Clear cell adenocarcinoma arising from anterior abdominal wall cesarean section scar endometriosis treated with excision and the addition of Trastuzumab for adjuvant chemotherapy: A case report.

Abdominal wall endometriosis with subsequent transformation to clear cell carcinoma is quite rare. The pathogenesis and pattern of this transformation is not well known; hence evaluation and management guidelines are not well established. We highlight a case of clear cell adenocarcinoma arising from the anterior abdominal wall in a previous cesarean section scar treated with excision and the unique addition of Trastuzumab for adjuvant chemotherapy.

A pilot trial of intravital microscopy in the study of the tumor vasculature of patients with peritoneal carcinomatosis.

Aberrancies in the tumor microvasculature limit the systemic delivery of anticancer agents, which impedes tumor response. Using human intravital microscopy (HIVM), we hypothesized that HIVM would be feasible in patients with peritoneal carcinomatosis (PC). During cytoreductive surgery with hyperthermic intraperitoneal chemotherapy for PC, HIVM was performed in both tumor and non-tumor areas. The primary outcome was HIVM feasibility to measure vessel characteristics. We secondarily evaluated associations between HIVM vessel characteristics and oncologic outcomes (RECIST response to neoadjuvant therapy and disease-specific survival). Thirty patients with PC were enrolled. Nineteen patients (63.3%) received neoadjuvant therapy. HIVM was feasible in all patients. Compared to non-tumor (control) areas, PC areas had a lower density of functional vessels, higher proportion of non-functional vessels, smaller lumenal diameters, and lower blood flow velocity. Qualitative differences in these vessel characteristics were observed among patients who had partial response, stable disease, or progressive disease after receiving neoadjuvant therapy. However, no statistically significant relationships were found between HIVM vessel characteristics and oncologic outcomes. These novel findings comprise the first-in-human, real-time evidence of the microscopic differences between normal and tumor-associated vessels and form the basis for our larger, ongoing clinical trial appropriately powered to determine the clinical utility of HIVM (NCT03823144).

Phase II trial of ribociclib and letrozole in patients with relapsed oestrogen receptor-positive ovarian or endometrial cancers.

OBJECTIVE: We describe a phase II clinical trial of the combination of ribociclib and letrozole for treatment of relapsed oestrogen receptor (ER)-positive ovarian cancer (OC) and endometrial cancer (EC). The primary endpoint was the proportion of patients alive, progression-free survival (PFS), and still on treatment at 12 weeks (PFS12), with 45% or greater considered positive. METHODS: Patients with measurable, relapsed ER-positive OC or EC (platinum-sensitive or resistant) were eligible and treated with 400 mg of oral ribociclib and 2.5 mg of oral letrozole daily. Patient-derived xenografts (PDXs) were created from imaging-guided tumour biopsies. RESULTS: Forty patients (20 OC and 20 EC) were enrolled. A PFS12 of 55% was observed in the EC cohort and 50% in the OC cohort. A PFS greater or equal to 24 weeks (PFS24) was seen in 20% (4/20) of the OC cohort and 35% (7/20) of the EC cohort. The greatest benefit was seen in low-grade serous OC (LGSOC) (3/3, 100% PFS24) and grades 1 and 2 EC (5/11, 45% PFS24). All three LGSOC patients obtained at least a partial response lasting for over 2 years, with two of the three patients still on treatment. PDX tumour engraftment was feasible in 45% of patients. Positive survival effects of the combination of ribociclib and letrozole were observed in two of three EC PDX models. CONCLUSION: Ribociclib and letrozole have promising clinical activity in relapsed ER-positive OC and EC, particularly in LGSOC and relapsed ER-positive grade 1 and 2 EC. Generation of PDX models is feasible with positive survival effects observed in EC models. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov registry (NCT02657928).

Variability between individual surgeons in route of hysterectomy for patients with endometrial cancer in Florida.

