Implementation and outcomes in benign gynecological surgery with HUGO™ RAS system 12 months initial experience.

We share our experience with the Hugo™ Robotic-Assisted Surgery system in benign gynecological surgeries. We retrospectively analyzed patients who underwent elective robotic surgeries for benign gynecological conditions at our surgical center from February 2023 to February 2024. Data collected included patient demographics, surgery indications, and outcomes. Perioperative data on port-placement time, arm configurations, docking, and console time were documented. Procedural outcome data including troubleshooting and overall satisfaction were also recorded. The primary outcome was perioperative data on port placement, docking time, arm configuration, and console time. The secondary outcome was defined as team satisfaction, system troubleshooting, arm repositioning, and complications graded 3-4 on the Clavien-Dindo Scale. A total of 60 patients underwent procedures for benign gynecological conditions using the Hugo™ RAS over the 12-month study period, primarily for pelvic endometriosis (53%), hysterectomies (27%), and adnexal surgery (10%). The mean port-placement time was 13 min and 41 s. In 31% of cases, low-port placement was used, with arm positioning being asymmetrical in 63% and symmetrical in 37%, demonstrating the system's flexibility in customizing port configurations while optimizing cosmetic outcomes. Docking time averaged 5 min and 51 s, and console time was 1 h and 5 min. Operational challenges included arm tremors and limited workspace for the assistant. This study details our knowledge using the Hugo™ RAS. Learning curves of port placement, arm positioning, docking, and procedure time can be rapidly adapted in a well-trained team. Our experience suggests the technology is still in its learning curve period.

Nerve-sparing surgery in deep endometriosis: Has its time come?

Nerve-sparing (NS) surgery was first introduced for the treatment of deep endometriosis (DE) 20 years ago, drawing on established neuroanatomy and success from oncological applications. It aims to identify and preserve autonomic nerve fibres, reduce iatrogenic nerve injury, and minimize postoperative visceral dysfunction, without compromising the therapeutic effectiveness against endometriosis. The evolution of NS surgical techniques over the past two decades has been supported by an expanding body of literature on anatomical details, dissection techniques, and functional outcomes. Recent evidence suggests that NS surgery results in reduced postoperative voiding dysfunction (POVD). Transient POVD may be influenced by preoperative dysfunction, with parametrial infiltration being a strong predictive factor for POVD. While the benefits in bowel and sexual functions are less pronounced and consistent, NS surgery potentially prevents de novo dysfunctions in these areas. Furthermore, perioperative complication rates, effectiveness in pain relief, and fertility outcomes are reportedly on par with conventional surgery.

Tailoring radicality in diaphragmatic surgery for deep endometriosis: A matter of choice.

Diaphragmatic endometriosis (DpE) is a rare disease localization which represents an important clinical challenge. The main criticisms toward the proper DpE management consist of poor consensus on both surgical indications and the choice between different surgical techniques available to treat the disease. Furthermore, only weak recommendations are provided by current guidelines and surgical management is mostly based on surgeon's experience. As consequence, the lack of standardization about the surgical treatment led to the risk of under- or over-treatments in patients suffering from this form of endometriosis. The latest evidence-based data suggest to adopt a lesion-oriented surgical approach serving as a guide in daily surgical activities, in order to ensure a tailored radicality and reduce the rate of surgery-related complications. Diaphragmatic endometriosis surgery should be performed only by expert surgeons with an extensive oncogynecologic expertise since it represents a technically demanding procedure. A multidisciplinary approach is also mandatory in order to adequately select and treat these patients by minimizing the risk of additional morbidity.

Feasibility study comparing synthesized mammography with digital breast tomosynthesis and digital mammography for simulated first round screening in a single BreastScreen NSW centre.

