[Application of molecular analysis in differential diagnosis of ovarian adult granulosa cell tumors].

Objective: To investigate the application value of molecular detection in the differential diagnosis of ovarian adult granulosa cell tumors (AGCT) by analyzing FOXL2, AKT1 and DICER1 mutations in these tumors. Methods: A total of 48 cases of ovarian sex cord-stromal tumor (SCST) were selected from July 2012 to June 2019 in Beijing Obstetrics and Gynecology Hospital, including 21 adult granulosa cell tumors (AGCT), 15 fibromas/fibrothecomas, 8 Sertoli-Leydig cell tumors (SLCT) and 4 other types of ovarian SCST. Genomic DNA was extracted from the formalin-fixed paraffin-embedded tissue sections. Polymerase chain reaction amplification for FOXL2, AKT1 and DICER1 genes was performed, followed by sequencing using capillary electrophoresis. Fisher exact test was used to compare the prevalence difference of FOXL2, AKT1 and DICER1 mutations among the groups. P<0.05 was considered significant. Results: Eighteen of the 21 (85.7%) AGCT harbored FOXL2 mutation. Compared with other SCST (13.0%, 3 of 23; including fibromas/fibrothecomas and SLCT), FOXL2 mutation was significantly higher in AGCT (P<0.001). In addition, FOXL2 mutation was also detected in one fibrothecoma, two SLCT and two gynandroblastomas. DICER1 mutation was identified in four of eight SLCT, and these cases were moderately to poorly differentiated. FOXL2 mutation was found in one SLCT with DICER1 mutation. There was no DICER1 mutation in other ovarian SCST. No AKT1 mutation was detected in all the patients. Conclusions: FOXL2 mutation is a highly specific biomarker for adult AGCT and may be helpful to resolve problematic cases. Diagnosis should also be taken into consideration of the clinical and histological features as FOXL2 mutation is also found in other SCST. The detection of DICER1 mutation is helpful for the differential diagnosis of ovarian SLCT. Synchronous DICER1 and FOXL2 mutation in the SLCT has been observed, and its significance needs to be further studied.

[Comparison between hybrid surgery and transabdominal preperitoneal surgery in treatment of irreducible inguinal hernia: A case-control study].

Objective: To compare the effects between hybrid surgery and transabdominal preperitoneal surgery in treatment of irreducible inguinal hernia. Methods: A total of 60 patients who underwent laparoscopic inguinal hernia repair between June 2011 and December 2017 were included in the study. Patients were divided into two group: hybrid surgery group (observation group, n=30) and transabdominal preperitoneal group (control group, n=30). The operation time, intraoperative bleeding, hospital stay, hospital cost and complications were analyzed. Results: The operative time of observation group and control group was 45 (35-65) minutes and 50(35-70) minutes, respectively. Intraoperative blood loss of two groups was 10(5-15) ml and 5(2-10) ml. The length of postoperative hospital stay was 2(1-4) days and 2(1-3) days in the two groups, respectively. And the hospitalization cost of two groups was 9 646 (9 066-11 560) yuan and 9 494(8 989-10 660) yuan, respectively. The intraoperative complications occurred in 4 cases in control group, including 1 case of vas deferens injury, 2 cases of spermatic vessel injury and 1 case of inferior epigastric artery injury. No intraoperative complications occurred in observation group. Perioperative complications in observation group and control group included dysuria (6.7% vs 10.0%), scrotum hematoma (3.4% vs 0%), wound pain (46.7% vs 6.7%) and fever (16.7% vs 20.0%). Twelve months of follow-up was completed in all the patients, and no recurrence or infections occurred in the two groups. The incidence of seroma in observation group and control group was 26.7%, 33.3%, respectively. One case of foreign body sensation and one case of chronic pain occurred in control group. The incidence of perioperative wound pain in patients undergoing hybrid surgery was higher than those undergoing transabdominal preperitoneal surgery (P<0.05), but no statistical differences were observed for other variables between the two groups (all P>0.05). Conclusion: Hybrid surgery is safe and feasible for the treatment of irreducible inguinal hernia. Though with a higher incidence of postoperative acute pain, it may have advantages of avoiding injuries of the vas deferens and spermatic vessels.

[Helical tomotherapy using simultaneously integrated boost and simultaneous integrated protection technique for unresectable biliary tract cancer].

