Long-term outcomes of vulvar or vaginal cancer patients undergoing laparoendoscopic single-site inguinal lymphadenectomy.

INTRODUCTION: Laparoendoscopic single-site inguinal lymphadenectomy (LESS-IL), a minimally invasive technique, has been reported in patients with vulvar or vaginal cancer regarding its safety and feasibility. However, the long-term outcomes, especially oncologic outcomes, are still lacking. We aimed to evaluate the long-term outcomes of LESS-IL to confirm its safety further. PATIENTS AND METHODS: Data were prospectively collected from patients with vulvar or vaginal cancer who underwent LESS-IL at our institution between July 2018 and June 2021. The patients were followed up for at least 12 months. All procedures were performed according to treatment standards. Short- and long-term complications and oncologic outcomes were analysed. RESULTS: A total of 16 patients undergoing 28 LESS-IL procedures were identified, amongst whom 4 underwent unilateral LESS-IL. The median numbers of excised groin lymph nodes were 9.0 (6.5-11.8) and 10.5 (8.3-12.0) in each left and right groin, respectively. Short-term complications occurred in 4 (25%) patients, including 18.7% lymphocele and 6.3% wound infection. Long-term complications regarding lower-limb lymphoedema appeared in 6 (37.5%) patients. Most short- and long-term complications were Clavien-Dindo 1 or 2, accounting for 90% of all post-operative issues. After a median follow-up of 27 (21.3-35.8) months, only 1 (6.3%) patient had isolated inguinal recurrence at 13 months postoperatively. No local or distant recurrence occurred. CONCLUSION: Our results suggest that LESS-IL is associated with little incidence of complications and promising oncologic outcomes, further demonstrating the safety and feasibility of the LESS-IL technique in patients requiring IL.

Percutaneous Endoscopic Posterior Lumbar Interbody Fusion with Unilateral Laminotomy for Bilateral Decompression Vs. Open Posterior Lumbar Interbody Fusion for the Treatment of Lumbar Spondylolisthesis.

Background: Endoscopic lumbar interbody fusion is a new technology that is mostly used for single-segment and unilateral lumbar spine surgery. The purpose of this study is to introduce percutaneous endoscopic posterior lumbar interbody fusion (PE-PLIF) with unilateral laminotomy for bilateral decompression (ULBD) for lumbar spondylolisthesis and evaluate the efficacy by comparing it with open posterior lumbar interbody fusion (PLIF). Methods: Twenty-eight patients were enrolled in PE-PLIF with the ULBD group and the open PLIF group. The perioperative data of the two groups were compared to evaluate the safety of PE-PLIF with ULBD. The visual analog scale (VAS) back pain, VAS leg pain, and Oswestry Disability Index (ODI) scores of the two groups preoperatively and postoperatively were compared to evaluate clinical efficacy. Preoperative and postoperative imaging data were collected to evaluate the effectiveness of the operation. Results: No differences in baseline data were found between the two groups (p > 0.05). The operation time in PE-PLIF with the ULBD group (221.2 ± 32.9 min) was significantly longer than that in the PLIF group (138.4 ± 25.7 min) (p < 0.05), and the estimated blood loss and postoperative hospitalization were lower than those of the PLIF group (p < 0.05). The postoperative VAS and ODI scores were significantly improved in both groups (p < 0.05), but the postoperative VAS back pain score in the PE-PLIF group was significantly lower than that in the PLIF group (p < 0.05). The excellent and good rates in both groups were 96.4% according to MacNab's criteria. The disc height and cross-sectional area of the spinal canal were significantly improved in the two groups after surgery (p < 0.05), with no difference between the groups (p > 0.05). The fusion rates in PE-PLIF with the ULBD group and the PLIF group were 89.3% and 92.9% (p > 0.05), respectively, the cage subsidence rates were 14.3% and 17.9% (p > 0.05), respectively, and the lumbar spondylolisthesis reduction rates were 92.72 ± 6.39% and 93.54 ± 5.21%, respectively (p > 0.05). Conclusion: The results from this study indicate that ULBD can be successfully performed during PE-PLIF, and the combined procedure is a safe and reliable treatment method for lumbar spondylolisthesis.

Cis-2-dodecenoic Acid Mediates Its Synergistic Effect with Triazoles by Interfering with Efflux Pumps in Fluconazole-resistant Candida albicans.

