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.

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.

Regulation of energy homeostasis by bombesin receptor subtype-3: selective receptor agonists for the treatment of obesity.

Bombesin receptor subtype 3 (BRS-3) is a G protein coupled receptor whose natural ligand is unknown. We developed potent, selective agonist (Bag-1, Bag-2) and antagonist (Bantag-1) ligands to explore BRS-3 function. BRS-3-binding sites were identified in the hypothalamus, caudal brainstem, and several midbrain nuclei that harbor monoaminergic cell bodies. Antagonist administration increased food intake and body weight, whereas agonists increased metabolic rate and reduced food intake and body weight. Prolonged high levels of receptor occupancy increased weight loss, suggesting a lack of tachyphylaxis. BRS-3 agonist effectiveness was absent in Brs3(-/Y) (BRS-3 null) mice but was maintained in Npy(-/-)Agrp(-/-), Mc4r(-/-), Cnr1(-/-), and Lepr(db/db) mice. In addition, Brs3(-/Y) mice lost weight upon treatment with either a MC4R agonist or a CB1R inverse agonist. These results demonstrate that BRS-3 has a role in energy homeostasis that complements several well-known pathways and that BRS-3 agonists represent a potential approach to the treatment of obesity.

Antiobesity efficacy of a novel cannabinoid-1 receptor inverse agonist, N-[(1S,2S)-3-(4-chlorophenyl)-2-(3-cyanophenyl)-1-methylpropyl]-2-methyl-2-[[5-(trifluoromethyl)pyridin-2-yl]oxy]propanamide (MK-0364), in rodents.

The cannabinoid-1 receptor (CB1R) has been implicated in the control of energy balance. To explore the pharmacological utility of CB1R inhibition for the treatment of obesity, we evaluated the efficacy of N-[(1S,2S)-3-(4-chlorophenyl)-2-(3-cyanophenyl)-1-methylpropyl]-2-methyl-2-[[5-(trifluoromethyl)pyridin-2-yl]oxy]propanamide (MK-0364) and determined the relationship between efficacy and brain CB1R occupancy in rodents. MK-0364 was shown to be a highly potent CB1R inverse agonist that inhibited the binding and functional activity of various agonists with a binding K(i) of 0.13 nM for the human CB1R in vitro. MK-0364 dose-dependently inhibited food intake and weight gain, with an acute minimum effective dose of 1 mg/kg in diet-induced obese (DIO) rats. CB1R mechanism-based effect was demonstrated for MK-0364 by its lack of efficacy in CB1R-deficient mice. Chronic treatment of DIO rats with MK-0364 dose-dependently led to significant weight loss with a minimum effective dose of 0.3 mg/kg (p.o.), or a plasma C(max) of 87 nM. Weight loss was accompanied by the loss of fat mass. Partial occupancy (30-40%) of brain CB1R by MK-0364 was sufficient to reduce body weight. The magnitude of weight loss was correlated with brain CB1R occupancy. The partial receptor occupancy requirement for efficacy was also consistent with the reduced food intake of the heterozygous mice carrying one disrupted allele of CB1R gene compared with the wild-type mice. These studies demonstrated that MK-0364 is a highly potent and selective CB1R inverse agonist and that it is orally active in rodent models of obesity.

Identification of differential genes in ovarian cancer using representational difference analysis of cDNA.

OBJECTIVE: To identify differential genes between normal ovarian epithelium tissue and ovarian epithelial cancer using representational difference analysis of cDNA (cDNA-RDA). METHODS: cDNA-RDA was performed to identify the differentially expressed sequences between cDNAs from cancer tissue and cDNAs from normal ovarian tissue in the same patient who was in the early stage of ovarian serous cystadenocarcinoma. These differentially expressed fragments were cloned and analyzed, then sequenced and compared with known genes. RESULTS: Three differentially expressed cDNA fragments were isolated using cDNA from normal ovarian tissue as tester and cDNA from cancer tissue as driver amplicon by cDNA-RDA. DP III-1 and DP III-2 cDNA clone showed significant homology to the cDNA of alpha actin gene; DP III-3 cDNA clone showed significant homology to the cDNA of transgelin gene. CONCLUSION: cDNA-RDA can be used to sensitively identify the differentially expressed genes in ovarian serous cystadenocarcinoma. Ovarian serous cystadenocarcinoma involves alteration of multiple genes.

Increased melanin concentrating hormone receptor type I in the human hypothalamic infundibular nucleus in cachexia.

Melanin-concentrating hormone (MCH) exerts a positive regulation on appetite and binds to the G protein-coupled receptors, MCH1R and MCH2R. In rodents, MCH is produced by neurons in the lateral hypothalamus with projections to various hypothalamic and other brain sites. In the present study, MCH1R was shown, by immunocytochemistry, to be present in the human infundibular nucleus/median eminence, paraventricular nucleus, lateral hypothalamic area, and perifornical area, although in the latter two regions, only a few MCH1R-containing cells were found. In addition, MCH1R staining was found in nerve fibers in the periventricular nucleus, dorsomedial and ventromedial nucleus, suprachiasmatic nucleus, and tuberomammillary nucleus. A significant 1.6 times increase in the number of MCH1R cell body staining was found in the infundibular nucleus in postmortem brain material of cachectic patients, compared with matched controls, supporting a role for this receptor in energy homeostasis in the human.

