[Long-term oncological outcomes of laparoscopic versus abdominal surgery in stage â a1 （LVSI+）-â b1 cervical cancer patients with different tumor size: a big database in China].

Objective: To compare the long-term oncological outcomes between laparoscopic and abdominal surgery in stage Ⅰa1 （lymph-vascular space invasion-positive, LVSI+）- Ⅰb1 cervical cancer patients with different tumor sizes. Methods: Based on the Big Database of Clinical Diagnosis and Treatment of Cervical Cancer in China (1538 project database), patients with stage Ⅰa1 （LVSI+）-Ⅰb1 cervical cancer who treated by laparoscopic or abdominal surgery were included. The 5-year overall survival (OS) and 5-year disease-free survival (DFS) between the two surgical approaches were compared under 1∶1 propensity score matching (PSM) in different tumor diameter stratification. Results: (1) A total of 4 891 patients with stage Ⅰa1 （LVSI+）-Ⅰb1 cervical cancer who underwent laparoscopy or laparotomy from January 1, 2009 to December 31, 2016 were included in the 1538 project database. Among them, 1 926 cases in the laparoscopic group and 2 965 cases in the abdominal group. There were no difference in 5-year OS and 5-year DFS between the two groups before matching. Cox multivariate analysis suggested that laparoscopic surgery was associated with lower 5-year DFS (HR=1.367, 95%CI: 1.105-1.690, P=0.004). After 1∶1 PSM matching, 1 864 patients were included in each group, and there was no difference in 5-year OS between the two groups （94.1% vs 95.4%, P=0.151）. While, the inferior 5-year DFS was observed in the laparoscopic group (89.0% vs 92.3%, P=0.004). And the laparoscopic surgery was associated with lower 5-year DFS (HR=1.420, 95%CI: 1.109-1.818, P=0.006). (2) In stratification analysis of different tumor sizes, and there were no difference in 5-year OS and 5-year DFS between the laparoscopic group and abdominal group in tumor size ≤1 cm, >1-2 cm and >2-3 cm stratification (all P>0.05). Cox multivariate analysis showed that laparoscopic surgery were not related to 5-year OS and 5-year DFS (P>0.05). In the stratification of tumor size >3-4 cm, there was no difference in 5-year OS between the two groups (P>0.05). The 5-year DFS in the laparoscopic group was worse than that in the abdominal group (75.7% vs 85.8%, P=0.025). Cox multivariate analysis suggested that laparoscopic surgery was associated with lower 5-year DFS (HR=1.705, 95%CI: 1.088-2.674, P=0.020). Conclusions: For patients with stage Ⅰa1 （LVSI+）-Ⅰb1 cervical cancer, laparoscopic surgery is associated with lower 5-year DFS, and the adverse effect of laparoscopic surgery on oncology prognosis is mainly reflected in patients with tumor size >3-4 cm. For patients with tumor sizes ≤1 cm, >1-2 cm and >2-3 cm, there are no difference in oncological prognosis between the two surgical approaches.

A Unique and Rare Case of Extramammary Paget Disease With Concomitant Herpes Simplex.

We describe a rare and unique case of extramammary Paget disease in the genitals with concomitant histological features of herpes virus infection. This is a very rare and interesting association that has only been reported in 1 article in the literature so far.

Circular RNA_LARP4 is lower expressed and serves as a potential biomarker of ovarian cancer prognosis.

OBJECTIVE: Circular RNAs (circRNAs) have been identified as important regulators in regulating cancer progression. The study aims to investigate the expression of circular RNA_LARP4 (circ LARP4) and clinical significance in ovarian cancer (OC). PATIENTS AND METHODS: The expression of circ LARP4 was detected in a total of 78 paired ovarian cancer tissue and adjacent normal tissue samples using quantitative Reverse Transcription-Polymerase Chain Reaction (qRT-PCR) analyses. The chi-square test was used to assess the association between expression of circLARP4 and clinical-pathological parameters. Survival plot was evaluated using the Kaplan-Meier method. The multivariate Cox analysis model was used for tumor prognosis analysis. RESULTS: We identified that circLARP4 expression was significantly down-regulated in ovarian cancer tissues compared with corresponding controls. Furthermore, we found that circLARP4 expression was significantly associated with International Federation of Gynecology and Obstetrics (FIGO) stage and lymph node metastases. Lower circLARP4 expression was associated with poor prognosis of OC patients. Moreover, multivariate Cox analysis showed that lower circLARP4 was an independent risk for OC prognosis. CONCLUSIONS: These results indicated that circLARP4 expression was lower and highlighted that circLARP4 was identified as a potential biomarker of ovarian cancer prognosis.

[Regulation of Ruxolitinib on matrix metalloproteinase in JAK2V617F positive myeloroliferative neoplasms cells].