OBJECTIVES: Minimally invasive surgery (MIS) was designated as a quality measure for endometrial cancer in 2014. However, national database analyses demonstrate that laparotomy is still performed for this indication. This study aims to assess the route of hysterectomy performed by gynecologic surgeons who manage endometrial cancer in the state of Florida. MATERIALS AND METHODS: All patients in Florida who were diagnosed with endometrial cancer (both ICD-9 Code 182.0 and ICD-10 Code C54.10), and who received a related surgical procedure from 2014 to 2016 were included. Eligible patients were identified using the Florida Inpatient Discharge Dataset, the Florida Ambulatory and Emergency Discharge Dataset, the Hospital Compare dataset, and the Healthcare Cost Report Information System. The primary surgeon was identified using their national provider identifier (NPI) number. Each surgeon's overall operative volume, MIS volume, and percentage of MIS procedures were collected. RESULTS: Hysterectomy for endometrial cancer was performed in 6086 patients; 4959 (81.5%) underwent MIS and 1127 (18.5%) had an abdominal approach. Hysterectomy for endometrial cancer was performed by 368 providers in Florida (range of 2-244 surgeries). The percentage of MIS to total hysterectomies for providers who performed 1-10 cases was 72.1%; 11-25 cases was 40.9%; 26-100 cases was 80.1%; and more than 100 cases was 86.1%. Variation in operative route exists amongst low- and high-volume providers. CONCLUSIONS: Statewide databases can be used to identify surgical trends for policy purposes. These findings support the referral of patients with endometrial cancer to surgeons with high MIS volumes.

Complex management of acute superior mesenteric venous thrombosis in the setting of metastatic ovarian cancer.

•Superior mesenteric vein thrombosis (SMVT) is rare but seen in patients with hypercoagulable states.•Prevention of mortality in patients with SMVT requires immediate diagnosis and complex management.•A hierarchical approach to treatment progresses to more aggressive treatment as needed.•Supportive care, medication, and endovascular and/or surgical interventions are available management options.•In patients with underlying conditions, long-term treatment such as anticoagulation must also be initiated.

Phase 2 trial of everolimus and letrozole in relapsed estrogen receptor-positive high-grade ovarian cancers.

OBJECTIVES: We report the results of a phase 2 clinical trial of the combination of everolimus and letrozole in patients with relapsed estrogen receptor-positive high-grade ovarian cancer. The trial's primary endpoint was the proportion of patients alive and progression-free after 12weeks of therapy with the combination of everolimus and letrozole. A 12-week PFS of 45% or greater was considered a positive result. The feasibility of generating patient-derived xenograft (PDX) models from biopsy specimens was also evaluated. METHODS: Eligibility criteria included relapsed estrogen receptor-positive ovarian, fallopian tube or primary peritoneal carcinomas with measurable disease, not previously treated with everolimus or AIs. Both platinum-resistant and sensitive tumors were included. Xenografts were created from image-guided tumor biopsies at baseline. Patients received oral everolimus 10mg daily and letrozole 2.5mg daily. RESULTS: Twenty patients were enrolled, 19 were evaluable. Nine out of 19 were alive, progression-free, and still on treatment at the 12week evaluation time-point (12-week PFS of 47%) with a median PFS of 3.9months (95% CI: 2.8-11.0). The median overall survival was 13.0months. Twelve patients (63%) experienced at least one grade 3 or worse adverse events. PDX tumor engraftment was feasible in the majority of patients (9 out of 17, 52.9%). CONCLUSIONS: The combination of everolimus and letrozole is associated with a promising 47% 12-week PFS rate in patients with ER-positive relapsed high-grade ovarian cancer with acceptable toxicity. PDX tumor models can be generated from biopsies of ovarian tumors.

High-grade endometrial stromal sarcoma as the initial presentation of an adult patient with Peutz-Jeghers Syndrome: a case report.

A 46-year-old female presents with a pelvic mass and is diagnosed as having a high-grade endometrial stromal sarcoma. During surgery, she is noted to have areas of intussusception of the small bowel secondary to large hamartomatous polyps. The patient had a previous history of small bowel obstruction secondary to what had been thought to be hyperplastic polyps but represented hamartomatous polyps on further review. Additional examination revealed the presence of subtle hyperpigmented macules on the fingers leading to a diagnosis of Peutz-Jeghers Syndrome (PJS). The diagnosis was confirmed by the presence of a germ-line STK11 mutation. Immunohistochemistry analysis of the tumor showed decreased expression of STK-11 as compared to one of the patient's hamartomatous polyps. Next generation sequencing of the tumor specimen failed to demonstrate a "second hit" somatic mutation in STK-11. This case represents the first case of endometrial stromal sarcoma associated with PJS and illustrates the importance of increased awareness of this condition among oncologists. PJS is associated with dysregulation of the mTOR pathway; treatment with an mTOR inhibitor was not effective in this case.