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Supplemental Digital Content is available in the text Objective: This multicenter randomized controlled trial was designed to test the hypothesis that early drain removal (EDR) could decrease the incidence of grade 2 to 4 complications for patients undoing pancreaticoduodenectomy (PD) with low or intermediate risk of postoperative pancreatic fistula (POPF). Background: The safety and effects of EDR on postoperative complications after PD are still controversial. Methods: A multicenter randomized controlled trial at 6 tertiary referral hospitals was carried out (NCT03055676). Patients who met the inclusion criteria, including drain amylase level less than 5000 U/L on postoperative day (POD) 1 and POD 3, and drain output less than 300 mL per day within 3 days after surgery, were enrolled. Patients were then randomized to the EDR group or the routine drain removal (RDR) group. In the EDR group, all drainage tubes were removed on POD3. In the RDR group, drainage tubes were removed on POD 5 or beyond. Primary outcome was the incidence of Clavien-Dindo grade 2 to 4 complications. Secondary outcomes were comprehensive complication index, grade B/C POPF, total medical expenses and postoperative in-hospital stay etc, within 90 days after surgery. Results: A total of 692 patients were screened, and 312 patients were eligible for randomization. Baseline characteristics were well balanced between the 2 groups and 96.8% of these 312 patients had low or intermediate risk of POPF, according to the 10-point fistula risk score. A total of 20.5% of the patients in the EDR group suffered at least 1 grade 2 to 4 complication, versus 26.3% in the RDR group (P = 0.229). Multi-variate analysis showed older age (>65 years old) and blood transfusion were independent risk factors for grade 2 to 4 complications. The rate of grade B/C POPF was low in either group (3.8% vs 6.4%, P = 0.305). The comprehensive complication index of the 2 groups was also comparable (20.9 vs 20.9, P = 0.253). Total medical expenses were not significantly different. Postoperative in-hospital stay was clinically similar (15 days vs 16 days, P = 0.010). Conclusions: Nearly half of the patients undergoing PD met the inclusion criteria, predicting low incidence of grade B/C POPF and major complications. EDR was safe in these patients but did not significantly decrease major complications. [ABSTRACT FROM AUTHOR]

Tumor-associated factors are related to increased accumulation of CD11b+Gr1+myeloid-derived suppressor cells (MDSCs). However, the exact mechanism of how genetic factors control the expansion of MDSCs in tumor-bearing hosts remains elusive. Herein, we found that tumor-associated MDSCs and their subsets, mononuclear MDSCs and polymorphonuclear MDSCs, have decreased expression of miR-223 when compared to CD11b+Gr1+ cells from the spleen of disease-free mice. With the differentiation of CD11b+Gr1+MDSCs from bone marrow cells (BMCs) upon exposure to tumor-associated factors, the expression of both pri-miR-223 and mature miR-223 was downregulated, indicating that the expression of miR-223 could be regulated by tumor-associated factors. Interestingly, miR-223 remarkably inhibits differentiation of BMCs into CD11b+Gr1+MDSCs in the presence of tumor-associated factors by targeting myocyte enhancer factor 2C (MEF2C). Using reconstituted s.c. tumor models, miR-223 also suppresses accumulation of CD11b+Gr1+MDSCs, whereas its targeting molecule MEF2C increases the number of MDSCs. Tumor growth is slower in mice infused by miR223-engineered BMCs than in mice infused with control transfected BMCs. As miR-223 and its target molecule MEF2C are highly conserved between mice and humans, the modulation of miR-223 in tumor-induced CD11b+Gr1+MDSCs may exert an important role in controlling the increased accumulation of CD11b+Gr1+MDSCs in patients with tumor. [ABSTRACT FROM AUTHOR]

