Response to treatment and prognostic significance of supradiaphragmatic disease in patients with high-grade serous ovarian cancer.

OBJECTIVES: This study was designed to investigate the response to chemotherapy of supradiaphragmatic disease diagnosed by preoperative imaging. As secondary objectives, oncologic outcomes of patients affected by supradiaphragmatic disease and their pattern of recurrence were also evaluated. METHODS: Data of consecutive patients with newly diagnosed FIGO stage IV (for supradiaphragmatic disease) epithelial ovarian cancer undergoing either primary debulking surgery or neoadjuvant chemotherapy plus interval debulking surgery between 2004 and 2021, were retrospectively collected. All patients were preoperatively evaluated by chest/abdominal CT scan or 18F-FDG PET/CT preoperatively and at follow-up to evaluate response to chemotherapy. At follow-up visits, site of recurrence diagnosed by imaging techniques was systematically recorded as it occurred. Progression-free and overall survival were measured by using Kaplan-Meier and Cox models. RESULTS: A total of 130 patients was included in this study with a median (range) follow-up of 32.9 (12.8-176.7) months. Complete or partial response was achieved in most of the patients after 3 cycles (77.7%) and 6 cycles (85.4%) of chemotherapy. At follow-up, recurrence occurred in 96 (73.8%) patients and the main site of recurrence was abdomen only in 64 (66.7%) patients. At multivariate analysis, residual disease after surgery was the only variable influencing survival outcomes. CONCLUSIONS: Supradiaphragmatic disease respond to chemotherapy in most patients affected by advanced EOC and recurrence mainly occurs in the abdomen. Results from this study confirms that abdominal optimal cytoreduction is the main surgical goal in the treatment of women affected by FIGO stage IV EOC.

Transvaginal sonography with vs without bowel preparation in diagnosis of rectosigmoid endometriosis: prospective study.

OBJECTIVES: The primary aim of this study was to compare the diagnostic accuracy of transvaginal sonography (TVS) with vs without bowel preparation (BP) in detecting the presence of rectosigmoid endometriosis. Secondary objectives were to compare the diagnostic accuracy of the two techniques in estimating infiltration of the submucosa, length of the largest rectosigmoid nodules, distance of the nodules from the anal verge and presence of multifocal disease. METHODS: This was a prospective study of patients with symptoms of pelvic pain for more than 6 months and/or suspicion of endometriosis referred to our institution between October 2016 and April 2018. Participants underwent a first TVS without BP followed by TVS with BP within a time interval of 1 week to 3 months. The examinations were performed independently and blindly by two sonographers. Only patients who underwent laparoscopy within the 6 months following the second ultrasound examination were included. Ultrasound results using the two techniques were compared with surgical and histological findings. RESULTS: Of the 262 patients included in the study, 118 had rectosigmoid endometriosis confirmed at surgery. There was no significant difference in accuracy between TVS with and that without BP in diagnosing the presence of rectosigmoid endometriosis (93.5% vs 92.3%; P = 0.453). No significant difference was observed in accuracy between TVS with and that without BP in diagnosing submucosal infiltration (88.8% vs 84.6%; P = 0.238) and multifocal disease (97.2% vs 95.2%; P = 0.727) in patients diagnosed sonographically with rectosigmoid endometriosis. The accuracy of TVS with BP was similar to that of TVS without BP in estimating the maximum diameter of the largest nodule (P = 0.644) and the distance between the more caudal rectosigmoid nodule and the anal verge (P = 0.162). CONCLUSION: BP does not improve the diagnostic performance of TVS in detecting rectosigmoid endometriosis and in assessing characteristics of endometriotic nodules. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

Influence of adenomyosis on pregnancy and perinatal outcomes in women with endometriosis.