OBJECTIVE: To evaluate the synergy of the Burkholderia signaling molecule cis-2-dodecenoic acid (BDSF) and fluconazole (FLU) or itraconazole (ITRA) against two azole-resistant C. albicans clinical isolates in vitro and in vivo. METHODS: Minimum inhibitory concentrations (MICs) of antibiotics against two azole-resistant C. albicans were measured by the checkerboard technique, E-test, and time-kill assay. In vivo antifungal synergy testing was performed on mice. Analysis of the relative gene expression levels of the strains was conducted by quantitative reverse-transcription polymerase chain reaction (qRT-PCR). RESULTS: BDSF showed highly synergistic effects in combination with FLU or ITRA with a fractional inhibitory concentration index of ⪕ 0.08. BDSF was not cytotoxic to normal human foreskin fibroblast cells at concentrations of up to 300 µg/mL. The qRT-PCR results showed that the combination of BDSF and FLU/ITRA significantly inhibits the expression of the efflux pump genes CDR1 and MDR1 via suppression of the transcription factors TAC1 and MRR1, respectively, when compared with FLU or ITRA alone. No dramatic difference in the mRNA expression levels of ERG1, ERG11, and UPC2 was found, which indicates that the drug combinations do not significantly interfere with UPC2-mediated ergosterol levels. In vivo experiments revealed that combination therapy can be an effective therapeutic approach to treat candidiasis. CONCLUSION: The synergistic effects of BDSF and azoles may be useful as an alternative approach to control azole-resistant Candida infections.

Correlation between Cyr61 expression and clinicopathologic parameters in adenomyosis.

Adenomyosis, a benign invasion of endometrium, is closely related to endometriosis. Cysteine-rich 61 (Cyr61), a protein present in all endometrial tissues and menstrual effluents, is known to be associated with endometriosis. However, its relation to adenomyosis has not been determined thus far. Therefore, here, we aimed to investigate the expression of Cyr61 protein in adenomyosis and determine the correlation between Cyr61 expression and clinicopathologic parameters in patients with adenomyosis. One hundred and twenty patients with histologically diagnosed adenomyosis, who underwent hysterectomy for non-endometrial disease were enrolled in this study. Patients were interviewed using a standard questionnaire consisting of sociodemographic characteristics and reproduction history. The severity of dysmenorrhea and menorrhagia was evaluated using the visual analogue scale (VAS) and pictorial blood-loss assessment chart (PBAC). Samples of serum, endometrial tissue, and peritoneal fluid were collected, and Cyr61 mRNA levels were determined by RT-PCR. The Cyr61 protein levels in endometrial and ectopic lesions were determined by immunohistochemistry and those in serum and peritoneal fluid, by ELISA. We found that expression of Cyr61 was higher in the ectopic endometrium than in the eutopic endometrium. Cyr61 expression in the endometrium was correlated with age, number of natural labors, PBAC score, VAS score, uterine volume, adenomyosis type, and concurrent endometriosis. The Cyr61 protein level in the ascites was higher than that in serum, and no correlation existed between them. Our results suggest that the expression of Cyr61 may be indirectly related to the degree of dysmenorrhea and Cyr61 may be involved in the pathogenesis of adenomyosis.

Single Port Transumbilical Laparoscopic Surgery versus Conventional Laparoscopic Surgery for Benign Adnexal Masses: A Retrospective Study of Feasibility and Safety.

BACKGROUND: Single port laparoscopic surgery (SPLS) is an innovative approach that is rapidly gaining recognition worldwide. The aim of this study was to determine the feasibility and safety of SPLS compared to conventional laparoscopic surgery for the treatment of benign adnexal masses. METHODS: In total, 99 patients who underwent SPLS for benign adnexal masses between December 2013 and March 2015 were compared to a nonrandomized control group comprising 104 conventional laparoscopic adnexal surgeries that were performed during the same period. We retrospectively analyzed multiple clinical characteristics and operative outcomes of all the patients, including age, body mass index, size and pathological type of ovarian mass, operative time, estimated blood loss (EBL), duration of postoperative hospital stay, etc. RESULTS: No significant difference was observed between the two groups regarding preoperative baseline characteristics. However, the pathological results between the two groups were found to be slightly different. The most common pathological type in the SPLS group was mature cystic teratoma, whereas endometrioma was more commonly seen in the control group. Otherwise, the two groups had comparable surgical outcomes, including the median operation time (51 min vs. 52 min, P = 0.909), the median decreased level of hemoglobin from preoperation to postoperation day 3 (10 g/L vs. 10 g/L, P = 0.795), and the median duration of postoperative hospital stay (3 days vs. 3 days, P = 0.168). In SPLS groups, the median EBL and the anal exsufflation time were significantly less than those of the conventional group (5 ml vs. 10 ml, P < 0.001; 10 h vs. 22 h, P < 0.001). CONCLUSIONS: SPLS is a feasible and safe approach for the treatment of benign adnexal masses. Further study is required to better determine whether SPLS has significant benefits compared to conventional techniques.

