Clozapine Treatment for Aggressive Behaviors in Youths with Neurodevelopmental Disorders.

Objectives: The aim of this study was to assess effectiveness and tolerability of Clozapine in the treatment of aggression in youth with Neurodevelopmental Disorders. Methods: Patients were consecutively admitted at our third-level university hospital with nationwide catchment from June 2018 to October 2022, and followed up to July 2023. Eligibility criteria were as follows: (1) Autism Spectrum Disorder (ASD) and/or Intellectual Disability/Borderline Cognitive Functioning, (2) behavioral dyscontrol with physical aggression; (3) age range between 8 and 18 years; (4) clinical indication for Clozapine treatment after at least two failed trials with other Second-Generation Antipsychotics (SGAs); (5) availability of an at least 6-month-long follow-up. To evaluate the response to Clozapine, we used the Clinical Global Impressions (CGI) rating scales (Clinical Global Impressions-Severity [CGI-S] and Clinical Global Impressions-Improvement [CGI-I]), the Children's Global Assessment Scale (CGAS), and the Aberrant Behavior Checklist (ABC). Results: Twenty-six children and adolescents (21 boys, age 13.47 ± 2.05 years, follow-up duration 9.77 ± 3.50 months) were included in the analysis. Clinical severity (CGI-S) and functional impairment (Clinical Global Assessment Scale) significantly improved, as well as the ABC Total Score and the scores in several subscales. Sixteen patients (61.54%) were responders (CGI-I ≤2), and 13 (50.00%) displayed remission of aberrant behaviors (ΔABC-Total >35), while response/remission condition was not affected by add-on medications and psychotherapy. Most frequent side effects were increased appetite (50.00%), sialorrhea (38.46%), and increased repetitive behaviors (26.92%). Two patients presented epileptic seizures, while no patients presented leucopoenia. Conclusions: Our results suggest that Clozapine may be helpful in ameliorating treatment-resistant aggression in youth with neurodevelopmental conditions. Possible pharmacological strategies for the management of most frequent side effects are also suggested.

Sentinel node mapping in high-intermediate and high-risk endometrial cancer: Analysis of 5-year oncologic outcomes.

OBJECTIVE: To assess 5-year oncologic outcomes of apparent early-stage high-intermediate and high-risk endometrial cancer undergoing sentinel node mapping versus systematic lymphadenectomy. METHODS: This is a multi-institutional retrospective, propensity-matched study evaluating data of high-intermediate and high-risk endometrial cancer (according to ESGO/ESTRO/ESP guidelines) undergoing sentinel node mapping versus systematic pelvic lymphadenectomy (with and without para-aortic lymphadenectomy). Survival outcomes were assessed using Kaplan-Meier and Cox proportional hazard methods. RESULTS: Overall, the charts of 242 patients with high-intermediate and high-risk endometrial cancer were retrieved. Data on 73 (30.1%) patients undergoing hysterectomy plus sentinel node mapping were analyzed. Forty-two (57.5%) and 31 (42.5%) patients were classified in the high-intermediate and high-risk groups, respectively. Unilateral sentinel node mapping was achieved in all patients. Bilateral mapping was achieved in 67 (91.7%) patients. Three (4.1%) patients had site-specific lymphadenectomy (two pelvic areas only and one pelvic plus para-aortic area), while adjunctive nodal dissection was omitted in the hemipelvis of the other three (4.1%) patients. Sentinel nodes were detected in the para-aortic area in eight (10.9%) patients. Twenty-four (32.8%) patients were diagnosed with nodal disease. A propensity-score matching was used to compare the aforementioned group of patients undergoing sentinel node mapping with a group of patients undergoing lymphadenectomy. Seventy patient pairs were selected (70 having sentinel node mapping vs. 70 having lymphadenectomy). Patients undergoing sentinel node mapping experienced similar 5-year disease-free survival (HR: 1.233; 95%CI: 0.6217 to 2.444; p = 0.547, log-rank test) and 5-year overall survival (HR: 1.505; 95%CI: 0.6752 to 3.355; p = 0.256, log-rank test) than patients undergoing lymphadenectomy. CONCLUSIONS: Sentinel node mapping does not negatively impact 5-year outcomes of high-intermediate and high-risk endometrial cancer. Further prospective studies are warranted.

Management of primary and recurrent Bartholin's gland carcinoma: A systematic review on behalf of MITO Rare Cancer Group.