OBJECTIVES: Several studies have investigated the correlation between endometriosis and adverse pregnancy and perinatal outcomes. However, the role of adenomyosis as a risk factor for adverse perinatal outcome in women with endometriosis has yet to be established. The aim of this study was to explore if fetal and maternal outcomes, in particular the incidence of a small-for-gestational-age (SGA) infant, are different in pregnant women with endometriosis only from in those with the concomitant presence of diffuse or focal adenomyosis. METHODS: This was a retrospective analysis of data collected prospectively during a 3-year period. We included 206 pregnant women with endometriosis: 148 (71.8%) with endometriosis only, 38 (18.4%) with focal adenomyosis and 20 (9.7%) with diffuse adenomyosis. Adenomyosis was diagnosed using ultrasonography and was classified as focal or diffuse. The study included patients who conceived spontaneously or by an assisted reproductive technique. Demographics, ultrasound variables and outcome were compared between women with endometriosis only and those with diffuse and those with focal adenomyosis. Logistic regression analysis was performed to assess the association of variables with SGA at birth in women with diffuse and those with focal adenomyosis. RESULTS: The three groups were similar in demographic characteristics (age, body mass index, mode of conception). Patients with diffuse adenomyosis compared with those with endometriosis only had significantly lower pregnancy-associated plasma protein A (0.61 vs 0.88 multiple of the median, P < 0.001), higher mean uterine artery pulsatility index in the first (2.23 vs 1.67, P < 0.001) and second (1.30 vs 0.94, P < 0.001) trimesters of pregnancy, and higher incidence of SGA (40% vs 10.8%, P < 0.001). No statistically significant differences were found in patients with focal adenomyosis compared with those with endometriosis only. Logistic regression analysis demonstrated that diffuse adenomyosis (odds ratio = 3.744; 95% CI, 1.158-12.099; P = 0.027) was the only independent risk factor for SGA. CONCLUSIONS: The presence of diffuse adenomyosis in pregnant women with endometriosis is strongly associated with delivery of a SGA infant. Women with diffuse adenomyosis should be treated as being at high risk of placental dysfunction, and these pregnancies might therefore need closer monitoring. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Tertiary cytoreductive surgery in recurrent epithelial ovarian cancer: A multicentre MITO retrospective study.

OBJECTIVES: To evaluate the impact of tertiary cytoreductive surgery (TCS) on survival in recurrent epithelial ovarian cancer (EOC), and to determine predictors of complete cytoreduction. METHODS: A multi-institutional retrospective study was conducted within the MITO Group on a 5-year observation period. RESULTS: A total of 103 EOC patients with a ≥6month treatment-free interval (TFI) undergoing TCS were included. Complete cytoreduction was achieved in 71 patients (68.9%), with severe post-operative complications in 9.7%, and no cases of mortality within 60days from surgery. Multivariate analysis identified the complete tertiary cytoreduction as the most potent predictor of survival followed by FIGO stage I-II at initial diagnosis, exclusive retroperitoneal recurrence, and TCS performed ≥3years after primary diagnosis. Patients with complete tertiary cytoreduction had a significantly longer overall survival (median OS: 43months, 95% CI 31-58) compared to those with residual tumor (median OS: 33months, 95% CI 28-46; p<0.001). After multivariate adjustment the presence of a single lesion and good (ECOG 0) performance status were the only significant predictors of complete surgical cytoreduction. CONCLUSIONS: This is the only large multicentre study published so far on TCS in EOC with ≥6month TFI. The achievement of postoperative no residual disease is confirmed as the primary objective also in a TCS setting, with significant survival benefit and acceptable morbidity. Accurate patient selection is of utmost importance to have the best chance of complete cytoreduction.

Computed tomographic colonography vs rectal water- contrast transvaginal sonography in diagnosis of rectosigmoid endometriosis: a pilot study.

OBJECTIVES: To compare the performance of computed tomographic colonography (CTC) and rectal water-contrast transvaginal sonography (RWC-TVS) in the diagnosis of rectosigmoid endometriosis, and compare precision in estimating the length of the rectosigmoid nodules and the distance between the nodules and the anal verge. METHODS: This prospective study included 70 patients of reproductive age with clinical suspicion of rectosigmoid endometriosis. Patients underwent RWC-TVS and CTC before laparoscopic excision of endometriotic nodules. The findings of RWC-TVS and CTC were compared with surgical and histological results. RESULTS: Of the 70 patients included in the study, 40 (57.1%) had rectosigmoid endometriosis. CTC and RWC-TVS had similar accuracy in the diagnosis of rectosigmoid endometriosis (P = 0.508) and similar precision in estimating the length of the endometriotic nodules (P = 0.077). CTC was more precise than RWC-TVS in estimating the distance between the rectosigmoid nodule and the anal verge (P < 0.001). The intensity of pain experienced during CTC was higher than that perceived during RWC-TVS (P < 0.001); however, intestinal distension for CTC was well-tolerated in all patients without significant adverse effects. CONCLUSIONS: RWC-TVS and CTC have similar accuracy in the diagnosis of rectosigmoid endometriosis and similar precision in estimating the size of the nodules; however, CTC is more precise than RWC-TVS in estimating the distance between the nodules and the anal verge, yet patients tolerate RWC-TVS better than CTC. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Diagnostic accuracy of midtrimester antenatal ultrasound for multicystic dysplastic kidneys.