Two-stage resection of a disseminated mixed endometrial stromal sarcoma and smooth muscle tumor with intravascular and intracardiac extension.

OBJECTIVE: Mixed endometrial stromal and smooth muscle tumor (MESSMT)-a rare mesenchymal uterine tumor of the uterus with atypical clinical symptoms-is susceptible to misdiagnosis and missed diagnosis. We report a case of a disseminated MESSMT with intravenous and intracardiac extensions treated with staging surgery and review previously documented cases of such tumors with intracardiac extension. CASE REPORT: The case involves a 45-year-old woman with disseminated MESSMT that originated in the uterus and progressed through the iliac vein, inferior vena cava, right atrium, and into the right ventricle, which closely resembled intravenous leiomyomatosis (IVL) grossly and microscopically. She presented with a 1-year history of dyspnea on exertion. IVL was highly suspected preoperatively based on computed tomography and magnetic resonance imaging findings. Two-stage surgeries were performed successfully. The postoperative pathology indicated a disseminated MESSMT. CONCLUSION: This case illustrates the important role of pathology and immunohistochemistry in the differential diagnosis of a rare tumor that mimics the characteristics of IVL with intracardiac involvement and demonstrates the therapeutic strategy for this rare entity.

The design and synthesis of potent, selective benzodiazepine sulfonamide bombesin receptor subtype 3 (BRS-3) agonists with an increased barrier of atropisomerization.

Bombesin receptor subtype 3 (BRS-3) is an orphan G-protein coupled receptor expressed primarily in the hypothalamus which plays a role in the onset of both diabetes and obesity. We report herein our progress made towards identifying a potent, selective bombesin receptor subtype-3 (BRS-3) agonist related to the previously described MK-7725(1) Chobanian et al. (2012) that would prevent atropisomerization through the increase of steric bulk at the C-2 position. This would thereby make clinical development of this class of compounds more cost effective by inhibiting racemization which can occur over long periods of time at room/elevated temperature.

Discovery of MK-7725, A Potent, Selective Bombesin Receptor Subtype-3 Agonist for the Treatment of Obesity.

Extensive structure-activity relationship studies of a series derived from atropisomer 1, a previously described chiral benzodiazepine sulfonamide series, led to a potent, brain penetrant and selective compound with excellent preclinical pharmacokinetic across species. We also describe the utilization of a high throughput mouse pharmacodynamic assay which allowed for expedient assessment of pharmacokinetic and brain distribution.

Bombesin receptor subtype-3 (BRS-3) regulates glucose-stimulated insulin secretion in pancreatic islets across multiple species.

Bombesin receptor subtype-3 (BRS-3) regulates energy homeostasis, and BRS-3 agonism is being explored as a possible therapy for obesity. Here we study the role of BRS-3 in the regulation of glucose-stimulated insulin secretion (GSIS) and glucose homeostasis. We quantified BRS-3 mRNA in pancreatic islets from multiple species and examined the acute effects of Bag-1, a selective BRS-3 agonist, on GSIS in mouse, rat, and human islets, and on oral glucose tolerance in mice. BRS-3 is highly expressed in human, mouse, rhesus, and dog (but not rat) pancreatic islets and in rodent insulinoma cell lines (INS-1 832/3 and MIN6). Silencing BRS-3 with small interfering RNA or pharmacological blockade with a BRS-3 antagonist, Bantag-1, reduced GSIS in 832/3 cells. In contrast, the BRS-3 agonist (Bag-1) increased GSIS in 832/3 and MIN6 cells. The augmentation of GSIS by Bag-1 was completely blocked by U73122, a phospholipase C inhibitor. Bag-1 also enhanced GSIS in islets isolated from wild-type, but not Brs3 knockout mice. In vivo, Bag-1 reduced glucose levels during oral glucose tolerance test in a BRS-3-dependent manner. BRS-3 agonists also increased GSIS in human islets. These results identify a potential role for BRS-3 in islet physiology, with agonism directly promoting GSIS. Thus, in addition to its potential role in the treatment of obesity, BRS-3 may also regulate blood glucose levels and have a role in the treatment of diabetes mellitus.

Pyridinesulfonylureas and pyridinesulfonamides as selective bombesin receptor subtype-3 (BRS-3) agonists.

Bombesin receptor subtype-3 (BRS-3) is an orphan G-protein coupled receptor belonging to the subfamily of bombesin-like receptors. BRS-3 is implicated in the development of obesity and diabetes. We report here small-molecule agonists that are based on a 4-(alkylamino)pyridine-3-sulfonamide core. We describe the discovery of 2a, which has mid-nanomolar potency, selectivity for human BRS-3 versus the other bombesin-like receptors, and good bioavailability.