Addendum to the consensus opinion from the International Deep Endometriosis Analysis (IDEA) group: sonographic evaluation of the parametrium.

Preoperative sonographic staging in patients with suspected parametrial endometriosis is essential to plan the surgical intervention and to anticipate the need for a multidisciplinary approach, and hence optimize surgical outcome. The results of a recent metanalysis suggest that defining more accurately the ultrasonographic criteria of parametrial involvement in endometriosis is needed. The aim of this addendum to the IDEA-consensus is to highlight the sonographic characteristics of the parametrium and identify ultrasound techniques to diagnose deep endometriosis in this area. This article is protected by copyright. All rights reserved.

Outcome of Nonketotic Hyperglycinemia in Lebanon: 14-Year Retrospective Review.

Nonketotic hyperglycinemia is a rare inborn error of glycine metabolism characterized by a severe metabolic encephalopathy with drug-resistant seizures. Here, we report the outcome of nonketotic hyperglycinemia in a cohort of patients diagnosed and followed-up at a tertiary care reference center in Lebanon, between 2000 and 2014.Eight out of 12 patients with nonketotic hyperglycinemia were retrospectively reviewed. The remainders were excluded for incomplete data. The majority of cases presented with seizures and hypsarrhythmia or burst suppression patterns. Half of the patients died. Survival varied between 7 days and 18 years. Seizures remained unresponsive with poor outcome, despite standard supportive care and antiepileptic therapy; however, two patients were responsive to ketogenic diet and one of them became seizure-free.Scarce data on the outcome of nonketotic hyperglycinemia patients from the Middle East and North Africa region are available. The ketogenic diet, in combination with standard therapies, appears to be effective in controlling the seizures in this devastating disorder. Larger multicenter studies are still needed to establish the role of the ketogenic diet in nonketotic hyperglycinemia.

Learning curve for ultrasonographic diagnosis of deep infiltrating endometriosis using structured offline training program.

OBJECTIVE: To assess the learning curves of trainees during a structured offline/hands-on training program for the ultrasonographic diagnosis of deep infiltrating endometriosis (DIE). METHODS: Four trainees (all Ob/Gyn postgraduates with at least 5 years' experience in ultrasonography in obstetrics and gynecology, but with no experience of sonographic examination of DIE) participated in the study. They underwent a 2-week training program with a single trainer. Day 1 was devoted to theoretical issues and guided offline analysis of 10 three-dimensional ultrasound volumes. During the following days, four sessions of real-time sonographic examinations were performed in a DIE referral center ultrasound unit. In between these sessions, the trainees analyzed four datasets offline, each containing 25 volumes. At the end of each set, misinterpreted volumes were reassessed with the trainer. Presence or absence of DIE at surgery was considered the gold standard. The trainees' learning process was evaluated by learning-curve cumulative summation (LC-CUSUM) and the deviations of the trainees' level of performance at the control stage was assessed by CUSUM (standard CUSUM), for different locations of DIE. RESULTS: The trainees reached competence after an average of 17 (range, 14-21) evaluations for bladder, 40 (range, 30-60) for rectosigmoid, 25 (range, 14-34) for forniceal, 44 (range, 25-66) for uterosacral ligament (USL) and 21 (range, 14-43) for rectovaginal septum (RVS) locations of DIE, and then kept the process under control, with error levels of less than 4.5% until the end of the test. The overall accuracy for each trainee in diagnosis of DIE at the different locations ranged from 0.91 to 0.98 for bladder DIE, from 0.80 to 0.94 for rectosigmoid DIE, from 0.90 to 0.94 for forniceal DIE, from 0.79 to 0.82 for USL DIE and from 0.89 to 0.98 for RVS DIE. CONCLUSIONS: The suggested 2-week training program, based on a mixture of offline and live scanning sessions, is feasible and apparently provides effective training for the ultrasonographic diagnosis of DIE. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

Clostridium difficile-related pancolitis in lung-transplanted patients with cystic fibrosis.

