Distant Liver Metastases as a Major Factor Influencing Survival in Patients with Colorectal Cancer

Abstract Aim: To assess the effect of the factor ‘hepatic metastatic disease’ on long-term outcomes in patients with colorectal cancer. Materials and methods: We analysed retrospectively 200 randomly selected patients. Forty-two of them were excluded from the study for different reasons so the study contingent was 158 patients over a period of 23 years. All were diagnosed and treated in the Lozenetz University Hospital, in the Department of General Surgery. 125 of the patients were diagnosed with colorectal cancer without distant metastases and 33 of the patients had liver metastases as a result of colorectal carcinoma. The statistical analysis was performed using SPSS 19 IMB, with a level of significance of P < 0.05 at which the null hypothesis is rejected. We also used descriptive analysis, Kaplan-Meier estimator, Log-Rank Test and Life-Table statistics models. Results: The median survival for patients without metastases was 160 months, and the median was 102 months. The median survival for patients with liver metastases was 28 months and the median was 21 months. One-year survival for patients without metastases was 92% versus 69% in patients with liver metastases. Conclusion: Average, annual and median survivals are influenced statistically significantly by the presence of liver metastases compared to overall survival and that of patients without metastatic colorectal cancer. Liver metastatic disease is a proven factor affecting long-term prognosis and survival in patients with colorectal cancer.

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The prognostic role of tissue TLR2 and TLR4 in colorectal cancer

Virchows Archiv ◽

10.1007/s00428-020-02833-5 ◽

2020 ◽

Vol 477 (5) ◽

pp. 705-715

Author(s):

Ines Beilmann-Lehtonen ◽

Camilla Böckelman ◽

Harri Mustonen ◽

Selja Koskensalo ◽

Jaana Hagström ◽

...

Keyword(s):

Colorectal Cancer ◽

Prognostic Factor ◽

Distant Metastases ◽

University Hospital ◽

Rank Test ◽

Pathogen Invasion ◽

Kaplan Meier ◽

Node Positive Disease ◽

Colorectal Cancer Patients ◽

Dukes C

Abstract Colorectal cancer (CRC), the second most common cancer globally, resulted in 881,000 deaths in 2018. Toll-like receptors (TLRs) are crucial to detecting pathogen invasion and inducing the host’s immune response. This study aimed to explore the prognostic value of TLR2 and TLR4 tumor expressions in colorectal cancer patients. We studied the immunohistochemical expressions of TLR2 and TLR4 using tissue microarray specimens from 825 patients undergoing surgery in the Department of Surgery, Helsinki University Hospital, between 1982 and 2002. We assessed the relationships between TLR2 and TLR4 expressions and clinicopathological variables and patient survival. We generated survival curves using the Kaplan-Meier method, determining significance with the log-rank test. Among patients with lymph node–positive disease and no distant metastases (Dukes C), a strong TLR2 immunoactivity associated with a better prognosis (p < 0.001). Among patients with local Dukes B disease, a strong TLR4 immunoactivity associated with a worse disease-specific survival (DSS; p = 0.017). In the multivariate survival analysis, moderate TLR4 immunoactivity compared with strong TLR4 immunoactivity (hazard ratio (HR) 0.66, 95% confidence interval (CI) 0.49–0.89, p = 0.007) served as an independent prognostic factor. In the multivariate analysis for the Dukes subgroups, moderate TLR2 immunoactivity (HR 2.63, 95% CI 1.56–4.44, p < 0.001) compared with strong TLR2 immunoactivity served as an independent negative prognostic factor in the Dukes C subgroup. TLR2 and TLR4 might be new prognostic factors to indicate which CRC patients require adjuvant therapy and which could spare from an unnecessary follow-up, but further investigations are needed.

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Early PET/CT scan compared with RECIST to predict long-term outcome of patients with liver metastases from colorectal cancer treated with preoperative chemotherapy plus bevacizumab.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.11008 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. 11008-11008

Author(s):

Maria Carmela Piccirillo ◽

Secondo Lastoria ◽

Guglielmo Nasti ◽

Corradina Caraco ◽

Luigi Aloj ◽

...

Keyword(s):

