Prediction of symptomatic anastomotic leak after rectal cancer surgery: A machine learning approach.

INTRODUCTION: Anastomotic leakage (AL) remains the most dreaded and unpredictable major complication after low anterior resection for mid-low rectal cancer. The aim of this study is to identify patients with high risk for AL based on the machine learning method. METHODS: Patients with mid-low rectal cancer undergoing low anterior resection were enrolled from West China Hospital between January 2008 and October 2019 and were split by time into training cohort and validation cohort. The least absolute shrinkage and selection operator (LASSO) method and stepwise method were applied for variable selection and predictive model building in the training cohort. The area under the receiver operating characteristic curve (AUC) and calibration curves were used to evaluate the performance of the models. RESULTS: The rate of AL was 5.8% (38/652) and 7.2% (15/208) in the training cohort and validation cohort, respectively. The LASSO-logistic model selected almost the same variables (hypertension, operating time, cT4, tumor location, intraoperative blood loss) compared to the stepwise logistic model except for tumor size (the LASSO-logistic model) and American Society of Anesthesiologists score (the stepwise logistic model). The predictive performance of the LASSO-logistics model was better than the stepwise-logistics model (AUC: 0.790 vs. 0.759). Calibration curves showed mean absolute error of 0.006 and 0.013 for the LASSO-logistics model and stepwise-logistics model, respectively. CONCLUSION: Our study developed a feasible predictive model with a machine-learning algorithm to classify patients with a high risk of AL, which would assist surgical decision-making and reduce unnecessary stoma diversion. The involved machine learning algorithms provide clinicians with an innovative alternative to enhance clinical management.

Can Organoid Model Reveal a Key Role of Extracellular Vesicles in Tumors? A Comprehensive Review of the Literature.

Extracellular vesicles (EVs) are small membrane-bound vesicles that are released by cells into the extracellular environment. The role of EVs in tumors has been extensively studied, and they have been shown to play a crucial role in tumor growth, progression, and metastasis. Past research has mainly used 2D-cultured cell line models to investigate the role of EVs in tumors, which poorly simulate the tumor microenvironment. Organoid technology has gradually matured in recent years. Organoids are similar in composition and behavior to physiological cells and have the potential to recapitulate the architecture and function of the original tissue. It has been widely used in organogenesis, drug screening, gene editing, precision medicine and other fields. The integration of EVs and organoids has the potential to revolutionize the field of cancer research and represents a promising avenue for advancing our understanding of cancer biology and the development of novel therapeutic strategies. Here, we aimed to present a comprehensive overview of studies using organoids to study EVs in tumors.

Frailty index is useful for predicting postoperative morbidity in older patients undergoing gastrointestinal surgery: a prospective cohort study.

BACKGROUND: Many assessment tools have been used to identify frail surgical patients. This study was designed to explore the prediction value of the frailty index (FI) for postoperative morbidity in older patients undergoing elective gastrointestinal surgery. METHODS: Between January 2019 and September 2020, we conducted a prospective study in our hospital, and patients aged over 65 years were enrolled. The FI assessment was conducted by two specialist nurses based on the 38-item scale, and patients were considered frail if the FI score was ≥ 0.25. The primary outcome was 30-day postoperative morbidity. Univariable and multivariable analyses were used to find the risk factors related to postoperative morbidity. RESULTS: A total of 246 consecutive patients were enrolled, for whom the median age was 72.0 [interquartile range (IQR): 67.0-77.0] years old, and 175 (71.1%) were male. Of these, 47 (19.1%) were frail. Patients with frailty were associated with older age (p < 0.001), higher American Society of Anesthesiologists (ASA) grade (p = 0.006), lower body mass index (p = 0.001), lower albumin (p = 0.003) and haemoglobin (p < 0.001) levels, increased blood loss (p = 0.034), increased risk of postoperative morbidity (p < 0.001), increased median length of stay (p = 0.017), and increased median postoperative hospital stay (p = 0.003). Multivariable analysis revealed that ASA grade [odds ratio (OR): 2.59, 95% confidence interval (CI) 1.19-5.64, p = 0.016], FI score (OR 7.68, 95% CI 3.19-18.48, p < 0.001) and surgical complexity (OR 22.83, 95% CI 5.46-95.51, p < 0.001) were independent predictors of 30-day postoperative morbidity. However, for patients with major surgery, FI score was the only independent predictor (OR 8.67, 95% CI 3.23-23.25, p < 0.001). CONCLUSION: Frailty was associated with adverse perioperative outcomes, and the 38-item FI scale was a useful frailty screening tool for older patients undergoing elective gastrointestinal surgery. For patients with major surgery, frailty was a more reliable predictor of postoperative 30-day morbidity than age and ASA grade.

