Sentinel Lymph Node Ultra-staging as a Supplement for Endometrial Cancer Intraoperative Frozen Section Deficiencies.

For endometrial cancer (EC), most surgeons rely on intraoperative frozen section (IFS) to determine the risk of nodal metastasis and necessity of lymphadenectomy. IFS remains a weak link in this practice due to its susceptibility to diagnostic errors. As a less invasive alternative, sentinel lymph node (SLN) mapping and ultra-staging have gradually gained acceptance for EC. We aimed to establish the SLN success rate, negative predictive value, and whether SLNs provide useful information for cases misdiagnosed on IFS. From 2013 to 2017, 100 patients (63 low-risk and 37 high-risk EC) underwent hysterectomy, bilateral salpingo-oophorectomy, and SLN. Among them, 56 had additional pelvic lymphadenectomy. A total of 337 SLNs were obtained in 86 cases: 55 bilaterally and 31 unilaterally. The remaining 14 cases failed because of patient obesity or leiomyoma. Pathology ultra-staging detected 2 positive SLNs from 2 patients (1 with isolated tumor cells, 1 with micrometastases). One of 773 nonsentinel pelvic nodes was positive on the contralateral hemi-pelvis in a patient who was mapped unilaterally, resulting in negative predictive value of 100%. During IFS, tumor grade and/or depth of myometrial invasion was misdiagnosed in 22 cases (22%). These errors would have resulted in under-staging in 10 high-risk patients or over-staging in 4 low-risk patients. SLNs were mapped in these misestimated patients, with one revealing metastases. SLN provides invaluable information on nodal status while detecting occult metastases in cases misdiagnosed on IFS. Our findings justify the incorporation of SLN in initial surgery for EC as an offset to IFS diagnostic errors, minimizing their negative impact on patient care.

Detection of endometrial precancer by a targeted gynecologic cancer liquid biopsy.

Endometrial cancer is the most common gynecologic malignancy in industrialized countries, and both its incidence and its associated mortality are increasing. The "liquid biopsy" is becoming an important transformative precision oncology tool, but barriers intrinsic to blood sampling have limited its use in early cancer detection. We hypothesized that using a more targeted sample for analysis-namely, a uterine lavage-should provide a more sensitive and specific diagnostic test for endometrial cancer. Using a custom 12-gene endometrial cancer panel, molecular analysis of uterine lavage fluid from an asymptomatic 67-yr-old female without histopathologic evidence of premalignant lesions or cancer in her uterine tissue revealed two oncogenic PTEN mutations. Ten months later, the patient returned with postmenopausal bleeding and a single microscopic focus of endometrial cancer. DNA isolated and sequenced from laser-capture microdissected tumor tissue revealed the same two PTEN mutations. These mutations were unlikely to occur by chance alone (P < 3 × 10-7). This illustrative case provides the first demonstration that future, tumor-specific mutations can be identified in an asymptomatic individual without clinical or pathologic evidence of cancer by using already established sequencing technologies but targeted sampling methods. This finding provides the basis for new opportunities in early cancer screening, detection, and prevention.

Responses of advanced directives by Jehovah's Witnesses on a gynecologic oncology service.

OBJECTIVES: To review the responses of advance directives signed by Jehovah's Witness patients prior to undergoing surgery at a gynecologic oncology service. STUDY DESIGN: A retrospective chart review of gynecologic oncology patients undergoing surgery at a bloodless surgery center from 1998-2007 was conducted. Demographic, pathologic, and clinical data were recorded. The proportion of patients who accepted and refused various blood-derived products was determined and was compared to previously published results from a similar study of labor and delivery unit patients. RESULTS: No gynecologic oncology patients agreed to accept transfusions of whole blood, red cells, white cells, platelets, or plasma under any circumstance, whereas 9.8% of pregnant patients accepted transfusion (P=0.0385). However, 98% of gynecologic oncology patients agreed to accept some blood products, including fractions such as albumin, immunoglobulins, and clotting factors, while only 39% of pregnant patients agreed (P<0.0001). In addition, all gynecologic oncology patients (100%) accepted intraoperative hemodilution, compared to 55% of pregnant patients (P<0.0001). CONCLUSION: Our results confirm the commonly held belief that the majority of Jehovah's Witness patients refuse to accept major blood components. However, Jehovah's Witness patients at a gynecologic oncology service will accept a variety of blood-derived products (minor fractions) and interventions designed to optimize outcomes when undergoing transfusion-free surgery. Patients presenting to a gynecologic oncology service respond differently to advanced directives related to bloodless surgery, as compared to patients from an obstetrical service.