Bartholin gland carcinoma is an extremely rare disease. Information regarding treatment is scarce and there is no strict consensus on best practice. All studies reporting cases of Bartholin's gland cancer were screened and evaluated for inclusion. Baseline characteristics of studies were extracted. A total number of 290 manuscripts collected were available for the review process. Studies included in a previous systematic review were not duplicated. In total, details of 367 patients were collected, as follows: histological features, clinical presentation, treatment, recurrent rate, treatment of recurrence and outcome. About 35% of Bartholin gland carcinoma were squamous cell carcinoma. Almost 50% of patients presented with advanced stage. The therapeutic approach was mainly surgery, and in 61% of those women lymph node assessment was performed. Recurrence occurred in 21% of cases. Bartholin gland cancer remains a challenge for gynecologic oncologists. Guidelines, centralization to referral centers and standardized therapy are needed.

Laparoscopic Double Discoid Colorectal Resection for the Treatment of Two Distinct Deep Endometriotic Nodules.

OBJECTIVE: To show the surgical steps used to perform a laparoscopic double discoid colorectal resection for the excision of 2 distinct deep endometriotic nodules (DENs). DESIGN: Stepwise demonstration of the technique with narrated video footage. SETTING: To date there is agreement that discoid resection should be the first choice procedure in patients eligible for surgical treatment with rectal, unifocal DENs measuring ≤ 3 cm [1-3]. For surgical management of lesions of the sigmoid colon, current international guidelines suggest to perform segmental resections [3]. Data on surgical treatment of multiple colorectal DENs separated by a great distance from each other are very limited, mostly owing to the rarity of such a diagnosis. In particular, there is paucity of data concerning the efficacy and safety of a double discoid resection for surgical management of distinct DENs found in the sigmoid colon and rectum [4]. In a context of multiple colorectal DENs, the decision-making process with respect to a double discoid excision must take into consideration both the distance between the 2 nodules and the nodules' distance from anal verge. When technically feasible, such organ-sparing surgery allows preserving the healthy bowel interposed between the endometriotic lesions, seeming to offer advantages in terms of quicker return of bowel function and better rectal functional outcomes than segmental colorectal resection. INTERVENTIONS: The patient was a 36-year-old woman experiencing drug treatment failure and presenting with refractory constipation, dyschezia, dysmenorrhea, dyspareunia, cyclical abdominal bloating, and chronic pelvic pain. Preoperative ultrasonography revealed the presence of an endometriotic nodule of 19 × 6 × 16 mm deeply infiltrating the tunica muscularis of the sigmoid colon. A second DEN was found at the level of the rectum, the latter measuring 19 × 5 × 12 mm and having a distance of 9 cm from the anal verge. Both the intestinal lesions resulted to have a circumferential extent of 30%. The distance between the 2 nodules was 15 cm. A 3-dimensional laparoscopy was performed. Sigmoid colon and rectal mobilization were performed according to our standardized technique [5-7]. A 31-mm circular stapler was used to excise first the nodule of the sigmoid colon. The stapler, in its closed position, was gently introduced into the rectum via the anus and then progressively advanced inside the large bowel up to the level of the sigmoid nodule. After correct positioning, the stapler was completely opened and the nodule was imbricate between the anvil and staple housing of the stapler. Then, the stapler was closed and fired. The procedure was repeated using a second 31 mm circular stapler to resect the rectal endometriotic nodule. The overall operative time was 90 minutes. The estimated blood loss was 5 mL. Neither intra- nor postoperative complications occurred. The patient was discharged 3 days after surgery. The sigmoid colon and rectal endometriotic nodules measured, respectively, 20 × 6 × 15 mm and 20 × 5 × 12 mm on fresh unfixed specimens. Both nodules were found to have endometriosis-free surgical margins on definitive pathology. CONCLUSIONS: The operative technique displayed in this video may contribute to the standardization of a procedure, which could be included among the options available in the surgical armamentarium, to be used in selected cases of multiple colorectal DENs each having 3 cm or less in diameter. Surgeon experience and an adequate preoperative evaluation are of utmost importance to plan the operative strategy and have the best chance of surgical success.

Intermittent self-catheterization training and effects on treatment adherence and infection.

BACKGROUND: Intermittent self-catheterization (CISC) is the preferred treatment for patients with bladder dysfunction due to spinal cord injuries or multiple sclerosis (MS). However, the learning phase plays a crucial role in the still frequent drop-out. AIM: To examine whether the timing of training affects the treatment compliance and the prevalence of urinary tract infections in patients with neurogenic urinary retention. DESIGN: This is a non-randomized observational study. SETTING: The study was carried out from January 2017 to December 2019 in outpatient settings at the Bari Polyclinic Unipolar Spinal Unit (Bari, Italy). POPULATION: The study included adults with a CISC prescription for neurogenic urinary retention and learning the technique for the first time. METHODS: One hundred patients were enrolled, 75 trained immediately after diagnosis and physician prescription, while 25 in the contest of a separate training visit, one or two days after physician prescription. After the training (T0), patient's data and number of prescribed daily catheterizations were recorded and compared with those collected after 6 and 12 months. Accuracy of the procedure and episodes of infections were assessed as well. RESULTS: Adherence to prescribed CISC frequency and complications were not affected by the timing of training. However, patients adherent to the prescribe frequency of catheterization had less risk of infection than those who were not. Further post-hoc analysis confirmed that urodynamic findings and the pathology did not impact the overall occurrence of complications, but infections occurred more frequently in patients with MS (P<0.03). CONCLUSIONS: The timing of CISC education does not affect treatment adherence or the occurrence of complications. However, the adherence to the CISC prescription seems to reduce the risk of infection. CLINICAL REHABILITATION IMPACT: Patient training can be scheduled according to the organization of the centers, as patient compliance and the occurrence of complications are not affected.

