.33-81.37)months for DFS,with 33.64%(36/107)of patients experiencing recurrence;21.5%of tumors were found to be LVI positive and 44.9%PNI positive.The 5-year DFS rate was greater for patients with LVI-negative tumors compared with LVI-positive tumors(74.0%vs 35.6%),and PNI was similar(82.5%vs 45.1%).On multivariate analysis,LVI[hazard ratio(HR)=3.368,95%confidence interval(CI):1.628-6.966,P=0.001]and PNI(HR=3.055,95%CI:1.478-6.313,P=0.002)were independent prognostic factors for DFS.All patients could be divided into three groups of patients with different prognosis according to LVI and PNI.The 5-year ROC curve for LVI,PNI and their combination prediction of DFS was 0.646,0.709 and 0.759,respectively.Similar results were seen for OS and CSS.CONCLUSION LVI and PNI could serve as independent prognostic factors of outcomes in N1c CRC patients.Patients with LVI or PNI should be given more attention during treatment.展开更多
BACKGROUND Lymphovascular invasion(LVI)and perineural invasion(PNI)are important prognostic factors for gastric cancer(GC)that indicate an increased risk of metastasis and poor outcomes.Accurate preoperative predictio...BACKGROUND Lymphovascular invasion(LVI)and perineural invasion(PNI)are important prognostic factors for gastric cancer(GC)that indicate an increased risk of metastasis and poor outcomes.Accurate preoperative prediction of LVI/PNI status could help clinicians identify high-risk patients and guide treatment deci-sions.However,prior models using conventional computed tomography(CT)images to predict LVI or PNI separately have had limited accuracy.Spectral CT provides quantitative enhancement parameters that may better capture tumor invasion.We hypothesized that a predictive model combining clinical and spectral CT parameters would accurately preoperatively predict LVI/PNI status in GC patients.AIM To develop and test a machine learning model that fuses spectral CT parameters and clinical indicators to predict LVI/PNI status accurately.METHODS This study used a retrospective dataset involving 257 GC patients(training cohort,n=172;validation cohort,n=85).First,several clinical indicators,including serum tumor markers,CT-TN stages and CT-detected extramural vein invasion(CT-EMVI),were extracted,as were quantitative spectral CT parameters from the delineated tumor regions.Next,a two-step feature selection approach using correlation-based methods and information gain ranking inside a 10-fold cross-validation loop was utilized to select informative clinical and spectral CT parameters.A logistic regression(LR)-based nomogram model was subsequently constructed to predict LVI/PNI status,and its performance was evaluated using the area under the receiver operating characteristic curve(AUC).RESULTS In both the training and validation cohorts,CT T3-4 stage,CT-N positive status,and CT-EMVI positive status are more prevalent in the LVI/PNI-positive group and these differences are statistically significant(P<0.05).LR analysis of the training group showed preoperative CT-T stage,CT-EMVI,single-energy CT values of 70 keV of venous phase(VP-70 keV),and the ratio of standardized iodine concentration of equilibrium phase(EP-NIC)were independent influencing factors.The AUCs of VP-70 keV and EP-NIC were 0.888 and 0.824,respectively,which were slightly greater than those of CT-T and CT-EMVI(AUC=0.793,0.762).The nomogram combining CT-T stage,CT-EMVI,VP-70 keV and EP-NIC yielded AUCs of 0.918(0.866-0.954)and 0.874(0.784-0.936)in the training and validation cohorts,which are significantly higher than using each of single independent factors(P<0.05).CONCLUSION The study found that using portal venous and EP spectral CT parameters allows effective preoperative detection of LVI/PNI in GC,with accuracy boosted by integrating clinical markers.展开更多
BACKGROUND Rectal cancer(RC)is one of the most common diagnosed cancers,and one of the major causes of cancer-related death nowadays.Majority of the current guidelines rely on TNM classification regarding therapy regi...BACKGROUND Rectal cancer(RC)is one of the most common diagnosed cancers,and one of the major causes of cancer-related death nowadays.Majority of the current guidelines rely on TNM classification regarding therapy regiments,however recent studies suggest that additional histopathological findings could affect the disease course.AIM To determine whether perineural invasion alone or in combination with lymphovascular invasion have an effect on 5-years overall survival(OS)of RC patients.METHODS A prospective study included newly diagnosed stage I-III RC patients treated and followed at the Digestive Surgery Clinic,Clinical Center of Serbia,between the years of 2014–2016.All patients had their diagnosis histologically confirmed in accordance with both TMN