In vitro analysis of cell salvage blood collection with a laparoscopic suction device.

STUDY OBJECTIVE: To determine whether cell salvage blood collection with a laparoscopic suction device is inferior to use of a traditional Yankauer suction device. DESIGN: Prospective, in vitro study. SETTING: Academic teaching hospital. INTERVENTIONS: Individual units of donated packed red blood cells were diluted with normal saline solution to a hematocrit level of 21%. The blood was divided into 2 equal parts and then suctioned with either a laparoscopic suction device or a Yankauer plastic suction catheter tip connected to double-lumen cell salvage tubing with a diluted heparin drip and a vacuum pressure of 100 mm Hg. Collected blood was processed with a cell salvage device. Red blood cell volume was calculated by multiplying the hematocrit level by the total volume of blood product at the time of testing. Mean hemolysis indexes were compared between the laparoscopic and Yankauer method of blood collection by use of a 2-sample t test. Assuming a clinically acceptable limit of loss to be 7%, percent loss in red blood cell volume was tested with a 95% one-sided confidence limit to assess noninferiority. MEASUREMENTS AND RESULTS: The mean hemolysis index was 43.33 with laparoscopic suction method and 34.67 with the Yankauer suction method. The mean difference was 8.67 and was not considered significant (p = .074). The percent loss in red blood cell volume after collection and cell salvage processing was 33.2% with the laparoscopic suction method and 29.57% with the Yankauer method. The mean difference was 3.63% and was within the acceptable 7% loss limit for noninferiority (p = .0278). CONCLUSIONS: Laparoscopic blood collection is not inferior to the standard Yankauer method for cell salvage collection.

Bloodless surgery in gynecologic oncology.

Bloodless medicine and surgery is an evolving field in the practice of medicine designed to avoid allogeneic transfusions. Although this field has largely developed in response to the growing needs of Jehovah's Witness patients refusing transfusions, all patients may potentially benefit from the avoidance of transfusions. The applications of bloodless techniques and strategies in the field of gynecologic oncology have been limited until recently, in part because of the generally large blood loss associated with gynecologic cancer surgeries. However, as advances in our understanding of bloodless surgery have developed and surgical techniques have been refined, the gynecologic oncology patient can now benefit from the avoidance of allogeneic transfusions. This review outlines bloodless surgery as it applies to gynecologic oncology patients and presents a structured approach to successfully managing these complex patients.

Blood salvage use in gynecologic oncology.

BACKGROUND: Blood salvage allows for collection and processing of surgical blood loss with the eventual reinfusion of washed red blood cells (RBCs) back to the patient. The use of blood salvage in patients undergoing surgery for malignancy is off-label. Controversy exists as to the risk of potential cancer dissemination resulting from the reinfusion of the processed blood, but no data are available to confirm this risk. Recent studies have demonstrated that filtering the salvaged blood using a leukoreduction filter (LRF) significantly decreases the number of cancer cells in the recovered RBC aliquot in a variety of cancer types. STUDY DESIGN AND METHODS: Patients on the gynecologic oncology service as part of the bloodless surgery program at Englewood Hospital and Medical Center from April 1998 to April 2007 were identified. Three patients that had reinfusion of cell salvage blood (all reinfusions were performed after filtration with a LRF) were studied further with emphasis placed on long-term outcomes. RESULTS: Two of the three patients did not show any evidence of metastases after surgery. The only patient that developed evidence of hematogenous progression had known liver metastases at the time of her initial diagnosis and therefore had hematogenous dissemination before her index surgery. CONCLUSION: In this series of patients undergoing surgery for malignancies on the gynecologic oncology service, blood salvage with LRF was not definitively associated with hematogenous dissemination. Further large controlled studies are needed to demonstrate the clinical safety of the use of blood salvage in this setting.