Ten-year outcomes following laparoscopic and open abdominal radical hysterectomy for "low-risk" early-stage cervical cancer: A propensity-score based analysis.

OBJECTIVE: Accumulating evidence suggested the detrimental effects of adopting minimally invasive surgery in the management of early-stage cervical cancer. However, long-term evidence on the role of minimally invasive radical hysterectomy in "low-risk" patients exists. METHODS: This is multi-institutional retrospective study comparing minimally invasive and open radical hysterectomy in low-risk early-stage cervical cancer patients. A propensity-score matching algorithm (1:2) was used to allocate patients into the study groups. Kaplan-Meir model was used to estimate 10-year progression-free and overall survival. RESULTS: Charts of 224 "low-risk" patients were retrieved. Overall, 50 patients undergoing radical hysterectomy were matched with 100 patients undergoing open radical hysterectomy. Minimally invasive radical hysterectomy was associated with a longer median operative time (224 (range, 100-310) vs. 184 (range, 150-240) minutes; p < 0.001), lower estimated blood loss (10 (10-100) vs. 200 (100-1000) ml, p < 0.001), and shorter length of hospital stay (3.8 (3-6) vs. 5.1 (4-12); p < 0.001). Surgical approach did not influence the risk of having intra-operative (4% vs. 1%; p = 0.257) and 90-day severe (grade 3+) postoperative complication rates (4% vs. 8%; p = 0.497). Ten-year disease-free survival was similar between groups (94% vs. 95%; p = 0.812; HR:1.195; 95%CI:0.275, 5.18). Ten-year overall survival was similar between groups (98% vs. 96%; p = 0.995; HR:0.994; 95%CI:0.182, 5.424). CONCLUSIONS: Our study appears to support emerging evidence suggesting that, for low-risk patients, laparoscopic radical hysterectomy does not result in worse 10-year outcomes compared to the open approach. However, further research is needed and open abdominal radical hysterectomy remains the standard treatment for cervical cancer patients.

Surgical Outcomes and Complications of Laparoscopic Hysterectomy for Endometriosis: A Multicentric Cohort Study.

STUDY OBJECTIVE: To investigate the postoperative morbidity of laparoscopic hysterectomy (LH) for endometriosis/adenomyosis in terms of operative outcomes and complications. DESIGN: Retrospective multicentric cohort study. SETTING: Eight European minimally invasive referral centers. PATIENTS: Data from 995 patients with pathologically confirmed endometriosis and/or adenomyosis who underwent LH without concomitant urological and/or gastroenterological procedures from January 2010 to December 2020. INTERVENTIONS: Total LH. MEASUREMENTS AND MAIN RESULTS: Demographic patients' characteristics, surgical outcomes, and intraoperative and postoperative complications were evaluated. We considered major postoperative surgical-related complications, any grade 2 or more events (Clavien-Dindo score) that occurred within 30 days from surgery. Univariate analysis and multivariable models fit with logistic regression were used to estimate the adjusted odds ratio (OR) and corresponding 95% confidence interval (CI) for major complications. Median age at surgery was 44 years (28-54), and about half of them (505, 50.7%) were on medical treatment (estro-progestins, progestin, or Gonadotropin hormone-releasing hormone-analogues) at the time of surgery. In association with LH, posterior adhesiolysis was performed in 387 (38.9%) cases and deep nodule resection in 302 (30.0%). Intraoperative complications occurred in 3% of the patients, and major postoperative complications were registered in 93 (9.3%). The multivariable analysis showed an inverse correlation between the occurrence of Clavien-Dindo >2 complications and age (OR 0.94, 95% CI 0.90-0.99), while previous surgery for endometriosis (OR 1.62, 95% CI 1.01-2.60) and intraoperative complications (OR 6.49, 95% CI 2.65-16.87) were found as predictors of major events. Medical treatment at the time of surgery has emerged as a protective factor (OR 0.50, 95% CI 0.31-0.81). CONCLUSION: LH for endometriosis/adenomyosis is associated with non-negligible morbidity. Knowing the factors associated with higher risks of complications might be used for risk stratification and could help clinicians during preoperative counseling. The administration of estro-progestin or progesterone preoperatively might reduce the risks of postoperative complications following surgery.

