Circulating extracellular vesicles are monitoring biomarkers of anti-PD1 response and enhancer of tumor progression and immunosuppression in metastatic melanoma.

BACKGROUND: Clinical drawback in checkpoint inhibitors immunotherapy (ICI) of metastatic melanoma (MM) is monitoring clinical benefit. Soluble forms of PD1(sPD1) and PD-L1(sPD-L1) and extracellular vesicles (EVs) expressing PD1 and PD-L1 have recently emerged as predictive biomarkers of response. As factors released in the blood, EVs and soluble forms could be relevant in monitoring treatment efficacy and adaptive resistance to ICI. METHODS: We used pre-therapy plasma samples of 110 MM patients and longitudinal samples of 46 patients. Elisa assay and flow cytometry (FCM) were used to measure sPD-L1 and sPD1 concentrations and the percentage of PD1+ EVs and PD-L1+ EVs, released from tumor and immune cells in patients subsets. Transwell assays were conducted to investigate the impact of EVs of each patient subset on MM cells invasion and interaction between tumor cells and macrophages or dendritic cells. Viability assays were performed to assess EVs effect on MM cells and organoids sensitivity to anti-PD1. FCM was used to investigate immunosuppressive markers in EVs and immune cells. RESULTS: The concentrations of sPD1 and sPD-L1 in pre-treatment and longitudinal samples did not correlate with anti-PD1 response, instead only tumor-derived PD1+ EVs decreased in long responders while increased during disease progression in responders. Notably, we observed reduction of T cell derived EVs expressing LAG3+ and PD1+ in long responders and their increase in responders experiencing progression. By investigating the impact of EVs on disease progression, we found that those isolated from non-responders and from patients with progression disease accelerated tumor cells invasiveness and migration towards macrophages, while EVs of long responders reduced the metastatic potential of MM cells and neo-angiogenesis. Additionally, the EVs of non-responders and of progression disease patients subset reduced the sensitivity of MM cells and organoids of responder to anti-PD1 and the recruitment of dendritic cells, while the EVs of progression disease subset skewed macrophages to express higher level of PDL-1. CONCLUSION: Collectively, we suggest that the detection of tumor-derived PD1 + EVs may represent a useful tool for monitoring the response to anti-PD1 and a role for EVs shed by tumor and immune cells in promoting tumor progression and immune dysfunction.

Cemiplimab in an Elderly Frail Population of Patients With Locally Advanced or Metastatic Cutaneous Squamous Cell Carcinoma: A Single-Center Real-Life Experience From Italy.

BACKGROUND: Cutaneous squamous cell carcinoma (CSCC) is the second most common skin cancer whose incidence is growing parallel to the lengthening of the average lifespan. Cemiplimab, an antiPD-1 monoclonal antibody, is the first approved immunotherapy for patients with locally advanced CSCC (laCSCC) or metastatic CSCC (mCSCC) thanks to phase I and II studies showing high antitumor activity and good tolerability. Nevertheless, at present, very few data are available regarding cemiplimab in real-life experience and in frail, elderly, and immunosuppressed patients as well as regarding biomarkers able to predict response so as to guide therapeutic choices. PATIENTS AND METHODS: We built a retroprospective cohort study including 30 non-selected patients with laCSCC (25) and mCSCC (five) treated with cemiplimab from August 2019 to November 2020. Clinical outcomes, toxicity profile, and correlations with disease, patients, and peripheral blood parameters are explored. RESULTS: The median age was 81 years (range, 36-95), with 24 males and five patients having an immunosuppressive condition, while the frailty prevalence was 83% based on index derived from age, Eastern Cooperative Oncology Group performance status, and Charlson Comorbidity Index. We reported 23 responses (76.7%) with nine complete responses (30%). A statistically significant higher response rate was observed in head and neck primary tumors and in patients with hemoglobin level >12 g/dl. No difference was observed with respect to frailty, median age, sex, and body mass index. The baseline low neuthophil/lymphocyte ratio and low platelet/lymphocyte ratio resulted to be also correlated with a better response. Moreover, lymphocyte, neutrophil, and monocyte behaviors had an opposite trend in responders and non-responders. An overall response was reported in four of five immunosuppressed patients. Seventeen patients (57.6%) have an ongoing response and are still alive. Six responders had interrupted treatment (two for toxicity and four for personal choice) but maintained their response. The treatment was well tolerated by the majority of patients. The most common adverse events were fatigue in seven patients (23.3%) and skin toxicity in 10 patients (33.3%), including pruritus in six patients, rash in three patients, and bullous erythema in one patient. CONCLUSIONS: In our real-life experience, cemiplimab showed a high antitumor activity with acceptable safety profile similar to those in trials with selected patients. Moreover, its antitumor activity resulted to be not impaired in very elderly patients and in those with immunocompromised status.