Colorectal Cancer ◽

Liver Metastases ◽

Metabolic Response ◽

Cox Model ◽

Rank Test ◽

Kappa Statistics ◽

Preoperative Treatment ◽

Long Term Outcome ◽

Pet Ct

11008 Background: Early changes in tumor metabolism measured with positron-emission-tomography/computerized tomography (PET/CT) could predict the long-term efficacy of treatment better than dimensional RECIST response. Methods: We performed PET/CT before and after 1 cycle of treatment in patients with resectable liver metastases from colorectal cancer, within a phase II trial of preoperative FOLFIRI plus bevacizumab. For each lesion, the maximum SUV (SUVmax) and the total lesion glycolisis (TLG) were determined. For both, based on previous studies, a ≤-50% change from baseline was used as threshold for significant response. Metabolic response was categorized no/yes by using three different methods that enter into the calculation (i) the largest observed value (highest SUVmax/TLG), or (ii) the sum of all the observed values (Total SUVmax/TLG), or (iii) each observed values (SUVmax/TLG-by-lesion). Standard RECIST response was assessed after 3 months of treatment. The association between metabolic and RECIST response was tested with the Mc Nemar’s test and their agreement was expressed as Kappa statistics; the ability to predict progression-free (PFS) and overall (OS) survival was tested with Log-rank test and a multivariable Cox model. Results: 33 patients were analyzed. After treatment, there was a notable decrease of all PET/CT parameters, with a median change of -33.9% for the highest SUVmax, -61.5% for the highest TLG, -34.9% for the total SUVmax, and -65.5% for the total TLG. The association of SUV-based metabolic response (but not the TLG-based) with RECIST was statistically significant. However, the agreement between RECIST and PET/CT responses was consistently small. PFS and OS were significantly longer among PET/CT responding patients, whichever the measure used. On the contrary, no significant outcome difference was evident according to RECIST response. Conclusions: Early PET/CT response was significantly predictive of long-term outcomes during preoperative treatment of patients with liver metastases from colorectal cancer and its predictive ability was higher than that of RECIST response. Clinical trial information: 2006-006572-38.

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The association of immunosurveillance and distant metastases in colorectal cancer

Journal of Cancer Research and Clinical Oncology ◽

10.1007/s00432-021-03753-w ◽

2021 ◽

Author(s):

Sven Jacob ◽

Vindi Jurinovic ◽

Christopher Lampert ◽

Elise Pretzsch ◽

Jörg Kumbrink ◽

...

Keyword(s):

Colorectal Cancer ◽

Liver Metastases ◽

Differentially Expressed Gene ◽

Distant Metastases ◽

Gene Set Enrichment Analysis ◽

Differentially Expressed ◽

University Hospital ◽

Gene Signatures ◽

Gene Set ◽

The Core

Abstract Background Colorectal cancer (CRC) is the third most common malignancy worldwide, but the key driver to distant metastases is still unknown. This study aimed to elucidate the link between immunosurveillance and organotropism of metastases in CRC by evaluating different gene signatures and pathways. Material and methods CRC patients undergoing surgery at the Department of General, Visceral and Transplantation Surgery at the Ludwig-Maximilian University Hospital Munich (Munich, Germany) were screened and categorized into M0 (no distant metastases), HEP (liver metastases) and PER (peritoneal carcinomatosis) after a 5-year follow-up. Six patients of each group were randomly selected to conduct a NanoString analysis, which includes 770 genes. Subsequently, all genes were further analyzed by gene set enrichment analysis (GSEA) based on seven main cancer-associated databases. Results Comparing HEP vs. M0, the gene set associated with the Toll-like receptor (TLR) cascade defined by the Reactome database was significantly overrepresented in HEP. HSP90B1, MAPKAPK3, PPP2CB, PPP2R1A were identified as the core enrichment genes. The immunologic signature pathway GSE6875_TCONV_VS_FOXP3_KO_TREG_DN with FOXP3 as downstream target was significantly overexpressed in M0. RB1, TMEM 100, CFP, ZKSCAN5, DDX50 were the core enrichment genes. Comparing PER vs. M0 no significantly differentially expressed gene signatures were identified. Conclusion Chronic inflammation might enhance local tumor growth. This is the first study identifying immune related gene sets differentially expressed between patients with either liver or peritoneal metastases. The present findings suggest that the formation of liver metastases might be associated with TLR-associated pathways. In M0, a high expression of FOXP3 + tumor infiltrating lymphocytes (TILs) seemed to prevent at least in part metastases. Thus, these correlative findings lay the cornerstone to further studies elucidating the underlying mechanisms of organotropism of metastases.

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Long-term survival of patients with unresectable colorectal cancer liver metastases following infusional chemotherapy with 5-fluorouracil, leucovorin, oxaliplatin and surgery

Annals of Oncology ◽

10.1023/a:1008347829017 ◽

1999 ◽

Vol 10 (6) ◽

pp. 663-669 ◽

Cited By ~ 446

Author(s):

S. Giacchetti ◽

M. Itzhaki ◽

G. Gruia ◽

R. Adam ◽

R. Zidani ◽

...

Keyword(s):

Colorectal Cancer ◽

Liver Metastases ◽

Colorectal Cancer Liver Metastases ◽

Term Survival ◽

Long Term Survival

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Colorectal cancer and brain metastases: An aggressive disease with a different response to treatment

Tumori Journal ◽

10.1177/0300891618765541 ◽

2018 ◽

Vol 105 (5) ◽

pp. 427-433 ◽

Cited By ~ 1

Author(s):

Georges Chahine ◽

Tony Ibrahim ◽

Tony Felefly ◽

Abir El-Ahmadie ◽

Pamela Freiha ◽

...