Alpha-melanocyte-stimulating hormone stimulates oxytocin release from the dendrites of hypothalamic neurons while inhibiting oxytocin release from their terminals in the neurohypophysis.

The peptides alpha-melanocyte stimulating hormone (alpha-MSH) and oxytocin, when administered centrally, produce similar behavioral effects. alpha-MSH induces Fos expression in supraoptic oxytocin neurons, and alpha-MSH melanocortin-4 receptors (MC4Rs) are highly expressed in the supraoptic nucleus, suggesting that alpha-MSH and oxytocin actions are not independent. Here we investigated the effects of alpha-MSH on the activity of supraoptic neurons. We confirmed that alpha-MSH induces Fos expression in the supraoptic nucleus when injected centrally and demonstrated that alpha-MSH also stimulates Fos expression in the nucleus when applied locally by retrodialysis. Thus alpha-MSH-induced Fos expression is not associated with electrophysiological excitation of supraoptic neurons because central injection of alpha-MSH or selective MC4 receptor agonists inhibited the electrical activity of oxytocin neurons in the supraoptic nucleus recorded in vivo. Consistent with these observations, oxytocin secretion into the bloodstream decreased after central injection of alpha-MSH. However, MC4R ligands induced substantial release of oxytocin from dendrites in isolated supraoptic nuclei. Because dendritic oxytocin release can be triggered by changes in [Ca2+]i, we measured [Ca2+]i responses in isolated supraoptic neurons and found that MC4R ligands induce a transient [Ca2+]i increase in oxytocin neurons. This response was still observed in low extracellular Ca2+ concentration and probably reflects mobilization of [Ca2+]i from intracellular stores rather than entry via voltage-gated channels. Taken together, these results show for the first time that a peptide, here alpha-MSH, can induce differential regulation of dendritic release and systemic secretion of oxytocin, accompanied by dissociation of Fos expression and electrical activity.

Exploring the site of anorectic action of peripherally administered synthetic melanocortin peptide MT-II in rats.

Melanotan-II (MT-II), a cyclic heptapeptide, is a potent, non-selective melanocortinergic agonist. When administered centrally or systemically, MT-II elicited a profound inhibitory effect on food intake in rodents, presumably via activation of melanocortin-4-receptor (MC4R). In this study, we sought to investigate whether penetration of MT-II and iodo-MT-II into brain parenchyma is required for the anorectic effect following intravenous (IV) administration. Firstly, both MT-II and iodo-MT-II were effective at suppressing appetite in rats following their IV administration. We next surveyed by in vitro autoradiographic studies the distribution of selective (125)I-MT-II binding sites in multiple brain regions including areas important for feeding regulation such as the hypothalamus and caudal brainstem. Upon IV administration of (125)I-MT-II, significant radioactivity could not be detected in various brain regions by autoradiography except for a group of circumventricular organs (CVOs), which are anatomically situated outside the blood-brain barrier (BBB). The most intensely labeled CVOs include the subfornical organ, median eminence, area postrema and choroid plexus, and accumulation of radioactivity at these sites can be blocked by co-injection of excess unlabeled MT-II. Direct measurement of MT-II in the brain and plasma by LC-MS-MS following IV injection confirmed that the degree of MT-II penetration into the brain is negligible. Furthermore, when given peripherally under conditions that suppressed food intake, MT-II did not result in a detectable induction of c-Fos-like immunoreactivity in brain regions where a significantly elevated c-Fos expression was observed following intracerebroventricular injection of this peptide. Our results indicate that MT-II has a very limited brain penetration capability, and its effect on feeding behavior following systemic administration may be mediated by either the brain regions in close proximity to the CVOs or sites outside of the BBB, including CVOs or other peripheral systems.

Melanin-concentrating hormone 1 receptor-deficient mice are lean, hyperactive, and hyperphagic and have altered metabolism.

Melanin-concentrating hormone (MCH) is a cyclic 19-aa hypothalamic neuropeptide derived from a larger prohormone precursor of MCH (Pmch), which also encodes neuropeptide EI (NEI) and neuropeptide GE (NGE). Pmch-deficient (Pmch-/-) mice are lean, hypophagic, and have an increased metabolic rate. Transgenic mice overexpressing Pmch are hyperphagic and develop mild obesity. Consequently, MCH has been implicated in the regulation of energy homeostasis. The MCH 1 receptor (MCH1R) is one of two recently identified G protein-coupled receptors believed to be responsible for the actions of MCH. We evaluated the physiological role of MCH1R by generating MCH1R-deficient (Mch1r-/-) mice. Mch1r-/- mice have normal body weights, yet are lean and have reduced fat mass. Surprisingly, Mch1r-/- mice are hyperphagic when maintained on regular chow, and their leanness is a consequence of hyperactivity and altered metabolism. Consistent with the hyperactivity, Mch1r-/- mice are less susceptible to diet-induced obesity. Importantly, chronic central infusions of MCH induce hyperphagia and mild obesity in wild-type mice, but not in Mch1r-/- mice. We conclude that MCH1R is a physiologically relevant MCH receptor in mice that plays a role in energy homeostasis through multiple actions on locomotor activity, metabolism, appetite, and neuroendocrine function.