C. difficile (C. d.) is the main cause of antibiotic-associated diarrhea and colitis. It is shown in literature a high asymptomatic carriage rate of C. d. in patients with cystic fibrosis (CF), though C. d.-related colitis is an uncommon complication in these patients, despite the use of multiple high-dose antibiotic regimes and the frequency of hospital admissions. Lung transplantation with the associated immunosuppression and aggressive antibiotic therapy may increase the risk of the clinical manifestation of C. d. In this paper, we describe three cases of severe C. d. colitis in patients with CF following lung transplantation and illustrate our experience in the diagnosis and management of these patients.

High-Dose Levetiracetam for Neonatal Seizures: A Retrospective Review.

BACKGROUND: Neonatal seizures are frequently encountered in the neonatal intensive care unit and may be associated with serious long-term neurological sequelae. Response to treatment continues to be modest, and treatment guidelines remain unclear. The use of levetiracetam has been on the rise in the past several years due to its favorable safety profile in the face of limited data on its efficacy and optimal dosing regimens. Unlike the older age groups, the benefit of escalating to high-dose levetiracetam of 80-100 mg/kg/day in neonates not responding to the standard used dosing regimen (40-60 mg/kg/day) is not studied. We sought to investigate the safety and efficacy of levetiracetam escalation to high dose regimens for neonatal seizures. METHODS: A retrospective chart review over a 7-year period was conducted at the American University of Beirut to identify neonates with electrographically proven seizures treated with levetiracetam. Data was collected on electroclinical seizure characteristics, underlying etiology, seizure control, other anti-seizure medications, and adverse effects. RESULTS: Electronic chart review revealed a total of 15 neonates with electrographically confirmed seizures treated with levetiracetam, with escalation to high doses in seven. As a first line drug, levetiracetam monotherapy terminated seizures in six out 10 neonates, two of whom had complete seizure cessation only after escalation to high doses of 80 or 100 mg/kg/day. When used in combination with other anti-seizure medications, four out of five neonates achieved complete seizure cessation upon escalation to high doses of levetiracetam. No adverse effects were noted. CONCLUSIONS: In neonates not responding to the standard used levetiracetam doses, incremental increases to 80-100 mg/kg/day may be considered. Prospective studies are needed to confirm the promising role of such high dosing regimens, and to better elucidate the role of levetiracetam in neonatal seizures.

Incidence of port-site metastasis after laparoscopic management of borderline ovarian tumors: a series of 22 patients.

PURPOSE: The aim of this work was to evaluate the incidence of port-site metastasis in patients undergoing laparoscopy for borderline ovarian carcinoma (BOT). METHODS: Twenty-two patients who underwent laparoscopy from 2004 to 2008 for BOT were evaluated retrospectively. RESULTS: In 15 patients an ultraconservative procedure with enucleation of the annexal neoplasia was carried out, while in five (23%) unilateral salpingo-oophorectomy was performed and in two cases (9%) bilateral salpingo-oophorectomy was done. CONCLUSION: The literature data report few cases of port-site metastasis in BOT patients. Residual cutaneous metastases have been reported to occur within 12 months from the first surgery, generally in association with serous histology. In our analysis, we found 17 out of 22 cases of serous BOT, three mucinous and two endometriod. In no case was cutaneous metastasis revealed after an average of 30 months of follow-up.

Pelvic lymphadenectomy in endometrial cancer: our current experience.

OBJECTIVE: Lymph node involvement is the single most important factor in the prognosis of endometrial cancer, because it is predictive of locoregional and distant metastases. The purpose of our study was to determine whether lymphadenectomy is useful in the surgical staging of endometrial cancer and if it may help establish a more accurate prognosis and reduce the need for postoperative therapy in patients without surgical complications. STUDY DESIGN: We conducted a retrospective study on 55 patients with diagnosis of endometrial cancer. RESULTS: Surgical staging of patients undergoing pelvic lymphadenectomy (47/55) showed that 59.6% of cases (n = 28) had Stage I cancer (IA in 4, IB in 16, IC in 8), 17.02% (n = 8) Stage II (IIA in 3, IIB in 5), 21.2% (n = 10) Stage III (IIIB in 5, IIIC in 5), and 2.1% (n = 1) Stage IVA. In the remaining eight patients with a very high anesthesiologic risk (ASA 4), surgical staging was incomplete because they underwent only node palpation. CONCLUSION: In conclusion, as we wait for the sentinel lymph node technique to demonstrate satisfactory results and be standardized also for endometrial cancer, we believe that surgical lymph node dissection plays a crucial role in debulking this type of cancer. When performed by a good surgical oncology team, it does not entail a significantly increased operative risk.