and Dukes classification.In addition,the patient’s demographics,surgical details,postoperative pathological details,differentiation degree and their correlation with OS was investigated.RESULTS Of 245 included patients with stage Ⅰ-Ⅲ RC,lymphovascular invasion(LVI)was identified in 92 patients(38%),whereas perineural invasion(PNI)was present in 46 patients(19%).Using Kaplan-Meier analysis for overall survival rate,we have found that both LVI and PNI were associated with lower survival rates(P<0.01).Moreover when Cox multiple regression model was used,LVI,PNI,older age,male gender were predictors of poor prognosis(HR=5.49;95%CI:2.889-10.429;P<0.05).CONCLUSION LVI and PNI were significant factors predicting worse prognosis in early and intermediate RC patients,hence more aggressive therapy should be reserved for these patients after curative resection.展开更多
AIM: To evaluate whether serum and tumor indoleamine 2,3-dioxygenase activities can predict lymphatic invasion (LI) or lymph node metastasis in colorectal carcinoma.METHODS: The study group consisted of 44 colorectal ...AIM: To evaluate whether serum and tumor indoleamine 2,3-dioxygenase activities can predict lymphatic invasion (LI) or lymph node metastasis in colorectal carcinoma.METHODS: The study group consisted of 44 colorectal carcinoma patients. The patients were re-grouped according to the presence or absence of LI and lymph node metastasis. Forty-three cancer-free subjects without any metabolic disturbances were included into the control group. Serum neopterin was measured by enzyme linked immunosorbent assay. Urinary neopterin and biopterin, serum tryptophan (Trp) and kynurenine (Kyn) concentrations of all patients were determined by high performance liquid chromatography. Kyn/Trp was calculated and its correlation with serum neopterin was determined to estimate the serum indoleamine 2,3-dioxygenase activity. Tissue sections from the studied tumors were re-examined histopathologically and were stained by immunohistochemistry with indoleamine-2,3-dioxygenase antibodies.RESULTS: Neither serum nor urinary neopterin was significantly different between the patient and control groups (both P > 0.05). However, colorectal carcinoma patients showed a significant positive correlation between the serum neopterin levels and Kyn/Trp (r = 0.450, P < 0.01). Urinary biopterin was significantly higher in cancer cases (P < 0.05). Serum Kyn/Trp was significantly higher in colorectal carcinoma patients (P < 0.01). Lymphatic invasion was present in 23 of 44 patients, of which only 12 patients had lymph node metastasis. Eleven patients with LI had no lymph node metastasis. Indoleamine-2,3-dioxygenase intensity score was significantly higher in LI positive cancer group (44.56% ± 6.11%) than negative colorectal cancer patients (24.04% ± 6.90%), (P < 0.05). Indoleamine 2,3-dioxygenase expression correlated both with the presence of LI and lymph node metastasis (P < 0.01 and P < 0.05, respectively). A significant difference between the accuracy of diagnosis by using either total indoleamine-2,3-dioxygenase immunostaining score or of lymph node metastasis was found during the evaluation of cancer patients.CONCLUSION: Indoleamine-2,3-dioxygenase expression may predict the presence of unrecognized LI and lymph node metastasis and may be included in the histopathological evaluation of colorectal carcinoma cases.展开更多
BACKGROUND Colorectal cancer(CRC)is one of the most common cancers worldwide.The gold standard screening methods for early detection and monitoring are colonoscopy and stool-based tests.However,innovative and minimall...BACKGROUND Colorectal cancer(CRC)is one of the most common cancers worldwide.The gold standard screening methods for early detection and monitoring are colonoscopy and stool-based tests.However,innovative and minimally invasive biomarkers need to be integrated into clinical practice.AIM To identify circulating microRNAs as potential CRC biomarkers through a com-parative analysis of tissue and plasma samples from patients with CRC.METHODS This case-control study conducted a quantitative real-time polymerase chain reaction analysis of 84 microRNAs in tumoral and peritumoral tissues,and 179 microRNAs in plasma from 19 patients with CRC.A control cohort for the tissue analysis and another control cohort for the plasma analysis have been enrolled.RESULTS In total,14 microRNAs were significantly differentially expressed in the tissue and plasma samples.Notably,five microRNAs(miR-26b-5p,miR-101-3p,miR-30d-5p,miR-107,and miR-21-5p)presented the same trend in terms of fold change in both types of biological samples.Significant associations between the circulating levels of miR-21-5p and miR-26b-5p and lymphovascular invasion were found.CONCLUSION These five microRNAs with significantly altered levels in plasma and tumoral tissue,could be good non-invasive CRC biomarkers candidates,enhancing screening,and supporting precision and individualized patient care.展开更多
