Identification and validation of SERPINE1 as a prognostic and immunological biomarker in pan-cancer and in ccRCC.

Background: SERPINE1, a serine protease inhibitor involved in the regulation of the plasminogen activation system, was recently identified as a cancer-related gene. However, its clinical significance and potential mechanisms in pan-cancer remain obscure. Methods: In pan-cancer multi-omics data from public datasets, including The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx), and online web tools were used to analyze the expression of SERPINE1 in different cancers and its correlation with prognosis, genetic alteration, DNA promoter methylation, biological processes, immunoregulator expression levels, immune cell infiltration into tumor, tumor mutation burden (TMB), microsatellite instability (MSI), immunotherapy response and drug sensitivity. Further, two single-cell databases, Tumor Immune Single-cell Hub 2 (TISCH2) and CancerSEA, were used to explore the expression and potential roles of SERPINE1 at a single-cell level. The aberrant expression of SERPINE1 was further verified in clear cell renal cell carcinoma (ccRCC) through qRT-PCR of clinical patient samples, validation in independent cohorts using The Gene Expression Omnibus (GEO) database, and proteomic validation using the Clinical Proteomic Tumor Analysis Consortium (CPTAC) database. Results: The expression of SERPINE1 was dysregulated in cancers and enriched in endothelial cells and fibroblasts. Copy number amplification and low DNA promoter methylation could be partly responsible for high SERPINE1 expression. High SERPINE1 expression was associated with poor prognosis in 21 cancers. The results of gene set enrichment analysis (GSEA) indicated SERPINE1 involvement in the immune response and tumor malignancy. SERPINE1 expression was also associated with the expression of several immunoregulators and immune cell infiltration and could play an immunosuppression role. Besides, SERPINE1 was found to be related with TMB, MSI, immunotherapy response and sensitivity to several drugs in cancers. Finally, the high expression of SERPINE1 in ccRCC was verified using qRT-PCR performed on patient samples, six independent GEO cohorts, and proteomic data from the CPTAC database. Conclusion: The findings of the present study revealed that SERPINE1 exhibits aberrant expression in various types of cancers and is associated with cancer immunity and tumor malignancy, providing novel insights for individualized cancer treatment.

Incidence of Gastric Neoplasms Arising from Autoimmune Metaplastic Atrophic Gastritis: A Systematic Review and Case Reports.

Autoimmune metaplastic atrophic gastritis (AMAG) is associated with an increased risk of gastric neoplasms. This study aimed to systematically analyze the incidence rate of gastric cancer (GC), low-grade dysplasia (LGD) and type-1 gastric neuroendocrine tumor (gNETs) development in AMAG adults. Studies on AMAG patients reporting the incidence of gastric neoplasms was identified through a systematic search in PUBMED and EMBASE. Study quality was assessed using the Joanna Briggs Institute quality assessment tool. Incidence rates of GC, LGD and type-1 gNETs were examined by meta-analysis. Thirteen studies met eligibility criteria. Incidence rate of gastric cancer calculated from the pooled data was 0.14% per person-year in both single-center studies and national registration studies. Meta-analysis showed a relative risk of 11.05 (95% CI: 6.39-19.11) for gastric cancer development in AMAG patients. The calculated pooled gastric LGD and type-1 gNETs incidence rates were 0.52% and 0.83% per person-year, respectively. As for experience from our center, we presented three distinctive cases of gastric neoplasm arising from the background of AMAG. This study underscores the potential for malignant transformation of precancerous lesions and reiterates the importance of careful esophagogastroduodenoscopy screening.

Single-port robot-assisted perineal radical prostatectomy with the da Vinci XI system: initial experience and learning curve using the cumulative sum method.