INTRODUCTION: While digital breast tomosynthesis (DBT) has proven to enhance cancer detection and reduce recall rates (RR), its integration into BreastScreen Australia for screening has been limited, in part due to perceived cost implications. This study aims to assess the cost effectiveness of digital mammography (DM) compared with synthesized mammography and DBT (SM + DBT) in a first round screening context for short-term outcomes. METHODS: Clients recalled for nonspecific density (NSD) as a single lesion by both readers at the Northern Sydney Central Coast BreastScreen service in 2019 were included. Prior images were excluded to simulate first-round screening. Eleven radiologists read DM and synthesized mammography with DBT (SM + DBT) images 4 weeks apart. Recall rates (RR), reading time, and diagnostic parameters were measured, and costs for screen reading and assessment were calculated. RESULT: Among 65 clients studied, 13 were diagnosed with cancer, with concordant cancer recalls. SM + DBT reduced recall rates (RR), increased reading time, maintained cancer detection sensitivity, and significantly improved other diagnostic parameters, particularly false positive rates. Benign biopsy recalls remained equivalent. While SM + DBT screen reading cost was significantly higher than DM (DM AU$890 ± 186 vs SM + DBT AU$1279 ± 265; P < 0.001), the assessment cost (DM AU$29,504 ± 9427 vs SM + DBT AU$18,021 ± 5606; P < 0.001), and combined screen reading and assessment costs were significantly lower (DM AU$30,394 ± 9508 vs SM + DBT AU$19,300 ± 5721; P = 0.001). SM + DBT screen reading and assessment of 65 patients resulted in noteworthy cost savings (AU$11,094), equivalent to assessing 12 additional clients. CONCLUSION: In first round screening, DBT yields significant cost savings by effectively reducing unnecessary recalls to assessment while maintaining diagnostic efficacy.

Treatment of rectosigmoid endometriosis by laparoscopic reverse submucosal dissection (LRSD): The Sydney partial thickness discoid excision technique.

BACKGROUND: Laparoscopic reverse submucosal dissection (LRSD) is a standardised surgical technique for removal of rectosigmoid endometriosis which optimises the anatomical dissection plane for excision of endometriotic nodules. AIM: This cohort study assesses the outcomes of the first cohort of women treated by LRSD, for deeply infiltrating rectosigmoid endometriosis. MATERIALS AND METHODS: Primary outcomes assessed were complication rate as defined by the Clavien-Dindo system, and completion of the planned LRSD. Secondary outcomes include mucosal breach, specimen margin involvement, length of hospital admission, and a comparison of pre-operative and post-operative pain, bowel function and quality of life surveys. These included the Endometriosis Health Profile Questionnaire (EHP-30), the Knowles-Eccersley-Scott Symptom Questionnaire (KESS) and the Wexner scale. RESULTS: Of 19 patients treated, one required a segmental resection. The median length of hospital admission was two days (range 1-5) and no post-operative complications occurred. Median pain visual analogue scales (scale 0-10) were higher prior to surgery (dysmenorrhoea 9.0, dyspareunia 7.5, dyschezia 9.0, pelvic pain 6.0) compared to post-surgical median scores (dysmenorrhoea 5.0, dyspareunia 4.0, dyschezia 2.0, pelvic pain 4.0) at a median of six months (range 4-32). Quality of life studies suggested improvement following surgery with pre-operative median EHP-30 and KESS scores (EHP-30: 85 (5-106), KESS score 9 (0-20)) higher than post-operative scores (EHP-30: 48.5 (0-80), KESS score: 3 (0-19)). CONCLUSION: This series highlights the feasibility of LRSD with low associated morbidity as a progression of partial thickness discoid excision (rectal shaving) for the treatment of rectosigmoid deep infiltrating endometriosis.

Personalized medicine in a community health system: the NorthShore experience.

