Abstract Metabolic reprogramming is one of the hallmarks of cancer. As nutrients are scarce in the tumor microenvironment (TME), tumor cells adopt multiple metabolic adaptations to meet their growth requirements. Metabolic reprogramming is not only present in tumor cells, but exosomal cargos mediates intercellular communication between tumor cells and non-tumor cells in the TME, inducing metabolic remodeling to create an outpost of microvascular enrichment and immune escape. Here, we highlight the composition and characteristics of TME, meanwhile summarize the components of exosomal cargos and their corresponding sorting mode. Functionally, these exosomal cargos-mediated metabolic reprogramming improves the "soil" for tumor growth and metastasis. Moreover, we discuss the abnormal tumor metabolism targeted by exosomal cargos and its potential antitumor therapy. In conclusion, this review updates the current role of exosomal cargos in TME metabolic reprogramming and enriches the future application scenarios of exosomes. 

/pdf/exosomal-cargos-mediated-metabolic-reprogramming-in-tumor-26k9xqe0.pdf

Exosomal cargos-mediated metabolic reprogramming in tumor microenvironment

PURPOSE To compare the difference of primary suture following 3-port laparoscopic common bile duct exploration (LCBDE) between modified transcystic and transcholedochal approach in the treatment of choledocholithiasis. MATERIALS AND METHODS Patients who underwent 3-port LCBDE by modified transcystic approach (n = 80) and those who underwent 3-port LCBDE by transcholedochal approach (n = 209) were included in this study. The operative time, duration of hospital stay, diameter of the cystic duct, diameter of the common bile duct (CBD), complications, and demographics were retrospectively analyzed in all patients. RESULTS All operations were successfully performed. No patient was converted to laparotomy. No mortality was associated with the 2 groups. There was no significant difference between the 2 groups for the operative time (91.94 ± 34.21 min vs. 96.13 ± 32.15 min), duration of hospital stay (9.82 ± 3.48 d vs. 10.74 ± 5.34 d), diameter of cystic duct (0.47 ± 0.09 cm vs. 0.47 ± 0.08 cm), and complications (2.5% vs. 2.87%) (all P > 0.05). A significant difference was observed in terms of the diameter of CBD (1.18 ± 0.29 cm vs. 1.04 ± 0.24 cm P < 0.05). CONCLUSIONS The modified transcystic LCBDE was safe and feasible for treating choledocholithiasis but it might be more suitable for the CBD with a smaller diameter.

Laparoscopic common bile duct exploration: choledochotomy versus transcystic approach?

Diagnostic liquid biopsy biomarkers in renal cell cancer.

Renal cell carcinoma (RCC) is a common urological malignancy and represents a leading threat to healthcare. Recent years have seen a series of progresses in the early diagnosis and management of RCC. Theranostic lipid nanoparticles (LNPs) are increasingly one of the focuses in this field, because of their suitability for tumor targeting and multimodal therapy. LNPs can be precisely fabricated with desirable chemical compositions and biomedical properties, which closely match the physiological characteristics and clinical needs of RCC. Herein, a comprehensive review of theranostic LNPs is presented, emphasizing the generic tool nature of LNPs in developing advanced micro-nano biomaterials. It begins with a brief overview of the compositions and formation mechanism of LNPs, followed with an introduction to kidney-targeting approaches, such as passive, active, and stimulus responsive targeting. With examples provided, a series of modification strategies for enhancing the tumor targeting and functionality of LNPs were discussed. Thereafter, research advances on applications of these LNPs for RCC including bioimaging, liquid biopsy, drug delivery, physical therapy, and gene therapy are summarized and discussed from an interdisciplinary perspective. The final part highlights the milestone achievements of translation medicine, current challenges as well as future development directions of LNPs for the diagnosis and treatment of RCC. This article is protected by copyright. All rights reserved.

Theranostic Lipid Nanoparticles for Renal Cell Carcinoma.

Renal cell carcinoma (RCC) represents an extremely challenging disease in terms of both diagnosis and treatment. It poses a significant threat to human health, with incidence rates increasing at a yearly rate of roughly 2%. Extracellular vesicles (EVs) are lipid-based bilayer structures of membranes that are essential for intercellular interaction and have been linked to the advancement of RCC. This review provides an overview of recent studies on the role of EVs in RCC progression, including involvement in the interaction of tumor cells with M2 macrophages, mediating the generation of immune tolerance, and assuming the role of communication messengers in the tumor microenvironment leading to disease progression. Finally, the “ troika “ of EVs in RCC therapy is presented, including engineered sEVs’ or EVs tumor vaccines, mesenchymal stem cell EVs therapy, and reduction of tumor-derived EVs secretion. In this context, we highlight the limitations and challenges of EV-based research and the prospects for future developments in this field. Overall, this review provides a comprehensive summary of the role of EVs in RCC and their potential as a viable pathway for the future treatment of this complex disease.