BACKGROUND Gastric signet ring cell carcinoma(SRCC)is a rare,aggressive subtype of gastric cancer characterized by poor prognosis and distinctive biological behavior.Despite advances in gastric cancer treatment,SRCC r...BACKGROUND Gastric signet ring cell carcinoma(SRCC)is a rare,aggressive subtype of gastric cancer characterized by poor prognosis and distinctive biological behavior.Despite advances in gastric cancer treatment,SRCC remains difficult to diagnose early and manage effectively due to its infiltrative pattern and molecular variability.Reliable prognostic markers are critical to guide clinical management.AIM To investigate the prognostic factors,including human epidermal growth factor receptor 2(HER2)expression,associated with survival outcomes in patients with gastric SRCC.METHODS A retrospective analysis of 100 cases diagnosed between 2015 and 2019 was conducted,assessing demographic,clinical,and pathological data.HER2 expression was analyzed using immunohistochemistry,and survival outcomes,including overall survival and disease-free survival,were examined.RESULTS With a median follow-up of 43 months,the median patient age was 50 years,and males exhibited a higher mortality rate(P=0.0107).Elevated serum carbohydrate antigen 19-9 and carcinoembryonic antigen levels were significantly associated with increased mortality(P=0.00149 and P=0.00163,respectively).Advanced tumornode-metastasis stage and lymphovascular invasion were strong predictors of poor outcomes(P<0.001 and P=0.019).HER2 positivity correlated with higher mortality(P=0.00882)but was not significantly linked to recurrence(P=0.53).Surgical treatment significantly improved survival compared with non-surgical approaches(P=0.0226).CONCLUSION These findings highlight the aggressive nature of SRCC with advanced disease stage,elevated tumor markers,and lymphovascular invasion contributing to poor outcomes.HER2 expression,though infrequent,may indicate worse prognosis,reinforcing the role of surgical intervention in survival improvement.展开更多
Colon cancer remains a significant clinical problem worldwide and in the United States it is the third most common cancer diagnosed in men and women.It is generally accepted that most malignant neoplasms of the colon ...Colon cancer remains a significant clinical problem worldwide and in the United States it is the third most common cancer diagnosed in men and women.It is generally accepted that most malignant neoplasms of the colon arise from precursor adenomatous polyps.This stepwise progression of normal epithelium to carcinoma,often with intervening dysplasia,occurs as a result of multiple sequential,genetic mutations-some are inherited while others are acquired.Malignant polyps are defined by the presence of cancer cells invading through the muscularis mucosa into the underlying submucosa(T1).They can appear benign endoscopically but the presence of malignant invasion histologically poses a difficult and often controversial clinical scenario.Emphasis should be initially focused on the endoscopic assessment of these lesions.Suitable polyps should be resected en-bloc,if possible,to facilitate thorough evaluation by pathology.In these cases,proper attention must be given to the risks of residual cancer in the bowel wall or in the surrounding lymph nodes.If resection is not feasible endoscopically,thenthese patients should be referred for surgical resection.This review will discuss the important prognostic features of malignant polyps that will most profoundly affect this risk profile.Additionally,we will discuss effective strategies for their overall management.展开更多
BACKGROUND Colorectal cancer is a frequent cause of cancer-related mortality in patients with lymph node or distant metastases.Pericolonic tumor deposits(TDs)are considered prognostically distinct from lymph node meta...BACKGROUND Colorectal cancer is a frequent cause of cancer-related mortality in patients with lymph node or distant metastases.Pericolonic tumor deposits(TDs)are considered prognostically distinct from lymph node metastases.AIM To investigate risk factors for extranodal TDs in stage III colon cancer.METHODS This was a retrospective cohort study.We selected 155 individuals diagnosed with stage III colon cancer from the database of the Cancer Registry of the Tri-Service General Hospital.The patients were allocated into the groups with/without N1c.Multivariate Cox regression analysis and Kaplan-Meier method were done.The primary outcomes investigate the association between the covariates and extranodal TDs,and prognostic significance of the covariates regarding the survival.RESULTS There were 136 individuals in the non-N1c group and 19 individuals in the N1c group.Patients with lymphovascular invasion(LVI)had a higher risk of TDs.Overall survival rates of patients with and without LVI were 6.64 years and 8.61 years,respectively(P=0.027).The N1c patients without LVI had higher overall survival than those who with LVI(7.73 years vs 4.42 years,P=0.010).CONCLUSION Patients having stage III colon cancer with LVI have a higher probability of having TDs than those with stage III colon cancer without LVI.Stage III colon cancer patients with TDs and LVI could have poor prognosis and outcome.展开更多
