Time Of Diagnostic Laparoscopy Research Articles

Ruptured Heterotopic Pregnancy Following Spontaneous Conception

Heterotopic pregnancy following natural conception cycles is a rare event, estimated at one in 30,000 pregnancies. This infrequent phenomenon leads to significant morbidity and potential mortality if not promptly diagnosed. We present the case of a 29-year-old with no identifiable risk factors who presented with hemoperitoneum and hypotension. The patient had a visualized intrauterine pregnancy (IUP) and a marked amount of free fluid on transvaginal ultrasound. At the time of diagnostic laparoscopy, a ruptured left tubal pregnancy was identified. This case highlights that diagnosis of an IUP does not exclude a simultaneous heterotopic pregnancy even in patients for whom no identifiable risks factors can be found. Similarly, diagnosis of an IUP should not lead to delay in treatment of hemoperitoneum. J Clin Gynecol Obstet. 2020;9(3):70-72 doi: https://doi.org/10.14740/jcgo673

Abstract A76: Immunologic changes following intraperitoneal administration of a formulated IL-12 plasmid in combination with standard neoadjuvant chemo in newly diagnosed advanced stage ovarian cancer patients

Abstract Background: This abstract describes the translational component of a phase I study of weekly intraperitoneal (IP) GEN-1, an IL-12 plasmid formulated with polyethyleneglycol-polyethyleneimine cholesterol lipopolymer, in combination with standard intravenous (IV) weekly taxane (T) and carboplatinum (C) every 3 weeks in epithelial ovarian, fallopian tube, or primary peritoneal cancer (EOC) patients undergoing neoadjuvant chemotherapy (NAC). Local administration of GEN-1 could provide persistent IL-12 secretion to induce type-1 immune responses in the immunosuppressive tumor microenvironment. Our hypothesis is that the GEN-1 plus NAC treatment will reprogram the tumor immune microenvironment towards a potent antitumor immune response. We have previously reported the clinical finding that GEN-1 is safe up to 79 mg/m2 IP weekly up to eight treatments. The most common related toxicities were Grade 1 nausea, vomiting, abdominal pain, and fatigue. Patients continue to be followed for progression and any drug-related safety events. Methods: Newly diagnosed advanced-stage EOC patients being treated with NAC were eligible. The trial utilized a 3+3 design with GEN-1 IP dose levels ranging from 36 mg/m2 to 79 mg/m2 weekly for 8 treatments with concurrent IV T/C. Tumor samples were collected at time of diagnostic laparoscopy and interval debulking (IDB). Blood and peritoneal ascites were collected before and after treatment. The immunologic analysis included frequency of immune cell populations and cytokine levels in tumor, blood, or peritoneal ascites. The levels of cytokines IL-12, IFN-γ, TNF-α, TGF-β, IL-10, and VEGF were quantified in blood plasma and ascites samples with commercially available cytokine-specific ELISA kits. The tumor tissue specimens were paraffin embedded and serial sections were stained with specific antibodies for various T-cell markers using immunohistochemistry. The density of various T-cells, dendritic cells, and myeloid-derived suppressor cells in blood or ascites was determined by flow cytometry. Results: The interim results obtained from Cohorts 1–4 (stage 1) show post-treatment changes in immune cell populations, including an increase in cytotoxic CD8+ T-cells and decrease in several immunosuppressive markers including FoxP3+, PD-1, PDL-1, and IDO-1. The cell ratio of CD8+ to all immunosuppressive markers appeared to be skewing beneficially towards more cytotoxic T lymphocyte and away from suppressive cells in most patients. There were no significant changes in the frequency of circulating T cells (or cytokine response). Analysis of ascites before and 24 hours after IP administration of GEN-1+NAC showed evidence of IL-12 gene transfer and activation of downstream signaling pathways, including increases in IFN-γ levels and inhibition of peritoneal VEGF levels. The cytokine response was predominantly in ascites while comparatively little changes were observed in blood plasma. Thus, the immunomodulatory and therapeutic effect of GEN-1 treatment is primarily localized within the tumor microenvironment and does not appear to have any untoward effect on systemic immune responses. The changes in cytokine levels appeared to be GEN-1 dose dependent. Additional analyses from this study are in progress. Conclusions: Adding GEN-1 to neoadjuvant T/C is safe and biologically active in EOC patients. Based on preliminary analyses of Cohorts 1–4 (stage 1), the treatment of EOC patients with GEN-1 and NAC has resulted in favorable immunologic responses. Final translational results will be presented at the meeting. Clinical trial information: NCT02480374. Citation Format: Khursheed Anwer, Junko Matsuzaki, Wiam Bshara, Amit Lugade, Angela Omilian, Premal H. Thaker, William H. Bradley, Rebecca Arend, Camille Gunderson, Jason Fewell, Nicholas Borys, Lauren Musso, Adekunle Odunsi. Immunologic changes following intraperitoneal administration of a formulated IL-12 plasmid in combination with standard neoadjuvant chemo in newly diagnosed advanced stage ovarian cancer patients. [abstract]. In: Proceedings of the AACR Conference: Addressing Critical Questions in Ovarian Cancer Research and Treatment; Oct 1-4, 2017; Pittsburgh, PA. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(15_Suppl):Abstract nr A76.