A perspective study on correlation between HPV DNA and lymph nodes in surgically treated cervical carcinoma patients. Preliminary data.

UNLABELLED: The purpose of this study was to analyze the presence of HPV DNA in lymph nodes in patients with cervical cancer. STUDY DESIGN: A prespective study was performed on a total of 18 patients with cervical cancer in FIGO Stage I-II. The surgical procedure consisted of systematic pelvic lymphadenectomy with removal of the common/external/internal (obturator) iliac lymph node chains, followed by radical hysterectomy depending on the clinical stage, or by Piver's type II radical laparohysterectomy for Stage IA2 carcinoma and Piver's type-III laparohysterectomy for Stage IB or Stage II carcinoma. After removal by a technique not yet described in the literature, the lymph nodes were processed directly in the operating room. HPV DNA testing was done using a cytobrush device. At the end of this operation, the lymph nodes were sent to the hospital's pathologist for metastasis detection. RESULTS: The correlation between a positive HPV DNA test in the cervix and lymph node metastasis was non significant (p < 0.63). By contrast, the correlation between a positive HPV DNA test in the lymph nodes and lymph node metastasis was highly significant (p < 0.005), as was the correlation between positive HPV DNA tests in the cervix and lymph nodes (p < 0.005). Finally, the correlation between disease stage and positive HPV DNA testing in the lymph nodes was also significant (p < 0.05). CONCLUSIONS: In conclusion, the technique that we used for HPV DNA extraction appears safe and reproducible. The results are comparable with, if not better, than those obtained with other techniques reported in the literature. The presence of HPV DNA in the lymph nodes is probably an early indicator of metastasis and as such it could be used as a predictor of relapse. Normally untreated patients who have this marker could then receive adjuvant therapy.

Uterine smooth muscle tumor of uncertain malignant potential: a three-case report.

Based on the degree of cytologic atypia, mitotic activity, and other features, uterine smooth muscle tumors have historically been grouped into two classes: benign leiomyomas and malignant leiomyosarcomas. However, this separation holds true more in principle than in practice because the tumor's biological potential may not always be determined with certainty, complicating diagnosis, and therapy. We report three cases of patients with uterine smooth muscle tumors of uncertain malignant potential. Surgery was radical in two and conservative in one. During the follow-up, one patient developed diffuse lung metastases. The two other patients have not shown any signs of relapse to date. Uterine smooth muscle tumors of uncertain malignant potential may have an unpredictable clinical course and may metastasize to seemingly low-grade neoplasms in distant sites even after several years and even in the absence of important negative prognostic predictors, such as coagulative tumor cell necrosis. At present, no final consensus has been reached on the choice of the best strategy for surgery and adjuvant therapy.

Vaginal versus abdominal hysterectomy in endometrial cancer: a retrospective study in a selective population.

The purpose of this study was to analyze the outcome of vaginal and abdominal hysterectomy for the treatment of early-stage endometrial cancer in a selected group of elder patients. This retrospective study analyzed a total of 154 patients: 113 (group I) underwent vaginal surgery and 41 (group II) underwent laparotomy. In both groups, we investigated the following parameters: intra- and postoperative complications, mean operative time, mean hospital stay, disease-free survival (DFS), overall survival (OS), and time of local or retroperitoneal recurrence. Medically compromised patients were significantly more frequent in the vaginal surgery group (P = 0.005), and the operative duration in this group was significantly shorter (P = 0.01). Intra- and postoperative complications, along with local and distant recurrence, did not show a statistically significant difference in the two groups. Total survival in the two populations, 85% at 5 years, did not reach statistically significant difference either in terms of DFS or in terms of OS. Vaginal surgery compared to traditional abdominal approach is feasible also in patients with high surgical risk; it does not require general anesthesia, abolishes abdominal trauma correlated to laparotomy, and allows a quicker reprise of the bladder and rectal function; therefore, it achieves high eradication rates and low intra- and postoperative morbidity rates.

Lung transplantation for cystic fibrosis in Italy.