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 ...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.展开更多
Urothelial bladder carcinoma(UBC)is an intricate malignancy with a variable natural history and clinical behavior.Despite developments in diagnosis/prognosis refi nement and treatment modalities,the recurrence rate is...Urothelial bladder carcinoma(UBC)is an intricate malignancy with a variable natural history and clinical behavior.Despite developments in diagnosis/prognosis refi nement and treatment modalities,the recurrence rate is high,and progression from non-muscle to muscle invasive UBC commonly leads to metastasis.Moreover,patients with muscle-invasive or extra-vesical disease often fail the standard chemotherapy treatment,and overall survival rates are poor.Thus,UBC remains a challenge in the oncology fi eld,representing an ideal candidate for research on biomarkers that could identify patients at increased risk of recurrence,progression,and chemo-refractoriness.However,progress toward personalized medicine has been hampered by the unique genetic complexity of UBC.Recent genome-wide expression and sequencing studies have brought new insights into its molecular features,pathogenesis and clinical diversity,revealing a landscape where classical pathology is intersected by the novel and heterogeneous molecular groups.Hence,it seems plausible to postulate that only an integrated signature of prognostic/predictive biomarkers inherent in different cancer hallmarks will reach clinical validation.In this review,we have summarized ours and others’research into novel putative biomarkers of progression and chemoresistance that encompass several hallmarks of cancer:tumor neovascularization,invasion and metastasis,and energy metabolism reprogramming of the tumor microenvironment.展开更多
基金supported by grants from the National Natural Science Foundation of China(No.82373303,No.82072922,No.82403750)a grant from the Natural Science Foundation of Shanghai(No.24ZR1412600)。
文摘Objective:Lymphovascular invasion(LVI)is a crucial step in metastasis and is closely associated with poor prognosis in patients with breast cancer.However,its clinical and molecular characteristics remain insufficiently defined.We aimed to identify molecular targets for LVI-positive(LVI+)breast cancer and predict patient prognosis via the analysis of genomic variations using targeted sequencing.Methods:We established a large-scale targeted sequencing cohort of 4,079 breast cancer samples,which included 3,159 early-stage and locally advanced patients with available LVI statuses.Comparisons of somatic mutation frequencies and germline pathogenic/likely pathogenic(P/LP)mutation frequencies,mutational signature analyses,and mutual exclusivity and co-occurrence analyses were performed to identify key genomic features involved in LVI+patients.Additionally,Kaplan-Meier survival analysis was conducted to further explore the prognostic value of co-mutations in LVI+cases.Results:We observed that LVI+patients with the hormone receptor-positive/human epidermal growth factor receptor 2-negative(HR+/HER2-)and triple-negative breast cancer(TNBC)subtypes exhibited worse disease-free survival.Notably,HR+/HER2-and HER2+breast cancer patients with LVI displayed distinct genomic features compared with LVI-tumors.Specifically,LVI+HR+/HER2-tumors exhibited greater frequencies of somatic mutations in TP53 and ESR1,germline BRCA2 P/LP variations,and an enrichment of clock-like single-base substitution(SBS)1 mutational signatures.In contrast,LVI+HER2+tumors demonstrated a higher incidence of somatic PIK3CA mutations and increased activity of the apolipoprotein B m RNA editing enzyme catalytic polypeptide(APOBEC)-associated SBS2 signature.Furthermore,we revealed that the co-mutation of TP53 and NF1 could serve as a potential prognostic marker for LVI+HR+/HER2-patients.Conclusions:Our findings provide a comprehensive overview of the genomic characteristics of LVI in breast cancer,thereby offering insights that may help in refining precision treatment strategies for LVI+breast cancer patients.