Phase I study of the safety and activity of formulated IL-12 plasmid administered intraperitoneally in combination with standard neoadjuvant chemotherapy in patients with newly diagnosed advanced stage ovarian cancer.

155 Background: This study evaluated weekly intraperitoneal GEN-1, an IL-12 plasmid formulated with polyethyleneglycol-polyethyleneimine cholesterol lipopolymer, in combination with dose-dense weekly taxane (T) and carboplatinum (C) every 3 weeks in newly diagnosed epithelial ovarian, fallopian tube, or primary peritoneal cancer (EOC) patients undergoing neoadjuvant therapy (NAC). The primary objective of this study was to evaluate the tolerability and safety of GEN-1 with NAC. Secondary objectives were objective clinical response and pathological complete response at interval debulking surgery (IDB). Methods: This protocol followed a standard 3+3 design. Patients received GEN-1 at escalating dose levels from 36 mg/m2, 47 mg/m2, 61 mg/m2, to 79 mg/m2 weekly for 8 treatments with concurrent T/C. After IDB, patients did not receive further GEN-1 but continued on T/C. Patients were assessed for dose limiting toxicities (DLT) and had tumor samples at a time of diagnostic laparoscopy and IDB. Translational endpoints are yet to be analyzed. Patients are being followed for every 3 months for 2 years. Results: Fifteen patients were enrolled and 9 patients received all 8 treatments with no DLTs. The 79 mg/m2GEN-1 cohort of patients are actively being treated. Two patients were screen failures; 1 patient discontinued prior to GEN-1 administration due to port site infection. Most common related toxicities were Gr 1 nausea, fatigue, abdominal pain, and vomiting. One patient experienced Gr 2 fevers associated with GEN-1 but responded to acetaminophen and fluids. One patient did not undergo IDB due to pulmonary embolism and severe deconditioning due to underlying cancer. Of the other 8 patients undergoing IDB: 3/8 had stable disease, 4/8 had partial responses (PR), and 1/8 had complete response (CR). There was 1 pathological CR, 3 micro PR, and 3 macro PR. All patients had a ≥ 89% drop in CA-125 following GEN-1. Conclusions: Adding GEN-1 to T/C is safe and appears to be active in NAC patients with newly diagnosed EOC. Updated results to be presented at meeting. Clinical trial information: NCT02480374.

Immunological changes following intraperitoneal administration of a formulated IL-12 plasmid in combination with standard neoadjuvant chemotherapy in patients with newly diagnosed advanced stage ovarian cancer.