Remote mentoring in laparotomic and laparoscopic cancer surgery during Covid-19 pandemic: an experimental setup based on mixed reality.

In this paper, Mixed Reality (MR) has been exploited in the operating rooms to perform laparoscopic and open surgery with the aim of providing remote mentoring to the medical doctors under training during the Covid-19 pandemic. The employed architecture, which has put together MR smartglasses, a Digital Imaging Player, and a Mixed Reality Toolkit, has been used for cancer surgery at the IRCCS Hospital 'Giovanni Paolo II' in southern Italy. The feasibility of using the conceived platform for real-time remote mentoring has been assessed on the basis of surveys distributed to the trainees after each surgery.

An Intrapancreatic accessory spleen presenting as a neuroendocrine tumor.

Although the second most common site of the accessory spleen is the tail of the pancreas, intrapancreatic accessory spleens (IPAS) are rarely recognized radiologically. When an accessory spleen is located in the pancreas, it may mimic a hypervascular pancreatic tumor. We report a case of intrapancreatic accessory spleen which radiologically (on TC) mimicked a neuroendocrine pancreatic tumor (PNET). It was not possible to be sure that the pancreatic nodule had no malignant potential; because of the close proximity to splenic vessel we performed en bloc resection of the spleen and distal pancreas. Postoperative course was uneventful. IPAS must be considered in the differential diagnosis of pancreatic tail tumors, particulary an asymptomatic small PNET; new and adequate diagnostic studies have demonstrated utility in defining these lesions. We review pertinent literature. KEY WORD: Intrapancreatic accessory spleen, Pancreatic neuroendocrine tumor.

The Management of Oligoprogression in the Landscape of New Therapies for Metastatic Melanoma.

Background: A limited degree of progression after a response to treatment is labelled as oligoprogression and is a hot topic of metastatic melanoma (MM) management. Rogue progressive metastases could benefit from local treatment, which could allow the continuation of ongoing systemic therapy, also known as treatment beyond progression (TBP). Methods: We retrospectively reviewed 214 selected MM patients who developed oligoprogression during treatment with v-Raf murine sarcoma viral oncogene homolog B (BRAF)/mitogen-activated-extracellular signal-regulated kinase (MEK) or programmed cell death protein 1 (PD-1) inhibitors and received a local treatment continuing TBP. We performed univariate and multivariable analyses to assess the association between therapy outcomes and a series of clinical and biological features. Results: We identified 27 (10%) oligoprogressed patients treated locally with surgery (14), radiosurgery (11), and electrochemotherapy (2). TBP included PD-1 inhibitors (13) and BRAF/MEK inhibitors (14). The median progression-free survival post oligoprogression (PFSPO) was 14 months (5-19 95% confidence interval (C.I.)). In the univariate analysis, a significantly longer PFSPO was associated with complete response (CR), Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0, neutrophils/lymphocytes ratio (N/L) <2, and progression-free survival (PFS) at oligoprogression >11 months. Nevertheless, in the multivariable analysis, only CR and N/L <2 were found to be associated with longer PFSPO. Conclusions: In selected patients, local treatments contribute to controlling oligoprogression for a long time, allowing the continuation of systemic treatment and prolongation of overall survival (OS). Increasing biological and clinical knowledge is improving the accuracy in identifying patients to apply for local ablative therapies.

Synergism of Adipocytokine Profile and ADIPOQ/TNF-α Polymorphisms in NAFLD-associated MetS Predict Colorectal Liver Metastases Outgrowth.