Genomic and personalized medicine implementation efforts have largely centered on specialty care in tertiary health systems. There are few examples of fully integrated care systems that span the healthcare continuum. In 2014, NorthShore University HealthSystem launched the Center for Personalized Medicine to catalyze the delivery of personalized medicine. Successful implementation required the development of a scalable family history collection tool, the Genetic and Wellness Assessment (GWA) and Breast Health Assessment (BHA) tools; integrated pharmacogenomics programming; educational programming; electronic medical record integration; and robust clinical decision support tools. To date, more than 225,000 patients have been screened for increased hereditary conditions, such as cancer risk, through these tools in primary care. More than 35,000 patients completed clinical genetic testing following GWA or BHA completion. An innovative program trained more than 100 primary care providers in genomic medicine, activated with clinical decision support and access to patient genetic counseling services and digital healthcare tools. The development of a novel bioinformatics platform (FLYPE) enabled the incorporation of genomics data into electronic medical records. To date, over 4,000 patients have been identified to have a pathogenic or likely pathogenic variant in a gene with medical management implications. Over 33,000 patients have clinical pharmacogenomics data incorporated into the electronic health record supported by clinical decision support tools. This manuscript describes the evolution, strategy, and successful multispecialty partnerships aligned with health system leadership that enabled the implementation of a comprehensive personalized medicine program with measurable patient outcomes through a genomics-enabled learning health system model that utilizes implementation science frameworks.

Clinical and imaging modality factors impacting radiological interpretation of breast screening in young women with neurofibromatosis type 1.

Young women with Neurofibromatosis type 1 (NF1) have a high risk of developing breast cancer and poorer survival following breast cancer diagnosis. International guidelines recommend commencing breast screening between 30 and 35 years; however, the optimal screening modality is unestablished, and previous reports suggest that breast imaging may be complicated by the presence of intramammary and cutaneous neurofibromas (cNFs). The aim of this study was to explore potential barriers to implementation of breast screening for young women with NF1.Twenty-seven women (30-47 years) with NF1 completed breast screening with breast MRI, mammogram and breast ultrasound. Nineteen probably benign/suspicious lesions were detected across 14 women. Despite the presence of breast cNFs, initial biopsy rate for participants with NF1 (37%), were comparable to a BRCA pathogenic variant (PV) cohort (25%) (P = 0.311). No cancers or intramammary neurofibromas were identified. Most participants (89%) returned for second round screening.The presence of cNF did not affect clinician confidence in 3D mammogram interpretation, although increasing breast density, frequently seen in young women, impeded confidence for 2D and 3D mammogram. Moderate or marked background parenchymal enhancement on MRI was higher in the NF1 cohort (70.4%) than BRCA PV carriers (47.3%), which is an independent risk factor for breast cancer.Breast MRI was the preferred mode of screening over mammogram, as the majority (85%) with NF1 demonstrated breast density (BI-RADS 3C/4D), which hinders mammogram interpretation. For those with high breast density and high cNF breast coverage, 3D rather than 2D mammogram is preferred, if MRI is unavailable.

An Unusual Case Study of Idiopathic Bilateral Deep Vein Thrombosis and Osteonecrosis of the Left Distal Tibia in an 11-year-old Girl.

Introduction: Deep vein thrombosis (DVTs) in children is rare, normally linked to pathologies such as major traumatic injury, thrombophilia, and malignancy. Osteonecrosis is still poorly understood. There is growing support to include hypercoagulable states as a predisposing factor, however, no definitive correlation has been found. At present, there are no conclusive literature on the links between osteonecrosis and DVT. Case Presentation: This report describes an unusual and rare case of osteonecrosis and idiopathic DVT in an 11-year-old girl who initially presented with a sprained left ankle. On follow-up, pain was persistent and subsequent radiological investigations revealed extensive DVT, and magnetic resonance imaging scan revealed osteonecrosis of the distal left tibia. Initial blood tests were normal, however with follow-up with hematology, a diagnosis of antithrombin deficiency was made, with the treatment of lifelong anticoagulation. Our patient had continued orthopedic input for clinical and radiographic surveillance to monitor leg length discrepancy. Conclusion: This case highlights the need to engage in close follow-up and the cautionary care required when young children present with non-resolving severe pain, to consider osteonecrosis and DVT. Our case also highlights the need for further research into the relationship between minor injuries and DVTs and osteonecrosis in children, and the potential synergistic relationship between DVTs and osteonecrosis.