文摘AIM: To investigate the meaning of lymphovascular invasion (LVI) in rectal cancer after neoadjuvant radiotherapy. METHODS: A total of 325 patients who underwent radical resection using total mesorectal excision (TME) from January 2000 to January 2005 in Beijing cancer hospital were included retrospectively, divided into a preoperative radiotherapy (PRT) group and a control group, according to whether or not they underwent preoperative radiation. Histological assessments of tumor specimens were made and the correlation of LVI and prognosis were evaluated by univariate and multivariate analysis. RESULTS: The occurrence of LVI in the PRT and control groups was 21.4% and 26.1% respectively. In the control group, LVI was signifi cantly associated with histological differentiation and pathologic TNM stage, whereas these associations were not observed in the PRT group. LVI was closely correlated to disease progression and 5-year overall survival (OS) in both groups. Among the patients with disease progression, LVI positive patients in the PRT group had a signifi cantly longer median disease-free period (22.5 mo vs 11.5 mo, P = 0.023) and overall survival time (42.5 mo vs 26.5 mo, P = 0.035) compared to those in the control group, despite the fact that no signifi cant difference in 5-year OS rate was observed (54.4% vs 48.3%, P = 0.137). Multivariate analysis showed the distance of tumor from the anal verge, pretreatment serum carcinoembryonic antigen level, pathologic TNM stage and LVI were the major factors affecting OS. CONCLUSION: Neoadjuvant radiotherapy does not reduce LVI significantly; however, the prognostic meaning of LVI has changed. Patients with LVI may benefi t from neoadjuvant radiotherapy.
文摘To systematically evaluate the prognostic value of lymphovascular invasion （LVI） in radical prostatectomy （RP） by a meta-analysis based on the published literature. To identify relevant studies, PubMed, Cochrane Library, and Web of Science database were searched from 1966 to May 2014. Finally, 25 studies （9503 patients） were included. LVI was found in 12.2% （1156/9503） of the RP specimens. LVI was found to be correlated with higher pathological tumor stages （greater than pT3 stage） （risk ratio [RR] 1.90, 95% confidence interval [CI] 1.73-2.08, P〈 0.00001）, higher Gleason scores （greater than GS = 7） （RR 1.30, 95% CI 1.23-1.38, P 〈 0.00001）, positive pathological node （pN） status （RR 5.67, 95% CI 3.14-10.24, P 〈 0.00001）, extracapsular extension （RR 1.72, 95% CI 1.46-2.02, P 〈 0.00001）, and seminal vesicle involvement （RR 3.36, 95% CI 2.41-4.70, P 〈 0.00001）. The pooled hazard ratio （HR） was statistically significant for Biochemical Recurrence-Free （BCR-free） probability （HR 2.05, 95% ／ CI 1.64-2.56; Z = 6.30, P〈 0.00001）. Sensitivity analysis showed that the pooled HR and 95% CI were not significantly altered by the omission of any single study. Begg＇s Funnel plots showed no significant publication bias （P = 0.112）. In conclusion, LVI exhibited a detrimental effect on the BCR-Free probability and clinicopathological features in RP specimens, and may prove to be an independent prognostic factor of BCR.
基金Supported by the National High Level Hospital Clinical Research Funding,No.2023-NHLHCRF-BQ-32 and No.2023-NHLHCRFYYPPLC-ZR-13the Elite Medical Professionals Project of China-Japan Friendship Hospital,No.ZRJY2024-GG01.
文摘BACKGROUND Lymphovascular invasion(LVI)and perineural invasion(PNI)are associated with decreased survival in colorectal cancer(CRC),but its significance in N1c stage remains to be clearly defined.AIM We retrospectively identified 107 consecutive patients who had CRC with N1c disease radically resected at our hospital.Tumors were reviewed for LVI and PNI by one pathologist blinded to the patients’outcomes.Disease-free survival(DFS),overall survival(OS)and cancer-specific survival(CSS)were determined using the Kaplan-Meier method,with LVI and PNI prognosis differences determined by multivariate analysis using the Cox multiple hazards model.Results were compared using log-rank test.The receiver operating characteristic(ROC)curve was used to evaluate the prognostic predictive ability.RESULTS The median follow-up time was 63.17(45.33-81.37)months for DFS,with 33.64%(36/107)of patients experiencing recurrence;21.5%of tumors were found to be LVI positive and 44.9%PNI positive.The 5-year DFS rate was greater for patients with LVI-negative tumors compared with LVI-positive tumors(74.0%vs 35.6%),and PNI was similar(82.5%vs 45.1%).On multivariate analysis,LVI[hazard ratio(HR)=3.368,95%confidence interval(CI):1.628-6.966,P=0.001]and PNI(HR=3.055,95%CI:1.478-6.313,P=0.002)were independent prognostic factors for DFS.All patients could be divided into three groups of patients with different prognosis according to LVI and PNI.The 5-year ROC curve for LVI,PNI and their combination prediction of DFS was 0.646,0.709 and 0.759,respectively.Similar results were seen for OS and CSS.CONCLUSION LVI and PNI could serve as independent prognostic factors of outcomes in N1c CRC patients.Patients with LVI or PNI should be given more attention during treatment.
