Three-dimensional transvaginal ultrasound vs magnetic resonance imaging for preoperative staging of deep myometrial and cervical invasion in patients with endometrial cancer: systematic review and meta-analysis.

OBJECTIVES: To evaluate and compare the diagnostic test accuracy (DTA) of three-dimensional transvaginal ultrasound (3D-TVS) and magnetic resonance imaging (MRI) for deep myometrial infiltration (DMI) and cervical invasion for preoperative staging and surgery planning in patients with endometrial cancer (EC). METHODS: This systematic review and meta-analysis investigated the DTA of MRI and 3D-TVS for DMI and cervical invasion in patients with EC. A literature search was performed using MEDLINE, Scopus, EMBASE, ScienceDirect, The Cochrane library, ClinicalTrials.gov, Cochrane Central Register of Controlled Trials, EU Clinical Trials Register and World Health Organization International Clinical Trials Registry Platform to identify relevant studies published between January 2000 and December 2021. Study quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool. RESULTS: Five studies, including a total of 450 patients, were included in the systematic review. All five studies compared the DTA of 3D-TVS vs MRI for DMI, and three studies compared the DTA of 3D-TVS vs MRI for cervical invasion. Pooled sensitivity, positive likelihood ratio and negative likelihood ratio for detecting DMI using 3D-TVS were 77% (95% CI, 66-85%), 4.57 and 0.31, respectively. The respective values for detecting DMI on MRI were 80% (95% CI, 73-86%), 4.22 and 0.24. Bivariate metaregression indicated a similar DTA of 3D-TVS and MRI (P = 0.80) for the correct identification of DMI. Pooled ln diagnostic odds ratio for detecting cervical invasion was 3.11 (95% CI, 2.09-4.14) for 3D-TVS and 2.36 (95% CI, 0.90-3.83) for MRI. The risk of bias was low for most of the four domains assessed in QUADAS-2. CONCLUSION: 3D-TVS demonstrated good diagnostic accuracy in terms of sensitivity and specificity for the evaluation of DMI and cervical invasion, with results comparable with those of MRI. Thus, we confirmed the potential role of 3D-TVS in the preoperative staging and surgery planning in patients with EC. © 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Diaphragmatic peritonectomy versus full thickness diaphragmatic resection and pleurectomy during cytoreduction in patients with ovarian cancer.

OBJECTIVES: Compare the surgical morbidity of diaphragmatic peritonectomy versus full thickness diaphragmatic resection with pleurectomy at radical debulking. DESIGN: Prospective cohort study at the Oxford University Hospital. METHODS: All debulking with diaphragmatic peritonectomy and/or full thickness resection with pleurectomy in the period from April 2009 to March 2012 were part of the study. Analysis is focused on the intra- and postoperative morbidity. RESULTS: 42 patients were eligible for the study, 21 underwent diaphragmatic peritonectomy (DP, group 1) and 21 diaphragmatic full thickness resection (DR, group 2). Forty patients out of 42 (93%) had complete tumour resection with no residual disease. Histology confirmed the presence of cancer in diaphragmatic peritoneum of 19 patients out of 21 in group 1 and all 21 patients of group 2. Overall complications rate was 19% in group 1 versus 33% in group 2. Pleural effusion rate was 9.5% versus 14.5% and pneumothorax rate was 14.5% only in group 2. Two patients in each group required postoperative chest drains (9.5%). CONCLUSIONS: Diaphragmatic surgery is an effective methods to treat carcinomatosis of the diaphragm. Patients in the pleurectomy group experienced pneumothorax and a higher rate of pleural effusion, but none had long-term morbidity or additional surgical interventions.

Didanosine polymorphism in a supercritical antisolvent process.

