Magee-Womens Hospital

INTRODUCTION: A uterine isthmocele is a pouch-like defect at a prior cesarean scar, also called a niche or cesarean scar defect. Estimates of the incidence of an isthmocele range from 20% to 80% among those with a prior cesarean delivery, with approximately 1/3 of patients becoming asymptomatic. An isthmocele may cause abnormal uterine bleeding, pelvic pain or dysmenorrhea, or secondary infertility. In pregnancy, an isthmocele may lead to cesarean-scar ectopic pregnancy, abnormal placentation, or uterine rupture. OBJECTIVE: In this video, we present a clinical case of a large, symptomatic uterine isthmocele. We demonstrate surgical techniques to facilitate laparoscopic hysterectomy in the setting of a complex isthmocele. METHODS: Our submission is a surgical video. RESULTS: Our patient is a 48-year-old G2P2 who initially presented to the emergency department with acute-onset left lower quadrant pain, nausea, and vomiting. Her past history was notable for two prior cesarean deliveries, tubal ligation, and an endometrial ablation. She initially went to the OR with general OB/GYN urgently due to concern for possible ovarian torsion. In the OR, she was noted to have normal-appearing bilateral ovaries and a bulge extending from the uterus into the left broad ligament. The patient was ultimately referred to minimally invasive gynecologic surgery and underwent a scheduled total laparoscopic hysterectomy, bilateral salpingectomy, cystoscopy with insertion and removal of ureteral stents. During the operation, the retroperitoneum was entered, a ureterolysis was performed, and the uterine artery was ligated at its origin. Ultimately, the case was successfully completed with minimal blood loss, and the patient was discharged home on the day of surgery. CONCLUSIONS: In conclusion, uterine isthmocele is a common yet under-recognized clinical entity. While often asymptomatic, they may present acutely with pain, abnormal uterine bleeding, or complicate future pregnancy. Here, we present a case of a patient with acute-onset pelvic pain and large uterine isthmocele, who ultimately underwent hysterectomy with a minimally invasive approach. For patients with complex uterine isthmoceles, knowledge of retroperitoneal anatomy and use of avascular surgical spaces is critical to the success of the operation. Surgeons should consider cytoscopic stent placement to aid in ureterolysis as well as ligation of the uterine artery at its origin to reduce blood loss.

While primary invasive lobular carcinoma (ILC) is well characterized, metastatic ILC remains understudied. Within the post-mortem tissue donation programs, UPTIDER (Belgium) and Hope for Others (USA), we first aimed to explore intra-patient heterogeneity of key prognostic and predictive markers (stromal tumor-infiltrating lymphocytes (sTIL), estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and KI67). Secondly, we compared detection of the metastases by pathology on autopsy samples versus pre-mortem imaging. In total, 306 metastases from 12 patients were collected at autopsy (median: 27 per patient). Both primary tumors (n = 15) and metastases (n = 232) had low sTIL levels, with a median of 2% (range: 0.67-6.67%) and 0.67% (range: 0-13.33%), respectively. Regression models showed lower ER- and PR-expression in metastases (respectively, n = 265 and n = 64) compared to primary tumors (both p < 0.01). KI67 was significantly higher in metastases (n = 262, p = 0.02). HER2-low metastases were found in all but one patient although in varying proportion of metastases (range: 7.5-100%). Central radiology and pathology review had a median concordance of 78% at organ level (range: 33.33-100%) and 71% at patient level (range: 55.88-85.29%). Our findings suggest that a single metastatic biopsy has great limitations to guide treatment and that more adequate methods are needed to detect and monitor ILC metastases.

The concept of "HER2-negative" breast cancer is evolving, with the recognition of HER2-low and HER2-ultralow subsets. These subsets are clinically relevant regarding treatment with the antibody-drug conjugate trastuzumab deruxtecan (T-DXd), which has shown survival benefit in patients with metastatic carcinoma with minimal HER2 protein expression that lack HER2 gene amplification by in situ hybridization. In clinical trials using T-DXd, HER2-low was defined as an immunohistochemistry (IHC) score 1+ or an IHC score 2+ without HER2 gene amplification. HER2-ultralow was defined as faint or barely perceptible, incomplete membrane staining in >0% to ≤10% of tumor cells (IHC score 0+/with membrane staining) and HER2-null as the complete absence of staining (IHC score 0/absent membrane staining). These results now necessitate more detailed evaluation and reporting of traditional "HER2-negative" results to identify patients with metastatic breast cancer who may benefit from T-DXd therapy. Both the US Food and Drug Administration and the European Medicines Agency have extended the regulatory approval of T-DXd to patients with metastatic breast cancer showing HER2-low or HER2-ultralow expressions. Updated clinical management guidelines now, therefore, incorporate the spectrum of HER2 results into treatment selection algorithms in the metastatic setting. To align histopathologic practice with these developments, the College of American Pathologists has issued a new biomarker-reporting template that recommends explicit distinction between IHC 0/absent membrane staining and IHC 0+/with membrane staining. Key concerns among pathologists include assay variability, scoring reproducibility, and quality assurance standards for accurately detecting such low levels of HER2 expression. This manuscript provides expert consensus, evidence-based practical recommendations for identifying and reporting tumors with HER2-low and HER2-ultralow expression. We emphasize standardized testing protocols, validated assays, robust internal and external controls, and focused training for pathologists. A universal structured pathology report is proposed to highlight the accurate distinction between IHC 0 (null), IHC 0+ (ultralow), and HER2-low expressions.

Urinary tract infections (UTIs) are common and burdensome in women. Here, we discuss challenges with our current models of care and how evolving insights into the female urogenital microbiome have advanced the understanding of how we diagnose, treat, and prevent recurrent UTIs in nonpregnant adult women. Traditional care models attribute recurrent UTIs mainly to gastrointestinal sources, resulting in significant emphasis on eradicating pathogens with potential overreliance on antibiotics. Evidence now shows that the bladder harbors a complex microbiome, with interactions between the urinary and vaginal environments and immune mechanisms at the bladder mucosal surface influencing infection susceptibility. Thus, in updated models of care, more emphasis is placed on enhancing the protective microbiome. This may be especially important in postmenopausal women, who experience microbiome shifts that increase vulnerability to recurrent infections, underscoring the role of estrogen therapy and microbiome-supportive interventions. Updated treatment approaches emphasize antimicrobial stewardship, advocating for confirmation of the diagnosis and delayed antibiotic initiation when safe, and judicious use of antibiotics for symptom relief. Prevention strategies highlight the importance of vaginal estrogen, methenamine salts, and other supplements rather than exclusive reliance on prophylactic antibiotics. Ongoing research into emerging therapies such as UTI vaccines and bacteriophage drugs may further decrease our reliance on antibiotics in the future. This clinical update underscores the need for individualized care plans that balance effective infection management while minimizing antibiotic-related harms, emphasizing a holistic, microbiome-centered approach to recurrent UTI prevention and treatment.