BACKGROUND/AIM: The aim of this study was to evaluate whether the altered profile of adipocytokine and genetic fingerprint in NAFLD-associated metabolic syndrome "cluster" represents synergistic risk factors predicting onset of liver colorectal cancer metastases. MATERIALS AND METHODS: A total of 165 colorectal cancer patients were enrolled, 56,3% were with metabolic syndrome/NAFLD. Serum samples were assayed for ADIPOQ, leptin and TNF-a levels by ELISA. ADIPOQ rs266729 C/G and TNF-308 A/G genotypes were analyzed in DNA isolated from whole blood. RESULTS: Reduction in adiponectin levels and increase in leptin and TNF-α was shown in patients with liver metastases. This trend was influenced by BMI, MetS/NAFLD, and insulin resistance. ADIPOQ G rs266729 and TNF- 308 A allele are associated with obesity, MetS/NAFLD and insulin resistance. ADIPOQ CG/GG and GA/AA TNF-alpha genotypes confer susceptibility to liver metastases. CONCLUSION: Obesity and hepatic steatosis significantly favor the development of colorectal cancer liver metastases and the individual adipocytokines genetic profile may play an important predictive role.

Assessment of Nutritional and Inflammatory Status to Determine the Prevalence of Malnutrition in Patients Undergoing Surgery for Colorectal Carcinoma.

BACKGROUND/AIM: Colorectal Cancer is the fourth most frequent cause of cancer death worldwide and its incidence increases from 50 years of age. It is often associated with protein-caloric malnutrition and 20% of cancer deaths occur due to this event. The aim of this study was to assess the prevalence of malnutrition and inflammatory status in 78 patients undergoing surgery for colorectal carcinoma. PATIENTS AND METHODS: Nutritional Status was assessed by Mini Nutritional Assessment (MNA). Serum levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were measured by ELISA, while albumin, C-reactive protein (CRP) and transferrin (TRF) were tested using an immunometric assay. RESULTS: The mean MNA score in colorectal patients was 20.4±8.4, while 23/78 patients (29.4%) were well nourished, 36/78 (46.1%) were at risk of malnutrition and 19/78 (24.3%) were malnourished, reporting in the previous six months from the date of diagnosis a significant weight loss (>10 kg), muscle mass loss and severe reduction of food intake due to loss of appetite and altered taste perception. The serum means of IL-6, TNF-α and CRP, were significantly higher in colorectal patients compared to the control group (p<0.001, p<0.0001, p<0.0001, respectively) while lower TRF, albumin and HCT serum levels in cancer patients vs. healthy subjects (p<0.0001; p<0.0001 and p<0.0001) were found. CONCLUSION: more than 50% of colorectal cancer patients were malnourished or at risk of malnutrition and reported an imbalance between nutritional and inflammatory status. They, therefore, require a nutritional intervention before treatment in order to have a more effective response and improve quality of life.

Microvascular density and endothelial area correlate with Ki-67 proliferative index in surgically-treated pancreatic ductal adenocarcinoma patients.

Previous experimental and clinical data have indicated that tumour cell proliferation is associated with angiogenesis; in addition, an increased microvascular density (MVD) of tumours has been associated with poor prognosis in solid and haematological malignancies. However, limited data exists regarding the association between tumour cell proliferation and angiogenesis in primary tumour tissue from pancreatic ductal adenocarcinoma (PDAC) patients; therefore, the present study aimed to investigate this association. A series of 31 PDAC patients with stage Tumour (T)2-3 Node (N)0-1 Metastasis (M)0 were recruited into the present study and subsequently underwent surgery. PDAC tissue and adjacent normal tissue (ANT), resected during surgery, were evaluated using immunohistochemistry and image analysis methods to determine MVD, endothelial area (EA) and Ki-67 expression, which is an indicator of cell proliferation rate. The results demonstrated a correlation between the above parameters with each other as well as the main clinico-pathological features of PDAC. Significant differences were identified in MVD, EA and Ki-67 proliferation index between PDAC and ANT. It was demonstrated that MVD, EA and Ki-67 proliferation index were significantly correlated with each other in tumour tissue (r=0.69-0.81; P=0.001-0.003). However, no other significant correlations were identified. These data therefore suggested that angiogenesis and cell proliferation rate were significantly increased in PDAC compared with ANT, which provides a biological basis for the potential use of novel combinations of angiogenesis inhibitors and anti-proliferative chemotherapeutic drugs in the treatment of PDAC.

Infiltrating mast cells correlate with angiogenesis in bone metastases from gastric cancer patients.