基金Supported by Science and Technology Project of Fujian Province,No.2022Y0025.
文摘BACKGROUND Lymphovascular invasion(LVI)and perineural invasion(PNI)are important prognostic factors for gastric cancer(GC)that indicate an increased risk of metastasis and poor outcomes.Accurate preoperative prediction of LVI/PNI status could help clinicians identify high-risk patients and guide treatment deci-sions.However,prior models using conventional computed tomography(CT)images to predict LVI or PNI separately have had limited accuracy.Spectral CT provides quantitative enhancement parameters that may better capture tumor invasion.We hypothesized that a predictive model combining clinical and spectral CT parameters would accurately preoperatively predict LVI/PNI status in GC patients.AIM To develop and test a machine learning model that fuses spectral CT parameters and clinical indicators to predict LVI/PNI status accurately.METHODS This study used a retrospective dataset involving 257 GC patients(training cohort,n=172;validation cohort,n=85).First,several clinical indicators,including serum tumor markers,CT-TN stages and CT-detected extramural vein invasion(CT-EMVI),were extracted,as were quantitative spectral CT parameters from the delineated tumor regions.Next,a two-step feature selection approach using correlation-based methods and information gain ranking inside a 10-fold cross-validation loop was utilized to select informative clinical and spectral CT parameters.A logistic regression(LR)-based nomogram model was subsequently constructed to predict LVI/PNI status,and its performance was evaluated using the area under the receiver operating characteristic curve(AUC).RESULTS In both the training and validation cohorts,CT T3-4 stage,CT-N positive status,and CT-EMVI positive status are more prevalent in the LVI/PNI-positive group and these differences are statistically significant(P<0.05).LR analysis of the training group showed preoperative CT-T stage,CT-EMVI,single-energy CT values of 70 keV of venous phase(VP-70 keV),and the ratio of standardized iodine concentration of equilibrium phase(EP-NIC)were independent influencing factors.The AUCs of VP-70 keV and EP-NIC were 0.888 and 0.824,respectively,which were slightly greater than those of CT-T and CT-EMVI(AUC=0.793,0.762).The nomogram combining CT-T stage,CT-EMVI,VP-70 keV and EP-NIC yielded AUCs of 0.918(0.866-0.954)and 0.874(0.784-0.936)in the training and validation cohorts,which are significantly higher than using each of single independent factors(P<0.05).CONCLUSION The study found that using portal venous and EP spectral CT parameters allows effective preoperative detection of LVI/PNI in GC,with accuracy boosted by integrating clinical markers.
文摘BACKGROUND Rectal cancer(RC)is one of the most common diagnosed cancers,and one of the major causes of cancer-related death nowadays.Majority of the current guidelines rely on TNM classification regarding therapy regiments,however recent studies suggest that additional histopathological findings could affect the disease course.AIM To determine whether perineural invasion alone or in combination with lymphovascular invasion have an effect on 5-years overall survival(OS)of RC patients.METHODS A prospective study included newly diagnosed stage I-III RC patients treated and followed at the Digestive Surgery Clinic,Clinical Center of Serbia,between the years of 2014–2016.All patients had their diagnosis histologically confirmed in accordance with both TMN and Dukes classification.In addition,the patient’s demographics,surgical details,postoperative pathological details,differentiation degree and their correlation with OS was investigated.RESULTS Of 245 included patients with stage Ⅰ-Ⅲ RC,lymphovascular invasion(LVI)was identified in 92 patients(38%),whereas perineural invasion(PNI)was present in 46 patients(19%).Using Kaplan-Meier analysis for overall survival rate,we have found that both LVI and PNI were associated with lower survival rates(P<0.01).Moreover when Cox multiple regression model was used,LVI,PNI,older age,male gender were predictors of poor prognosis(HR=5.49;95%CI:2.889-10.429;P<0.05).CONCLUSION LVI and PNI were significant factors predicting worse prognosis in early and intermediate RC patients,hence more aggressive therapy should be reserved for these patients after curative resection.