BACKGROUND: To evaluate the early functional and oncological outcomes of single-port robot-assisted perineal radical prostatectomy (sp-pRARP) using the da Vinci XI system and analyze its learning curve using the cumulative sum (CUSUM) method. METHODS: The clinical data of 50 patients who underwent sp-pRARP for localized prostate cancer between May 2020 and May 2022 in our center by a single surgeon were analyzed retrospectively. Demographic information, preoperative and postoperative variables, complications, early functional and oncological outcomes of patients were recorded. The CUSUM method was used to illustrate the learning curve based on operation time. RESULTS: All surgeries were completed without conversion. The median (interquartile range, IQR) operation time was 205.0 (82.5) min, whereas the median (IQR) docking time was 30.0 (15.0) min and the console time was 120.0 (80.5) min. The median (IQR) estimated blood loss (EBL) was 50.0 (137.5) mL. Positive surgical margins were detected in five patients (10.0%). The continence rate was 40.9%, 63.6%, 88.4%, and 97.7% at the 1, 3, 6, and 12 months after surgery. According to the CUSUM plot, the inflection points of the learning curve were 20 cases, splitting the case series into "early phase" and "late phase." In "late phase" cases, there was less time spent on each step of the operation and less EBL. CONCLUSIONS: Sp-pRARP using the da Vinci XI system was verified to be a feasible and reliable surgical approach. According to the CUSUM plot, 20 cases was considered the turning point for surgeons to master the novel technique.

Endoscopic surveillance alone is feasible and safe in type I gastric neuroendocrine neoplasms less than 10 mm in diameter.

PURPOSE: Type I gastric neuroendocrine neoplasms (g-NENs) have a low risk of metastasis and a generally favourable prognosis. Patients with small type I g-NENs (≤10 mm) frequently require no treatment, whereas those with larger polyps usually undergo resection. We evaluated the safety and outcomes of endoscopic surveillance after no initial treatment in selected patients with type I g-NENs. METHODS: Retrospective analysis of type I g-NEN patients across two European Neuroendocrine Tumour Society Centers of Excellence 2003-2019. RESULTS: Following initial assessment, 87 of 115 patients with type I g-NEN (75 with polyps ≤10 mm) received no initial treatment and underwent endoscopic surveillance. 79/87 (91%) demonstrated no clinically meaningful change in tumour size or grade over a median 62 month follow up. Only two patients developed NEN progression that required a change in management and two other patients developed gastric adenocarcinoma/high grade dysplasia; all four initially had ≥11 mm g-NENs. CONCLUSIONS: Patients with ≤10 mm type I g-NENs were unlikely to develop clinically significant tumour progression and in most cases, resection was not needed. The endoscopic surveillance interval could therefore potentially be safely increased to every 2-3 years in such patients. However, lifelong surveillance is still advocated due to the additional risk of developing gastric adenocarcinoma.

Gastric lesions in patients with autoimmune metaplastic atrophic gastritis: a retrospective study in a single center.

OBJECTIVES: The presence of autoimmune metaplastic atrophic gastritis (AMAG) may lead to an increased risk of associated gastric neoplastic lesions. This study aims to investigate the prevalence of gastric neoplasia in AMAG patients and to explore the possibility of PGI/II ratio as a predictor for AMAG diagnosis. PATIENTS AND METHODS: Retrospective audit of 135 patients diagnosed with AMAG on endoscopic gastric biopsy between January 2017 and December 2020 at Beijing Friendship Hospital. The study was registered in Chinese Clinical Trial Registry (ChiCTR2000041163). RESULTS: A total of 135 patients (the mean age 61.9 ± 10.9 years,109 female) had histologically confirmed AMAG. 31.1% (42/135) had AMAG without neoplasia on the initial biopsy; 37% (50/135) had multiple type 1 gastric neuroendocrine tumors (g-NETs), 36 grade 1 and 14 grade 2, the median diameter was 5 mm (range 1-25); 31.9% (43/135) had multiple gastric hyperplastic polyps (GHPs), including 15 cases of GHPs with neoplastic transformation, the median diameter was 14.5 mm (range 3-50). 3.7% (5/135) had single gastric low-grade dysplasia/adenoma, the median diameter was 5 mm (range 3-15). 5.9% (8/135) had single or double gastric high-grade dysplasia or adenocarcinoma, the median diameter was 15 mm (range 8-43). 40.7% (55/135) had pepsinogen (PG) I< 10 ng/ml, 45.9% (62/135) had PG I/II ratio ≤1 and each group had a median of PG I/II ratio <1. CONCLUSIONS: Lower serum PG I level and PGI/II ratio may be a predictor to indicate the diagnosis of AMAG. It's necessary to perform regular endoscopic surveillance for AMAG patients to recognize associated gastric neoplasia timely.