Correction to: CircCPA4 Promotes the Malignant Phenotypes in Glioma via miR-760/MEF2D Axis.

The article titled "CircCPA4 Promotes the Malignant Phenotypes in Glioma via miR-760/MEF2D Axis", written by Yunjuan Zhang, Zengyan Cai, Jin Liang, Erqing Chai, Anqing Lu, Yinwu Shang was originally published electronically on the publisher's internet portal (currently SpringerLink) on 17 October 2020 with open access.

CircCPA4 Promotes the Malignant Phenotypes in Glioma via miR-760/MEF2D Axis.

Circular RNA carboxypeptidase A4 (circCPA4) has been shown to involve in the tumorigenesis of glioma. However, the function and the molecular mechanism of circCPA4 in glioma remain inadequate. Levels of circCPA4 and microRNA (miR)-760 were detected by quantitative real-time polymerase chain reaction. Cell proliferation, apoptosis, migration, and invasion were analyzed using MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide), colony formation, flow cytometry, and transwell assays, respectively. Western blot was used to detect the protein levels of matrix metallopeptidase 2 (MMP2), MMP9 and myocyte enhancer factor 2D (MEF2D). The interaction between miR-760 and circCPA4 or MEF2D was analyzed by the dual-luciferase reporter assay or RNA pull-down assay. In vivo experiments were conducted using murine xenograft models. We found circCPA4 was highly expressed in glioma, and circCPA4 knockdown suppressed tumor cell proliferative, migratory and invasive behaviors, but enhanced cell apoptosis and radiosensitivity in glioma. CircCPA4 directly bound to miR-760 to suppress its expression, and miR-760 inhibition reversed circCPA4 knockdown-mediated inhibition of cell malignant phenotypes in glioma. MEF2D was a target of miR-760, and miR-760 performed anti-tumor effects by targeting MEF2D in glioma cells. Meanwhile, we found circCPA4 could indirectly regulate MEF2D by sponging miR-760. Importantly, xenograft analysis suggested that circCPA4 knockdown impeded tumor growth in vivo via regulating miR-760 and MEF2D. In conclusion, circCPA4 knockdown suppressed cell malignant phenotypes in glioma via miR-760/MEF2D axis to impede the progression of glioma, suggesting potential therapeutic targets for glioma treatment.

Application of double circular suturing technique (DCST) in repair of giant incision hernias.

BACKGROUND: Our study aims to explore the feasibility and safety of a double circular suturing technique (DCST) in the repair of giant incision hernias. METHODS: The clinical data of 221 patients (95 men and 126 women; the average age was 61.6 years) receiving DCST in the repair of giant incision hernia between January 2010 and December 2018 was analyzed retrospectively. One hundred and five primary and 16 recurrent patients underwent herniorrhaphy with anti-adhesion underlay mesh repair using DCST. RESULTS: All the 221 operations were performed successfully. The average preparation time before the operation and hospital stays were 3.7 days (range, 1-6 days) and 7.5 days (range, 2-16 days), respectively. The average diameter of the hernia ring defect observed intraoperatively was 16.4 cm (range, 12-22 cm). The average time of operation was 83.6 min (range, 43-195 min). There were 2 cases of intestinal fistula, 4 cases of wound infection, 2 cases of mesh infection, 7 cases of serum tumescence, 3 cases of pulmonary infection, and 2 cases of wound dehiscence occurred. One hundred and ninety-five patients were followed up for 6.7 years (range, 0.8-9.5 years) postoperatively. Of them, 9 patients recurred; 14 patients had chronic pain whose visual analog scale (VAS) was 2-4 cm (average 2.7 cm). CONCLUSIONS: With limited preparation time before operations, few postoperative complications, and recurrence rate, DCST in the repair of giant incision hernia is safe and possible clinically.

Application of double circular suturing technique (DCST) in the repair of large abdominal wall defects after resection of abdominal wall tumor.