While gastric cancer is a well established angiogenesis driven tumor, no data has been published regarding angiogenesis stimulated by mast cells (MCs) positive for tryptase in bone metastases from gastric cancer patients (BMGCP). It is well established that MCs play a role in immune responses and more recently it was demonstrated that MCs have been involved in tumor angiogenesis. We analyzed infiltrating MCs and neovascularization in BMGCP diagnosed by histology. A series of 15 stage T3-4N2-3M1 (by AJCC for Gastric Cancer Staging 7th Edition) BMGCP from bone biopsies were selected. Tumour tissue samples were evaluated by mean of immunohistochemistry and image analysis methods in terms of MCs density positive to tryptase (MCDPT), MCs area positive to tryptase (MCAPT), microvascular density (MVD) and endothelial area (EA). A significant correlation between MCDPT, MCAPT, MVD and EA groups to each other was found by Pearson and t-test analysis (r ranged from 0.68 to 0.82; p-value ranged from 0.00 to 0.02). Our very preliminary data suggest that infiltrating MCs positive for tryptase may play a role in BMGCP angiogenesis, and could be further evaluated as a novel target of anti-angiogenic therapy.

Correlation between serum tryptase, mast cells positive to tryptase and microvascular density in colo-rectal cancer patients: possible biological-clinical significance.

BACKGROUND: Tryptase is a serin protease stored and released from mast cells (MCs) that plays a role in tumour angiogenesis. In this study we aimed to evaluate serum tryptase levels in colo-rectal cancer (CRC) patients before (STLBS) and after (STLAS) radical surgical resection. We also evaluated mast cell density positive to tryptase (MCDPT) and microvascular density (MVD) in primary tumour tissue. METHODS: A series of 61 patients with stage B and C CRC (according to the Astler and Coller staging system) were selected. Serum blood samples were collected from patients one day before and one day after surgery. Tryptase levels were measured using the UniCAP Tryptase Fluoroenzymeimmunoassay (Pharmacia, Uppsala, Sweden). Tumour sections were immunostained with a primary anti-tryptase antibody (clone AA1; Dako, Glostrup, Denmark) and an anti CD-34 antibody (QB-END 10; Bio-Optica Milan, Italy) by means of immunohistochemistry and then evaluated by image analysis methods. RESULTS: The mean ± s.d. STLBS and STLAS was 5.63±2.61 µg/L, and 3.39±1.47 µg/L respectively and a significant difference between mean levels was found: p = 0.000 by t-test. The mean ± s.d. of MCDPT and MVD was 8.13±3.28 and 29.16±7.39 respectively. A strong correlation between STLBS and MVD (r = 0.83, p = 0.000); STLBS and MCDPT (r = 0.60, p = 0.003); and MCDPT and MVD (r = 0.73; p = 0.001) was found. CONCLUSION: Results demonstrated higher STLBS in CRC patients, indicating an involvement of MC tryptase in CRC angiogenesis. Data also indicated lower STLAS, suggesting the release of tryptase from tumour-infiltrating MCs. Serum tryptase levels may therefore play a role as a novel bio-marker predictive of response to radical surgery. In this context tryptase inhibitors such as Gabexate and Nafamostat Mesilate might be evaluated in adjuvant clinical trials as a new anti-angiogenic approach.

Transanal tube NO COIL® after rectal cancer proctectomy. The "G. Paolo II" Cancer Centre experience.