Objective: To investigate the regulation of JAK2 tyrosine kinase inhibitor ruxolitinib on extracellular matrix metalloproteinase (MMP in JAK2V617F positive myeloproliferative neoplasms (MPN) cells. Methods: ①Forty cases of newly diagnosed JAK2V617F positive MPN patients and 15 healthy volunteers as control in Baoding No.1 Hospital between January 2012 and December 2015 were enrolled in this study. JAK2V617F/JAK2 ratio was detected by real-time-PCR; the expression levels of phosphorylation protein tyrosine kinase 2 (p-JAK2) , MMP-2 and MMP-9 in pathological tissues of bone marrow were detected by immunohistochemistry. The bone marrow cells of JAK2V617F positive MPN patients were treated with ruxolitinib, then the migration ability and MMP-2, MMP-9 gene and protein expression levels were detected. ②The human erythroleukemia cell line HEL cells were treated with different concentrations of ruxolitinib (0, 50, 100, 250, 500, 1 000 nmol/L) . The cell viability was detected by CCK-8 test; cell migration ability was tested by transwell chambers. The mRNA expression levels of JAK2, MMP-2 and MMP-9 were detected by real-time-PCR. The protein expression levels of p-JAK2, MMP-2 and MMP-9 were detected by Western blot. Results: ①The expression levels of p-JAK2, MMP-2 and MMP-9 in the newly diagnosed group were significantly higher than control group respectively [ (78.56±24.55) % vs (41.59±17.29) %, P<0.05; (48.25±18.74) % vs (22.79±13.89) %, P<0.05; (53.29±19.28) % vs (15.56±14.96) %, P<0.05]. Spearman correlation analysis showed the positive correlation of MMP-2 and MMP-9 protein expression levels with JAK2V617F mutation (r=0.526, P=0.001; r=0.543, P=0.001) . ②The proliferation of HEL cells was inhibited by different concentrations of ruxolitinib in time and dose dependent manner. ③Cell migration test showed the number of cells leaked to the low chamber in MPN patients bone marrow cells and HEL cells treated with 5 nmol/L of ruxolitinib group were significantly lower than that without ruxolitinib treatment after 24 h [ (154.7±27.5) vs (320.3±67.3) , t=13.47, P<0.05; (70.7±10.5) vs (135.3±16.7) , t=13.89, P<0.05]. The mRNA and protein expression levels of JAK2, MMP-2 and MMP-9 decreased with the increased concentration of ruxolitinib. Conclusion: Ruxolitinib inhibits MPN cell migration and expression of MMP-2 and MMP-9 via JAK2 signal pathway.

Stretta radiofrequency for gastroesophageal reflux disease-related respiratory symptoms: a prospective 5-year study.

AIM: The aim of the present study was to prospectively evaluate the Stretta radiofrequency (RF) treatment for gastroesophageal reflux disease (GERD) -related respiratory symptoms over a 5-years follow-up period. METHODS: A total of 132 patients underwent the Stretta procedure between April 2007 and February 2009; 122 of the patients (92.4%) completed the 5-year follow-up. Symptom scores and PPI usage were evaluated at baseline, 6 months, 1 year, 3 years and 5 years after treatment. RESULTS: A total of 122 patients (age, 51.7 ± 13.0 years, M:F, 52: 70) were followed up for 5 years and their outcomes were analyzed. At 5 years after treatment, the symptom scores were significantly reduced (heartburn score, from 5.67 ± 1.52 to 2.41 ± 1.13; regurgitation score, from 5.43 ± 1.66 to 2.27 ± 1.33; chest pain score, from 4.45 ± 1.47 to 2.40 ± 0.88; cough score, from 6.62 ± 1.73 to 3.14 ± 1.43; and asthma score, from 6.83 ± 1.46 to 3.26 ± 1.53, P<0.001). Moreover, 56.6% of the patients were completely off PPIs. CONCLUSION: Stretta RF significantly improves the symptoms and reduces PPI usage at 5 years. Therefore, it is a viable, effective, and minimally invasive endoluminal procedure for patients with GERD-related respiratory symptoms.

Five-year follow-up of a prospective study comparing laparoscopic Nissen fundoplication with Stretta radiofrequency for gastroesophageal reflux disease.

AIM: Laparoscopic Nissen fundoplication (LNF) and Stretta radiofrequency (RF) are used as main alternative strategies to manage medication-refractory GERD. This study was therefore prospectively evaluated outcomes of patients with refractory GERD 5 years after LNF or Stretta RF. METHODS: A total of 215 consecutive patients with refractory GERD underwent LNF (N.=102) and Stretta RF (N.=113) in our department between 2007 and 2008. They were followed-up for 5 years, during which the outcome measures including symptom scores of regurgitation, heartburn, chest pain, belching, hiccup, cough and asthma as well as the proton pump inhibitor (PPI) use and complications. RESULTS: Of the 215 patients, 179 patients following LNF (N.=87) or Stretta RF (N.=92) completed the designated 5-year follow-up and were included in the final analysis. At the end of 5-year follow-up, the post-treatment scores were statistically lower as compared with the pre-treatment scores in both groups, while the symptom improvements after Stretta were significantly lower than that after LNF (p < 0.05). Besides, 81 (91%) patients achieved complete PPI therapy independence after LNF, comparing with 47 (51.1%) after Stretta RF (P<0.05). No significant differences in post-treatment complications were observed except for the abdominal distention. CONCLUSION: Even though laparoscopic Nissen fundoplication and Stretta RF are capable of controlling GERD symptoms effectively and safely in selected patients, LNF could improve more in symptoms and PPI elimination.