Lung transplantation (LT) is the only effective form of therapy for cystic fibrosis (CF) associated with end-stage pulmonary failure. In Italy, the management of CF is regulated by national law, which has instituted regional centers for care and follow-up of all CF patients. LT has been performed since 1992 in only nine LT certified centers. The structured national organization has led to a unified database for LT for CF. As of December 2006, 197 bilateral LT (96 male and 94 female patients; 7 retransplants) have been performed. Of these, four had also liver or heart and liver transplantation, and three are long-term survivors. Overall median survival is 7 years. Mean age at transplantation is 26.5 years, and the mortality on the waiting list is 33.6%. Patients listed for transplant either received a suitable donor within a mean of 10 months or died within a mean of 5.5 months. The most frequent cause of death is bronchiolitis obliterans syndrome (BOS). Our nationwide database indicates the excellent results obtained by LT in FC. Still, mortality on the waiting list remains a challenge and long-term outcome is limited by BOS.

Lung transplantation for cystic fibrosis: ten years of experience.

Lung transplantation represents the only therapeutic option for patients affected by end-stage cystic fibrosis (CF). We performed 76 lung transplantations in 73 patients from 1996-2007. The mean time on the waiting list was 10+/-6 months. The median follow-up after the transplantation was 69.3 months. Twenty-one transplants (27.6%) were performed under cardiopulmonary bypass. Perioperative mortality, excluding retransplants, was 16.4% (12 patients) and the causes of death were sepsis, primary graft failure, and myocardial infarction. The overall survival was 74.5%+/-5%, 62.9%+/-5%, 54.1%+/-6%, and 43.4%+/-6% at 1, 3, 5, and 10 years, respectively. The accurate selection of potential recipients and the correct timing of referral and transplantation are factors that play crucial roles to obtain satisfactory results in term of improvement of quality of life and long-term survival.

Non-Hodgkin's lymphoma, presenting as an isolated endobronchial mass after bilateral lung transplantation: a case report.

BACKGROUND: Lymphoma is a serious complication following solid organ transplantation. Endobronchial involvement of non-Hodgkin's lymphoma (NHL) is rare usually occurring in the setting of widely disseminated disease. Only a few cases of isolated endobronchial NHL have been reported. They were mostly confined to the main bronchi. METHODS: Herein we have described a case of an obstructive endobronchial NHL lesion in a young patient, which developed 6 years after bilateral lung transplantation for cystic fibrosis. RESULTS: Successful treatment was obtained with endoscopic resection of the lesion followed by chemotherapy. CONCLUSIONS: In rare cases NHL may present as an isolated endobronchial mass in the main bronchi. Because in these cases the prognosis seems to be better, early diagnosis is essential. Rigid bronchoscopy offers the opportunity to safely obtain large amounts of tissue for complete histological diagnosis and to de-obstruct the airway to relieve the symptoms.

Malignancies following lung transplantation.

During the last 2 decades, long-term survival after lung transplantation has significantly improved. However, among the complications related to the continuous administration of immunosuppressive drugs, malignancy plays an important role. We retrospectively revisited our series of patients to report our experience. From January 1991 we performed 134 lung transplantations in 128 recipients (mean age, 33.4 +/- 13.5 years). In all patients the first-line immunosuppressive regimen was based on a calcineurin inhibitor (cyclosporine or tacrolimus), an antimetabolic agent (azathioprine), and steroids. Five patients (4.2%) developed malignancy and the mean time of occurrence after the transplantation was 46.4+/-23 months. The mean age was 41 +/- 16 years (P = not significant [ns]). The tumors were as follows: laryngeal cancer (radiotherapy), colon cancer (surgery plus adjuvant chemotherapy), gastric cancer (surgery plus adjuvant chemotherapy), endobronchial non-Hodgkin lymphoma (NHL) (endoscopic resection plus chemoradiotherapy), and cutaneous and visceral Kaposi's sarcoma (KS) (chemotherapy). All patients have reduced the dose of immunosuppressive drugs; in 1 of them, tacrolimus was changed to rapamycin. Two patients died because of neoplastic dissemination, another 1 due to obliterans bronchiolitis. The 2 patients with NHL and KS are alive at 6 and 9 months, respectively, without signs of recurrence. Malignancies after lung transplantation represent an important problem. A multidisciplinary approach is mandatory to obtain satisfactory results in terms of improved quality of life and long-term survival.