Preclinical Characterization and Phase I Study of an Anti-HER2-TLR7 Immune-Stimulator Antibody Conjugate in Patients with HER2+ Malignancies.

Immune-stimulator antibody conjugates (ISAC) combining tumor-targeting monoclonal antibodies with immunostimulatory agents allow targeted delivery of immune activators into tumors. NJH395 is a novel, first-in-class ISAC comprising a Toll-like receptor 7 (TLR7) agonist conjugated to an anti-HER2 antibody via a noncleavable linker payload. Preclinical characterization showed ISAC-mediated activation of myeloid cells in the presence of antigen-expressing cancer cells, with antigen targeting and TLR7 agonism contributing to antitumor activity. Safety, efficacy, immunogenicity, pharmacokinetics, and pharmacodynamics were investigated in a phase I, multicenter, open-label study in patients with HER2+ non-breast advanced malignancies (NCT03696771). Data from 18 patients enrolled in single ascending dose escalation demonstrated delivery of the TLR7-agonist payload in HER2+ tumor cells and induction of type I IFN responses, which correlated with immune modulation in the tumor microenvironment. Cytokine release syndrome was a common, but manageable, drug-related adverse event. Antidrug antibodies and neuroinflammation at high doses represented significant clinical challenges. Data provide proof-of-mechanism and critical insights for novel immunotherapies.

Superior Hypogastric Plexus Nerve Block in Minimally Invasive Gynecology: A Randomized Controlled Trial.

STUDY OBJECTIVE: To assess the efficacy of a superior hypogastric plexus nerve block in reducing opioid requirements in the first 24 hours after minimally invasive gynecologic surgery. DESIGN: Patient-blinded randomized controlled trial. SETTING: Single-center academic institution (Sydney Women's Endosurgery Centre). Two surgeons administering the blocks in their own surgeries. PATIENTS: Patients undergoing either laparoscopic or robot-assisted laparoscopic hysterectomy or myomectomy for benign indications. INTERVENTIONS: Ropivacaine 10 mL (0.75%) infiltrated into the retroperitoneal space overlying the superior hypogastric plexus vs control of no block given at the completion of surgery. MEASUREMENTS AND MAIN RESULTS: The primary outcome was the total opioid use in the first 24 hours after surgery, measured in morphine milligram equivalents (MME). Standardized fentanyl patient-controlled analgesia was given to all patients in the trial. The secondary outcome was pain measured on a visual analog scale (1 to 10) at 1, 2, 6, 12, and 24 hours after surgery. Fifty patients out of 56 approached for the study participated in, and completed, the study (89.2%). The patients were randomized over a 5-month period, March 2020 to July 2020. A total of 27 patients were randomized to receive a nerve block, and 23 were randomized to the control. There was a difference of -21.8 MME in the block group compared with the no-block group (95% confidence interval [CI], -38.2 to -5.5; p = .008). This correlated to a 38% reduction in opioid use in the block group. The mean opioid use in the patients in the block group was 33.1 MME (95% CI, 24.2-41.9) and in those in the no-block group 54.9 MME (95% CI, 40.7-69.1). For the block group, opioid use ranged from 1.0 to 76.5 MME, with an interquartile range of 37 (14-51). For the control group, the range was 7.5 to 113.5 MME, with a higher interquartile range of 60 (28-88). Pairwise comparisons of the mean pain scores over the 24 hours showed a lower pain score with a nerve block of 1.8 (95% CI, 1.5-2.1) compared with a no-block score of 2.6 (95% CI, 2.3-2.9) No adverse effects of local anesthetic toxicity, nerve injury, or bowel/vascular injury were noted in any patient. CONCLUSION: A superior hypogastric plexus nerve block is a simple technique for reducing postoperative opioid requirements and pain in the first 24 hours after minimally invasive gynecologic surgery.