Background: Solid pseudopapillary neoplasm (SPN) of the pancreas is a rare, low-grade malignant pancreatic tumor with a highly favorable prognosis. Most SPN patients are young and middle-aged women. The main controversial topic for SPN is local resection (LR) versus radical resection (RR). Theoretically, LR could lead to better gastrointestinal function (GIF) and less mental stress. However, no data is available to support this hypothesis., Methods: All SPN patients undergoing surgical treatment in Peking Union Medical College Hospital from 2001 to 2021 were included in the study. A cross-sectional online multiquestionnaire survey containing 110 questions was sent to them (Clinicaltrial.org, NCT05604716). This online multiquestionnaire survey focused on GIF and mental stress and consisted of eight questionnaires. Multiple linear regression analysis was conducted to identify independent factors impacting GIF and mental stress., Results: A total of 183 cases provided valid results. Among them, 46 patients (25.1%) underwent LR, and 137 (74.9%) underwent RR. Ninety-four cases (51.4%) underwent minimally invasive surgery (MIS), while 89 (48.6%) underwent open surgery. The average GSRS score of the patients was 1.9±0.7, indicating that most suffered from mild gastrointestinal dysfunction. The scores of PHQ-9 and GAD-7 in 16 patients (8.7%) and 27 (14.8%) patients, respectively, were beyond 10.0, which indicated clinical depression and anxiety. Additionally, 19 (10.4%) patients reported poor ability to work, and 31(16.9%) patients had significant body image concerns. Compared to other clinicopathological characteristics, LR (LR vs. RR: PHQ-9 score, P =0.018; WAI average score, P =0.010; EORTC QLQ-C30, nine subdomains, P <0.05; GSRS average score, P =0.006) and MIS (MIS vs. open surgery: EORTC QLQ-C30, three subdomains, P <0.05; GSRS average score, P =0.006) were the most significant factors predicting improved GIF and reduced mental stress., Conclusions: This study systematically presents postoperative GIF and mental stress of SPN patients using validated multiquestionnaires for the first time. It provides solid evidence that LR and MIS can improve GIF and reduce mental stress after surgery for SPN patients, which could be helpful for the surgeons to make more personalized surgical plans for their patients., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Radical antegrade modular pancreatosplenectomy (RAMPS) has been proven to improve R0 resection and lymph harvest in treating patients with distal pancreatic cancer. The development of minimally invasive surgery has advantages in postoperative recovery. Therefore, minimally invasive (MI-) RAMPS may combine the advantages of both benefits to improve survival. Nevertheless, evidence to validate the safety and efficacy of MI-RAMPS is limited., Method/design: The MIRROR trial will be the first multicenter prospective randomized clinical trial to investigate the outcome of MI-RAMPS. The hypothesis is that MI-RAMPS is superior in postoperative recovery. The primary outcome is the length of postoperative stay. Based on the hypothesis and primary outcome, the sample size is 250 patients (125 participants in each group). The trial will investigate factors related to surgical safety, short-term outcome, pathological assessment, and survival as secondary outcomes., Conclusion: This study will offer a relatively higher level of evidence to further illustrate the accessibility and benefits of MI-RAMPS for the treatment of distal pancreatic cancer., Clinical Trial Registration: Clinicaltrials.gov, NCT03770559., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Dai, Zhang, Yang, Xiu, Peng, Sun, Cao, Wu, Wang, Yuan, Chen, Wang, Tian, Wang, Liu, Xu, Liu, Zhao and MIRROR study group.)

Circular RNA (circRNA) is a special type of endogenous noncoding RNAs (ncRNAs), and are characterized by a covalently closed loop structure without a 5' cap and poly-adenylated tails. Abnormal expression of circRNAs has been implicated in a wide range of human cancers, where they function as either tumor suppressor genes or oncogenes. CircHIPK3, circRNA homeodomain-interacting protein kinase 3, is associated with human cancers such as lung cancer, bladder cancer, hepatocellular carcinoma, colorectal cancer, osteosarcoma, glioma and prostate cancer, et al. Numerous studies have indicated that circHIPK3 functions as a miRNA sponge to regulate the target genes and exert specific biological effects, including regulation of cell proliferation, invasion, and migration. Furthermore, circHIPK3 is thought to be a novel diagnostic biomarker, therapeutic target, and prognostic biomarker in different cancer types. Here, we reviewed the recent progress of the mechanism and functions of circHIPK3 during the evolution of malignancies., Competing Interests: None., (AJTR Copyright © 2020.)

Tumor-associated factors are related to increased accumulation of CD11b(+) Gr1(+) myeloid-derived suppressor cells (MDSCs). However, the exact mechanism of how genetic factors control the expansion of MDSCs in tumor-bearing hosts remains elusive. Herein, we found that tumor-associated MDSCs and their subsets, mononuclear MDSCs and polymorphonuclear MDSCs, have decreased expression of miR-223 when compared to CD11b(+) Gr1(+) cells from the spleen of disease-free mice. With the differentiation of CD11b(+) Gr1(+) MDSCs from bone marrow cells (BMCs) upon exposure to tumor-associated factors, the expression of both pri-miR-223 and mature miR-223 was downregulated, indicating that the expression of miR-223 could be regulated by tumor-associated factors. Interestingly, miR-223 remarkably inhibits differentiation of BMCs into CD11b(+) Gr1(+) MDSCs in the presence of tumor-associated factors by targeting myocyte enhancer factor 2C (MEF2C). Using reconstituted s.c. tumor models, miR-223 also suppresses accumulation of CD11b(+) Gr1(+) MDSCs, whereas its targeting molecule MEF2C increases the number of MDSCs. Tumor growth is slower in mice infused by miR223-engineered BMCs than in mice infused with control transfected BMCs. As miR-223 and its target molecule MEF2C are highly conserved between mice and humans, the modulation of miR-223 in tumor-induced CD11b(+) Gr1(+) MDSCs may exert an important role in controlling the increased accumulation of CD11b(+) Gr1(+) MDSCs in patients with tumor., (Copyright © 2011 UICC.)