Laparoscopy and ovarian cancer: a paradigm change in the management of ovarian cancer?

A MEDLINE search was conducted using the keywords "laparoscopy ovarian cancer," "laparoscopy and borderline ovarian tumors," "advanced stage ovarian cancer," "laparoscopic cytoreduction ovarian cancer," "laparoscopy intraperitoneal catheter," "port-site metastases," and "carbon dioxide pneumoperitoneum." The publications were further limited to English-language articles, those addressing adnexal mass management, early stage ovarian cancer, and advanced stage ovarian cancer treatments. The articles were divided into 4 broad categories: adnexal masses, low malignant potential tumors, early stage ovarian cancer, and advanced ovarian cancer. For each category, a further subdivision into case reports, case series, and finally cohorts was developed and summarized. Additional articles were obtained based on the bibliographic cross-reference of the initial articles reviewed. The current literature defining the role of laparoscopy in the diagnosis and treatment of ovarian cancer is limited to case reports, case series, and cohort studies. However, these limited studies suggest equal efficacy of laparoscopy compared with laparotomy in both early and advanced stage ovarian cancer.

Successful placement of a right ventricular assist device for treatment of a presumed amniotic fluid embolism.

Amniotic fluid embolism is a rare and often fatal complication of pregnancy. We report the successful multidisciplinary management of a woman who developed a coagulopathy from a presumed amniotic fluid embolism after forceps-assisted vaginal delivery requiring recombinant factor VIIa, and pulmonary arterial hypertension requiring a right ventricular assist device.

Bloodless surgery in a Jehovah's Witness patient with a 12.7-kg uterine leiomyosarcoma.

INTRODUCTION: Bloodless surgery aims to optimize outcomes in patients undergoing surgical procedures who wish to avoid allogeneic transfusion. Using a series of interventions and management strategies related to this goal, patients who were previously considered extremely high risk or inoperable without a blood transfusion can now undergo complex surgical procedures with acceptable outcomes. The techniques of bloodless surgery have been incorporated in order to care for a patient with a large uterine sarcoma with involvement and invasion into adjacent organs. CASE: A 52-year-old female Jehovah's Witness patient refusing allogeneic blood transfusion presented to the gynecologic oncology division with a 40-cm pelvic mass and anemia. She was enrolled into the bloodless surgery program at the authors' institution and subsequently underwent surgical resection of a 12.7-kg uterine leiomyosarcoma. Although her intraoperative course was significant for severe anemia with a hemoglobin of 2.5 g/dl and her postoperative course required long-term hospitalization, the patient regained full function to her preoperative performance status. CONCLUSIONS: Bloodless surgery in patients with a potential for large-volume intraoperative blood loss requires a well-organized systematic, multidisciplinary approach to achieve the best possible outcome.

Complete surgical resection of a 40-cm leiomyosarcoma of the large bowel mesentery.