Laparoscopic Nissen fundoplication is more effective in treating patients with GERD-related chronic cough than Stretta radiofrequency.

AIM: Chronic cough is the most common extra-esophageal manifestation of gastroesophageal reflux disease (GERD). This study aimed to retrospectively analyze outcomes in patients with GERD-related cough following laparoscopic Nissen fundoplication (LNF) and Stretta radiofrequency (RF) respectively. METHODS: Medical charts of 83 patients with GERD-related cough that underwent LNF or Stretta RF between 2007 and 2012 were retrieved. Symptom scores (heartburn, regurgitation and cough) and proton pump inhibitors (PPIs) usages were evaluated. RESULTS: A total of 83 patients with GERD-related cough underwent LNF (N.=35) and Stretta RF (N.=48), and were followed up 36.78 ± 16.12 months (range 13-55 months). During the follow-up, the post-treatment scores were statistically lower as compared with the pre-treatment scores in both groups, while the cough improvement after Stretta was significantly lower than that after LNF (P<0.001). Besides, 27 (77.1%) patients achieved complete PPI therapy independence after LNF, comparing with 27 (65.1%) after Stretta (P<0.05). No significant differences in post-treatment complications were observed except for the abdominal distention. CONCLUSION: Even though laparoscopic Nissen fundoplication and Stretta are capable of controlling GERD-related cough effectively and safely in selected patients, laparoscopic Nissen fundoplication could improve more in symptoms and PPI elimination.

Inflammatory pseudotumour arising from periampullary carcinoid: a "cancer-like" tumour in a "fake" tumour.

Carcinoid tumours of the gastrointestinal tract are uncommon, generally slow-growing and associated with a good prognosis. We present a 52-year-old Chinese woman with a carcinoid at the ampulla of Vater, a site far less common than other areas of the gastrointestinal tract. Preoperative imaging showed a pancreatic mass with displacement and possible invasion of the portal vein associated with peripancreatic nodal enlargement. A radical pancreaticoduodenectomy with portal vein wedge excision was performed. An intraoperative biopsy of the enlarged nodes was negative for malignancy and postoperative histology of the large pancreatic mass yielded a surprising finding of a carcinoid tumour at the ampulla of Vater with a large inflammatory pancreatic mass adherent to the portal vein. This is an uncommon case associated with "pseudotumour pancreatitis", causing biliary and pancreatic duct obstruction mimicking a large tumour in the head of the pancreas.

Influence of the route of administration on the pharmacokinetics of pirprofen enantiomers in the rat.

The pharmacokinetics of the enantiomers of the non-steroidal anti-inflammatory drug pirprofen were studied in male Sprague-Dawley rats after oral and intravenous (iv) doses of the racemate. No significant differences were detected between the enantiomers after oral or iv dosing in t1/2, Vd, or sigma Xu. However, the R:S area under the plasma concentration (AUC) ratio after oral doses (0.92 +/- 0.13) was slightly but significantly lower than after matching iv doses (1.05 +/- 0.036). The absolute bioavailability of the active S-enantiomer (78.5%) after oral doses was higher than the inactive R-enantiomer (69.3%). The plasma protein binding of both enantiomers was saturable over a fivefold range of plasma concentrations. At higher plasma concentrations, the S-enantiomer was less bound than the R-enantiomer. In an in vitro experiment using everted rat jejunum, no chiral inversion was discernible. The dependency of the AUC ratio of the enantiomers on the route of administration may be due to stereoselective first-pass metabolism.

Stereospecific high-performance liquid chromatographic assay of pirprofen enantiomers in rat plasma and urine.

A stereospecific high-performance liquid chromatographic method was developed for the assay of pirprofen enantiomers in rat plasma and urine. Following addition of internal standard (ketoprofen) and acidifier (L-ascorbic acid) to biological fluids, pirprofen was extracted into an isopropanol-isooctane (5:95) mixture. Diastereomers of pirprofen enantiomers, which were formed using L-leucinamide, were separated on a reversed-phase column with ultraviolet detection at 275 nm using 0.06 M KH2PO4-acetonitrile-triethylamine (64:36:0.1) as mobile phase. The limit of quantitation was 0.1 microgram/ml for each enantiomer, based on 100 microliters of rat plasma. No spontaneous oxidation of pirprofen to its pyrrole metabolite occurred during sample preparation and analysis. In three female rats which were dosed with 10 mg/kg racemic pirprofen orally, plasma concentrations of the enantiomers could be followed for 24 h. Pirprofen enantiomers in plasma were virtually unconjugated, and negligible concentrations of pyrrole metabolites were observed. Less than 10% of the total dose was recovered in urine as intact drug and its glucuroconjugates. The assay was found suitable for the study of the pharmacokinetics of pirprofen enantiomers in the rat.