基金Supported by Gazi UniversityScientific Research Projects DivisionNo.01/2007-62
文摘AIM: To evaluate whether serum and tumor indoleamine 2,3-dioxygenase activities can predict lymphatic invasion (LI) or lymph node metastasis in colorectal carcinoma.METHODS: The study group consisted of 44 colorectal carcinoma patients. The patients were re-grouped according to the presence or absence of LI and lymph node metastasis. Forty-three cancer-free subjects without any metabolic disturbances were included into the control group. Serum neopterin was measured by enzyme linked immunosorbent assay. Urinary neopterin and biopterin, serum tryptophan (Trp) and kynurenine (Kyn) concentrations of all patients were determined by high performance liquid chromatography. Kyn/Trp was calculated and its correlation with serum neopterin was determined to estimate the serum indoleamine 2,3-dioxygenase activity. Tissue sections from the studied tumors were re-examined histopathologically and were stained by immunohistochemistry with indoleamine-2,3-dioxygenase antibodies.RESULTS: Neither serum nor urinary neopterin was significantly different between the patient and control groups (both P > 0.05). However, colorectal carcinoma patients showed a significant positive correlation between the serum neopterin levels and Kyn/Trp (r = 0.450, P < 0.01). Urinary biopterin was significantly higher in cancer cases (P < 0.05). Serum Kyn/Trp was significantly higher in colorectal carcinoma patients (P < 0.01). Lymphatic invasion was present in 23 of 44 patients, of which only 12 patients had lymph node metastasis. Eleven patients with LI had no lymph node metastasis. Indoleamine-2,3-dioxygenase intensity score was significantly higher in LI positive cancer group (44.56% ± 6.11%) than negative colorectal cancer patients (24.04% ± 6.90%), (P < 0.05). Indoleamine 2,3-dioxygenase expression correlated both with the presence of LI and lymph node metastasis (P < 0.01 and P < 0.05, respectively). A significant difference between the accuracy of diagnosis by using either total indoleamine-2,3-dioxygenase immunostaining score or of lymph node metastasis was found during the evaluation of cancer patients.CONCLUSION: Indoleamine-2,3-dioxygenase expression may predict the presence of unrecognized LI and lymph node metastasis and may be included in the histopathological evaluation of colorectal carcinoma cases.
基金Supported by European Union’s NextGeneration PNRR-III-C9-2022-I5,managed by the Ministry of Research,Innovation and Digitization,No.760009/30.12.2022,code CF 14/16.11.2022Ministry of Research,Innovation and Digitization of Romania,No.PN 23.16.02.04.
文摘BACKGROUND Colorectal cancer(CRC)is one of the most common cancers worldwide.The gold standard screening methods for early detection and monitoring are colonoscopy and stool-based tests.However,innovative and minimally invasive biomarkers need to be integrated into clinical practice.AIM To identify circulating microRNAs as potential CRC biomarkers through a com-parative analysis of tissue and plasma samples from patients with CRC.METHODS This case-control study conducted a quantitative real-time polymerase chain reaction analysis of 84 microRNAs in tumoral and peritumoral tissues,and 179 microRNAs in plasma from 19 patients with CRC.A control cohort for the tissue analysis and another control cohort for the plasma analysis have been enrolled.RESULTS In total,14 microRNAs were significantly differentially expressed in the tissue and plasma samples.Notably,five microRNAs(miR-26b-5p,miR-101-3p,miR-30d-5p,miR-107,and miR-21-5p)presented the same trend in terms of fold change in both types of biological samples.Significant associations between the circulating levels of miR-21-5p and miR-26b-5p and lymphovascular invasion were found.CONCLUSION These five microRNAs with significantly altered levels in plasma and tumoral tissue,could be good non-invasive CRC biomarkers candidates,enhancing screening,and supporting precision and individualized patient care.