156 Background: The translational component of a Phase I study of weekly intraperitoneal GEN-1, an IL-12 plasmid formulated with polyethyleneglycol-polyethyleneimine cholesterol lipopolymer, in combination with dose-dense weekly taxane (T) and carboplatinum (C) every 3 weeks in newly diagnosed epithelial ovarian, fallopian tube, or primary peritoneal cancer (EOC) patients undergoing neoadjuvant therapy (NAC). Our hypothesis is that the GEN-1 plus NAC treatment will reprogram the tumor immune microenvironment towards a potent antitumor immune response. Methods: Patients received GEN-1 at escalating dose levels from 36 mg/m2, 47 mg/m2, 61 mg/m2, to 79 mg/m2weekly for 8 treatments with concurrent T/C. Tumor samples collected at time of diagnostic laparoscopy and interval debulking (IDB). Blood and peritoneal ascites were collected before and after treatment. The immunological analysis included frequency of immune cell populations and cytokine levels in tumor, blood, and peritoneal ascites and cell-specific mRNA expression profile. Results: The preliminary results obtained from first two cohorts show that GEN-1 may be enhancing post-treatment changes in immune cell populations including an increase in cytotoxic CD8+ T-cells and decrease in immunosuppressive FoxP3+ T-reg cells in tumor at IDB. The CD8:Foxp3 ratio appeared to be skewing beneficially towards more cytotoxic T lymphocyte and away from suppressive cells in most patients. The analysis of circulating immune cells 21 days after first GEN-1 treatment showed a decrease in circulating CD123+ plasmacytoid dendritic cells, but no change in CD11c+ myeloid dendritic cells. There were no major changes in the frequency of circulating T-cells. Additional analyses from this study are in progress. Conclusions: Based on preliminary analyses of cohorts 1 & 2 samples analyzed, the treatment of EOC patients with GEN-1 and NAC has resulted in favorable immunological responses. Updated results to be presented at meeting. Clinical trial information: NCT02480374.

Adolescent Endometriosis: Report of a Series of 55 Cases With a Focus on Clinical Presentation and Long-Term Issues.

To report the clinical presentation and long-term issues of adolescent endometriosis. Retrospective cohort study. Single private clinical center, Bordeaux, France. Adolescents with a confirmed diagnosis of endometriosis. Surgical excision or ablation or lesions performed at laparoscopy. Fifty-five adolescents, ages from 12 to 19 years (mean age 17.8), who were diagnosed with endometriosis from March 1998 to April 2013 were included in the study. Pain of various types was the leading symptom in all patients, except 2. Twenty-three patients had an adnexal mass identified preoperatively, and 5 had an associated infertility issue at the time of diagnostic laparoscopy. Four patients had an associated genital malformation. Fifty-one percent of the patients had a history of appendectomy. A familial history of endometriosis was reported by 19 patients (34.5%), with a first-degree relative affected in 14 cases (25.45%), and 47.3% of patients were smoking at least 5 cigarettes a day. Superficial implants was encountered in 31 cases (56.4%), endometriomas in 18 cases (32.72%), and deep infiltrating endometriosis (DIE) in 6 cases (10.90%). Sixty percent of patients were scored as stages I to II and 40% as stages III to IV. Five patients were lost to follow-up, and 37 had a follow-up ranging from 36 to 315 months (mean follow-up 125.5 months). Among the 50 patients not lost to follow-up, 13 (26%) had either no pain, or improved and had acceptable pain with medical treatment. Seventeen patients of the 50 adolescents not lost to follow-up (34%) underwent a repeat laparoscopy. A subsequent laparoscopic and/or magnetic resonance imaging scan was performed in 35 patients because of persistent pain. Among these, there was 12 endometriomas (7 recurrences) and 12 DIEs (3 recurrences), giving recurrence rates for endometriomas and DIEs of 36.84% and 50%, respectively. During the study, 18 patients wished to have a child. Thirteen had a delivery (72.2%), and 9 pregnancies occurred in patients who initially presented with stage I to II endometriosis. Of the 11 patients who had subfertility, 6 successfully conceived (54.5%). Adolescent endometriosis is not a rare condition. In our study a familial history was reported in more than one-third of patients. Among those patients treated for DIE, there was a trend for higher rates of recurrences (symptoms or lesions) that required repeat laparoscopy. However, the impact on subsequent fertility appeared to have been limited.