BACKGROUND: The aim of this study was to investigate the clinical effects of repairing large defects using the double circular suturing technique (DCST) after resection of abdominal wall tumor. METHODS: The clinical data of 62 patients (25 men, 37 women; average age 41.7±22.4 years) who underwent DCST between October 2010 and November 2018 for the repair of large abdominal wall defects with anti-adhesion underlay mesh after resection of abdominal wall tumor were retrospectively analyzed. The maximum diameter of abdominal wall defect after resection of abdominal wall tumor was 10.4±5.6 cm. The course of disease was 1-341 months, and the average was 32.4 months. Operative time, postoperative hospitalization time, perioperative complications, tumor recurrence in situ, incidence of postoperative chronic pain, and hernia were recorded. RESULTS: All 62 operations were completed successfully. The operative time was 73.2±31.4 minutes, and the mean postoperative hospitalization time was 9.6 days (range, 2-20 days). In total, 54 patients were followed up postoperatively for a median 6.7 years (range, 0.9-9.0 years). Partial splitting of incisions occurred in 2 patients, fat liquefaction of incisions occurred in 3 patients, and chronic pain occurred in 4 patients. No tumor in situ recurrence, hernia, or other complications were found in any cases in the follow-up. Tumor metastasis occurred in 9 patients with 6 of these patients dying of tumour progression. CONCLUSIONS: With simple operations, short procedure time, few complications, low tumor recurrence rate, and low incidence of postoperative chronic pain, application of DCST in the repair of large abdominal wall defects is effective after resection of abdominal wall tumor.

LncRNA CPS1-IT1 serves as anti-oncogenic role in glioma.

Carbamoyl-phosphate synthetase 1 intronic transcript 1 (CPS1-IT1) is identified recently as a novel tumor suppressive long non-coding RNA (lncRNA). However, the expression status and clinical significance of CPS1-IT1 expression remained unknown in glioma. In our study, we observed CPS1-IT1 levels were decreased in glioma tissues and cells compared with paired normal brain tissues and human astrocyte cell line, respectively. Moreover, we analyzed the associations of CPS1-IT1 expression with clinicopathological characteristics, and found low CPS1-IT1 expression was correlated with high World Health Organisation (WHO) grade and large tumor size in glioma patients. Survival analysis showed glioma patients in low CPS1-IT1 expression group had shorter overall survival than those in high CPS1-IT1 expression group, and low CPS1-IT1 expression was an independent prognostic factor for overall survival in glioma patients. The in vitro studies suggested up-regulation of CPS1-IT1 expression resulted in the decrease of proliferation, migration and invasion abilities of glioma cells. In conclusion, CPS1-IT1 plays an anti-oncogenic role in glioma.

A critical review to traumatic brain injury clinical practice guidelines.

The aim of this study was to assess the quality of clinical practice guidelines of traumatic brain injury (TBI) and investigate the evidence grading systems.A systematic search of relevant guideline websites and literature databases (including PubMed, NGC, SIGN, NICE, GIN, and Google) was undertaken from inception to May 2018 to identify and select TBI guidelines. Four independent reviewers assessed the eligible guidelines using the Appraisal of Guidelines for Research and Evaluation (AGREE II) instrument. The degree of agreement was evaluated with intraclass correlation coefficient (ICC).From 1802 records retrieved, 12 TBI guidelines were included. The mean scores for each AGREE II domain were as follows: scope and purpose (mean ± SD= 74.2 ±â€Š9.09); stakeholder involvement (mean± SD= 54.6 ±â€Š11.6); rigor of development (mean ± SD=70.1 ±â€Š13.6); clarity and presentation (mean ± SD=78.4 ±â€Š11.5); applicability (mean ± SD= 60.5 ±â€Š13.6); and editorial independence (mean ± SD=61.7 ±â€Š14.8). Ten guidelines were rated as "recommended." The ICC values ranged from 0.73 to 0.95. Seven grading systems were used by TBI guidelines to rate the level of evidence and the strength of recommendation.Most TBI guidelines got a high-quality rating, whereas a standardized grading system should be adopted to provide clear information about the level of evidence and strength of recommendation in TBI guidelines.

A prospective Study on Femoral Hernia Repair: Is the Inguinal Better Than The Infrainguinal Approach?

