Biomass pretreatment aims at separating and providing easier access to the main biomass components (cellulose, hemicellulose and lignin), eventually removing lignin, preserving the hemicellulose, ...reducing the cellulose crystallinity and increasing the porosity of the material. Pretreatment is an essential step towards the development and industrialization of efficient 2nd generation lignocellulosic ethanol processes. The present work reviewed the main options available in pretreatment. Autohydrolysis and steam explosion were then selected for further investigation. Experimental work was carried out on batch scale reactors, using Miscanthus as biomass feedstock: the effects on sugar solubilization and degradation products generation have been examined for each of these two pretreatment systems. A new process using only water and steam as reacting media was then developed, experimentally tested, and results compared to those achieved by the autohydrolysis and steam explosion processes. Products obtained with the new pretreatment contained a lower amount of usual fermentation inhibitor compounds compared to that typically obtained in steam explosion. This result was achieved under operating conditions that at the same time allowed a good xylan yield, preventing degradation of hemicelluloses. The new pretreatment process was also able to act as an equalization step, as the solid material from the pretreatment phase had a similar composition even under different operating conditions. As regards the effect of pretreatment on enzymatic hydrolysis, the new process achieved yields similar to steam explosion on glucans: however, this was obtained reducing the formation of degradation products from sugars, mainly from C5 sugars. These results made the proposed pretreatment system suitable for further development and industrialization on pilot and industrial scale.
Pain is the most evident clinical manifestation of deep infiltrating endometriosis (DIE). Several hormonal and immunologic mechanisms are markedly altered in DIE compared with superficial peritoneal ...and ovarian endometriosis, and may explain its most aggressive behavior and the presence of severe pain symptoms. Hormonal therapies, such as combined hormonal contraceptives and progestogens, should be regarded as first-line treatment, as they are efficacious, safe, and well tolerated. Gonadotropin-releasing hormone agonists may be used in patients with symptoms persisting after the administration of first-line therapies. Scanty literature is available for danazol treatment in patients with DIE and, however, it has become less popular due to the high rates of androgenic adverse events (AEs). The partial relief of pain that often is achieved with available therapies and its recurrence after the suspension of the treatment have brought to the development of new therapies (such as aromatase inhibitors, oral GnRH antagonists) that are currently under investigation. Surgical excision of DIE should be considered in patients with pain symptoms persisting after first-line hormonal therapies. The benefits of surgery in terms of pain improvement should be always balanced with the risk of intraoperative complications and for this reason surgical cases should be referred to tertiary centers for the treatment of DIE. A multidisciplinary approach is mandatory in patients with DIE involving the bowel and/or the urinary tract.
Uterine myomas and endometriosis are benign hormone-dependent diseases affecting women of reproductive age. Substantial efforts have been made to develop innovative medical options for treating these ...gynecologic diseases. Elagolix and relugolix have been approved in some countries for treating endometriosis and myomas, respectively; however, linzagolix (OBE 2109, KLH 2109) is a new oral gonadotropin-releasing hormone (GnRH) antagonist in phase II-III trials. Treatment options for women with contraindications for hormonal therapies or who refuse particular options, are the driving force behind the development of new drugs in this area.
This drug evaluation highlights definitive and preliminary results from previous and ongoing studies of linzagolix for the treatment of endometriosis and myomas.
Linzagolix showed a dose-dependent and rapidly reversible action on the pituitary-gonadal axis. In a recent phase II trial (EDELWEISS), linzagolix significantly reduced pain related to endometriosis and improved quality of life at single daily doses of 75-200 mg. The preliminary results of international, double-blind phase III trials (PRIMROSE 1 and 2) reported its efficacy in treating heavy menstrual bleeding related to myomas with a good safety profile. Further studies will determine the necessity of add-back therapy during long-term use of linzagolix.
Abstract Context The bladder is the most common site affected in urinary tract endometriosis. There is controversy regarding the pathogenesis, clinical management (diagnosis and treatment), impact on ...fertility, and risk of malignant transformation of bladder endometriosis (BE). Objective To systematically evaluate evidence regarding the pathogenesis, diagnosis, medical and surgical treatment, impact on female fertility, and risk of malignant transformation of BE. Evidence acquisition A systematic review of PubMed/Medline from inception until October 2016 was performed in accordance with the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) statement and was registered in the PROSPERO registry ( www.crd.york.ac.uk/prospero; CRD42016039281). Eighty-seven articles were selected for inclusion in this analysis. Evidence synthesis BE is defined as the presence of endometrial glands and stroma in the detrusor muscle. Ultrasonography is the first-line technique for assessment of BE owing to its accuracy, safety, and cost. Clinical management can be conservative, using hormonal therapies, or surgical. When conservative treatment is preferred, estrogen-progestogen combinations and progestogens should be chosen because of their favorable profile that allows long-term therapy. Surgery should guarantee complete removal of the bladder nodule to minimize recurrence, so transurethral surgery alone should be avoided in favor of segmental bladder resection. There is not a strong rationale for hypothesizing a detrimental impact of BE per se on fertility. Furthermore, current evidence does not support the removal of bladder endometriotic lesions because of the potential risk of malignant transformation since this phenomenon is exceedingly rare. Conclusions BE is a challenging condition, and the common coexistence of other types of endometriosis means that clinical management of BE should involve collaboration between gynecologists and urologists. Patient summary In this article we review available knowledge on bladder endometriosis. The review provides a useful tool to guide physicians in the management of this complex condition.