Clinical characteristics, prognostic factors, and survival trends in esophageal neuroendocrine carcinomas: A population-based study.

BACKGROUND: Esophageal neuroendocrine carcinoma (ENEC) is an extremely rare type of malignancy. Clinical data of ENEC are limited to case reports and case series. More information is needed on its clinical feature, management, and prognosis. METHODS: This study collected information of ENEC patients diagnosed pathologically from 2010 to 2018. Data including demographic information, clinical features, and survival trends were obtained from the Surveillance, Epidemiology, and End Results (SEER) database. Statistical analyses were performed with STATA/SE 15.1, SPSS 25.0, and GraphPad Prism 8. RESULTS: A total of 283 ENEC patients were included in this study. The small-cell and large-cell subtypes of ENEC possess similar clinical features. The lower third of the esophagus (58%) was the most common location of ENEC. At the time of diagnosis, most ENEC patients were AJCC 7th stage IV (48.1%). Metastasis occurred in more than half of the ENEC patients (53.4%), and the most common metastatic site was the liver (37.1%). Compared with poorly differentiated esophageal squamous cell carcinoma (ESCC), another aggressive malignancy of the esophagus sometimes confused with ENEC because of similar histological features, our study showed differences in tumor location and metastatic rate, but similar poor survival rates. Multivariate survival analysis showed that ENEC located at the middle third of esophagus (p = 0.013), "Brain metastasis" (p = 0.019), and "Liver metastasis" (p < 0.001) were independent predictors of worse outcomes. "Surgery" (p = 0.003), and "Chemotherapy" (p < 0.001) were associated with better survival. CONCLUSION: A significant proportion of patients with newly diagnosed ENEC presented with metastatic disease. Predictors of poor survival included tumor location, brain metastasis, and liver metastasis. ENEC and poorly differentiated ESCC share certain histological features, but differ in tumor location and metastatic rate. Yet, no standard treatment strategy has been established, but surgery and chemotherapy were related to better outcomes.

Disposable versus reusable gastroscopes: a prospective randomized noninferiority trial.

BACKGROUND AND AIMS: Disposable gastroscopes have recently been developed to eliminate the risk of infection transmission from contaminated reusable gastroscopes. We compared the performance of disposable and reusable gastroscopes in patients undergoing gastroscopy. METHODS: Patients requiring gastroscopy were randomized to either the disposable or reusable digital gastroscope group. The primary endpoint was the success rate of photographing customary anatomic sites, with a noninferiority margin of -8%. Secondary endpoints were technical performance factors such as gastroscope imaging quality, maneuverability, gastroscopy completion rate, device failure/defect rate, operating time, and safety. Data were analyzed using the Newcombe-Wilson score method and Fisher exact 2-tailed t test. RESULTS: Of 110 patients, 55 were treated using disposable gastroscopes and 55 using reusable gastroscopes. The success rate for capturing images of customary anatomic sites was 100% in both groups. The average imaging quality score was significantly lower (37.02 ± 3.09 vs 39.47 ± 1.92, P < .001) and the operating time significantly longer (P < .001) in the disposable gastroscope group. No significant differences in maneuverability, gastroscopy completion rate, device failure/defect rate, operating time, or safety were found between the 2 groups. CONCLUSIONS: Given the overall safety profile and similar technical performance, disposable gastroscopes represent an alternative to reusable gastroscopes for routine examination, bedside first aid, and some certain circumstances.

Visual-electromagnetic system: A novel fusion-based monocular localization, reconstruction, and measurement for flexible ureteroscopy.

BACKGROUND: During flexible ureteroscopy (FURS), surgeons may lose orientation due to intrarenal structural similarities and complex shape of the pyelocaliceal cavity. Decision-making required after initially misjudging stone size will also increase the operative time and risk of severe complications. METHODS: A intraoperative navigation system based on electromagnetic tracking (EMT) and simultaneous localization and mapping (SLAM) was proposed to track the tip of the ureteroscope and reconstruct a dense intrarenal three-dimensional (3D) map. Furthermore, the contour lines of stones were segmented to measure the size. RESULTS: Our system was evaluated on a kidney phantom, achieving an absolute trajectory accuracy root mean square error (RMSE) of 0.6 mm. The median error of the longitudinal and transversal measurements was 0.061 and 0.074 mm, respectively. The in vivo experiment also demonstrated the effectiveness. CONCLUSION: The proposed system worked effectively in tracking and measurement. Further, this system can be extended to other surgical applications involving cavities, branches and intelligent robotic surgery.