/pdf/extracellular-vesicles-in-renal-cell-carcinoma-challenges-30d6edm5.pdf

Extracellular vesicles in renal cell carcinoma: challenges and opportunities coexist

Abstract Background There are no proven tumor biomarkers for the early diagnosis of clear cell renal cell carcinoma (ccRCC) thus far. This study aimed to identify novel biomarkers of ccRCC based on exosomal mRNA (emRNA) profiling and develop emRNA-based signatures for the early detection of ccRCC. Methods Four hundred eighty-eight participants, including 226 localized ccRCCs, 73 patients with benign renal masses, and 189 healthy controls, were recruited. Circulating emRNA sequencing was performed in 12 ccRCCs and 22 healthy controls in the discovery phase. The candidate emRNAs were evaluated with 108 ccRCCs and 70 healthy controls in the test and training phases. The emRNA-based signatures were developed by logistic regression analysis and validated with additional cohorts of 106 ccRCCs, 97 healthy controls, and 73 benign individuals. Results Five emRNAs, CUL9, KMT2D, PBRM1, PREX2, and SETD2, were identified as novel potential biomarkers of ccRCC. We further developed an early diagnostic signature that comprised KMT2D and PREX2 and a differential diagnostic signature that comprised CUL9, KMT2D, and PREX2 for RCC detection. The early diagnostic signature displayed high accuracy in distinguishing ccRCCs from healthy controls, with areas under the receiver operating characteristic curve (AUCs) of 0.836 and 0.830 in the training and validation cohorts, respectively. The differential diagnostic signature also showed great performance in distinguishing ccRCCs from benign renal masses (AUC = 0.816), including solid masses (AUC = 0.810) and cystic masses (AUC = 0.832). Conclusions We established and validated novel emRNA-based signatures for the early detection of ccRCC and differential diagnosis of uncertain renal masses. These signatures could be promising and noninvasive biomarkers for ccRCC detection and thus improve the prognosis of ccRCC patients. 

https://bmcmedicine.biomedcentral.com/counter/pdf/10.1186/s12916-022-02467-1

Circulating exosomal mRNA signatures for the early diagnosis of clear cell renal cell carcinoma

BACKGROUND Intra-operative cholangiography has been shown to be a sensitive and specific method of demonstrating bile duct stones. This study investigated the feasibility, safety, and clinical value of selective trans-cystic intra-operative cholangiography in primary suture following three-port laparoscopic common bile duct exploration, and identified the factors that positively predict the presence of common bile duct stones. METHODS From January 2008 to January 2011, 252 of 1013 patients undergoing laparoscopic cholecystectomy received selective trans-cystic intra-operative cholangiography and primary suture following three-port laparoscopic common bile duct exploration. Their clinical data were analyzed retrospectively. RESULTS All operations were successful and none was converted to open surgery. The intra-operative cholangiography time was (8.3 ± 2.5) minutes, and the operative duration was (105.4 ± 23.1) minutes. According to selective intra-operative cholangiography, the positive predictive values of current jaundice, small gallstones ( 0.3 cm), dilated common bile duct (> 0.8 cm), history of jaundice or gallstone pancreatitis, abnormal liver function test, and preoperative demonstration of suspected common bile duct stones on imaging were 87%, 25%, 42%, 15%, 32%, and 75% for common bile duct stones, respectively. Patients with several factors suggestive of common bile duct stones yielded higher numbers of positive cholangiograms. Unexpected stones were found in 13 patients (5.2%) by intra-operative cholangiography. The post-operative hospital stay was (4.7 ± 2.2) days. Post-operative bile leakage occurred in two cases, and these patients recovered by simple drainage for 3 - 7 days without re-operation. Of the 761 patients who underwent laparoscopic cholecystectomy alone, 5 (0.7%) presented with a retained common bile duct stone requiring intervention. The median follow-up was 12 months, and only one patient who once suffered from bile leakage presented with obstructive jaundice due to bile duct stenosis 6 months postoperatively. The other patients recovered without any serious complications. CONCLUSIONS Selective intra-operative cholangiography yields acceptably high positive results. It is a safe, effective, and minimally invasive approach in patients with suspected choledocholithiasis and primary suture following three-port laparoscopic common bile duct exploration.

Clinical efficacy and safety of selective trans-cystic intra-operative cholangiography in primary suture following three-port laparoscopic common bile duct exploration.

Laparoscopy-assisted radical distal gastrectomy for gastric cancer is challenging to perform, particularly when conducted with D2 lymph node dissection. Successful completion of this procedure requires collaboration among all members of the surgical team. On the basis of the clinical data of 52 patients undergone laparoscopy-assisted radical distal surgery for gastric cancer from September 2009 to October 2010, we describe cooperative techniques for first and laparoscopic-holder assistants that are required to ensure successful outcomes. Precautions for surgical assistants are also described.

Cooperative techniques for surgical assistants in laparoscopy-assisted radical distal gastrectomy for gastric cancer.

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Circulating exosomal mRNA signatures for the early diagnosis of clear cell renal cell carcinoma

Clinical efficacy and safety of selective trans-cystic intra-operative cholangiography in primary suture following three-port laparoscopic common bile duct exploration.

Cooperative techniques for surgical assistants in laparoscopy-assisted radical distal gastrectomy for gastric cancer.