MUC1 Tissue Expression and Its Soluble Form CA15-3 Identify a Clear Cell Renal Cell Carcinoma with Distinct Metabolic Profile and Poor Clinical Outcome.

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.

Renal Cell Carcinoma as a Metabolic Disease: An Update on Main Pathways, Potential Biomarkers, and Therapeutic Targets.

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.

The Thousand Faces of Malignant Melanoma: A Systematic Review of the Primary Malignant Melanoma of the Esophagus.

Primary Malignant Melanoma of the Esophagus (PMME) is an extremely rare cancer of the esophagus, accounting for 0.1−0.8% of all oro-esophageal cancers and <0.05% of all melanoma subtypes, with an estimated incidence of 0.0036 cases per million/year. We conduct a careful analysis of the literature starting from 1906 to the beginning of 2022, searching the PubMed, Science.gov, Scopus and Web of Science (WoS) databases. A total of 457 records were initially identified in the literature search, of which 17 were duplicates. After screening for eligibility and inclusion criteria, 303 publications were ultimately included, related to 347 patients with PMME. PMME represents a very rare entity whose very existence has been the subject of debate for a long time. Over time, an increasing number of cases have been reported in the literature, leading to an increase in knowledge and laying the foundations for a discussion on the treatment of this pathology, which still remains largely represented by surgery. In recent times, the possibility of discovering greater mutations in gene hotspots has made it possible to develop new therapeutic strategies of which nivolumab is an example. Future studies with large case series, with clinicopathological and molecular data, will be necessary to improve the outcome of patients with PMME.

Predictors of Long-Term Outcomes of Video-Laparoscopic Versus Open Surgery in Obese Patients with Colorectal Cancer: A Propensity Score Matching Study.

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.

Metabolomic Approaches for Detection and Identification of Biomarkers and Altered Pathways in Bladder Cancer.

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.

Novel Insights into Autophagy and Prostate Cancer: A Comprehensive Review.

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.

Laparoscopic partial splenectomy for symptomatic benign cystic lesions: technical notes.

The purpose of this study was to explore the feasibility of laparoscopic partial splenectomy in patients with symptomatic benign lesions. During the period from April 2017 to February 2020, a single surgeon performed 7 LPS for benign lesions. As primary endpoint, we retrospectively analyzed the patient's short-term outcome and the operative results. As secondary endpoints, we considered 6-month follow-up. Laparoscopic partial splenectomy was performed successfully in all cases, with no major complications. Thirty-day mortality was nil. No post-operative transfusions were required and the median hospital stay was 4 (range 3-5) days. The median operative time was 110 (range 75-140) min and there was neither conversion to open surgery nor need for total splenectomy. Mean blood loss was 135.7 ± 103.6 ml and no intraoperative blood transfusions were necessary. All patients recovered successfully, with significant decrease of Ca 19.9 (98.22 ± 118.10 U/mL vs. 4.78 ± 3.35 U/mL, P = 0.015) and normal platelet count (215.7 × 103 ± 42.2 × 103 per µL vs. 236.0 × 103 ± 58.3 × 103 per µL, P = 0.285) at 1-month follow-up. No cases of recurrence were detected during the 6-month follow-up. Laparoscopic splenic resection for benign lesions is a challenging but feasible procedure. This technique combines the advantages of both mini-invasive surgery and spleen preservation.

Modified Technique for Wirsung-Pancreatogastric Anastomosis after Pancreatoduodenectomy: A Single Center Experience and Systematic Review of the Literature.

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.

Video-Laparoscopic versus Open Surgery in Obese Patients with Colorectal Cancer: A Propensity Score Matching Study.

Background: 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. Methods: We performed a retrospective analysis of a surgical database including 138 patients diagnosed with CRC, undergoing VL (n = 87, 63%) and open (n = 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 (N = 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. Results: The study sample was predominantly male (N = 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 (p < 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. Conclusion: 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.

Simultaneous Colon and Liver Laparoscopic Resection for Colorectal Cancer with Synchronous Liver Metastases: A Single Center Experience.

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.

Correlation between intraoperative surgical diagnosis of complicated acute appendicitis and the pathology report: clinical implications.

BACKGROUND: The post-operative management of appendectomy for acute appendicitis is based primarily on the operative findings. The surgeon describes the severity of the disease, and antibiotic therapy is administered accordingly. The histologic findings are not always considered in the decision about the management and may not be correlated with the clinical outcome. The aim of this study was to investigate the agreement between the surgeon's intra-operative visual description of the appendix and the pathologist's report in a consecutive series of patients with acute appendicitis. Complications were analyzed in relation to the classification. METHODS: A comparative observational study was performed in 69 patients who underwent surgery for acute appendicitis at the same hospital during a one-year period (the entire year of 2011). The surgeon's classification of the severity of appendicitis was compared with the pathologist's report using the kappa coefficient. Patient demographics, surgical techniques, and post-operative complications also were analyzed. RESULTS: Complicated appendicitis (gangrenous or perforated) was considered to be present in 36.2% of patients in the surgeon's classification and 43% of the patients in the histopathologic reports (p=0.033). The kappa coefficient showed only a weak correlation between the surgeons' and pathologists' descriptions (κ=0.25). Significant differences in post-operative complications were found only in the surgeon's classification. CONCLUSION: We found a weak correlation between the surgeon's macroscopic diagnosis and the pathologic findings. However, the differences did not have meaningful clinical implications. Further studies are required to evaluate the clinical meaning of these results.