Outcomes of High-Grade Cervical Dysplasia with Positive Margins and HPV Persistence after Cervical Conization.

The objective of this work is to assess the 5-year outcomes of patients undergoing conization for high-grade cervical lesions that simultaneously present as risk factors in the persistence of HPV infection and the positivity of surgical resection margins. This is a retrospective study evaluating patients undergoing conization for high-grade cervical lesions. All patients included had both positive surgical margins and experienced HPV persistence at 6 months. Associations were evaluated with Cox proportional hazard regression and summarized using hazard ratio (HR). The charts of 2966 patients undergoing conization were reviewed. Among the whole population, 163 (5.5%) patients met the inclusion criteria, being at high risk due to the presence of positive surgical margins and experiencing HPV persistence. Of 163 patients included, 17 (10.4%) patients developed a CIN2+ recurrence during the 5-year follow-up. Via univariate analyses, diagnosis of CIN3 instead of CIN2 (HR: 4.88 (95%CI: 1.10, 12.41); p = 0.035) and positive endocervical instead of ectocervical margins (HR: 6.44 (95%CI: 2.80, 9.65); p < 0.001) were associated with increased risk of persistence/recurrence. Via multivariate analyses, only positive endocervical instead of ectocervical margins (HR: 4.56 (95%CI: 1.23, 7.95); p = 0.021) were associated with worse outcomes. In this high-risk group, positive endocervical margins is the main risk factor predicting 5-year recurrence.

Evaluation of Peri-Operative Management in Women with Deep Endometriosis Who are Candidates for Bowel Surgery: A Survey from the Italian Society of Gynecologic Endoscopy.

STUDY OBJECTIVE: There is great consensus that the implementation of the enhanced recovery after surgery (ERAS) approach is beneficial for surgical patients, but there is a paucity of data concerning its application in women with deep endometriosis (DE) who are candidates for bowel surgery. The survey described herein was aimed at gathering detailed information on perioperative management of DE patients who were undergoing sigmoid/rectal (discoid or segmental) resection within the Italian Society of Gynecologic Endoscopy (SEGI) group. DESIGN: Baseline survey. SETTING: National survey conducted within the main Italian cooperative group in minimally invasive gynecologic surgery (SEGI). PATIENTS: The study did not involve patients. INTERVENTIONS: A 63-item questionnaire covering ERAS items for gynecologic/elective colorectal surgery was sent to SEGI centers. Only questionnaires from centers that reported performing ≥10 sigmoid/rectal resections per year were considered for this analysis. MEASUREMENTS AND MAIN RESULTS: Thirty-three of 38 (86.8%) of the questionnaires were analyzed. The rates of concordance with the ERAS guidelines were 40.4%, 64.4%, and 62.6% for preoperative, intraoperative, and postoperative items, respectively. The proportion of overall agreement was 56.6%. Preoperative diet, fasting and bowel preparation, correction of anemia, avoidance of peritoneal drains, postoperative feeding, and early mobilization were the most controversial items. Comparative analysis revealed that the referred rates of complete disease removal and conversion to open surgery were significantly different depending on case volume (p = .044 and p = .003, respectively) and gynecologist's/surgeon's experience (p = .042 and p = .022, respectively), with higher chances of obtaining a complete laparoscopic/robotic excision of endometriosis in centers that reported ≥30 DE surgeries performed per year and/or ≥90% of bowel resections performed by a gynecologist/general surgeon specifically dedicated to DE management. In contrast, the rates of concordance with the ERAS guidelines were not significantly different according to case volume (p = .081) or gynecologist's/surgeon's experience (p = .294). CONCLUSION: This is the first study on DE conducted on a national scale. The current survey results revealed suboptimal compliance with the ERAS recommendations and underline the need to improve the quality of perioperative care in DE patients undergoing sigmoid/rectal resection. This study is a first step toward building a consistent, structured reporting platform for the SEGI units and facilitating wide implementation and standardization of the ERAS protocol for DE patients in Italy.

How COVID-19 Phases Have Impacted Psychiatric Risk: A Retrospective Study in an Emergency Care Unit for Adolescents.