OBJECTIVES: To establish the diagnostic accuracy of obstetric ultrasound at a tertiary fetal medicine center in the prenatal detection of unilateral and bilateral multicystic dysplastic kidney (MCDK) in fetuses in which this condition was suspected, and to undertake a systematic review of the relevant literature. METHODS: This was a retrospective observational study of all cases referred to a regional tertiary fetal medicine unit due to suspicion of either unilateral or bilateral MCDK between 1997 and 2015. Diagnosis was confirmed by postnatal ultrasound reports or postmortem examination. The accuracy of prenatal ultrasound in the diagnosis of MCDK was calculated. Using a systematic search strategy we also performed a review of the literature regarding the prenatal diagnosis and diagnostic accuracy of MCDK. RESULTS: We included 144 women in our analysis; 37 (25.7%) opted for pregnancy termination (TOP) (due to unilateral MCDK with additional abnormalities, suspected bilateral MCDK or severe obstructive uropathy). Complete pre- and postnatal data were available in 126 pregnancies, including 104 livebirths, 19 TOPs with postmortem findings available and three intrauterine fetal deaths. Two infants died shortly after birth (due to known bilateral MCDK or known cranial vault defect). The overall number of cases of MCDK confirmed postnatally was 100; of these, 98 were diagnosed prenatally (true positive), while two were thought to be hydronephrosis prenatally (false negative) and the diagnosis of MCDK was made after birth. In nine cases, the initial antenatal diagnosis of suspected MCDK was revised, either later in pregnancy (n = 2) or postnatally (n = 7) (false positive). Overall, the diagnostic accuracy in our population for the use of antenatal ultrasound to detect MCDK was 91.3%, while that reported in the existing literature was found to range from 53.3% to 100%. MCDK was isolated in the majority (71%) of cases, while in 29% of cases it was found to be associated with other renal and extrarenal fetal abnormalities. CONCLUSIONS: Antenatal ultrasound had a diagnostic accuracy of about 91% in the prediction of postnatal MCDK and can therefore be used to guide antenatal counseling. However, prenatal or postnatal revision of the diagnosis occurred in about 7% of cases and parents should be counseled appropriately. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Endometriotic ovarian cysts do not negatively affect the rate of spontaneous ovulation.

STUDY QUESTION: Do endometriotic ovarian cysts influence the rate of spontaneous ovulation? SUMMARY ANSWER: Endometriotic cysts, no matter what their volume, do not influence the rate of spontaneous ovulation in the affected ovary. WHAT IS KNOWN ALREADY: Endometriotic ovarian cysts may negatively affect spontaneous ovulation in the affected ovary. STUDY DESIGN, SIZE, DURATION: This was a prospective observational study performed between September 2009 and June 2013. PARTICIPANTS/MATERIALS, SETTING, METHODS: This study included women of reproductive age with regular menstrual cycles and unilateral ovarian endometriomas (diameter ≥20 mm) desiring to conceive. Exclusion criteria were: hormonal therapies in the 3 months prior to study entry and previous adnexal surgery. Patients underwent serial transvaginal ultrasound to assess the side of ovulation (for up to six cycles). MAIN RESULTS AND THE ROLE OF CHANCE: Ovulation was monitored in 1199 cycles in 244 women (age, mean ± SD, 34.3 ± 4.9 years). 55.3% of the patients had left endometriomas and 44.7% had right endometriomas (P = 0.024). The mean (±SD) diameter of the endometriomas was 5.3 cm (±1.7 cm). Ultrasonographically documented ovulation occurred in 596 cycles in the healthy ovary (49.7%; 95% CI, 46.8-52.6%) and in 603 cycles in the affected ovary (50.3%; 95% CI, 47.1-53.2%; P = 0.919). This observation was confirmed in patients with diameter of the cyst ≥4 cm (n = 166) and in those with diameter of the cyst ≥6 cm (n = 45). One hundred and five patients spontaneously conceived (43.0%; 95% CI, 36.7-49.5%). LIMITATIONS, REASON FOR CAUTION: The high pregnancy rate reported in this study was observed in a selected population of women with endometriomas and cannot be extrapolated to all patients with endometriosis. WIDER IMPLICATIONS OF THE FINDINGS: Since ovarian endometriomas do not impair spontaneous ovulation, the impact on fertility of surgical excision of ovarian endometriomas should be further investigated.

The Kidney Donor Profile Index (KDPI) of marginal donors allocated by standardized pretransplant donor biopsy assessment: distribution and association with graft outcomes.