Reproductive outcome after laparoscopic treatment of minimal and mild endometriosis using Helica Thermal Coagulator

Objective To investigate the reproductive outcome following Helica Thermal Coagulator (Helica TC) in an infertile population with early-stage endometriosis. Design A clinical observational trial conducted in a NHS tertiary referral centre for treatment of endometriosis. Forty-four healthy infertile women (mean age 21 years, range 18–34 years) with laparoscopically confirmed diagnosis of minimal (stage I) or mild (stage II) endometriosis were included. All visible endometriotic lesions and adhesions were treated using Helica TC at the same time of diagnostic laparoscopy. Following laparoscopy, women attempted to conceive spontaneously and were followed for 12 months or until delivery. No hormonal therapy for endometriosis was given whatsoever. Results One woman was lost to follow-up and the remaining 43 women were considered in the final analysis. The cumulative pregnancy rate was 23.2% (10/43). All pregnancies occurred spontaneously and neither miscarriages nor ectopic pregnancies were observed. Pregnancy rate did not differ between women with stage I and those with stage II endometriosis. The time-to-pregnancy was similar in women with different stage endometriosis. No surgical complications were encountered. Conclusions These findings suggest that Helica TC is a simple and safe conservative laparoscopic surgery for early-stage endometriosis. Helica TC appears to improve reproductive outcome in women with otherwise unexplained infertility. Large RCTs are needed to define these preliminary data.

Mechanism of elevated vascular endothelial growth factor levels in peritoneal fluids from patients with endometriosis.

In order to investigate the mechanism of elevated vascular endothelial growth factor (VEGF) in peritoneal fluids from patients with endometriosis, macrophages were recovered from peritoneal fluids obtained at the time of diagnostic laparoscopy from infertile women with endometriosis (EMT group, n=20) and without endometriosis (control group, n=20). Macrophages were cultured in vitro. The VEGF levels of peritoneal fluid and the supernatant of macrophages culture were determined by enzyme linked immunoassay (ELISA). Meanwhile, the eutopic (n=20) and ectopic endometrium (n=20) from endometriosis patients, and normal edometrium (n=20) from non-endometriosis patients were obtained for the analysis of VEGF expression by labeled Streptavidin Biotin (LSAB). It was found that VEGF levels in peritoneal fluid and macrophages culture supernatant were significantly higher in EMT group than in control group (P<0.01). In normal endometrium, VEGF showed a cyclic changes and similar in eutopic and ectopic endometrium from patients with endometriosis. There was no difference in the intensity of VEGF in endometrium between two groups within each menstrual phase. It is suggested that altered VEGF production by peritoneal macrophages and ectopic endometrium secretion may contribute to the elevated VEGF levels in the peritoneal fluid of patients with endometriosis.

Laparoscopic Spectral Analysis of Endometriosis

Study Objective To determine if lesions of endometriosis will preferentially absorb light of the blue spectrum thus enabling the detection of nonvisualized disease. Design Retrospective analysis (Canadian Task Force classification II-2). Setting University based teaching hospital. Patients Twenty-five women with pain suggestive of endometriosis. Intervention A noninvasive technique was employed to better visualize lesions of endometriosis at time of diagnostic laparoscopy. Measurements and Main Results A Storz PDD light source, which delivers a blue light at a specified frequency of 440 Hz, was used concurrently with full-spectrum white light. A Storz PDD laparoscope, which utilizes filters to detect the blue spectrum of light, was then coupled to the blue-light source. Lesions of endometriosis were compared using standard white light to that of blue light. The new lesions seen using blue light were sampled to confirm pathology. Using standard white light, black, red, and clear lesions were identified, and the borders of the lesions were marked. The same lesions were observed using the blue spectrum of light. The lesions absorbed blue light, but nonvisible endometriosis surrounding the classic lesions were also identified. Biopsies confirmed endometriosis in newly visible lesions. Conclusion Lesions of endometriosis preferentially absorb the blue-light spectrum. Laparoscopic spectral analysis enables visualization of previously nonvisible endometriosis and makes other visible lesions easier to identify.

The routine use of diagnostic laparoscopy in the intensive care unit.