Dramatic events during the COVID-19 pandemic have acutely impacted the psychosocial environment worldwide, with negative implications for mental health, particularly for more vulnerable children and adolescents with severe psychiatric illnesses. Some data suggest that the pandemic waves may have produced different psychopathological consequences, further worsening in the second phase of the pandemic, compared to those in the first lockdown, soon after March 2020. To test the hypothesis of a further worsening of psychiatric consequences of COVID-19 in the second lockdown compared to the first lockdown, we focused our analysis on a consecutive sample of youth referred to a psychiatric emergency unit for acute mental disorders in the time period between March 2019-March 2021. The sample, consisting of 241 subjects (123 males and 118 females, ranging in age from 11 to 17 years), was divided into three groups: Pre-Lockdown Group (PLG, 115 patients); First Lockdown Group (FLG, 65 patients); and Second Lockdown Group (SLG, 61 patients). Patients in the SLG presented more frequently with non-suicidal self-injuries (NSSIs), suicidal ideation, and suicidal behavior, while no significant differences in self-harm were found between PLG and FLG. Eating disorders were more frequent in both the FLG and SLG, compared to the PLG, while sleep problems were higher only in the SLG. Furthermore, patients in the SLG presented with more frequent psychological maltreatments and neglect, as well as with psychiatric disorders in the parents. Adverse traumatic experiences and internalizing disorders were significantly associated with an increased risk of suicidality. Intellectual disability was less represented from the PLG to SLG, and similarly, the rate of ADHD was lower in the SLG. No differences were found for the other psychiatric diagnoses. This information may be helpful for a better understanding and management of adolescents with severe emotional and behavioral disorders after the exposure to long-lasting collective traumas.

"Intestinal-Type" Vulvar Adenocarcinoma: A Review of the MITO Rare Tumors Group.

Intestinal-type adenocarcinoma (VAIt) represents a sporadic variant of vulvar carcinoma. It appears frequently localized to epithelial glands in the vulvar region, and it probably derives from cloacal remnants persisting in the adult. We performed a systematic review of the limited cases reported in the literature, with the intent to assess the specific peculiarities of this rare neoplasia and to state consistent management recommendations. The principal histological VAIt characteristic is that it resembles mucinous colonic carcinomas. Therefore, immunohistochemical workup, with different tumor markers including CK20, CDX2, and CK7 staining, is needed. To confirm vulvar origin, a thorough diagnostic, and radiological examination is required to rule out other primary malignancies. The gold standard of treatment for VAIt is surgery, with local excision with tumor-free margins. Lymph node staging is an option advised if the tumor size is >2 cm or if lymph node metastases are suspected on imaging. On the other hand, the role of neoadjuvant therapy is still in doubt, but a good response to adjuvant chemotherapy treatments has been described in both advanced and recurrent diseases. Sometimes, VAIt behavior can be unpredictable, with relapses even after many years, so more experiences and longer follow-up periods are needed to elucidate the best therapeutic management and its long-term prognosis.

Liver Fibrosis Indices Predict the Severity of SARS-CoV-2 Infection.

Discovering novel risk and prognostic factors for COVID-19 may help not only in reducing severity and mortality but also in creating targeted therapies considering patients' individual features. Liver fibrosis is considered a complication in Non-alcoholic Fatty Liver Disease (NAFLD), it is a feature of steatohepatitis (NASH), and it has already been related to an increased risk for a wide range of diseases. Here, we aimed to define if any parameter assessing metabolic status has predictive power in identifying inpatients at risk for poorer prognosis and an increased mortality from COVID-19. This retrospective study was conducted at the Sub-Intensive Medicine Care Unit of the Presidio Maxi-Emergenze Fiera del Levante, Azienda Ospedaliero-Universitaria Policlinico di Bari, Italy. We evaluated 271 inpatients with moderate-to-severe SARS-CoV-2-related respiratory failure by comparing biochemical features and non-invasive liver fibrosis scores among discharged, transferred to Intensive Care Units (ICU) and non-survivor patients. Moreover, by performing ROC curves, we defined cut-off values to predict mortality and disease severity for each score. We found that non-invasive scores of liver fibrosis, obtained at day of admission, such as AAR (p < 0.001), FIB-4 and mFIB-4, FORNS, and AARPRI (p < 0.05) strongly predict not only in-hospital mortality but also the length of hospitalization and eventual admission to ICU. FIB-4 was the best score to identify non-survivor patients (sensitivity of 80% and specificity of 63%) and predict the need for ICU or mortality (71% of sensitivity and 65% of specificity), with a cut-off value of 1.94. Therefore, we present the predictive power and the cut-off values of several liver fibrosis scores here for disease severity and mortality in SARS-CoV-2 in-patients and we proposed the use of the present scores to identify ab initio the clinical therapeutic and diagnostic protocols for high-risk patients.

Evaluation of perioperative management of advanced ovarian (tubal/peritoneal) cancer patients: a survey from MITO-MaNGO Groups.