Solid-state properties of active ingredients are crucial in pharmaceutical development owing to their significant clinical and economical implications. In the present work we investigated the solid-state properties and the solubility in water of didanosine, DDI, re-crystallized from a dimethylsulfoxide solution using supercritical CO(2) as an antisolvent (SAS process) for comparison with the commercially available drug product. We also applied modern solid-state NMR (SS NMR) techniques, namely 2D (1)H DQ CRAMPS (Combined Rotation And Multiple Pulse Spectroscopy) and (1)H-(13)C on- and off-resonance CP (cross polarization) FSLG-HETCOR experiments, known for providing reliable information about (1)H-(1)H and (1)H-(13)C intra- and intermolecular proximities, in order to address polymorphism issues arising from the crystallization of a new form in the supercritical process. A new polymorph of didanosine was obtained from the supercritical antisolvent process and characterized by means of 1D and 2D multinuclear ((1)H, (13)C, (15)N) SS NMR. The particle size of the new crystal phase was reduced by varying the antisolvent density through a pressure increase. The structural differences between the commercial product and the SAS re-crystallized DDI are highlighted by X-ray diffractometry and well described by solid-state NMR. The carbon C6 (13)C chemical shift suggests that both commercial and re-crystallized didanosine samples are in the enol form. The analysis of homo- and heteronuclear proximities obtained by means of 2D NMR experiments shows that commercial and SAS re-crystallized DDI possess very similar molecular conformation and hydrogen bond network, but different packing. The new polymorph proved to be a metastable form at ambient conditions, showing higher solubility in water and lower stability to mechanical stress.

Copy number variations in three children with sudden infant death.

Sudden death of an infant is a devastating event that needs an explanation. When an explanation cannot be found, the case is labeled as sudden infant death syndrome or unclassified sudden infant death. The influence of genetic factors has been recognized for sudden infant death, but copy number variations (CNVs) as potential risk factors have not been evaluated yet. Twenty-seven families were enrolled in this study. The tissue specimens from deceased children were obtained and array-based comparative genomic hybridization (array-CGH) experiments were performed on the genomic DNA isolated from these specimens using Agilent Technologies Custom 4 x 44K arrays. Quantitative polymerase chain reaction experiments were performed to confirm the overlapping duplication and deletion region in two different cases. A de novo CNV is detected in 3 of 27 cases (11%). In case 1, an approximately 3-Mb (chr 8: 143,211,215-qter) duplication on 8q24.3-qter and a 4.4-Mb deletion on the 22q13.3-qter (chr 22: 45,047,068-qter) were detected. Subtelomeric chromosome analysis of the father and the surviving sibling of case 1 showed a balanced reciprocal translocation, 46,XY,t(8;22)(q24.3;q13.3). A 240-kb (chr 6: 26,139,810-26,380,787) duplication and a 1.9-Mb deletion (chr 6: 26,085,971-27,966,150) at chromosome 6p22 were found in cases 2 and 3, respectively. Array-CGH and conventional cytogenetic studies did not reveal the observed CNVs in the parents and the siblings of cases 2 and 3. The detected CNVs in cases 2 and 3 encompassed several genes including the major histone cluster genes. Array-CGH analysis may be beneficial during the investigations after sudden infant death.

Laparoscopic debulking of bulky lymph nodes in women with cervical cancer: indication and surgical outcomes.

OBJECTIVE: To describe the technique and the surgical outcome of laparoscopic resection of bulky lymph nodes before adjuvant treatment. DESIGN: Prospective pilot study. SETTING: Gynaecological oncology cancer centre. POPULATION: From January 2006 to February 2008, 22 consecutive women presented with cervical cancer and bulky metastatic lymph nodes (>2 cm). METHODS: All women underwent resection of bulky lymph nodes by laparoscopy. A prospective record of the main surgical outcomes was performed. MAIN OUTCOME MEASURES: Safety and efficacy of laparoscopic resection of bulky lymph nodes, conversion to laparotomy, intra- and perioperative morbidity. RESULTS: All the operations were completed by laparoscopy. Median operative time was 197 minutes (range 180-320). Median blood loss was 60 cc (range 10-100), two women experienced complications: one thermal injury of the sciatic root provoking postoperative leg palsy and one chylous ascites. The woman with the thermal injury has recovered most leg function with physiotherapy and the woman with chylous ascites recovered within 2 weeks, slightly delaying the adjuvant treatment. All women were discharged within 4 days from the operation (range 2-4). Pathology reports confirmed the presence of tumour metastases and the lymph nodes size. The adjuvant treatment started at a median time of 12 days (range 3-22). CONCLUSION: Debulking of large pelvic and para-aortic lymph nodes was effectively accomplished by laparoscopy in all 22 women with 9% complication rate. The surgical outcome is similar to historical series on women operated on by laparotomy, with the advantage of a faster recovery and an early start of adjuvant treatment.