Rectal Shaving for Bowel Endometriosis by Laparoscopic Reverse Submucosal Dissection for Easier, Safer and More Complete Excision of Disease.

STUDY OBJECTIVE: To demonstratefull-thickness excision of the affected muscularis along the submucosal plane. DESIGN: Stepwise demonstration of LRSD technique with narrated video footage. SETTING: LRSD takes advantage of the submucosal layer of the bowel wall and uses it as an easier line of excision for rectal endometriosis compared with the very difficult traditional line of excision of irregular disease-muscularis interface. The expansion of the submucosal layer by the injection separates the affected muscularis away from the mucosa, making it safer to excise the lesion with less chance of entering the bowel lumen. Excision of disease is more complete with LRSD because the full-thickness excision of the muscularis layer includes the healthy deep muscularis, which will form the disease-free deep excision margin. INTERVENTION: This video will highlight anatomic and technical aspects of LRSD including the following key steps: 1. Mobilization of diseased bowel segment 2. Submucosal injection 3. Circumferential incision of the muscularis 4. Submucosal dissection along the submucosal plane 5. Bowel wall integrity test 6. Muscularis defect repair CONCLUSION: Rectal shaving by LRSD appears to be easier, safer, and more complete in excision of bowel endometriosis than the classical rectal shaving technique. This modification requires further evaluation to confirm its potential in the surgical management of rectosigmoid deep infiltrative endometriosis.

Cytokine profiles and Lactobacillus species presence in pre-menopausal subjects with genital Mycoplasma genitalium or Ureaplasma urealyticum colonization.

BACKGROUND AND PURPOSE: Lactobacilli play a vital role in protecting the vagina against pathogens. Cytokines are vital components of defense against infections in women. The genital mycoplasmas, Mycoplasma genitalium and Ureaplasma urealyticum, are associated with various infectious diseases in adults and infants. The objective of our study is to identify differences in cytokine profile and Lactobacillus species dominance between a study group of non-pregnant pre-menopausal women with genital M. genitalium or U. urealyticum colonization and a control group of non-pregnant pre-menopausal women without genital M. genitalium or U. urealyticum colonization. METHODS: A real-time polymerase chain reaction was performed to measure Lactobacillus species in vaginal swab samples. Cytokine analysis was performed using multiplex immunoassay techniques. Analysis of variance confirmed a significant difference in cytokine profiles between patient groups, with t-tests identifying the most significantly different cytokines. Categorical data analysis identified significant patterns of relative Lactobacillus species dominance in the study group. RESULTS: Lactobacillus iners was the predominant Lactobacillus species in the control group (p = 0.005). There were no dominant Lactobacillus species observed in the study group. Vascular endothelial growth factor A (p = 0.002), interleukin-8 (p = 0.001), and interleukin-1ß (p = 0.049) were expressed significantly higher in the study group, whereas interleukin-1 receptor antagonist (p < 0.001), interleukin-10 (p = 0.001), interleukin-12 (p = 0.002), and interferon-γ (p = 0.022) were expressed higher in the control group. Association matrices for cytokines were significantly different between two groups (p < 0.001), with mostly negative associations in the control group and mostly positive associations in the study group. CONCLUSION: Cytokine levels, their associations, and the patterns of Lactobacillus species dominance are observed to significantly diverge on the basis of M. genitalium and U. urealyticum colonization among non-pregnant pre-menopausal women.

Diagnostic Considerations in the Evaluation of Large B-Cells on Lymph Node Cytology Specimens.

Fine needle aspiration (FNA) has become increasingly popular in the evaluation of lymph nodes for lymphoproliferative disorders, but there are limitations to accurate subclassification of lymphoma using morphology alone. This case aims to expand diagnostic considerations of large B-cell populations identified on FNA material. We also address the significance of Epstein-Barr virus (EBV) DNA in the workup of patients with suspected lymphoma by FNA.

Endoscopic Equipment-From Simple to Advanced.