AIMS AND BACKGROUND: Covering stoma is the main method used to protect low-lying anastomosis after cancer proctectomy. Intraluminal rectal pressure could be a potential risk factor for anastomotic leakage. We present our personal experience with an alternative and original device, the transanal tube NO COIL®, evaluating its feasibility and safety based on a preliminary manometric study. METHODS: From May 1998 to March 1999, an experimental manometric study on 35 subjects was performed to assess the pathophysiological basis of intraluminal rectal pressure with or without the transanal tube. Subsequently, from April 1999 to December 2009, 184 patients (107 males, 77 females, average age 68.2 ± 10 years) with primary adenocarcinoma of the rectum (≤12 cm from anal verge) were selected. Eighty-two underwent total proctectomy and 102 subtotal proctectomy. No stoma were fashioned. At the end of the operation, the silicone transanal tube NO COIL ®, 60-80 mm long, 2 mm thick with a calibre of up to 2 cm, was applied and secured to the perineal skin by two stitches, then removed on the seventh postoperative day if no signs of leakage occurred. RESULTS: The intraluminal rectal pressure with transanal tube was strongly reduced from 13.8 + 8.5 mmHg to 4.8 + 3.7 mmHg (P <0.01). Nine patients (4.8%) developed an anastomotic leakage, 2 males and 7 females. In 10 patients, the transanal tube NO COIL® did not remain in situ for the planned seven days, and 18 patients suffered from ulcers in the perianal skin. Leakage subsided with conservative treatment in 4 patients, whereas 5 patients required loop colostomy. The stoma rate was 2.7%. No leakage-related deaths occurred, and overall mortality was 1.3%. CONCLUSIONS: The transanal tube NO COIL® does not abolish the risk of anastomotic leakage but could be an alternative option to covering stoma after cancer proctectomy in selected patients. In our experience, this simple and cheap device could reduce the rate of stoma without leakage-related mortality. Further studies within a randomized controlled trial are required to better define our results.

Duplication cyst of the stomach with respiratory epithelium in adult: an uncommon finding. Report of case and review of literature.

Gastrointestinal duplication is a congenital rare disease entity. Duplication cyst of the stomach with pseudo stratified columnar ciliated epithelium is extremely rare. The very appearance of a gastric duplication cyst in an adult can present a diagnostic dilemma. In majority of reported cases, the diagnosis is established during surgical exploration. We report on a 34 year-old female patient suffering from repeated episodes of epigastric pain and gastroesophageal reflux. Abdominal computed tomography and endoscopic ultrasound demonstrated a intramural lesion attached to the gastric fundus, suggestive of gastrointestinal stromal tumor (GIST). At exploratory laparotomy a non-communicating cyst, was found along the greater curvature of the stomach in the esophagogastric transition. The lesion was excised along with an adjacent sleeve of the stomach and esophagus wall because shared muscular layer with the stomach and esophagus. The final pathologic examination revealed that the inner wall of the cyst was lined by a pseudostratified columnar ciliated epithelium (respiratory type) and, in part, columnar and gastric foveolar epithelium. Even though a panel of imaging modalities is available, it is still difficult to obtain a preoperative diagnosis. Duplication cyst can be mistaken for a soft tissue tumor of the gastrointestinal tract. There is no therapeutic algorithm. Surgical treatment is recommended for symptomatic cases.

Vascular endothelial growth factor concentrations from platelets correlate with tumor angiogenesis and grading in a spontaneous canine non-Hodgkin lymphoma model.

Published data strongly suggest that tumor progression and malignancy are associated with increased angiogenesis. However, no data have been published concerning the relationship between microvascular density (MVD), tumor cytosol, and blood vascular endothelial growth factor (VEGF) concentrations in canine non-Hodgkin lymphoma (C-NHL), a neoplasm that shares biological and clinical characteristics with human NHL. We have evaluated MVD and tumor cytosol, serum (S), platelet-poor plasma (P-PP), plasma-activated platelet rich (P-APR) VEGF concentration in a series of 63 B-cells C-NHL by means of immunohistochemistry and enzyme-linked immuno-sorbent assay (ELISA) detection of VEGF. We found that MVD, VEGF from cytosol, and VEGF from P-APR are significantly correlated (p ranging from 0.001 to 0.003) and that these parameters paralleled with the malignancy degree of NHL. Accordingly, spontaneous C-NHL seems to be an interesting model to study the role of angiogenesis as interspecies pathway of tumor malignancy and we suggest that VEGF from P-APR might be a novel useful circulating bio-marker of tumor angiogenesis.

Isolated splenic metastasis from colon cancer. Report of a case.

Isolated splenic metastasis is an uncommon event, except in the case of secondary involvement by lymphoma. The most common sites of metastases of colorectal cancer are the regional lymph nodes, liver and peritoneum; lung and bone are rarely involved, the spleen exceptionally. In this paper we report a case of metachronous isolated splenic metastasis of transverse colon cancer in an 80-year-old woman who was successfully treated by splenectomy. The peculiar clinical-pathological aspects of this kind of metastasis are discussed on the basis of our clinical observation and a review is presented of similar cases reported in the literature. Only 14 reported cases of isolated splenic metastasis from colorectal cancer were found in Medline.