OBJECTIVE: The European Society of Gynaecological Oncology (ESGO)-quality indicators (QIs) for advanced ovarian cancer (AOC) have been assessed only by few Italian centers, and data are not available on the proportion of centers reaching the score considered for a satisfactory surgical management. There is great consensus that the Enhanced Recovery After Surgery (ERAS) approach is beneficial, but there is paucity of data concerning its application in AOC. This survey was aimed at gathering detailed information on perioperative management of AOC patients within MITO-MaNGO Groups. METHODS: A 66-item questionnaire, covering ESGO-QIs for AOC and ERAS items, was sent to MITO/MaNGO centers reporting to operate >20 AOC/year. RESULTS: Thirty/34 questionnaires were analyzed. The median ESGO-QIs score was 31.5, with 50% of centers resulting with a score ≥32 which provides satisfactory surgical management. The rates of concordance with ERAS guidelines were 46.6%, 74.1%, and 60.7%, respectively, for pre-operative, intra-operative, and post-operative items. The proportion of overall agreement was 61.3%, and with strong recommendations was 63.1%. Pre-operative diet, fasting/bowel preparation, correction of anaemia, post-operative feeding and early mobilization were the most controversial. A significant positive correlation was found between ESGO-QIs score and adherence to ERAS recommendations. CONCLUSION: This survey reveals a satisfactory surgical management in only half of the centers, and an at least sufficient adherence to ERAS recommendations. Higher the ESGO-QIs score stronger the adherence to ERAS recommendations, underlining the correlations between case volume, appropriate peri-operative management and quality of surgery. The present study is a first step to build a structured platform for harmonization within MITO-MaNGO networks.

Ultrasound Evaluation of Retrocervical and Parametrial Deep Endometriosis on the Basis of Surgical Anatomic Landmarks.

STUDY OBJECTIVES: To assess the value of combined transvaginal/transabdominal ultrasonographic evaluation performed by experienced examiners for deep infiltrating endometriosis (DIE) lesions of the retrocervical (torus uterinus and uterosacral ligaments) and parametrial areas and summarize the features and anatomic criteria for identification of these lesions and their extent in the above-mentioned pelvic compartments. DESIGN: Retrospective study. SETTING: A specialized endometriosis center in Avellino, Italy. PATIENTS: A retrospective cohort of patients who underwent laparoscopic surgery for clinically suspected DIE between January 1, 2014, and December 31, 2018, with a dedicated ultrasound (US) evaluation performed no more than 1 month before the intervention. INTERVENTIONS: Preoperative US findings and surgical reports were reviewed. Using the findings of laparoscopic surgery as the gold standard, the sensitivity and specificity of preoperative US evaluation for retrocervical and parametrial endometriotic lesions were calculated with the corresponding 95% confidence intervals. MEASUREMENTS AND MAIN RESULTS: A total of 4983 patients were included. US evaluation showed high diagnostic accuracy for DIE detection in the examined pelvic compartments, with sensitivity and specificity of 97% to 98% and 98% to 100%, respectively, for both retrocervical (torus uterinus and uterosacral ligaments insertion) and parametrial lesions. CONCLUSION: Parametrial extension of DIE indicates major surgical technical difficulties and risk of complications, and urologic and nerve-sparing procedures may be required in such cases. Preoperative evaluation of such scenarios will allow proper counseling of patients and facilitate adequate surgical planning in referral centers; moreover, when necessary, it can guide the constitution of a dedicated multidisciplinary surgical team as an alternative to treatment by a pelvic surgeon alone. Detailed imaging evaluation of DIE lesions and their extension is crucial for clinical management of affected patients. It can facilitate optimization of surgical timing and strategies, thereby potentially preventing ineffective, or even harmful, repeated procedures.

Development of a Nomogram Predicting the Risk of Persistence/Recurrence of Cervical Dysplasia.

Background: Cervical dysplasia persistence/recurrence has a great impact on women's health and quality of life. In this study, we investigated whether a prognostic nomogram may improve risk assessment after primary conization. Methods: This is a retrospective multi-institutional study based on charts of consecutive patients undergoing conization between 1 January 2010 and 31 December 2014. A nomogram assessing the importance of different variables was built. A cohort of patients treated between 1 January 2015 and 30 June 2016 was used to validate the nomogram. Results: A total of 2966 patients undergoing primary conization were analyzed. The median (range) patient age was 40 (18-89) years. At 5-year of follow-up, 6% of patients (175/2966) had developed a persistent/recurrent cervical dysplasia. Median (range) recurrence-free survival was 18 (5-52) months. Diagnosis of CIN3, presence of HR-HPV types, positive endocervical margins, HPV persistence, and the omission of HPV vaccination after conization increased significantly and independently of the risk of developing cervical dysplasia persistence/recurrence. A nomogram weighting the impact of all variables was built with a C-Index of 0.809. A dataset of 549 patients was used to validate the nomogram, with a C-index of 0.809. Conclusions: The present nomogram represents a useful tool for counseling women about their risk of persistence/recurrence after primary conization. HPV vaccination after conization is associated with a reduced risk of CIN2+.

Fertility-sparing treatment for serous borderline ovarian tumors with extra-ovarian invasive implants: Analysis from the MITO14 study database.