A Prospective and Retrospective Clinical Controlled Observation of Chinese Herbal Decoction (SMLJ01) for Type 1 Gastric Neuroendocrine Tumors.

INTRODUCTION: Type 1 gastric neuroendocrine tumors (g-NETs) have a good prognosis but a high recurrence rate. AIM: To observe the clinical efficacy of the treatment of type 1 g-NETs with the Chinese herbal decoction SMLJ01. MATERIALS AND METHODS: A prospective and retrospective, clinical, controlled observation was conducted in 4 Chinese centers from 2012 to 2019. Patients with type 1 g-NETs were nonrandomly divided into treatment and control groups after endoscopic treatment based on herbal treatment administered according to their wishes. The treatment group received oral SMLJ01, with follow-up every 6 to 12 months, while the control group received follow-up alone. Patient follow-up (via telephone) from 2012 to 2017 was mainly retrospective. All patients after 2017 were followed prospectively. The recurrence times and rates were compared after treatment for at least 6 months. Symptom improvements were evaluated in the treatment group. The follow-up ended on October 31, 2019. RESULTS: During a median follow-up of 22 months (range: 2-86 months), the survival rate was 100%, and no metastases occurred. Twenty-one of the 82 treated patients (25.6%) had recurrence after a median of 22 months, and 22 of the 54 control patients (40.7%) had recurrence after a median of 8 months (P = .063). The Kaplan-Meier curve analysis showed that the patients in the treatment group had a significantly longer median recurrence-free survival (RFS) time than those in the control group (P = .001). The risk of recurrence in the treatment group was 0.38 relative to that in the control group (95% CI: 0.20-0.70). The symptom score of the patients after taking Chinese medicine was 19.5 (10.3, 28.0), which was significantly lower than before treatment (31.5 (19.3, 38.0)). The difference was statistically significant (P < .01). CONCLUSION: SMLJ01, with the effects of soothing the liver, strengthening the spleen, increasing acid and harmonizing the stomach, may help reduce the recurrence rate, relieve symptoms and prolong the recurrence time in patients with type 1 g-NETs and is worthy of evaluation with further randomized research with large sample sizes and longer follow-up periods.

Risk factors and clinical correlates of neoplastic transformation in gastric hyperplastic polyps in Chinese patients.

Gastric hyperplastic polyps (GHPs) have a potential risk of neoplastic transformation, but the responsible mechanisms have not yet been established. We conducted a study involving 55 patients (33 female) who had undergone endoscopic or surgical resection of GHPs. We compared 16 patients who had GHPs showing neoplastic transformation with 39 patients who had non-neoplastic GHPs. We analyzed differences in serology, gastroscopic manifestations and pathology between the two groups in order to establish risk factors that may be associated with neoplastic transformation. The mean age of the cohort was 61.73 ± 9.024 years. The prevalence of positive serum gastric parietal cell antibody (PCA) was 61.8%. 30 of the GHPs with neoplastic formation had a "strawberry-like" appearance with erosions of polyps (P = 0.000). A history of anaemia was a risk factor for GHPs which demonstrated neoplastic transformation (odds ratio [OR], 3.729; 95% confidence interval [CI], 1.099-12.649; P = 0.035). Although the differences were not significant, our data showed higher prevalences of positive serum PCA (P = 0.057), hypergastrinemia (P = 0.062) and female gender (P = 0.146) in the GHP patients who had neoplastic transformation. Multiple polyps in the corpus (P = 0.024) occurred more frequently in serum PCA positive patients. Hypergastrinemia occurred more frequently in Helicobacter pylori negative patients and of these 20/22 patients had a positive PCA (P = 0.007). GHPs are associated with autoimmune metaplastic atrophic gastritis (AMAG). AMAG is probably one of the risk factors for GHPs to undergo neoplastic transformation.

Multiple myeloma with primary amyloidosis presenting with digestive symptoms: A case report and literature review.