BACKGROUND: Femoral hernia repair has various surgical methods. However, controversy still exists regarding the best method for management. This study aimed to compare the infrainguinal with the inguinal approach in the treatment of femoral hernias. MATERIALS AND METHODS: Eighty patients with primary unilateral femoral hernias were prospectively randomized to either the infrainguinal (n = 40) or inguinal approach groups (n = 40). Patient demographics, operative time, duration of hospital stay, postoperative complications, and recurrence rate were recorded. RESULTS: There were no statistically significant differences between both study groups with respect to the patients' demographics and associated comorbidities. Regarding inpatient outcomes, there were no differences between the infrainguinal and inguinal approach groups concerning the postoperative duration of stay (P = 0.248), urinary retention (P = 0.494), superficial wound infection (P = 0.494), seroma (P = 0.615), foreign body sensation (P = 0.615), and chronic pain (P = 0.359). However, total complications were encountered in 3 patients (7.5%) in the infrainguinal approach group compared to 11 patients (27.5 %) in the inguinal approach group (P = 0.037). Also, the mean operative time was significantly shorter in the infrainguinal approach group compared to that in the inguinal group (P < 0.001). Throughout the 15 mo median follow-up duration, there was no recurrence in the inguinal approach group and one (2.5%) recurrence in the infrainguinal approach group (P = 1.000). CONCLUSIONS: In patients undergoing elective primary femoral hernia repair, the infrainguinal approach has a similar clinical curative effect to that of the inguinal approach. However, the former has the advantages of simple operation, short operation time, and fewer complications.

Retrospective analysis of smaller than 3-cm umbilical hernia repair with the lightweight macroporous mesh.

There is evidence that mesh repair for primary umbilical hernias results in fewer recurrences and similar wound complication rates compared to tissue repair. Various devices and surgical approaches are used in umbilical hernia repair. The ULTRAPRO PLUG (UPP) has been adopted for inguinal hernias and femoral hernias with excellent results. However, there are few reports on the use of UPP for umbilical hernia repair. Thus, the aim of this study was to evaluate efficacy and safety in the treatment of smaller than 3-cm umbilical hernias using the UPP.The medical records of 123 patients who underwent umbilical hernia repair using the UPP between October 2011 and September 2017 were reviewed. All patients were followed-up after 1 month and later in 2018. Demographics, surgical information, and immediate postoperative and long-term complications were assessed.Out of 123 patients, there were 37 male and 86 female patients with a mean age of 50.6 years. The median duration of hernia surgery was 20.5 min (range, 12-34), and 109 (88.6%) patients underwent day surgery. The median defect diameter was 1.4 cm (range, 0.5-3). No mortality or major complications occurred during the perioperative period. Long-term follow-up data were available for 107 (87.0%) patients. The median follow-up duration was 33 months (range, 5-76 months). Early postoperative complications included 1 case of seroma, 2 cases of fat liquefaction, and 1 case of superficial surgical site infection. During follow-up, there were 2 recurrences, 1 case of chronic mesh infection, and 2 patients with chronic postoperative pain.The ULTRAPRO PLUG offers a simple and quick means of repairing smaller than 3-cm umbilical hernias with lower recurrence rates and fewer postoperative complications.

[EFFECTIVENESS OF PREPERITONEAL HERNIORRHAPHY WITH Ultrapro Plug MESH FOR UMBILICAL HERNIA REPAIR IN ADULTS].

OBJECTIVE: To explore the effectiveness of preperitoneal herniorrhaphy with Ultrapro Plug (UPP) mesh for umbilical hernia repair in adults. METHODS: Between September 2011 and June 2015, 71 patients with umbilical hernia underwent preperitoneal herniorrhaphy with UPP mesh. There were 26 males and 45 females, aged 19-92 years (mean, 54.3 years). The disease duration was 45 days to 30 years (median, 18 months). Umbilical hernia was diagnosed through physical examination, ultrasound, and other relevant auxiliary examination. According to American Society of Anesthesiologists (ASA) classification, 12 cases were rated as grade Ⅰ, 34 cases as grade Ⅱ, 21 cases as grade Ⅲ, and 4?cases as grade Ⅳ. The operation time, postoperative hospitalization time, complication, and recurrence were recorded. RESULTS: The diameter of hernia ring ranged 0.5-3.0 cm (mean, 1.8 cm). There was no vessel or intestine injury. The operation time was 12-35 minutes (mean, 22.4 minutes); postoperative hospitalization time was 12-48 hours (mean, 16.3 hours). Fat liquefaction of incision occurred in 2 cases, and primary healing of incision was obtained in the other cases. Sixty-nine patients were followed up 8-51 months (median, 28 months). Hernia recurrence and patch infection occurred in 1 case respectively during follow-up. No postoperative foreign body sensation and chronic pain occurred. CONCLUSIONS: Repairing umbilical hernia in adults with UPP mesh should be safe and reliable, because it has the advantages of short operation time, short hospital stay, less complication, and lower incidence of recurrence.