INTRODUCTION: Leiomyosarcoma of the large bowel mesentery is a rare entity and characteristically behaves in an aggressive fashion. Surgical resection is the mainstay of treatment and offers both symptomatic and therapeutic benefit. CASE: We describe the case of a 55-year-old woman who presented with weight loss, increasing abdominal girth and a large solid inhomogenous mass within the abdomen and pelvis demonstrated on a computed tomography (CT) scan. The patient underwent an exploratory laparotomy and extensive tumor debulking procedure with complete resection of her tumor. Final pathology revealed leiomyosarcoma of the large bowel mesentery. The patient has chosen not to receive adjuvant therapy. CONCLUSIONS: Leiomyosarcoma of the large bowel mesentery often presents as an advanced lesion making surgical resection a challenging and potentially morbid procedure. Although surgical resection may be faced with significant morbidity, maximum surgical effort with complete resection offers the best overall outcome for patients with this disease.

Renal artery thrombosis following secondary cytoreduction in a patient with ovarian cancer.

BACKGROUND: In order to successfully perform aggressive cytoreductive surgery for patients with recurrent epithelial ovarian cancer, resection of retroperitoneal disease in close proximity to major vessels is often required. CASE: We describe a case of a 44-year-old female patient with a history of Stage IV carcinoma of the ovary, who underwent a successful secondary debulking procedure. To remove the left para-aortic tumor implant she required complete mobilization of the left kidney, with skeletonization of the left renal artery and vein. Postoperatively, the patient developed left renal artery thrombosis necessitating a unilateral nephrectomy. CONCLUSION: This is, to our knowledge, the first reported case of renal artery thrombosis following a debulking procedure. Gynecologic oncologists should be aware of this possibility and be familiar with the diagnosis and management of this condition.

Total laparoscopic radical hysterectomy and pelvic lymphadenectomy using harmonic shears.

STUDY OBJECTIVE: To describe the feasibility and outcome of total laparoscopic radical hysterectomy with or without pelvic lymphadenectomy for patients with stage I cervical cancer or severe pelvic endometriosis using harmonic shears as the sole instrument for dissection, division, and maintenance of hemostasis of all major surgical pedicles. DESIGN: Retrospective review (Canadian Task Force classification II-2). SETTING: University hospital and affiliate institutions. PATIENTS: Seven patients who underwent total laparoscopic radical hysterectomy using harmonic shears for International Federation of Gynecology and Obstetrics stage IA2 to IB1 cervical cancer and pelvic endometriosis at our institution or affiliate hospital from January 2004 through February 2005. INTERVENTION: A retrospective review of patients that underwent total laparoscopic radical hysterectomy with or without pelvic lymphadenectomy at our institution using harmonic shears was performed. Information regarding preoperative, intraoperative, and postoperative events was recorded and analyzed. MEASUREMENTS AND MAIN RESULTS: Pelvic lymphadenectomy was performed in all cancer cases. Mean patient age was 40 years (range 30-53 years). Mean estimated blood loss was 143 mL (range 100-200 mL). Mean operating time was 293 minutes (range 255-385 minutes). Mean pelvic node count was 27.8 (range 24-34) for cancer cases. Mean hospital stay was 3.2 days (range 2-7 days). One patient developed a vaginal cuff abscess postoperatively that was managed conservatively with drainage in the office setting followed by intravenous antibiotics. Another patient developed urinary retention for 2 weeks after surgery. There were no other intraoperative or postoperative complications. CONCLUSION: Total laparoscopic radical hysterectomy with pelvic lymphadenectomy using harmonic shears is a technically feasible and safe procedure. Larger studies and long-term follow-up are required to determine the oncologic outcomes of these patients.

Post-transplant lymphoproliferative disorder of the cervix.

BACKGROUND: Post-transplant lymphoproliferative disorder involving the female genital tract is a rare event. CASE: A 67-year-old female status post orthotopic liver transplant 5 years previously for hepatitis B and sarcoidosis presented with vaginal bleeding. Endometrial biopsy revealed a high-grade malignant tumor with immunologic marker studies consistent with lymphoma. The patient underwent an exploratory laparotomy, modified radical hysterectomy, bilateral salpingo oophorectomy, bilateral selective pelvic and para-aortic lymphadenectomy, and omentectomy. Final pathology confirmed monomorphic B-cell post-transplantation lymphoproliferative disorder consistent with non-Hodgkin's B cell lymphoma confined to the endocervix and lower uterine segment. She remains recurrence free after 4 years with no adjuvant therapy. CONCLUSION: Post-transplant complications can present in the female reproductive organs. Gynecologic oncologists need to be aware of this disease process when treating patients for gynecologic symptoms after transplant surgery.