We present a case of multiple myeloma with primary systemic amyloidosis presenting with digestive symptoms in a 32-year-old male. Initial symptoms included upper abdominal discomfort for 4 months, and stool with mucous and blood for 1 month. Erosive gastritis, Helicobacter pylori infection, haematochezia, and weight loss were noted, but without bone pain, anaemia, or hypercalcaemia. Bone marrow examination showed 18.5% mature monoclonal plasma cells that were λ light chain protein and CD38 positive. Three courses of 28-day PTD therapy (i.e., bortezomib, dexamethasone, and thalidomide) were administered. Gastrointestinal symptoms and laboratory parameters improved. Post-treatment follow-up showed 0.5% plasma cells with normal morphology in bone marrow, urine λ light chain 10.1 mg/L, and negative M protein. Nevertheless, the patient died of multiple organ system failure 8 months after treatment. CONCLUSIONS: Amyloidosis is an uncommon finding in patients with multiple myeloma, especially in younger individuals.

Retracted: Identification of Prognosis Biomarkers of Prostatic Cancer in a Cohort of 498 Patients from TCGA.

The article entitled, "Identification of prognosis biomarkers of prostatic cancer in a cohort of 498 patients from TCGA," by Chen Z and Hu H. (J Comput Biol Dec 2019: e-pub ahead of print; DOI: 10.1089/cmb.2019.0224) is being officially retracted at the authors' request due to errors found in the data after publication of the article. The detected errors render the results and conclusion irreproducible, and therefore, invalid. Based on the communications received from the authors, the editorial leadership of Journal of Computational Biology agreed to retract the published paper. However, after retracting the article, it was also discovered that the same article had been previously published in volume 43, issue 6 of the journal, Current Problems in Cancer, published by Elsevier. The publisher of Journal of Computational Biology was in communication with Elseivier since simultaneous submission and/or publication is a violation of the proper protocols of peer review, and they are conducting their own evaluation. Journal of Computational Biology also notified the authors' institution of the infraction. Journal of Computational Biology, its Editor, and its Publisher are committed to preserving the integrity of the scientific record for the community it serves.

Identification of prognosis biomarkers of prostatic cancer in a cohort of 498 patients from TCGA.

OBJECTIVE: Prostatic cancer (PCa) is the first common cancer in male, and the prognostic variables are beneficial for clinical trial design and treatment strategies for PCa. This study was performed to identify more potential biomarkers for the prognosis of patients with PCa. METHODS AND RESULTS: The transcriptome data and survival information of a cohort including 498 subjects with PCa were downloaded from TCGA. A total of 4293 differentially expressed genes (DEGs), including 1362 prognosis-related DEGs, were identified in PCa tissues compared with normal tissues. Upregulated genes, including serine/arginine-rich splicing factors (SRSFs; such as SRSF2, SRSF5, SRSF7 and SRSF8), and ubiquitin conjugating enzyme E2 (UBE2) members (such as UBE2D2, UBE2G2, UBE2J1 and UBE2E1), were identified as negative prognostic biomarkers of PCa, as the high expression of them correlated with poor overall survival of PCa patients. Several downregulated Golgi-ER traffic mediators (such as SEC31A, TMED2, and TMED10) were identified as positive prognostic biomarkers of PCa, as the high expression of them correlated with good overall survival of PCa patients. CONCLUSIONS: These genes were of great interests in prognosis of PCa, and some of them may be constructive for the augmentation of clinical trial design and treatment strategies for PCa.

Robot-Assisted Laparoscopic Left Renal Vein Transposition for the Treatment of Nutcracker Syndrome: A Preliminary Experience.

BACKGROUND: The aim of this study was to describe our robot-assisted laparoscopic left renal vein (LRV) transposition experiences for nutcracker syndrome treatment. METHODS: From August 2016 through May 2017, three patients with nutcracker syndrome underwent robot-assisted laparoscopic LRV transpositions. The patient demographics, surgical outcomes, and postoperative morbidities were reviewed. RESULTS: Successful surgical procedures were performed in all three patients. The operative times for the three cases were 150, 175, and 162 minutes, respectively, while the LRV anastomosis times were 19, 22, and 13 minutes, respectively. No major perioperative complications were encountered, and the hematuria and flank pain were resolved in all three cases. At the 6-month follow-up, the computed tomography scan showed that the LRV narrowing had disappeared in two of the patients. Although one patient still exhibited LRV flattening, his symptoms were also relieved, and the varicose tributaries spontaneously ceased. CONCLUSIONS: Robot-assisted laparoscopic LRV transposition can be a viable minimally invasive treatment option for patients with nutcracker syndrome.