The ureter is the second most common site affected by urinary tract endometriosis, after the bladder. Optimal strategies in the diagnosis and treatment of ureteral endometriosis (UE) are not yet well ...defined.
The aim of this study was to systematically review evidence regarding the epidemiology, pathophysiology, diagnosis, medical and surgical treatment, impact on fertility and risk of malignant transformation of UE.
A systematic literature review, by searching the MEDLINE and PUBMED database until April 2018, was performed in accordance with the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) statement and was registered in the PROSPERO registry (www.crd.york.ac.uk/PROSPERO CRD42017060065). A total of 67 articles were selected to be included in this review.
The involvement of the ureter by endometriosis is often asymptomatic or leads to non-specific symptoms. When the diagnosis is delayed, UE may lead to persistent hydronephrosis and eventually loss of renal function. Ultrasonography is the first-line technique for the assessment of UE; alternatively, magnetic resonance imaging provides an evaluation of ureteral type involvement. The surgical treatment of UE aims to relieve ureteral obstruction and avoid disease recurrence. It includes conservative ureterolysis or radical approaches, such as ureterectomy with end-to-end anastomosis or ureteroneocystostomy performed in relation to the type of ureteral involvement. Fertility and pregnancy outcomes are in line with those observed after surgical treatment of deep infiltrating endometriosis (DIE). Current evidence does not support the potential risk of malignant transformation of UE.
In this article, we review available evidence on ureteral endometriosis, providing a useful tool to guide physicians in the management of this disease. Diagnosis and management of UE remain a challenge. In relation to the degree of ureteral involvement and the association with other DIE implants, the surgical approach should be planned and carried out in an interdisciplinary collaboration between gynecologist and urologist.
Objective To investigate the impact on ovarian reserve of second laparoscopic surgery for recurrent unilateral endometriomas. Design Case-control study. Setting University teaching hospital. ...Patient(s) This study included patients who underwent stripping of endometriomas (diameter ≥4 cm) and were followed-up at our institution. Case subjects had second surgery for recurrent unilateral endometriomas (n = 18); control subjects had no recurrence and no second surgery (n = 18). Intervention(s) This case-control study was based on a retrospective analysis of a prospectively collected database including patients who underwent surgery for endometriomas at our institution. Main Outcome Measure(s) The primary outcome of the study was to assess the changes in antimüllerian hormone (AMH) levels in each study group and between the two study groups. The secondary outcomes of the study were to assess the changes in basal FSH, antral follicle count (AFC), and ovarian volume in each study group and between the two study groups. Result(s) In both study groups, primary surgery decreased AMH, increased basal FSH, and decreased the AFC of the operated ovary. Before second surgery, case subjects had AMH, basal FSH, and AFC similar to control subjects. After second surgery, case subjects had lower AMH, higher basal FSH, and lower AFC of the affected ovary than before surgery; the volume of the operated ovary was lower than that of the contralateral ovary. Conclusion(s) The laparoscopic stripping of recurrent ovarian endometriomas is associated with a high risk of ovarian reserve damage and ovarian failure. Clinical Trial Registration Number NCT02047838.
Epithelial ovarian cancer (EOC) is the sixth most commonly diagnosed cancer among women. Results with available therapies are far from being satisfactory and, therefore, current research is focusing ...on new anticancer drugs to improve the clinical response of these patients. Nintedanib is an oral multiple tyrosine kinases inhibitor, which targets angiogenesis. Considering the current scenario, the aim of this systematic review is to highlight the prevailing knowledge about pharmacokinetics, pharmacodynamics, clinical efficacy, and safety of Nintedanib for the treatment of advanced EOC.
We performed a systematic review of the literature, screening all available articles about the treatment of advanced EOC with Nintedanib, including phase I, II, and III trials.
Although in early phase clinical trials, Nintedanib has demonstrated anticancer activity and tolerability as monotherapy or in combination with carboplatin and paclitaxel. In the phase III trial AGO-OVAR 12, it obtained a modest improvement in progression-free survival (PFS) as first-line combination therapy for patients with advanced EOC. Interestingly, a PFS increase was observed in patients with non-high progression risk or low tumor burden.
Despite the promising results, further studies are needed to evaluate Nintedanib efficacy in women affected by EOC.
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