The incidence of port-site metastases in gynecologic cancers.

OBJECTIVES: To determine the incidence of port-site metastases in patients undergoing laparoscopic procedures for gynecologic cancers. METHODS: The charts of patients treated by laparoscopy for diagnosis, treatment, or staging of gynecologic cancers by the academic faculty attending physicians were studied from July 1, 1997 to June 30, 2001. No patient without a histological or cytological diagnosis of cancer from the index procedure were included. Fisher's exact test was used for statistical analysis. RESULTS: Eighty-three patients were identified accounting for 87 procedures. Types of cancer treated included endometrial (39), ovarian (29), and cervical (14). Twenty procedures were performed for recurrence of ovarian or peritoneal cancer, and ascites was present in 10 cases. Port-site metastases occurred in 2 patients accounting for 8 sites. Five sites were diagnosed in a single patient 13 days after a second-look laparoscopy for stage IIIB ovarian cancer, and 3 sites were diagnosed in a patient 46 days after an interval laparoscopy for stage IIIC primary peritoneal cancer. Ascites was present in both patients. The overall incidences of port-site metastases per procedure and per port placed were 2.3% (2/87) and 2.4% (8/330), respectively. In patients with a recurrence of ovarian or peritoneal cancer, no port-site metastases (0/16) occurred in the absence of ascites, whereas 50% (2/4) of patients with ascites developed port-site metastases (P < .035). CONCLUSIONS: The overall incidence of port-site metastases in gynecologic cancers in our study was 2.3%. The risk of port-site metastases is highest (5%) in patients with recurrence of ovarian or primary peritoneal malignancies undergoing procedures in the presence of ascites.

Progestin-induced apoptosis in the Macaque ovarian epithelium: differential regulation of transforming growth factor-beta.

BACKGROUND: Oral contraceptive (OC) use is associated with a reduced risk of ovarian cancer. An OC component, progestin, induces apoptosis in the primate ovarian epithelium. One regulator of apoptosis is transforming growth factor-beta (TGF-beta). We determined the effect of progestin on TGF-beta expression in the primate ovarian epithelium and examined the relationship between TGF-beta expression and apoptosis. METHODS: Female cynomolgus macaques were randomly assigned to receive a diet for 35 months containing no hormones (n = 20); the OC Triphasil (n = 17); or each of its constituents, ethinyl estradiol (estrogen, n = 20) or levonorgestrel (progestin, n = 18 ), alone. Ovarian sections were immunostained with monoclonal antibodies against TGF-beta1 or TGF-beta2 plus TGF-beta3 (TGF-beta2/3) isoforms. The expression of TGF-beta isoforms in four ovarian compartments (epithelium, oocytes, granulosa cells, and hilar vascular endothelium) was compared among treatment groups. The association between TGF-beta expression and apoptosis, as determined by morphology and histochemistry, was examined in ovarian epithelium. All statistical tests were two-sided. RESULTS: Compared with ovaries from the control and estrogen-only-treated monkeys, the ovaries of progestin-treated monkeys showed 1) a marked decrease in the expression of TGF-beta1 and a concomitant increase in the expression of the TGF-beta2/3 isoforms in the ovarian epithelium (P<.001), 2) an increase in the expression of TGF-beta2/3 in the hilar vascular endothelium (P<.001), and 3) a marked decrease in TGF-beta2/3 expression in granulosa cells (P<.001). The apoptotic index of the ovarian epithelium was highly associated with the change in expression from TGF-beta1 (P<.001) to TGF-beta2/3 (P