Objective: To evaluate the safety and efficacy of helical tomotherapy using simultaneously integrated boost and simultaneous integrated protection technique in the treatment of unresectable biliary tract cancers. Methods: The data of 23 patients with unresectable biliary tract cancer who received tomotherapy-based hypofractionated radiotherapy at Comprehensive Cancer Centre of Drum Tower Hospital,the Affiliated Drum Tower Clinical College of Nanjing Medical University between February 2015 and October 2017 were analyzed. There were 10 males and 13 females, aged from 40 to 85 years(median:58 years). Pathological type included intrahepatic cholangiocarcinomas(n=11), gallbladder cancers(n=6),extrahepatic cholangiocarcinomas(n=6). The irradiated sites covered primary tumors and areas of local invasion,including metastatic lymph nodes which were confined to the abdominal or retroperitoneal space. Dose escalation was achieved using simultaneously integrated boost(SIB) technique, and simultaneous integrated protection(SIP)technique was used to protect gastrointestinal tracts and other adjacent organs. Cox regression modal and Kaplan-Meier analysis were used to analyze the associations between patients' characteristics and overall survival(OS). Results: The median total radiation dose was 54 Gy(range: 28-72 Gy)and median biologically effective dose(BED)was 74.4 Gy(range: 37.8-115.2 Gy).The median planning target volume(PTV)was 445.79 cm(3)(range:126.02-950.12 cm(3)). Based on the various PTV,patients received 2.4-6.0 Gy/fraction with 8-28 fractions. The local control rate was 65.2% and the median OS was 11.3 months(range:2.1-31.9 months).The most common cause of death was out-field failure and only 3 patients died of in-field failures. The longest survival was 31.9 months. BED≥70 Gy significantly improved OS,compared to BED<70 Gy(16.8 months vs.5.1 months)(HR=0.146, 95%CI:0.028-0.762, P=0.022). No patients developed grade ≥4 toxicities. Conclusions: Helical tomotherapy-based hypofractionated radiotherapy is effective and well tolerated for patients with unresectable biliary tract cancer. The dose escalation with higher BED could improve the survival for such patients.

Titanium-coated mesh versus standard polypropylene mesh in laparoscopic inguinal hernia repair: a prospective, randomized, controlled clinical trial.

OBJECTIVE: We aimed to compare the clinical outcome of titanium-coated mesh and polypropylene mesh in laparoscopic inguinal hernia repair. METHODS: A total of 102 patients who received laparoscopic inguinal hernia repair in January-June 2016 in Beijing Chao-Yang Hospital were enrolled in this study. Patients were randomly divided into two groups, receiving either titanium-coated mesh (n = 50) or standard polypropylene mesh (n = 52). Multiple clinical parameters were collected and analyzed, including clinical manifestations, operative time, intraoperative blood loss, hospital stay, hospital cost, recovery time, and postoperative complications. RESULTS: All procedures were completed. A statistical difference between two groups was not identified in regards to operative time, intraoperative blood loss, hospital stay, and recovery time (P > 0.05). Three cases with seroma and 15 with foreign body sensation were reported in the titanium-coated mesh group; 9 cases with seroma and 17 with foreign body sensation were reported in the standard polypropylene mesh group. There was no significant difference in the incidence of seroma and/or foreign body sensation. A lower hospital cost but longer recovery period was documented in the standard polypropylene mesh group (P < 0.05). No recurrence, infection or chronic pain was observed during 1-year follow-up in both groups. CONCLUSION: Titanium-coated mesh possesses comparable clinical qualities as the standard polypropylene mesh but with a shorter recovery period. Therefore, this mesh is promising for clinical practice though the cost is higher than the standard polypropylene mesh.

[Chinese multicenter randomized trial of customized chemotherapy based on BRCA1 (breast cancer susceptibility gene 1)-RAP80 (receptor-associated protein 80) mRNA expression in advanced non-small cell lung cancer (NSCLC) patients].