Drug targets to pro-angiogenetic factors with special reference to primary peritoneal mesothelioma.

Angiogenesis is necessary for growth and the spread of human tumors. Animal studies also suggest that angiogenesis is an important interspecies biological mechanism of tumor development. Angiogenesis is a complex multistep cascade modulated by both positive soluble factors, such as vascular endothelial growth factor, thymidine phosphorylase, basic-fibroblast growth factor and negative soluble factors such as angiostatin and endostatin. From the imbalance of the above angiogenesis regulators, tumor endothelial cells may divide up to 50 times more frequently than endothelial cells of normal tissue. Published studies have suggested that the assessment of microvessel density (MVD) or endothelial area (EA) can be considered as surrogate markers of angiogenesis with biological and prognostic relevance. Literature data on angiogenesis of mesothelioma are inconclusive, with only a few studies performed in primary peritoneal mesothelioma (PPM) due to the rarity of the disease. We assessed immunohistochemically MVD and EA and their biological and clinical significance in a consecutive series of 23 PPM cases. MVD and EA were detected in "hot spots" by a computerized image analyzer. The mean value of MVD and EA was 27 +/- 14 and 26.04 +/- 8.35 x10(-2) micro(2) per field (400x), respectively. Patients with a high MVD or EA tumors showed a more clinical aggressiveness due to the presence of ascites and a shorter overall survival. Our results suggest that PPM is an angiogenesis-dependent neoplasia. Therefore, antiangiogenic compounds should be tested particularly in those patients with highly vascularized PPM.

Vascular endothelial growth factor (VEGF) as a target of bevacizumab in cancer: from the biology to the clinic.

Angiogenesis is important in the growth and progression of solid tumours. The main pro-angiogenic factor, namely vascular endothelial growth factor (VEGF), also known as vascular permeability factor, is a potent angiogenic cytokine that induces mitosis and also regulates the permeability of endothelial cells. The soluble isoform of VEGF is a dimeric glycoprotein of 36-46 kDa, induced by hypoxia and oncogenic mutation and it binds to two specific tyrosine-kinase receptors: VEGF-1 (flt-1) and VEGF-2 (KDR/flk1). An increase in VEGF expression in tumour tissue or some blood compartments (i.e. serum or plasma) has been found in solid and haematological malignancies of various origins and is associated with metastasis formation and poor prognosis. Bevacizumab, a recombinant humanised monoclonal antibody developed against VEGF, binds to soluble VEGF, preventing receptor binding and inhibiting endothelial cell proliferation and vessel formation. Pre-clinical and clinical studies have shown that bevacizumab alone or in combination with a cytotoxic agent decreases tumour growth and increases median survival time and time to tumour progression. Bevacizumab is the first anti-angiogenetic treatment approved by the American Food and Drug Administration in the first-line treatment of metastatic colorectal cancer. It has shown preliminary evidence of efficacy for breast, non-small-cell lung, pancreatic, prostate, head and neck and renal cancer as well as haematological malignancies. Common toxicities associated with bevacizumab include hypertension, proteinuria, bleeding episodes and thrombotic events. This review summarises the critical role of VEGF and discusses the data available on bevacizumab, from the humanisation of its parent murine monoclonal antibody (mAb) A.4.6.1 to its use in cancer clinical trials.

Serum lipid profile in colorectal cancer patients with and without synchronous distant metastases.

OBJECTIVE: In this study, the serum lipid profile, including total cholesterol (TC), triglycerides (TG), high-density (HDL-C) and low-density lipoprotein cholesterol (LDL-C), has been investigated in colorectal cancer patients (CRC) with and without synchronous distant metastases. The aim of this study was to verify whether the presence of metastases was associated to serum lipid abnormalities, and whether lipoprotein abnormalities were linked to the nutritional status. METHODS: The fasting serum lipid profile was examined in 84 CRC patients using colorimetric methods. To determine the nutritional status, the body mass index (BMI) was calculated and serum albumin was measured. RESULTS: Patients with distant metastases showed significantly higher levels of TC, LDL-C and the LDL-C/HDL-C ratio than patients without metastases (p< 0.05). The presence of metastases was positively associated with TC, LDL-C and the LDL-C/HDL-C ratio, being independent of sex, age and BMI. CONCLUSIONS: Elevated serum lipid levels may facilitate the development of distant metastasis in CRC patients.