Flexible endoscopic procedures, such as esophagogastroduodenoscopies and colonoscopies, allow for diagnosis and treatment of numerous gastrointestinal disorders. Advanced endoscopic procedures, such as endoscopic ultrasounds, endoscopic retrograde cholangiopancreatography, and balloon enteroscopies, offer therapeutic options that are minimally invasive and effective. As technology advances, the equipment and tools in an endoscopist's armamentarium continue to grow. This article highlights key endoscopic equipment and supplies, from simple to advanced.

The diagnostic challenges and clinical course of a myeloid/lymphoid neoplasm with eosinophilia and ZBTB20-JAK2 gene fusion presenting as B-lymphoblastic leukemia.

We report the diagnostic challenges and the clinical course of a patient with an extraordinary presentation of B-lymphoblastic leukemia (B-ALL) with eosinophilia. We identified a novel ZBTB20-JAK2 gene fusion as a chimeric RNA transcript using the Archer platform. This gene fusion from the same patient was recently identified by Peterson et al. (2019) at the genomic level using a different sequencing technology platform. The configuration of this gene fusion predicts the production of a kinase-activating JAK2 fusion protein, which would normally lead to a diagnosis of Philadelphia chromosome-like B-ALL (Ph-like B-ALL). However, the unusual presentation of eosinophilia led us to demonstrate the presence of this gene fusion in nonlymphoid hematopoietic cells by fluorescence in situ hybridization (FISH) studies with morphologic correlation. Therefore, we believe this disease, in fact, represents blast crisis arising from an underlying myeloid neoplasm with JAK2 rearrangements. This case illustrates the difficulty in differentiating Ph-like B-ALL and myeloid/lymphoid neoplasm with eosinophilia and gene rearrangements (MLN-EGR) in blast crisis. As currently defined, the diagnosis of MLN-EGR relies on the hematologic presentations and the identification of marker gene fusions (including PCM1-JAK2, ETV6-JAK2, and BCR-JAK2). However, these same gene fusions, when limited to B-lymphoblasts, also define Ph-like B-ALL. Yet, our case does not conform to either condition. Therefore, the assessment for lineage restriction of gene rearrangements to reflect the pathophysiologic difference between B-ALL and MLN-EGR in blast crisis is likely a more robust diagnostic approach and allows the inclusion of MLN-EGR with novel gene fusions.

Transvaginal Ultrasound Can Accurately Predict the American Society of Reproductive Medicine Stage of Endometriosis Assigned at Laparoscopy.

STUDY OBJECTIVE: To evaluate the diagnostic accuracy of transvaginal ultrasound in predicting a laparoscopic, surgically assigned, revised American Society of Reproductive Medicine (ASRM) endometriosis stage. DESIGN: A multicenter, retrospective, diagnostic accuracy study. SETTING: The patients visited 1 of 2 academic gynecologic ultrasound units and underwent laparoscopy led by 1 of 6 surgeons in metropolitan Sydney, Australia, between 2016 and 2018. PATIENTS: Patients with suspected endometriosis (n = 204). INTERVENTIONS: Ultrasound followed by laparoscopy. MEASUREMENTS AND MAIN RESULTS: Surgical cases were identified. The preoperative ultrasound report and surgical operative notes were each used to retrospectively assign an ASRM score and stage. The breakdown of surgical findings was as follows: ASRM 0 (i.e., no endometriosis), 24/204 (11.8%); ASRM 1, 110/204 (53.9%); ASRM 2, 22/204 (10.8%); ASRM 3, 16/204 (7.8%); ASRM 4, 32 204 (15.7%). The overall accuracy of ultrasound in predicting the surgical ASRM stage was as follows: ASRM 1, 53.4%; ASRM 2, 93.8%; ASRM 3, 89.7%; ASRM 4, 93.1%; grouped ASRM 0, 1, and 2, 94.6%; and grouped ASRM 3 and 4 of 94.6%. Ultrasound had better test performance in higher disease stages. When the ASRM stages were dichotomized, ultrasound had sensitivity and specificity of 94.9% and 93.8%, respectively, for ASRM 0, 1, and 2 and of 93.8% and 94.9%, respectively, for ASRM 3 and 4. CONCLUSION: Ultrasound has high accuracy in predicting the mild, moderate, and severe ASRM stages of endometriosis and can accurately differentiate between stages when ASRM stages are dichotomized (nil/minimal/mild vs moderate/severe). This can have major positive implications on patient triaging at centers of excellence in minimally invasive gynecology for advanced-stage endometriosis.

