Clear cell renal cell carcinoma (ccRCC) is the most frequent histological kidney cancer subtype. Over the last decade, significant progress has been made in identifying the genetic and metabolic ...alterations driving ccRCC development. In particular, an integrated approach using transcriptomics, metabolomics, and lipidomics has led to a better understanding of ccRCC as a metabolic disease. The metabolic profiling of this cancer could help define and predict its behavior in terms of aggressiveness, prognosis, and therapeutic responsiveness, and would be an innovative strategy for choosing the optimal therapy for a specific patient. This review article describes the current state-of-the-art in research on ccRCC metabolic pathways and potential therapeutic applications. In addition, the clinical implication of pharmacometabolomic intervention is analyzed, which represents a new field for novel stage-related and patient-tailored strategies according to the specific susceptibility to new classes of drugs.
An altered metabolism is involved in the development of clear cell renal carcinoma (ccRCC). MUC1 overexpression has been found to be associated with advanced disease and poor prognosis. In this ...study, we evaluated the metabolomic profile of human ccRCC, according to MUC1 expression, and integrated it with transcriptomic data. Moreover, we analyzed the role of MUC1 in sustaining ccRCC aggressiveness and the prognostic value of its soluble form CA15-3. Integrated metabolomic and transcriptomic analysis showed that MUC1-expressing ccRCC was characterized by metabolic reprogramming involving the glucose and lipid metabolism pathway. In addition, primary renal cancer cells treated with a small interfering RNA targeting MUC1 (siMUC1) migrated and proliferated at a slower rate than untreated cancer cells. After cisplatin treatment, the death rate of cancer cells treated with siMUC1 was significantly greater than that of untreated cells. Kaplan-Meier curves showed significant differences in CSS and PFS among groups of patients with high versus low levels of CA15-3. In a multivariate analysis, CA15-3 was an independent adverse prognostic factor for cancer-specific and progression-free survival. In conclusion, MUC1 expressing ccRCC is characterized by a particular metabolic reprogramming. The inhibition of MUC1 expression decreases cell motility and viability and improves cisplatin susceptibility, suggesting that this pathway can regulate de novo chemotherapy resistance in ccRCC.
Metabolomic analysis has proven to be a useful tool in biomarker discovery and the molecular classification of cancers. In order to find new biomarkers, and to better understand its pathological ...behavior, bladder cancer also has been studied using a metabolomics approach. In this article, we review the literature on metabolomic studies of bladder cancer, focusing on the different available samples (urine, blood, tissue samples) used to perform the studies and their relative findings. Moreover, the multi-omic approach in bladder cancer research has found novel insights into its metabolic behavior, providing excellent start-points for new diagnostic and therapeutic strategies. Metabolomics data analysis can lead to the discovery of a "signature pathway" associated with the progression of bladder cancer; this aspect could be potentially valuable in predictions of clinical outcomes and the introduction of new treatments. However, further studies are needed to give stronger evidence and to make these tools feasible for use in clinical practice.
Autophagy is a complex process involved in several cell activities, including tissue growth, differentiation, metabolic modulation, and cancer development. In prostate cancer, autophagy has a pivotal ...role in the regulation of apoptosis and disease progression. Several molecular pathways are involved, including PI3K/AKT/mTOR. However, depending on the cellular context, autophagy may play either a detrimental or a protective role in prostate cancer. For this purpose, current evidence has investigated how autophagy interacts within these complex interactions. In this article, we discuss novel findings about autophagic machinery in order to better understand the therapeutic response and the chemotherapy resistance of prostate cancer. Autophagic-modulation drugs have been employed in clinical trials to regulate autophagy, aiming to improve the response to chemotherapy or to anti-cancer treatments. Furthermore, the genetic signature of autophagy has been found to have a potential means to stratify prostate cancer aggressiveness. Unfortunately, stronger evidence is needed to better understand this field, and the application of these findings in clinical practice still remains poorly feasible.