Supercritical extraction of carotenoids from Rosa canina L. hips and their formulation with beta-cyclodextrin.

The purpose of this research was to preliminary assess the suitability of a new method for the preparation of a solid formulation in form of powder composed by beta-cyclodextrin and the supercritical extract of Rosa canina hips. The method implies the extraction of carotenoids, in particular beta-carotene, from freeze dried fruits of R. canina with supercritical CO2 at 70 degrees C and 300 bar, in the presence of varying quantity of ethanol as entrainer. The obtained supercritical solution is then expanded at ambient conditions into an aqueous solution of beta-cyclodextrin to favour the interaction between beta-cyclodextrin and the lipophilic components of the extract. beta-carotene solubility (mole fraction) in supercritical CO2 or in supercritical CO2/ethanol mixtures were in the order of 1 10(-7). The beta-carotene extracted from R. canina fruits (nearly 10 microg/g of dry matrix), interacts almost quantitatively with beta-cyclodextrin affording a solid phase, which presents a low apparent solubility in water. Finally the interaction with beta-cyclodextrin results in a higher concentration of the beta-carotene trans- form relative to the cis- form in the extracted product when collected in an aqueous solution of beta-cyclodextrin with respect to the extract in n-hexane.

Histochemical study of cardiac mast cells degranulation and collagen deposition: interaction with the cathecolaminergic system in the rat.

Although their role in the cardiovascular system is still largely unknown, mast cells are present in the myocardium of both experimental animals and humans. Interestingly, cathecolaminergic nerve fibres and mast cells are often described in close morphological and functional interactions in various organs. In the present study we investigated the effects of chronic interference with beta-adrenergic receptors (via either sympathectomy or beta-blockade) on cardiac mast cell morphology/activation and on interstitial collagen deposition. In rats subjected to chemical sympathectomizy with the neurotoxin 6-hydroxydopamine (6-OHDA) we observed a significant increase of mast cell density, and in particular of degranulating mast cells, suggesting a close relationship between the cardiac catecholaminergic system and mast cell activation. In parallel, chronic 6-OHDA treatment was associated with increased collagen deposition. The influence of the beta-adrenergic receptor component was investigated in rats subjected to chronic propranolol administration, that caused a further significant increase in mast cell activation associated with a lower extent of collagen deposition when compared to chemical sympathectomy. These data are the first demonstration of a close relationship between rat cardiac mast cell activation and the catecholaminergic system, with a complex interplay with cardiac collagen deposition. Specifically, abrogation of the cardiac sympathetic efferent drive by chemical sympathectomy causes mast cell activation and interstitial fibrosis, possibly due to the local effects of the neurotoxin 6-hydroxydopamine. In contrast, beta-adrenergic blockade is associated with enhanced mast cell degranulation and a lower extent of collagen deposition in the normal myocardium. In conclusion, cardiac mast cell activation is influenced by beta-adrenergic influences.

Time course of matrix metalloproteases and tissue inhibitors in bleomycin-induced pulmonary fibrosis.