Role of miRNA-146 in proliferation and differentiation of mouse neural stem cells.

Neural stem cells (NSCs) have been defined as neural cells with the potential to self-renew and eventually generate all cell types of the nervous system. NSCs serve as an ideal cell type for nervous system repair. In the present study, miR-146 overexpression and predicted target (notch 1) were used to study proliferation and differentiation of mouse NSCs. shRNA were used to demonstrate the function of Notch 1 in proliferation of mouse NSCs and luciferase reporter assay was used to assess and confirm the binding sequence of 3'-UTR between Notch 1 and miR-146. Results showed that miR-146 overexpression and knockdown of notch 1 inhibited proliferation of mouse NSCs under serum-free cultural conditions and promoted spontaneous differentiation of mouse NSCs under contained serum cultural conditions respectively. Mouse NSCs spontaneously underwent differentiation into neurogenic cells with contained serum medium. However, when miR-146 was overexpressed, differentiation efficiency of glial cells from NSCs was increased, suggesting that Notch1 promoted NSC proliferation and repressed spontaneous differentiation of NSC in serum-free medium. In conclusion, our results demonstrate that miR-146 promoted spontaneous differentiation of NSCs, and this mechanism was influenced by miR-146, as well as its target (notch 1) and downstream gene.

Long-term results of femoral hernia repair with ULTRAPRO Plug.

BACKGROUND: The infrainguinal plug technique for femoral hernia (FH) has gained popularity for its feasibility, simplicity, and encouraging rate of success, but materials and structures of traditional mesh plugs may cause postoperative discomfort, plug migration, and even recurrence. The new hernia repair device ULTRAPRO Plug (UPP) may avoid those problems. MATERIALS AND METHODS: In 121 of patients, a total of 125 elective FH repairs with UPP were performed between March 2009 and March 2013. Demographics, surgical information, and outcome were assessed. RESULTS: Out of 121 patients, 105 were female. The mean age was 57.6 y. FHs occurred more often on the right (72) than the left (45), and in 4 patients the hernias were bilateral. Mean duration of a hernia surgery was 14.7 min, and 91% patients were discharged within 24 h. Mean time to complete return to daily activities was 7.4 d. No mortality or major complications occurred during the perioperative period. Median follow-up was 26 mo, and the total follow-up rate was 91%. No recurrence or chronic mesh infection was noted. Postoperative chronic pain in two patients, sensory loss in one patient, and foreign body sensation in three patients were found in the follow-up. CONCLUSIONS: Repair of FHs with UPP through an infrainguinal approach is a simple and effective procedure without major postoperative events.

[Effectiveness of tension-free herniorrhaphy with UPP mesh through a femoris approach for femoral hernia repair].

OBJECTIVE: To explore the effectiveness of tension-free herniorrhaphy with Ultrapro Plug (UPP) mesh through a femoris approach for femoral hernia repair. METHODS: Between March 2009 and January 2013, 123 patients (126 sides) underwent tension-free herniorrhaphy with UPP mesh through a femoris approach. There were 17 males and 106 females, aged 32-95 years (mean, 63.3 years). The locations were the left side in 48 cases, the right side in 72 cases, and both sides in 3 cases. The disease duration was 1 month to 26 years (median, 25 months). Of 123 cases, 35 cases (36 sides) were reducible and 88 cases (90 sides) were irreducible. According to American Society of Anesthesiologists (ASA) classification, 20 cases were rated as grade I, 42 cases as grade II, 56 cases as grade III, and 5 cases as grade IV. The operation time, postoperative hospitalization time, complication, recurrence, and chronic pain were recorded. RESULTS: The operation time was 7-28 minutes (mean, 14.5 minutes); postoperative hospitalization time was 2-96 hours (mean, 19.4 hours) (112 patients discharged from hospital within 24 hours). Wound dehiscence occurred in 1 case and fat liquefaction in 2 cases. A total of 119 patients (122 sides) were followed up 4-50 months (median, 18 months); no recurrence was noted. Two cases (2 sides) suffered from chronic pain after operation, whose visual analogue scale (VAS) was 20 mm and 30 mm, respectively. CONCLUSION: Tension-free herniorrhaphy with UPP mesh through a femoris approach should be recommended because it has the advantages of simple operation, short operation time, less complication, and lower incidence of chronic pain.