Pretransplant donor biopsy (PTDB)-based marginal donor allocation systems to single or dual renal transplantation could increase the use of organs with Kidney Donor Profile Index (KDPI) in the highest range (e.g. >80 or >90), whose discard rate approximates 50% in the United States. To test this hypothesis, we retrospectively calculated the KDPI and analyzed the outcomes of 442 marginal kidney transplants (340 single transplants: 278 with a PTDB Remuzzi score<4 [median KDPI: 87; interquartile range (IQR): 78-94] and 62 with a score=4 [median KDPI: 87; IQR: 76-93]; 102 dual transplants [median KDPI: 93; IQR: 86-96]) and 248 single standard transplant controls (median KDPI: 36; IQR: 18-51). PTDB-based allocation of marginal grafts led to a limited discard rate of 15% for kidneys with KDPI of 80-90 and of 37% for kidneys with a KDPI of 91-100. Although 1-year estimated GFRs were significantly lower in recipients of marginal kidneys (-9.3, -17.9 and -18.8 mL/min, for dual transplants, single kidneys with PTDB score<4 and =4, respectively; p<0.001), graft survival (median follow-up 3.3 years) was similar between marginal and standard kidney transplants (hazard ratio: 1.20 [95% confidence interval: 0.80-1.79; p=0.38]). In conclusion, PTDB-based allocation allows the safe transplantation of kidneys with KDPI in the highest range that may otherwise be discarded.

A 12-week treatment with fractional CO2 laser for vulvovaginal atrophy: a pilot study.

OBJECTIVE: This pilot study aimed to assess the efficacy and feasibility of fractional CO2 laser in the treatment of vulvovaginal atrophy (VVA) in postmenopausal women. METHODS: VVA symptoms were assessed before and after three applications of laser over 12 weeks in 50 women (age 59.6 ± 5.8 years) dissatisfied with previous local estrogen therapies. Subjective (visual analog scale) and objective (Vaginal Health Index Score, VHIS) measures were used during the study period to assess VVA. Quality of life was measured by using the SF-12. A subjective scale to evaluate the degree of pain related to the laser application and the degree of difficulty to perform the laser procedure was used. RESULTS: Fractional CO2 laser treatment was effective to improve VVA symptoms (vaginal dryness, vaginal burning, vaginal itching, dyspareunia, dysuria; p < 0.001) at 12-week follow-up, as well as the VHIS (13.1 ± 2.5 at baseline vs. 23.1 ± 1.9; p < 0.001). Both physical and mental scores of quality of life were significantly improved in comparison with baseline (p < 0.001). Satisfaction with the laser procedure was reported by 42 women (84%) and a minimal discomfort was experienced at the first laser application, mainly because of the insertion and the movements of the probe. Finally, the technique was very easy to perform in all women starting from the second application at week 4 and no adverse events were recorded during the study period. CONCLUSIONS: A 12-week treatment with the fractional CO2 laser was feasible and induced a significant improvement of VVA symptoms by ameliorating vaginal health in postmenopausal women. Further controlled studies should be performed to confirm the present data and to assess the long-term effects of the laser procedure on vaginal tissues.

Trends in immune cell function assay and donor-specific HLA antibodies in kidney transplantation: A 3-year prospective study.

The immune cell function assay (ICFA) and de novo anti-donor-specific HLA antibodies (DSA) have been proposed as assays for immune monitoring in renal transplantation, but longitudinal studies examining the modification of both parameters over time and their relation with clinical events are lacking. We prospectively measured longitudinal changes in ICFA and DSA levels in 55 kidney transplant recipients over 3-year follow-up (534 visits) and analyzed their relation with the risk of developing acute rejections or infections. Seven patients (12.7%) developed biopsy-proven acute rejection, and 20 (36.4%) developed viral infections. At 3 years posttransplant, 28% of the patients had developed de novo DSA. ICFA levels peaked at 1-2 months posttransplant (p = 0.005) and leveled off thereafter. They were not associated with the risk of acute rejections, viral infections or development of de novo DSA. Instead, the incidence of de novo DSA was higher in patients who previously had viral infections (adjusted-odds ratio of de novo DSA associated with prior infections: 6.03 [95% CI, 1.64-22.06; p = 0.007]). Our prospective, longitudinal study does not support using ICFA to quantify the immune risk in kidney transplantation. Further studies are needed to confirm the relationship between viral infections and the subsequent development of de novo DSA.

EBV-associated leukoencephalopathy with late onset of central nervous system lymphoma in a kidney transplant recipient.