To investigate simultaneously localization and relative activity of MMPs during extracellular matrix (ECM) remodeling in bleomycin-induced pulmonary fibrosis in rat, we analyzed the time course of the expression, activity and/or concentration of gelatinases MMP-2 and MMP-9, collagenase MMP-1, matrylisin MMP-7, TIMP-1 and TIMP-2, both in alveolar space (cellular and extracellular compartments) and in lung tissue. MMP and TIMP expression was detected (immunohistochemistry) in lung tissue. MMP activity (zymography) and TIMP concentration (ELISA) were evaluated in lung tissue homogenate (LTH), BAL supernatant (BALs) and BAL cell pellet (BALp) 3, 7, 14, and 28 days after bleomycin intratracheal instillation. Immunohistochemistry showed an extensive MMP and TIMP expression from day 7 in a wide range of structural and inflammatory cells in treated rats. MMP-2 was present mainly in epithelia, MMP-9 in inflammatory cells. MMP-2 and MMP-9 activity was increased respectively in BAL fluid and BAL cells, with a peak at day 7. TIMP-1 and TIMP-2 concentration (ELISA) enhancement was delayed at day 14. In conclusion gelatinases and their inhibitors are significantly activated during bleomycin-induced pulmonary fibrosis. Marked changes in gelatinases activity are observed early in the alveolar compartment, with a prevailing extracellular activity of MMP-2 and a predominant intracellular distribution of MMP-9, while enzyme activity changes in lung parenchyma were less evident. In the repairing phase the reduction of gelatinases activity is synchronous with a peak of alveolar concentration of their inhibitors.

Laparoscopic coagulation of the uterine blood supply in laparoscopic-assisted vaginal hysterectomy is associated with less blood loss.

BACKGROUND: Does laparoscopic coagulation of the uterine blood supply decrease blood loss compared with transvaginal ligature of the uterine vessels? METHODS: Intra- and postoperative data of 446 patients undergoing laparoscopic-assisted vaginal hysterectomy at the Department of Gynecology, University of Jena, between 1998 and 2001 were analysed. In 213 patients the uterine blood supply was transected laparoscopically at the origin of the uterine vessels (LAVH type II) and in 233 patients (LAVH type I) transvaginally. RESULTS: Patients in both groups were comparable with respect to median age, Quetelet index, and parity. The drop of hemoglobin between the preoperative day and postoperative day 3 was 0.8 mmol/l or 0.6 mmol/l for LAVH type I without or with BSO vs 0.3 mmol/l or 0.4 mmol/l for LAVH type II without or with BSO (p = 0.001), respectively. Median operative time was similar for both techniques: LAVH type I 136 min or with BSO 128 min vs LAVH type II 126 min or with BSO 131 min. The weight of the removed uteri was significantly lower in LAVH type I vs type II (220 vs 270 grams), but similar when LAVH was combined with BSO (160 vs 178 grams). The rate of intraoperative complications was 2.2% vs 0.9% between LAVH type I or II (n.s.), but 9% vs 3.3% for overall postoperative complications (p = 0.01). CONCLUSIONS: Laparoscopic coagulation of the uterine blood supply at the origin of uterine vessels is a safe technique which minimizes blood loss in LAVH. In patients with a low preoperative hemoglobin value this technique is indicated.

Resection of presacral ganglioneurofibroma by laparoscopy.

BACKGROUND: Tumors of the retrorectal space are rare. They comprise a heterogeneous group of benign or malignant tumors that cause similar symptoms due to their location in presacral space. If possible, complete surgery excision is the therapy of choice mainly through a sacral, abdominal-sacral, or a pure abdominal or perineal axis. CASE REPORT: A 15-year-old asymptomatic patient was diagnosed with a retrouterine tumor during her first gynecological examination. Magnetic resonance imaging of the pelvis showed a 10 x 8.5 x 7-cm encapsulated presacral tumor. Retrorectal ganglioneurofibroma was removed by laparoscopy with preservation of the sympathetic and parasympathetic nerves and the sacral roots of the ischiadic nerves. No sensory or motoric dysfunction of the legs, bladder, or rectum was observed postoperatively. CONCLUSION: This is the first case report of a complete endoscopic removal of large presacral ganglioneurofibroma in an asymptomatic woman.

Laparoscopic-assisted vaginal hysterectomy with lateral transsection of the uterine vessels.