Delay in the diagnosis of intraabdominal pathology is a major contributor to the morbidity and mortality of intensive care unit (ICU) patients. Laparoscopy is a valuable diagnostic tool that can be used safely and efficiently in the evaluation of intraabdominal processes that may be difficult to diagnose with conventional methods. Our goal was to show that laparoscopy performed at the bedside in the ICU could be used as a routine diagnostic tool in the evaluation of critically ill patients, just as computed tomography (CT), ultrasonography (US), and radiography are. We present 11 patients who underwent 12 bedside examinations in the ICU of a community teaching hospital. Several different surgeons with varying degrees of laparoscopic experience performed these procedures over a 1-year period. Four patients had previously undergone recent abdominal operations. Nontherapeutic laparotomy was avoided in six patients because of diagnostic laparoscopy. One patient also underwent a therapeutic maneuver at the time of diagnostic laparoscopy. None of the patients required general anesthesia, although local anesthetics and sedation with midazolam or propofol were used. One patient underwent the procedure without endotracheal intubation. There were no complications or mortalities directly related to the procedure. We conclude that bedside laparoscopy in the ICU under local anesthesia is a diagnostic and potentially therapeutic tool that can be used safely in the work-up of potential abdominal pathology in critically ill patients.

Laparoscopic methotrexate instillation in unruptured tubal pregnancyis it worthwhile?

This study documents the success rate and risks of laparoscopic local injection of methotrexate in the unruptured tubal pregnancy. This was a prospective study conducted in two centres, King Abdulaziz University Hospital and Dr Erfan & Bagedo Hospital, Jeddah, Saudi Arabia. Twenty-one patients with an intact tubal pregnancy were selected for laparoscopic local treatment with the use of a single injection of 12·5 mg of methotrexate into the ectopic site at the time of diagnostic laparoscopy. In 80·9% (17 patients), serum g -hCG level decreased to the nonpregnant level with no further intervention and the patients recovered without any serious side effect. In 19·9% (four patients) mini-laparotomy was indicated because of a rising g -hCG. Local methotrexate therapy in an early intact tubal ectopic at the time of laparoscopy is a possible alternative to surgery in selected cases. It also has some advantage over systemic (intramuscular) methotrexate as it avoids potentially serious side effects.

Basal and stimulated secretion of cytokines by peritoneal macrophages in women with endometriosis

To evaluate basal (constitutive) and stimulated synthesis of tumor necrosis factor α (TNF α ), interleukin (IL)-8, and IL-10 by peritoneal macrophages (PM) in women with endometriosis. Peritoneal macrophages were cultured in the presence or absence of lipopolysaccha-ride (LPS) for 24 hours. Peritoneal fluids (PF) and PM supernatants were assayed for cytokines using ELISA. Institute for the Study and Treatment of Endometriosis and university-based research laboratories. Fertile controls undergoing tubal ligation (n = 8) and women with endometriosis (n = 17). Peritoneal fluid samples were obtained at the time of diagnostic laparoscopy (endometriosis group) or laparoscopy for tubal ligation; both were performed in the midluteal phase of the cycle. Both basal and LPS stimulated production of TNF α , IL-8, and IL-10 by the PM were elevated significantly in women with endometriosis as compared with the fertile controls. This study demonstrated that cytokines TNF α , IL-8, and IL-10 are synthesized at greater than normal levels by basal and stimulated PM from women with endometriosis. The levels of TNF α and IL-8 correlated with the levels in the PF, suggesting that PM are the principal source of these cytokines in the PF.

Laparoscopic diagnosis and treatment of an infarcted epiploic appendage

A patient experienced acute abdominal pain that was diagnosed at laparoscopy as being due to an infarcted epiploic appendage. To our knowledge, this is the second report of laparoscopic diagnosis and treatment of an epipolic disorder. Infarcted epiploic appendages may be associated with bowel obstruction and abscess formation. Therefore, they should be looked for at the time of diagnostic laparoscopy for acute abdominal pain of unclear etiology, and removed if present.