Objective: BRCA1 (breast cancer susceptibility gene 1) and RAP80 (receptor-associated protein 80) play key roles in predicting chemosensitivity of platinum and taxanes. A randomized trial was carried out to compare non-selected cisplatin-based chemotherapy with therapy customized according to BRCA1 and RAP80 expression. Methods: Advanced stage NSCLC patients whose tumor specimen was sufficient for molecular analysis were randomized (1∶3) to the control or experimental arm. Patients in the control arm received docetaxel/cisplatin; in the experimental arm, patients with low RAP80 expression received gemcitabine/cisplatin (Arm 1), those with intermediate/high RAP80 expression and low/intermediate BRCA1expression received docetaxel/cisplatin (Arm 2), and those with intermediate/high RAP80 expression and high BRCA1 expression received docetaxel alone (Arm 3). The primary end point was progression-free survival (PFS). Results: 226 patients were screened and 124 were randomized in this trial. ORR in the four subgroups was 22.6%, 48.4%, 30.3% and 19.2%, respectively (P=0.08); PFS was 4.74, 5.59, 3.78 and 2.73 months, respectively (P=0.55); and OS was 10.82, 14.44, 10.86 and 10.86 months, respectively (P=0.84). The common adverse effects included neutropenia, nausea, anemia and fatigue. Conclusions: No statistically significant difference of ORR, PFS or OS is observed in the experimental arms compared with the control arm. Patients with low RAP80 mRNA levels have a trend of better survival and higher response rate to gemcitabine/cisplatin chemotherapy.

Effects of different remifentanil target concentrations on MAC BAR of sevoflurane in gynaecological patients with CO2 pneumoperitoneum stimulus.

BACKGROUND: To investigate the effects of different target plasma remifentanil concentrations on the minimum alveolar concentration of sevoflurane (MAC) for blocking adrenergic response (BAR) during laparoscopic gynaecological surgery with carbon dioxide insufflation. METHODS: Seventy-five gynaecological patients with ASA I-II undergoing laparoscopic surgery were randomly assigned to three groups. Anaesthesia was induced by sevoflurane, and 0.1 mg kg(-1) of vecuronium i.v. was injected to facilitate tracheal intubation. After intubation the target plasma concentrations of remifentanil in Groups 1, 2, and 3 were adjusted to 0, 1, and 2 ng ml(-1), respectively. The changes in haemodynamics were observed before and after the creation of carbon dioxide pneumoperitoneum. The MAC BAR of sevoflurane in each group was determined by using an up-and-down sequential-allocation technique, and blood samples were collected at corresponding time points to determine the concentrations of remifentanil, norepinephrine, and epinephrine. RESULTS: In Groups 1, 2 and 3, the MAC BAR of sevoflurane was 4.6% (CI 95%: 4.3-4.9%), 2.4% (CI 95%: 2.2-2.6%), and 1.7% (CI 95%: 1.4-2.1%), respectively. No significant differences were found in the increase of norepinephrine, epinephrine, and mean arterial pressure after compared with before insufflation of pneumoperitoneum among the three groups. CONCLUSIONS: Remifentanil can effectively decrease the sevoflurane concentration to block sympathetic adrenergic response to CO2 pneumoperitoneum stimulus. At similar MAC BAR the haemodynamic and adrenergic response is not affected by the infused remifentanil concentration. CLINICAL TRIAL REGISTRATION: The number of this clinical trial registry is ChiCTR-TRC-13004005, and the Universal Trial Number is U1111-1151-5630.

Screening of the FUS gene in familial and sporadic amyotrophic lateral sclerosis patients of Chinese origin.

BACKGROUND: According to studies in European, North American, Australian, and Asian populations, FUS gene mutations occur in 0.6-20.2% of the patients with familial amyotrophic lateral sclerosis (ALS) and 0.4-2.0% of sporadic ALS cases. In China, FUS mutations have been reported in several familial ALS pedigrees but not in sporadic ALS cases. Here, we screened for FUS mutations in Chinese patients with ALS. METHODS: We sequenced all of the 15 exons of FUS in 10 familial ALS pedigrees, exons 5, 6, 14, and 15 in 210 patients with sporadic ALS and 151 healthy controls. All patients were negative for SOD1, TARDBP, and ANG mutations. RESULTS: A c.1562G>T (p.R521L) missense mutation was identified in one familial ALS proband and her asymptomatic daughter. A c.1562G>A (p.R521H) missense mutation was identified in two patients with sporadic ALS. Three synonymous mutations (c.453C>T, c.648C>T, and c.1464C>T) were detected among four patients with sporadic ALS, and a untranslated region variant (*14C>T) was identified in one familial ALS proband and one patient with sporadic ALS. CONCLUSIONS: The frequency of FUS mutations is approximately 1.0% in our SOD1-, ANG-, TARDBP-mutation-negative sporadic ALS cohort and similar to that reported in previous studies from Asia in our familial ALS cohort. [Correction added on 31 May 2012, after first online publication: the gene FUS- was changed to ANG-]. Our findings provide an overview of the occurrence of FUS mutations in Chinese sporadic and familial ALS cases and highlight the importance of screening for FUS mutations in ALS patients of Chinese origin.