Screening methods available for colorectal cancer (CRC) to date are burdened by poor reliability and low patient adherence and compliance. An altered pattern of volatile organic compounds (VOCs) in ...exhaled breath has been proposed as a non-invasive potential diagnostic tool for distinguishing CRC patients from healthy controls (HC). The aim of this study was to evaluate the reliability of an innovative portable device containing a micro-gas chromatograph in enabling rapid, on-site CRC diagnosis through analysis of patients' exhaled breath. In this prospective trial, breath samples were collected in a tertiary referral center of colorectal surgery, and analysis of the chromatograms was performed by the Biomedical Engineering Department. The breath of patients with CRC and HC was collected into Tedlar bags through a Nafion filter and mouthpiece with a one-way valve. The breath samples were analyzed by an automated portable gas chromatography device. Relevant volatile biomarkers and discriminant chromatographic peaks were identified through machine learning, linear discriminant analysis and principal component analysis. A total of 68 subjects, 36 patients affected by histologically proven CRC with no evidence of metastases and 32 HC with negative colonoscopies, were enrolled. After testing a training set (18 CRC and 18 HC) and a testing set (18 CRC and 14 HC), an overall specificity of 87.5%, sensitivity of 94.4% and accuracy of 91.2% in identifying CRC patients was found based on three VOCs. Breath biopsy may represent a promising non-invasive method of discriminating CRC patients from HC.
Clear cell renal cell carcinoma (ccRCC) is fundamentally a metabolic disease. Given the importance of lipids in many cellular processes, in this study we delineated a lipidomic profile of human ccRCC ...and integrated it with transcriptomic data to connect the variations in cancer lipid metabolism with gene expression changes. Untargeted lipidomic analysis was performed on 20 ccRCC and 20 paired normal tissues, using LC-MS and GC-MS. Different lipid classes were altered in cancer compared to normal tissue. Among the long chain fatty acids (LCFAs), significant accumulations of polyunsaturated fatty acids (PUFAs) were found. Integrated lipidomic and transcriptomic analysis showed that fatty acid desaturation and elongation pathways were enriched in neoplastic tissue. Consistent with these findings, we observed increased expression of stearoyl-CoA desaturase(SCD1) and FA elongase 2 and 5 in ccRCC. Primary renal cancer cells treated with a small molecule SCD1 inhibitor (A939572) proliferated at a slower rate than untreated cancer cells. In addition, after cisplatin treatment, the death rate of tumor cells treated with A939572 was significantly greater than that of untreated cancer cells. In conclusion, our findings delineate a ccRCC lipidomic signature and showed that SCD1 inhibition significantly reduced cancer cell proliferation and increased cisplatin sensitivity, suggesting that this pathway can be involved in ccRCC chemotherapy resistance.
Minimally invasive surgery in obese patients is still challenging, so exploring one more item in this research field ranks among the main goals of this research. We aimed to compare short-term ...postoperative outcomes of open and video-laparoscopic (VL) approaches in CRC obese patients undergoing colorectal resection.
We performed a retrospective analysis of a surgical database including 138 patients diagnosed with CRC, undergoing VL (
= 87, 63%) and open (
= 51, 37%) colorectal surgery. As a first step, propensity score matching was performed to balance the comparison between the two intervention groups (VL and open) in order to avoid selection bias. The matched sample (
= 98) was used to run further regression models in order to analyze the observed VL surgery advantages in terms of postoperative outcome, focusing on hospitalization and severity of postoperative complications, according to the Clavien-Dindo classification.
The study sample was predominantly male (
= 86, 62.3%), and VL was more frequent than open surgery (63% versus 37%). The two subgroup results obtained before and after the propensity score matching showed comparable findings for age, gender, BMI, and tumor staging. The specimen length and postoperative time before discharge were longer in open surgery (OS) patients; the number of harvested lymph nodes was higher than in VL patients as well (
< 0.01). Linear regression models applied separately on the outcomes of interest showed that VL-treated patients had a shorter hospital stay by almost two days and about one point less Clavien-Dindo severity than OS patients on average, given the same exposure to confounding variables. Tumor staging was not found to have a significant role in influencing the short-term outcomes investigated.