Incidence of fungal infections in a solid organ recipients dedicated intensive care unit.

UNLABELLED: Invasive fungal infections are a significant cause of morbidity and mortality for patients undergoing solid organ transplantation. Our aim was to evaluate the incidence of invasive fungal infections in solid organ recipients within a dedicated intensive care unit (ICU). MATERIALS AND METHODS: From May 2002 to May 2005, 278 patients undergoing solid organ transplantation (105 liver, 142 kidney, 20 lung, 2 combined liver-kidney, 9 combined pancreas-kidney) were admitted to our posttransplant intensive care unit. We retrospectively analyzed data obtained from the ICU stay. Fungal infection was defined by positivity of normally sterile biological samples and by elevated positivity of normally non sterile biological samples. We did not consider superficial fungal infections and asymptomatic colonizations. RESULTS: Forty-six patients (16.5%) developed a fungal infection; at least one mycotic agent was isolated from each patient. Candida albicans was the most common pathogen, isolated from 71 % of infected patients (33 of 46). Infected patients showed a mortality rate of 35%, while that for non infected recipients was 3.5%. Total length of ICU stay was the most significant risk factor among infected patients (30.26 days vs 5.04 days P < .0001). Mean time between transplantation and first positive samples was 6.17 days (SD 8.88). CONCLUSION: Fungal infections in solid organ transplant patients are a major issue because of their associated morbidity and mortality. Candida albicans was the most common pathogen and total length of ICU stay was the most important risk factor.

Therapeutic strategies for postremission treatment in childhood acute myeloid leukemia (AML). The AIEOP experience 1987-1991.

From 1987 to 1990, intensive postremission chemotherapy was compared to autologous bone marrow transplant in previously untreated children with AML who received identical induction therapy with two courses of Daunorubicin (DNR) and conventional dose ARA-C (protocol AIEOP LAM 87). Overall, 121 of the 155 eligible patients achieved complete remission (CR) (78%). Patients in CR who lacked HLA-MLC compatible donor were randomized to receive either autologous BMT (Auto-BMT) or further sequential postremission therapy. Patients with HLA-MLC compatible donor were assigned to allogeneic BMT (Allo-BMT). Projected 3-years disease free survival (DFS) are 58% for Allo-BMT group, 24% for Auto-BMT group, 26% for chemotherapy group and 30% for a group of not randomized patients (intention to treat analysis). On March 1990 a pilot study LAM 87M was initiated. Patients in CR after induction therapy (identical to the previous protocol) receive a single intensification course consisting of high dose ARA-C plus DNR. The study continues to accrue patients.

Effects of recombinant human insulin-like growth factor I administration on spontaneous and growth hormone (GH)-releasing hormone-stimulated GH secretion in anorexia nervosa.

Exaggerated GH and reduced insulin-like growth factor I (IGF-I) levels are common features in anorexia nervosa (AN). A reduction of the negative IGF-I feedback could account, in part, for GH hypersecretion. To ascertain this, we studied the effects of recombinant human (rh)IGF-I on spontaneous and GH-releasing hormone (GHRH)-stimulated GH secretion in nine women with AN [body mass index, 14.1 +/- 0.6 kg/m2] and in weight matched controls (normal weight). Mean basal GH concentrations (mGHc) and GHRH (2.0 microg/kg, iv) stimulation were significantly higher in AN. rhIGF-I administration (20 microg/kg, sc) significantly reduced mGHc in AN (P < 0.01), but not normal weight, and inhibited peak GH response to GHRH in both groups; mGHc and peak GH, however, persisted at a significantly higher level in AN. Insulin, glucose, and IGFBP-1 basal levels were similar in both groups. rhIGF-I inhibited insulin in AN, whereas glucose remained unaffected in both groups. IGFBP-1 increased in both groups (P < 0.05), with significantly higher levels in AN. IGFBP-3 was under basal conditions at a lower level in AN (P < 0.05) and remained unaffected by rhIGF-I. This study demonstrates that a low rhIGF-I dose inhibits, but does not normalize, spontaneous and GHRH-stimulated GH secretion in AN, pointing also to the existence of a defective hypothalamic control of GH release. Moreover, the increased IGFBP-1 levels might curtail the negative IGF-I feedback in AN.