OBJECTIVE: Only 10-15% of serous borderline ovarian tumors (BOTs) with extra-ovarian disease have invasive implants, and conservative treatments have been rarely reported. The MITO14 is a multi-institutional retrospective study conducted with the aim of systematically collecting data from consecutive BOT patients. The present analysis reports the oncological and reproductive outcomes of women with serous BOT and invasive implants registered into the MITO14 database and conservatively treated between August 2002 and May 2019. METHODS: Thirteen patients (FIGO2014 stage II-III serous BOT with invasive implants) were recruited. Primary and secondary endpoints were, respectively, recurrence and death rates, and pregnancy and live birth rates. Only patients undergoing fertility-sparing surgery (FSS) were included, while patients were excluded in case of: age > 45 years; second tumor(s) requiring therapy interfering with the treatment of BOT. RESULTS: Median follow-up time from primary cytoreduction was 146 months (range 27-213 months). Eleven patients (84.6%) experienced at least one recurrence (median time to first relapse 17 months, range 4-190 months), all of these undergoing secondary surgery (FSS in 7). Five patients attempted to conceive: 3 achieved at least one pregnancy and 2 gave birth at least to a healthy child. At the end of the observation period, all patients were alive with no evidence of disease. CONCLUSIONS: Fertility-sparing treatment should be considered in a context of serous BOT with invasive implants. Despite the high rate of recurrence, FSS provides good chances of reproductive success without a negative impact on overall survival.

Acute Tolerability of Methylphenidate in Treatment-Naïve Children with ADHD: An Analysis of Naturalistically Collected Data from Clinical Practice.

OBJECTIVES: The acute tolerability of methylphenidate (MPH) in children with attention-deficit/hyperactivity disorder (ADHD) has been studied mainly in research samples. Taking advantage of the mandatory test-dose procedure required for starting MPH in Italy, this study aimed to assess the incidence of intolerable adverse events after initial exposure to MPH in routine clinical practice. METHODS: The medical records of 480 consecutively treated, previously drug-naïve children and adolescents with ADHD (90% male, mean age 10.6 ± 3.0 years) were retrospectively analyzed. All children received an initial single dose of MPH immediate release (5 or 10 mg) followed by a 4-hour direct medical observation. Heart rate and blood pressure were measured at dosing and 1, 2, and 3 hours afterwards. If the first dose was well tolerated, the child continued treatment with MPH 5-20 mg daily, and was reassessed a week later. RESULTS: Eleven patients (2.3%, 95% CI 1.1-4.1) interrupted treatment within a week of initiation because of the following adverse events: irritability (n = 3), tics worsening (n = 3), reduced appetite (n = 1), enuresis (n = 1), hallucinations (n = 1), hyperfocus (n = 1), and 'rebound' behavioral worsening (n = 1). The most common adverse events were reduced appetite (20%), irritability (14.2%), headache (10.6%), sleep problems (9.4%), stomachache (9.4%), and tics (5%). Intellectual disability increased the risk of any adverse event in general and of irritability in particular. No cardiovascular symptom was clinically reported. However, routine assessments of vital signs during the first 3 hours after the first dose of MPH showed that 9% of the children had a 20% increase in heart rate, 8.8% had a 20% increase in diastolic blood pressure and 4.5% had a 20% increase in systolic blood pressure. Of these, 25.2% still had an elevated heart rate 1 week later. CONCLUSIONS: Among stimulant-naïve children in clinical practice, the incidence of acute MPH intolerance can be estimated to be between 1.2 and 4.1%. An asymptomatic elevation in cardiovascular parameters can be observed in about 1 out of 10 children and warrants monitoring during ongoing treatment.

Totally Laparoscopic Resection with Transanal Natural Orifice Specimen Extraction for Deep Endometriosis Infiltrating the Rectum.