Keyword(s):

Colorectal Cancer ◽

Brain Metastases ◽

Median Survival ◽

Metastatic Disease ◽

Antiangiogenic Therapy ◽

Response To Treatment ◽

Aggressive Disease ◽

Dismal Prognosis ◽

Poor Outcomes ◽

Different Response

Introduction: Brain metastases (BM) are rare in colorectal cancer (CRC) and are associated with a dismal prognosis. This work aims to report the rate of BM in CRC patients treated in a single institution, along with survival and prognostic factors. Methods: Medical charts for patients with histologically proven CRC were retrospectively reviewed. Results: A total of 538 patients were identified, of whom 33% developed any metastatic disease and 4.4% presented BM. Lung was the most frequently associated metastatic site (in 68% of the cases). The only factor independently associated with BM development was the presence of metastatic disease at the time of initial presentation. The median duration from initial diagnosis to BM development was 38.6 months (SD 29.1 months). Median survival after BM development was 62 days (95% confidence interval [CI] 56–68). Patients diagnosed with BM within 1 year of cancer diagnosis responded significantly better to treatment than those who acquired BM later, with a median survival after BM diagnosis of 261 days versus 61 days, respectively ( p = .002). Patients with BM who received antiangiogenic therapy had an improved median survival compared to those who did not (151 days vs 59 days, p = 0.02; hazard ratio for death 0.29 [95% CI 0.09–0.94]). Conclusion: CRC with BM is an aggressive disease resistant to standard treatment and is associated with poor outcomes. Adding antiangiogenic therapy might be of value for those patients. Patients with BM developing early in the disease course might respond better to treatment.

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ALPPS for Colorectal Cancer Liver Metastases—Short and Long-Term Results

Colorectal Cancer Liver Metastases ◽

10.1007/978-3-030-25486-5_35 ◽

2019 ◽

pp. 469-486

Author(s):

Kerollos Nashat Wanis ◽

Bao Tram Nghiem ◽

Roberto Hernandez-Alejandro

Keyword(s):

Colorectal Cancer ◽

Liver Metastases ◽

Long Term Results ◽

Colorectal Cancer Liver Metastases ◽

Short And Long Term

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Long-Term Immunological and Virological Outcomes in Children Receiving Highly Active Antiretroviral Therapy at Hawassa University College of Medicine and Health Sciences, Southern Ethiopia

Journal of Immunology Research ◽

10.1155/2021/2498025 ◽

2021 ◽

Vol 2021 ◽

pp. 1-9

Author(s):

Demissie Assegu Fenta ◽

Temesgen Bizuayehu Wube ◽

Metsihet Mohammed Nuru

Keyword(s):

Viral Load ◽

Virological Failure ◽

Highly Active Antiretroviral Therapy ◽

University Hospital ◽

Rank Test ◽

Southern Ethiopia ◽

Viral Load Suppression ◽

Highly Active ◽

Hawassa University

Purpose. To determine immunological and virological failure and associated factors among children infected with human immunodeficiency virus receiving antiretroviral treatments at Hawassa University Hospital, Southern Ethiopia. Methods. A hospital-based cross-sectional study was conducted among 273 HIV-infected children from July 1 to December 1, 2019. Data were collected using a structured questionnaire and review of patient records. Blood samples for viral load and CD4 count were collected. Data were analyzed using SPSS version 20. Significance group comparison was done by the Kaplan-Meier log-rank test. The Cox proportional hazard model was used to select significant factors of the variability between groups. Results. A total of 273 children, between the age ranges of 1 to 14 years, were included. Of these, 139 (50.9%) and 134 (49.1%) were males and females, respectively. Children from the rural area were almost five times more vulnerable for virological and immunological failure than those children from the urban area ( AOR = 4.912 , (1.276-8.815), P = 0.032 ). The overall viral load suppression was 196 (71.8%) with a good adherence of 226 (82.9%). Nonsuppressed HIV viral load was found to be 77 (28.2%) which had two times more viral load copies ( AOR = 2.01 , (1.21–2.66), P = 0.001 ) when compared to those who had suppressed viral load copies. The proportions of children who had immunological nonresponse were 45.6% (21 out of 46), 30.4% (14 out of 46), and 23.9% (11 out of 46) among children with baseline CD4 of <200, 201-500, and >500 cells/μl, respectively. Unimproved outcomes among females were noted for immunological and virological failure in this study ( AOR = 1.901 , (1.038-3.481), P = 0.038 ). Conclusion. In conclusion, the highly active antiretroviral treatment appeared highly effective in terms of immunological and virological long-term outcomes. However, viral suppression (71.8%) in our study was far apart from the UNAIDS target of 90% in 2020. For that reason, strengthening adherence counseling and early initiation of HAART is important.

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