Dysregulated expression of homebox gene HOXA13 is correlated with the poor prognosis in bladder cancer.

BACKGROUND: The homeobox (HOX) genes have been implicated playing important roles in many human cancers. HOXA13 is a member of HOX genes that encode transcription factors regulating embryonic development and cell fate. In the present study, we aimed to investigate the expression and prognostic significance of HOXA13 in bladder cancer. METHODS: Immunohistochemical staining was initially performed to screen the differentially expressed HOXA13 between bladder cancer tissues and paired adjacent non-cancerous tissues. Subsequent Western blotting analysis validation was conducted using tissue samples from patients with bladder cancer. RESULTS: The expression level of HOXA13 was significantly higher in bladder cancer tissues compared to that in adjacent non-cancerous tissues (P < 0.001). The χ2-test showed that expression of HOXA13 was positively correlated with lymphatic metastasis (P = 0.013), bladder tumor TNM stage (P = 0.002) and pathological grade (P < 0.001). Kaplan-Meier survival analysis revealed that patients with bladder cancer with high expression of HOXA13 had shorter overall survival time (P = 0.001) and disease-free survival time (P = 0.001) compared to patients with low expression of HOXA13. Multivariate analysis indicated that HOXA13 was an independent prognostic factor for overall survival for bladder cancer patients. CONCLUSIONS: The results of our study show that high expression of HOXA13 is associated with the progression of bladder cancer and that HOXA13 might serve as a biomarker for prognosis of bladder cancer.

Comparison of safety and efficacy of laparoscopic pyelolithotomy versus percutaneous nephrolithotomy in patients with large renal pelvic stones: a meta-analysis.

To compare percutaneous nephrolithotomy (PCNL) and laparoscopic pyelolithotomy (LP) for surgical management for large (>2 cm) renal stones. We searched MEDLINE, Cochrane, and EMBASE databases until March 11, 2015, using the following search terms: renalpelvic stone, percutaneous nephrolithotomy, laparoscopic pyelolithotomy. Randomized controlled and prospective and retrospective two-armed studies were included. Sensitivity analysis and assessment of the quality of the included studies and publication bias were performed. Nine studies were included in the study with a patient population of 622. The studies were homogeneous with respect to the primary end point of stone-free rate, but were heterogeneous with respect to operation time, length of hospital stay, and blood loss. A higher percentage of patients who received LP remained stone-free following surgery compared with patients who were treated with PCNL (p=0.001). However, the mean operation time was longer for patients with LP than for those treated with PCNL (p=0.002). There was no difference between procedures with regard to length of hospital stay or blood loss (p≥0.071). Sensitivity and quality analysis indicated that the data are reliable and the included studies are of good quality. No publication bias was observed. The study suggests that both procedures are effective and safe for removing large renal stones. However, LP may be more efficacious than PCNL in treating large kidney stones.

Laparoscopic colonic anastomosis using a degradable stent in a porcine model.

AIM: To explore the feasibility and safety of laparoscopic colonic anastomosis using a degradable stent in a porcine model. METHODS: Twenty Bama mini-pigs were randomly assigned to a stent group (n = 10) and control group (hand-sewn anastomosis, n = 10). The anastomotic completion and operation times were recorded, along with histological examination, postoperative general condition, complications, mortality, bursting pressure, and the average anastomotic circumference (AC). RESULTS: All pigs survived postoperatively except for one in the stent group that died from ileus at 11 wk postoperatively. The operation and anastomotic completion times of the stent group were significantly shorter than those of the control group (P = 0.004 and P = 0.001, respectively). There were no significant differences in bursting pressure between the groups (P = 0.751). No obvious difference was found between the AC and normal circumference in the stent group, but AC was significantly less than normal circumference in the control group (P = 0.047, P < 0.05). No intestinal leakage and luminal stenosis occurred in the stent group. Histological examination revealed that the stent group presented with lower general inflammation and better healing. CONCLUSION: Laparoscopic colonic anastomosis with a degradable stent is a simple, rapid, and safe procedure in this porcine model.