Central nervous system (CNS) lymphoma is a rare posttransplant lymphoproliferative disorder (PTLD), which usually has a poor outcome. To date, no specific conditions predisposing to this complication have been identified. We here describe the case of a renal transplant patient who was initially diagnosed as having Epstein-Barr virus (EBV)-associated leukoencephalopathy and ultimately developed EBV-positive CNS lymphoma. The patient was a young lady who, 2 years after transplantation, presented with focal neurological and electroencephalographic abnormalities and diffuse white matter lesions on brain magnetic resonance imaging. EBV-DNA was detected in the cerebrospinal fluid (CSF) by polymerase chain reaction. After acyclovir therapy and immunosuppressive drug tapering, the symptoms and electroencephalographic abnormalities subsided, and EBV-DNA disappeared from the CSF. Ten years later, a bulky cerebral mass was found. After excision, a diagnosis of EBV-positive, Hodgkin-like monomorphic B-cell PTLD was made. This case illustrates the potential pathophysiological relationships between EBV infection, leukoencephalopathy and CNS lymphoma; although a long time elapsed from the initial neurological illness to CNS lymphoma, a link between these two conditions cannot be excluded. Therefore, a careful long-term follow-up of EBV-related encephalopathy is advisable.

Outbreak of acute renal failure due to cefodizime-vancomycin association in a heart surgery unit.

OBJECTIVE: To describe an outbreak of acute renal failure (ARF) occurring in a group of patients undergoing open-heart surgery, simultaneously to a change in perioperative antibiotic prophylaxis. DESIGN: Case series. SETTING: A nine-bed heart surgery intensive care unit, serving a 1,300-bed University teaching hospital. PATIENTS: Thirty-two patients undergoing open-heart surgery during an 11-day period, when the preoperative surgical prophylaxis protocol had been changed from the usual antibiotic association of ceftriaxone + vancomycin to cefodizime + vancomycin. RESULTS: ARF occurred in 16 of the 32 (50%) patients exposed to the new antibiotic prophylaxis regimen; seven patients had oliguric ARF, and nine patients had an increase in serum creatinine (SCr) levels >50% over 24-48 h. In the seven patients with oliguric ARF, SCr increased from a median preoperative level of 88 micromol/l (80-115 micromol/l) to a peak value of 725 micromol/l (521-857 micromol/l) in 5 days (4-6). Eight patients out of the sixteen with ARF (50%) were diabetics, as opposed to none of the 16 patients not experiencing ARF. Renal biopsy (three patients) showed tubular dilation and necrosis, interstitial edema, and lymphomononuclear infiltrate of moderate degree. Only one patient required hemodialysis, and all recovered renal function. No other cases of unexplained ARF occurred in the unit after the original prophylaxis protocol was resumed. CONCLUSION: The simultaneous infusion of cefodizime and vancomycin may involve a high risk of substantial renal function derangement, especially in diabetics.

[Early diagnosis of rapidly progressive glomerulonephritis]. / Diagnosi precoce delle glomerulonefriti rapidamente progressive.

The term rapidly progressive glomerulonephritis (RPGN) designates a group of glomerular diseases with different pathogenetic and clinical features, rapidly leading to renal or patient death in about 90% of the untreated cases. Histopathologically, it is characterized by glomerular crescents in at least 50-75% of the glomeruli (necrotizing crescentic glomerulonephritis), and very often, glomerular necrosis. The situation is, however, potentially reversible if adequately treated, and a favourable outcome depends largely on early diagnosis and treatment. Early diagnosis can be achieved if due importance is given to even seemingly unspecific manifestations such as "flu like syndrome" associated with "glomerular" hematuria. These manifestations are detectable before the down-hill course of renal functional derangement becomes evident and should lead the physician to consider RPGN among the diagnostic possibilities. Final diagnosis rests on serological tests and kidney biopsy. The battery of diagnostic serological tests (anti-GBM, anti-DNA antibodies, cryoglobulins, etc.) has recently been enriched by the assay of anti-neutrophil cytoplasmic antibodies (ANCA). These antibodies are detectable in over 90% of cases of Wegener's granulomatosis and primary necrotizing crescentic glomerulonephritis with or without lung involvement. ANCA-associated glomerulonephritis is the commonest form of RPGN, and the new serological assay provides an important tool for its early recognition. Renal biopsy is necessary to evaluate the severity of the nephritic process and modulate treatment accordingly. Timely diagnosis is one of the most important factors contributing to successful treatment outcome over both the short and the long term.