BACKGROUND: Increased safety and diminished blood loss are achieved through laparoscopic-assisted vaginal hysterectomy by selective coagulation and transsection of the uterine vessels at their origin. METHODS: Three laparoscopic steps are performed: coagulation and transsection of the round ligament, of the uterine artery at its origin, and of the fallopian tube and ovarian ligament or (in BSO) the infundibulopelvic ligament. The uterine vessels are identified from the pararectal space and, following the internal liliac artery, and the ureter. Hysterectomy is completed transvaginally. RESULTS: Two hundred and sixty-seven patients underwent this procedure. Mean operation time was 121 min, and hemoglobin decreased to 0.6 g/dl by postoperative day 3. It took 8.4 min on average to identify and coagulate the uterine artery. CONCLUSIONS: Lateral transsection of the uterine vessels is safe and blood sparing and can be used in patients in whom blood loss must be minimized.

Color Doppler sonography in Graves' disease: value in assessing activity of disease and predicting outcome.

OBJECTIVE: The aims of the study were to establish the usefulness of color Doppler sonography in assessing changes in thyroid blood flow during the course of Graves' disease and to investigate which of several variables (thyroid volume, number of intraparenchymal vessels, and blood flow in the thyroid artery) were best related to thyroid hyperfunction and therefore could be used to evaluate the course of the disease. SUBJECTS AND METHODS: Fifty-six patients with Graves' disease were selected and divided on the basis of clinical and laboratory data into four groups: patients untreated at first diagnosis, patients undergoing antithyroid drug treatment, patients in remission after withdrawal of therapy, and patients having a relapse of hyperthyroidism. Ten healthy subjects served as controls. RESULTS: Patients with active hyperthyroidism (at first diagnosis, during treatment, or at relapse) had a significantly enlarged thyroid (p = .005); intrathyroid vascularization, evaluated as number of vessels per square centimeter (p < .0001); and blood flow in the thyroid artery (p < .0001) compared with control subjects and with patients in remission after withdrawal of therapy. During treatment, sonographic values were slightly lower but not significantly different from those registered in patients at the onset of hyperthyroidism, indicating that normalization of vascularity does not parallel the drug-induced decrease of hormonal synthesis. Among 21 patients in remission, the nine patients who had a relapse shortly after the examination had a higher number of vessels per square centimeter (2.18 +/- 0.34 versus 1.03 +/- 0.16, p = .03) and higher flow in the thyroid artery (80.3 +/- 19.1 versus 10.6 +/- 2.3 ml/min, p = .01) than did the other 12 patients who remained in stable remission, despite normal hormonal levels in both groups. CONCLUSION: Our results suggest that color Doppler sonography can be used to assess activity of Graves' disease and to predict the outcome of the disease after withdrawal of medical therapy.

Human lymphocyte antigens in Graves' disease: correlation with persistent course of disease.

Graves' disease is a thyroid autoimmune disorder associated with specific human lymphocyte antigen (HLA) alleles, characterized by an unpredictable long-term course. To investigate possible relations between HLA phenotype and outcome of the disease, the authors typed for HLA antigens in 105 patients with Graves' disease with different course of disease. All patients were treated with antithyroid drugs for at least 12 months; 29 patients had stable remission 24 or more months after withdrawal of treatment; 76 patients had persistent disease--66 unremitting/relapsing hyperthyroidism, 10 stable hypothyroidism--36 or more months after onset of disease. The following findings emerged from this study: 1) HLA B8 and DR3 were increased significantly in Graves' patients versus 6,682 control subjects from the same geographic area (23.80% vs 12.01%, odds ratio [OR] 1.98, and 31.43% vs 18.00%, OR 1.75, respectively); the antigen combinations B8-DR3, B8-Cw7-DR3, and A1-B8-Cw7-DR3 were significantly more frequent in Graves' patients vs control subjects; in addition, these combinations were present exclusively in patients with persistent disease (B8-DR3 28.95%, OR 7.14, B8-Cw7-DR3 27.63%, OR 11.24, and A1-B8-Cw7-DR3 18.42%, OR 11.29). These data provide evidence that not only susceptibility to Graves' disease, but also persistent activity of the autoimmune process, producing either hyperthyroidism or stable hypothyroidism, is associated with specific HLA antigen phenotypes.