Effects of recombinant human insulin-like growth factor I administration on growth hormone (GH) secretion, both spontaneous and stimulated by GH-releasing hormone or hexarelin, a peptidyl GH secretagogue, in humans.

The negative feedback exerted by insulin-like growth factor I (IGF-I) on GH secretion occurs at the pituitary, as well as the hypothalamic level, via stimulation of SS and/or inhibition of GHRH release. In fact, recombinant human IGF-I (rhIGF-I) administration inhibits basal GH secretion, at least in fasted humans, though its effect on the GH response to GHRH is still controversial. GH secretagogues (GHS) are peptidyl and nonpeptidyl molecules that act on specific receptors at the pituitary and/or the hypothalamic level. Contrary to GHRH, the GH-releasing activity of GHS is strong, reproducible, and even partially refractory to inhibitory influences such as exogenous somatostatin. We studied the effects of rhIGF-I administration (20 microg/kg s.c. at 0 min) on GH secretion, either spontaneous or stimulated by GHRH (2 microg/kg i.v. at +180 min) or Hexarelin (HEX, 2.0 microg/kg i.v at +180 min), a GHS, in eight normal young women (age, mean +/- SEM, 28.3 +/- 1.2 yr; body mass index, 20.1 +/- 0.5 kg/m2). rhIGF-I administration increased IGF-I levels (peak vs. baseline: 420.3 +/- 30.5 vs. 274.4 +/- 25.3 microg/L, P < 0.05) within the physiological range from +120 to +300 min. No variation in glucose or insulin levels was recorded. rhIGF-I did not reduce spontaneous GH secretion [areas under curves (AUC)(0-300 min) 140.6 +/- 66.3 vs. 114.6 +/- 32.1 microg/L x h], whereas it inhibited the GH response to both GHRH (AUC(180-300 min) 447.7 +/- 159.4 vs. 715.9 +/- 104.3 microg/L x h, P < 0.05) and HEX (620.3 +/- 110.4 vs. 1705.9 +/- 328.9 microg/L x h, P < 0.03). The percent inhibitory effect of rhIGF-I on the GH response to GHRH (41.7 +/- 12.8%) was lower than that on the response to HEX (57.7 +/- 11.0%). In fact, the GH response to GHRH alone was clearly lower than that to HEX alone (P < 0.05), whereas the GH responses to GHRH and HEXwere similar after rhIGF-I. Our findings show that the sc administration of low rhIGF-I doses inhibits the GH response to GHRH and, even more, that to HEX; whereas, at least in this experimental design in fed conditions, it does not modify the spontaneous GH secretion. Because GHS generally show partial refractoriness to inhibitory inputs, including exogenous somatostatin, the present results point toward a peculiar sensitivity of GHS to the negative feedback action of IGF-I.

Failure of glucose infusion to suppress the exaggerated GH response to GHRH in patients with anorexia nervosa.

The growth hormone (GH) response to GH-releasing hormone (GHRH) is characteristically exaggerated in anorexia nervosa (AN). Hyperglycemia suppresses the GH response to GHRH in normal subjects. To test whether this inhibitory action of hyperglycemia is preserved in AN, we performed a GHRH (GHRH 1-40, 1 micrograms/kg) test under basal conditions (saline infusion) and during steady-state hyperglycemia (200 mg/dl, induced by the intravenous administration of 8 mg/min.kg of glucose) in 6 adolescent girls with acute-stage AN (as diagnosed by psychopathological, hormonal, and nutritional criteria) and in 5 age-matched female controls. In control subjects, GHRH stimulated GH release during saline, but not glucose, infusion. In the anorectic patients, the GH response to GHRH was exaggerated during both saline infusion (2.97 +/- 0.79 versus 0.52 +/- 0.22 micrograms.120 min.ml-1, p less than 0.02) and under hyperglycemic conditions (4.61 +/- 0.56 versus 0.33 +/- 0.10, p less than 0.001). We conclude that the inhibitory action of hyperglycemia on GHRH-induced GH release is lost in the acute phase of AN.