Shaving for Bowel Endometriosis.

STUDY OBJECTIVE: To demonstrate laparoscopic shaving of deeply infiltrative endometriosis affecting the rectosigmoid colon, with particular emphasis on the anatomic and technical aspects of the procedure. DESIGN: Stepwise demonstration of the technique with narrated video footage. SETTING: Intestinal involvement in deep endometriosis is estimated to occur in 8% to 12% of patients, with 90% of occurrences being located in the colorectal segment. Deep endometriosis of the rectosigmoid is defined as endometriosis involving the muscular layer of the bowel wall, usually >5 mm deep, thus excluding superficial lesions that only affect the serosal layer. In cases in which medical therapy is unsatisfactory, rectosigmoid deep endometriosis can be surgically managed by 3 recognized surgical techniques: (1) rectal shaving, (2) disc excision, and (3) segmental resection. There are helpful recommendations for different approaches on the basis of the characteristics of the lesion, including the size, length, depth of invasion, involved rectal circumference, and number of lesions, among other factors [1]. Rectal shaving is well suited for smaller lesions, typically <3 cm, and involves "shaving" the lesion in the affected muscular layer of the bowel wall off the mucosa, ideally without entering the bowel lumen. It is associated with lower rates of perioperative complications and lower probability of long-term postoperative bladder and bowel dysfunctions [2]. INTERVENTIONS: This video demonstrates and highlights the anatomic and technical aspects of the following important steps of the rectal shaving procedure: (1) suspension of ovaries; (2) mobilization of the diseased segment of the rectum; (3) shaving of the lesions, with pertinent comments at different stages of nodule excision; (4) checking for the integrity of the bowel wall; and (5) suture of the muscularis defect after excision of the lesions from the muscularis layer of the bowel. CONCLUSION: Compared with other alternatives, shaving for bowel endometriosis is a more conservative procedure with lower rates of perioperative complications, and it is less likely to result in long-term bladder and bowel dysfunctions. Therefore, shaving is preferable and recommended for appropriate lesions.

Menin inhibitor MI-3454 induces remission in MLL1-rearranged and NPM1-mutated models of leukemia.

The protein-protein interaction between menin and mixed lineage leukemia 1 (MLL1) plays a critical role in acute leukemias with translocations of the MLL1 gene or with mutations in the nucleophosmin 1 (NPM1) gene. As a step toward clinical translation of menin-MLL1 inhibitors, we report development of MI-3454, a highly potent and orally bioavailable inhibitor of the menin-MLL1 interaction. MI-3454 profoundly inhibited proliferation and induced differentiation in acute leukemia cells and primary patient samples with MLL1 translocations or NPM1 mutations. When applied as a single agent, MI-3454 induced complete remission or regression of leukemia in mouse models of MLL1-rearranged or NPM1-mutated leukemia, including patient-derived xenograft models, through downregulation of key genes involved in leukemogenesis. We also identified MEIS1 as a potential pharmacodynamic biomarker of treatment response with MI-3454 in leukemia, and demonstrated that this compound is well tolerated and did not impair normal hematopoiesis in mice. Overall, this study demonstrates, for the first time to our knowledge, profound activity of the menin-MLL1 inhibitor as a single agent in clinically relevant PDX models of leukemia. These data provide a strong rationale for clinical translation of MI-3454 or its analogs for leukemia patients with MLL1 rearrangements or NPM1 mutations.