OBJECTIVE: To show the surgical steps used to perform a totally laparoscopic segmental rectal resection, with intracorporeal anastomosis and transanal natural orifice specimen extraction (NOSE), in a context of deep endometriosis. DESIGN: Step-by-step video demonstration of the technique. SETTING: Even though the combined use of intracorporeal anastomosis and NOSE has increasingly been investigated during the last decade, there is still lack of defined consensus, both in terms of patient eligibility and operative technique. In particular, experience with intracorporeal anastomosis and NOSE for treatment of deep rectal endometriosis is very limited. Preliminary reports have documented that a totally laparoscopic rectal resection is equally effective and safe compared with the conventional approach using an abdominal minilaparotomy for extracorporeal anastomosis and specimen retrieval. In comparison to the latter, intracorporeal anastomosis with NOSE seems to offer advantages in terms of less postoperative pain, fewer wound-related complications, better cosmetic results, quicker return of bowel function and shorter hospital stay. PATIENT: A 31-year-old woman with a history of constipation, dyschezia, dysmenorrhea, dyspareunia, and chronic pelvic pain unresponsive to hormonal therapies. Preoperative ultrasonography showed partial obliteration of the Douglas' pouch due to a rectal endometriotic nodule of 42 × 12 × 18 mm in contiguity with a deeply infiltrating retrocervical lesion of 13 × 3 × 17 mm. The rectal nodule resulted in the infiltration of the tunica muscularis with a distance of 12 cm from the anal verge and a circumferential extent of 45%. INTERVENTIONS: A 3-dimensional laparoscopic system was used. Rectal mobilization was performed according to our standardized technique [1]. After determining the proximal and distal resection margins, the rectum was transected using a tissue sealing-device. The resected specimen was placed in a retrieval bag and pulled out through the anus. Proximal and distal resection lines were closed using a 60 mm linear endo-stapler, and a totally intracorporeal, side-to-end anastomosis was performed using a 29 mm circular stapler. MAIN RESULTS: The overall operative time was 85 minutes. The estimated blood loss was 10 mL. Neither intra- nor postoperative complications occurred. The patient was discharged 5 days after surgery. The bowel endometriotic nodule measured 41 × 12 × 18 mm on the fresh unfixed specimen. CONCLUSIONS: Advanced surgical skills are needed to perform an effective and safe, totally laparoscopic rectal resection. The operative technique displayed in this video may contribute to the standardization of such surgical procedure. Accurate patient selection, including adequate preoperative evaluation, is of utmost importance for the best chance of surgical success.

Indocyanine green fluorescence angiography after full-thickness bowel resection for rectosigmoid endometriosis: A multicentric experience with quantitative analysis.

OBJECTIVE: To evaluate effectiveness and reproducibility of qualitative and quantitative near-infrared indocyanine green (NIR-ICG) analyses as a tool for anastomotic perfusion assessment after full-thickness bowel resection for rectosigmoid endometriosis (RSE). METHODS: Symptomatic women with RSE undergoing minimally invasive full-thickness surgical excision of RSE and NIR-ICG evaluation from November 2019 to July 2020 were included. Study outcomes were the accuracy of qualitative and quantitative NIR-ICG analyses in predicting bowel fistula and their reproducibility. NIR-ICG predictive accuracy was assessed by calculating sensitivity, specificity, and area under the curve on receiver operating characteristic curves with 95% confidence intervals (CI). NIR-ICG reproducibility was assessed through Cohen's k coefficient to determine interoperator agreement between two observers. RESULTS: Of 33 patients, 2 (6%) developed bowel fistula. In predicting bowel fistula, qualitative and quantitative NIR-ICG evaluations showed sensitivity of 100% and 100%, specificity of 71% and 93%, and area under the curve of 0.86 (95% CI 0.67-1.00) and 0.96 (95% CI 0-1.00), respectively. Regarding interoperator agreement rate, it was reported as excellent for the qualitative analysis and very good for the quantitative analysis. CONCLUSION: Qualitative and quantitative NIR-ICG evaluations might be effective and reproducible tools for anastomotic perfusion assessment after discoid or segmental resection for RSE. Quantitative evaluation might be even more effective than qualitative evaluation in predicting bowel fistula.

Fertility-sparing treatment in advanced-stage serous borderline ovarian tumors. An analysis from the MITO14 study database.

OBJECTIVES: To evaluate oncological and reproductive outcomes of women undergoing fertility-sparing surgery (FSS) for stage II-III serous borderline ovarian tumors (BOTs). METHODS: A multi-institutional retrospective study was conducted within the MITO Group. RESULTS: A total of 91 patients were recruited. The median follow-up time from primary cytoreduction was 127 months (IQR range 91-179). Forty-nine patients (53.8%) experienced at least one recurrence (median time to first relapse 22 months, IQR range 9.5-57). At univariable analysis, significant predictors of relapse were: size of largest extra-ovarian lesion, peritoneal cancer index, completeness of cytoreduction, type of implants. After multivariable analysis, the size of extra-ovarian lesions and the presence of invasive implants resulted as the only independent predictors of recurrence. Median disease-free survival (DFS) was 96 months (95% CI, 24.6-167.3), while median disease-specific survival (DSS) was not reached. Twenty-nine patients (31.8%) attempted to conceive: 20 (68.9%) achieved at least one pregnancy and 18 (62%) gave birth to a healthy child. At the end of the observation period, 88 patients (96.7%) showed no evidence of disease, 2 (2.2%) were alive with disease, and 1 patient (1.1%) died from BOT. CONCLUSIONS: Despite the recurrence high rate, FSS provides good chances of reproductive success with no impact on DSS. The presence of invasive peritoneal implants affects the DFS but not DSS nor reproductive outcome. The risk of recurrence would not seem to be related to the ovarian preservation per se, but to the natural history of the initial peritoneal spread.