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.

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.

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.

Background: The mortality rate following pancreaticoduodenectomy (PD) has been decreasing over the past few years; nonetheless, the morbidity rate remains elevated. The most common complications after PD are post-operative pancreatic fistula (POPF) and delayed gastric emptying (DGE) syndrome. The issue as to which is the best reconstruction method for the treatment of the pancreatic remnant after PD is still a matter of debate. The aim of this study was to retrospectively analyze the morbidity rate in 100 consecutive PD reconstructed with Wirsung-Pancreato-Gastro-Anastomosis (WPGA), performed by a single surgeon applying a personal modification of the pancreatic reconstruction technique. Methods: During an 8-year period (May 2012 to March 2020), 100 consecutive patients underwent PD reconstructed with WPGA. The series included 57 males and 43 females (M/F 1.32), with a mean age of 68 (range 41–86) years. The 90-day morbidity and mortality were retrospectively analyzed. Additionally, a systematic review was conducted, comparing our technique with the existing literature on the topic. Results: We observed eight cases of clinically relevant POPF (8%), three cases of “primary” DGE (3%) and four patients suffering “secondary” DGE. The surgical morbidity and mortality rate were 26% and 6%, respectively. The median hospital stay was 13.6 days. The systematic review of the literature confirmed the originality of our modified technique for Wirsung-Pancreato-Gastro-Anastomosis. Conclusions: Our modified double-layer WPGA is associated with a very low incidence of POPF and DGE. Also, the technique avoids the risk of acute hemorrhage of the pancreatic parenchyma.

Background: The one-stage approach for colorectal cancer (CRC) with synchronous liver metastases (SLM) has demonstrated advantages, when feasible, in terms of oncological radicality and reduction in sanitary costs. The simultaneous laparoscopic approach to both colon cancer and liver metastases joins the advantages of mini-invasiveness to the one-stage approach. Methods: During the period from February 2011 to July 2017, a single surgeon performed 17 laparoscopic colorectal operations with simultaneous liver resection for CRC with SLM. Colorectal procedures included 9 rectal resections, 6 left colectomies, and 2 right colectomies. Associated hepatic resections included 1 left hepatectomy, 1 right posterior sectionectomy, 2 segmentectomies, and 13 wedge resections. We analyzed retrospectively the patient's short-term outcome and operative and oncologic results. Results: There was no conversion to open surgery. Six patients (35%) had minor complications (Clavien–Dindo grade I–II), whereas only 2 patients (12%) had major complications (Clavien–Dindo grade III–IV) and no mortality occurred. The median time of discharge was 8.6 (range 5–36) days. We obtained 94% of R0 resection margin on the liver specimen and 100% of negative distal and circumferential margin in case of rectal resection. An average of 20 lymphnodes were retrieved in the colorectal specimen. Conclusions: Simultaneous mini-invasive colorectal and liver resection is a challenging but feasible procedure. The advantages of treating primary cancer and metastases in the same recovery justify the morbidity rate, especially because the most of the complications are minor and no cases of mortality occurred. Further experience is needed to better understand how to reduce the morbidity rate.