文摘BACKGROUND Gastric signet ring cell carcinoma(SRCC)is a rare,aggressive subtype of gastric cancer characterized by poor prognosis and distinctive biological behavior.Despite advances in gastric cancer treatment,SRCC remains difficult to diagnose early and manage effectively due to its infiltrative pattern and molecular variability.Reliable prognostic markers are critical to guide clinical management.AIM To investigate the prognostic factors,including human epidermal growth factor receptor 2(HER2)expression,associated with survival outcomes in patients with gastric SRCC.METHODS A retrospective analysis of 100 cases diagnosed between 2015 and 2019 was conducted,assessing demographic,clinical,and pathological data.HER2 expression was analyzed using immunohistochemistry,and survival outcomes,including overall survival and disease-free survival,were examined.RESULTS With a median follow-up of 43 months,the median patient age was 50 years,and males exhibited a higher mortality rate(P=0.0107).Elevated serum carbohydrate antigen 19-9 and carcinoembryonic antigen levels were significantly associated with increased mortality(P=0.00149 and P=0.00163,respectively).Advanced tumornode-metastasis stage and lymphovascular invasion were strong predictors of poor outcomes(P<0.001 and P=0.019).HER2 positivity correlated with higher mortality(P=0.00882)but was not significantly linked to recurrence(P=0.53).Surgical treatment significantly improved survival compared with non-surgical approaches(P=0.0226).CONCLUSION These findings highlight the aggressive nature of SRCC with advanced disease stage,elevated tumor markers,and lymphovascular invasion contributing to poor outcomes.HER2 expression,though infrequent,may indicate worse prognosis,reinforcing the role of surgical intervention in survival improvement.
文摘Colon cancer remains a significant clinical problem worldwide and in the United States it is the third most common cancer diagnosed in men and women.It is generally accepted that most malignant neoplasms of the colon arise from precursor adenomatous polyps.This stepwise progression of normal epithelium to carcinoma,often with intervening dysplasia,occurs as a result of multiple sequential,genetic mutations-some are inherited while others are acquired.Malignant polyps are defined by the presence of cancer cells invading through the muscularis mucosa into the underlying submucosa(T1).They can appear benign endoscopically but the presence of malignant invasion histologically poses a difficult and often controversial clinical scenario.Emphasis should be initially focused on the endoscopic assessment of these lesions.Suitable polyps should be resected en-bloc,if possible,to facilitate thorough evaluation by pathology.In these cases,proper attention must be given to the risks of residual cancer in the bowel wall or in the surrounding lymph nodes.If resection is not feasible endoscopically,thenthese patients should be referred for surgical resection.This review will discuss the important prognostic features of malignant polyps that will most profoundly affect this risk profile.Additionally,we will discuss effective strategies for their overall management.
文摘BACKGROUND Colorectal cancer is a frequent cause of cancer-related mortality in patients with lymph node or distant metastases.Pericolonic tumor deposits(TDs)are considered prognostically distinct from lymph node metastases.AIM To investigate risk factors for extranodal TDs in stage III colon cancer.METHODS This was a retrospective cohort study.We selected 155 individuals diagnosed with stage III colon cancer from the database of the Cancer Registry of the Tri-Service General Hospital.The patients were allocated into the groups with/without N1c.Multivariate Cox regression analysis and Kaplan-Meier method were done.The primary outcomes investigate the association between the covariates and extranodal TDs,and prognostic significance of the covariates regarding the survival.RESULTS There were 136 individuals in the non-N1c group and 19 individuals in the N1c group.Patients with lymphovascular invasion(LVI)had a higher risk of TDs.Overall survival rates of patients with and without LVI were 6.64 years and 8.61 years,respectively(P=0.027).The N1c patients without LVI had higher overall survival than those who with LVI(7.73 years vs 4.42 years,P=0.010).CONCLUSION Patients having stage III colon cancer with LVI have a higher probability of having TDs than those with stage III colon cancer without LVI.Stage III colon cancer patients with TDs and LVI could have poor prognosis and outcome.
文摘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.
文摘Urothelial bladder carcinoma(UBC)is an intricate malignancy with a variable natural history and clinical behavior.Despite developments in diagnosis/prognosis refi nement and treatment modalities,the recurrence rate is high,and progression from non-muscle to muscle invasive UBC commonly leads to metastasis.Moreover,patients with muscle-invasive or extra-vesical disease often fail the standard chemotherapy treatment,and overall survival rates are poor.Thus,UBC remains a challenge in the oncology fi eld,representing an ideal candidate for research on biomarkers that could identify patients at increased risk of recurrence,progression,and chemo-refractoriness.However,progress toward personalized medicine has been hampered by the unique genetic complexity of UBC.Recent genome-wide expression and sequencing studies have brought new insights into its molecular features,pathogenesis and clinical diversity,revealing a landscape where classical pathology is intersected by the novel and heterogeneous molecular groups.Hence,it seems plausible to postulate that only an integrated signature of prognostic/predictive biomarkers inherent in different cancer hallmarks will reach clinical validation.In this review,we have summarized ours and others’research into novel putative biomarkers of progression and chemoresistance that encompass several hallmarks of cancer:tumor neovascularization,invasion and metastasis,and energy metabolism reprogramming of the tumor microenvironment.