Comparing open and VL surgery, improved postoperative outcomes were observed for VL surgery in obese patients after surgical resection for CRC. Both postoperative recovery time and Clavien-Dindo severity were better with VL surgery.
Goblet cell carcinoma (GCC) is a rare primary tumor of the appendix characterized by both epithelial and neuroendocrine components containing goblet cells. While in the past, the GCC has been ...associated with neuroendocrine tumors, recent studies consider that GCC is closer to adenocarcinoma than a neuroendocrine component. The association between gastro-intestinal (GI) carcinoids and second primary malignancies (SPMs) is widely described in the literature, but there is no reported case of GCC and synchronous adjacent adenocarcinoma of the colon. We describe the first case in the literature, to our knowledge, of synchronous colorectal adenocarcinoma of the cecum and GCC of the appendix that are incidentally discovered in the resected primary cancer specimen. The association between the two neoplasms seems to be not causal and maybe the “paracrine-effect theory” may explain the development of a second tumor close to the primary.
Background
Although isolated caudate lobe (CL) liver resection is not a contraindication for minimally invasive liver surgery (MILS), feasibility and safety of the procedure are still poorly ...investigated. To address this gap, we evaluate data on the Italian prospective maintained database on laparoscopic liver surgery (IgoMILS) and compare outcomes between MILS and open group.
Methods
Perioperative data of patients with malignancies, as colorectal liver metastases (CRLM), hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (ICC), non-colorectal liver metastases (NCRLM) and benign liver disease, were retrospectively analyzed. A propensity score matching (PSM) analysis was performed to balance the potential selection bias for MILS and open group.
Results
A total of 224 patients were included in the study, 47 and 177 patients underwent MILS and open isolated CL resection, respectively. The overall complication rate was comparable between the two groups; however, severe complication rate (Dindo–Clavien grade ≥ 3) was lower in the MILS group (0% versus 6.8%,
P
= ns). In-hospital mortality was 0% in both groups and mean hospital stay was significantly shorter in the MILS group (
P
= 0.01). After selection of 42 MILS and 43 open CL resections by PSM analysis, intraoperative and postoperative outcomes remained similar except for the hospital stay which was not significantly shorter in MILS group.
Conclusions
This multi-institutional cohort study shows that MILS CL resection is feasible and safe. The surgical procedure can be technically demanding compared to open resection, whereas good perioperative outcomes can be achieved in highly selected patients.
Background: Minimally invasive methods in colorectal surgery offer unquestionable advantages, especially in the context of obesity. The current study addresses the lack of scientific evidence on the ...long-term oncologic safety of video-laparoscopic (VL) approaches in excess-weight CRC patients undergoing surgery. Methods: We retrospectively analyzed a surgical database consisting of 138 CRC patients undergoing VL (n = 87, 63%) and open CRC surgery (n = 51, 37%). To reduce selection bias, a propensity score matching was applied as a preliminary step to balance the comparison between the two surgery groups, i.e., VL and open surgery. Data from patients treated by the same surgeon were used.to minimize bias. Additional Cox regression models were run on the matched sample (N = 98) to explore the observed benefits of VL surgery in terms of overall and cancer-free survival. The nonparametric Kaplan-Meier method was used to compare the two surgical approaches and assess the likelihood of survival and cancer relapse. Results: The study sample was mostly male (N = 86, 62.3%), and VL outnumbered open surgery (63% versus 37%). Both before and after the matching, the VL-allocated group showed better overall survival (p < 0.01) with comparable cancer-free survival over more than five years of median observation time (66 months). Kaplan Meier survival probability curves corroborated the VL significant protective effect on survival (HR of 0.32; 95% CI: 0.13 to 0.81) even after adjusting for major confounding factors (age, gender, comorbidity index, BMI, tumor localization, tumor staging, tumor grading, clearance, CRM). Findings on oncologic performance by tumor relapse were comparable but lacked significance due to the small number of events observed. Conclusions: Comparing CRC surgical approaches, VL allocation showed comparable cancer-free survival but also a better performance on overall mortality than open surgery over more than five years of median observation.
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