Laparoscopic evaluation and treatment of women with chronic pelvic pain

Study Objective. To evaluate the effectiveness of operative laparoscopic treatment at the time of diagnostic laparoscopy in patients with chronic pelvic pain (CPP). Design. A retrospective study of women with CPP and at least 6 months of follow-up after laparoscopic evaluation and treatment. Setting. A faculty practice and community teaching hospital. Patients. A series of 65 consecutive women with greater than 1 month of pelvic pain who underwent laparoscopy. Thirty-two were referred by other physicians for evaluation of CPP. Interventions. Patients had operative laparoscopic treatment of all abnormal findings at the time of diagnostic laparoscopy. Nonspecific treatment such as presacral neurectomy or uterine nerve ablation was not performed. Measurements and Main Results. After laparoscopic evaluation and treatment, 78% of patients had decreased pain and 45% were pain free. Prior unsuccessful medical or surgical treatment did not affect the response rate. Endometriosis and adhesive disease were the most common diagnoses, 38% and 34%, respectively. Conclusions. Laparoscopic surgical treatment of pathology noted at the time of diagnostic laparoscopy in women with CPP is appropriate, but less than one-half of patients may be expected to have complete pain relief.

Staging ovarian cancer diagnosed during laparoscopy: accuracy rather than immediacy.

Immediate staging and debulking of an unsuspected ovarian malignancy detected at the time of diagnostic laparoscopy is appropriate when personnel knowledgeable in these procedures are available. However, when assistance is unavailable, termination of the diagnostic laparoscopy and timely referral is acceptable. This report reviews techniques to preoperatively distinguish a benign from a malignant adnexal mass, steps to evaluate an adnexal mass during laparoscopy, and ovarian cancer staging procedures.

Terminal tuboplasties by laparoscopy: 65 consecutive cases

A series of 65 consecutive laparoscopic distal tuboplasties, performed from May 1986 to May 1988 is reported. Thirty-one were fimbrioplasties and 34 were neosalpingostomies. Outcome was evaluated at 18 months postoperatively. Twenty-two patients obtained pregnancies (33.8%), of which 18 were intrauterine (27.7%). The intrauterine pregnancy rate was 25.8% after fimbrioplasty and 29.4% after neosalpingostomy. These results are comparable with those obtained after microsurgery. Progress in operative laparoscopy may be attributed to the development of an appropriate atraumatic instrumentation and the CO2 laser. The major advantage of laparoscopic techniques is their availability at the time of diagnostic laparoscopy. Immediate opening of hydrosalpinges allows for precise evaluation of the tubal mucosa, thereby establishing prognosis. In cases with a severely altered mucosa, in vitro fertilization may be considered immediately. When the mucosa is satisfactory, laparoscopic fimbrioplasty or neosalpingostomy may be performed. Within 1 year after one of these procedures, a pregnancy is generally achieved in 1 of 3 patients.

Endometrial synthesis and secretion of complement component-3 by patients with and without endometriosis

In the present study we examined complement-3 (C3) synthesis and secretion from early proliferative endometrium of infertile patients with and without endometriosis. One gram of tissue was obtained by endometrial sampling at the time of diagnostic laparoscopy and incubated for 12 to 16 hours in the presence of radioactive methionine. Immunoprecipitation was performed with rabbit antihuman C3 immunoglobulin G and only a single 180-kDa radiolabeled protein (C3) was immunoprecipitated. This protein dissociates into 113- and 69-kDa subunits in the presence of dithiothreitol. The amount of C3 produced and secreted by the endometrium was quantitated as a percentage of counts per minute recovered by immunoprecipitation. Patients with minimal endometriosis produced significantly greater amounts of endometrial C3 than patients with no endometriosis or patients with severe endometriosis.

Combined Diagnostic Laparoscopy And Follicular Aspiration For Human In Vitro Fertilization

Laparoscopic retrieval of oocytes from stimulated follicles for in vitro fertilization and embryo transfer (IVF-ET) was performed at the time of diagnostic laparoscopy in 36 infertile women. Their mean rates of cleavage, embryo transfer and pregnancy did not differ from those obtained in 86 patients (101 cycles) who underwent ultrasonically guided transvaginal oocyte retrieval following diagnostic laparoscopy performed earlier as a separate procedure. In view of the advantages in terms of reduced patient morbidity, time and cost benefits, and the opportunity for oocyte-sperm compatibility testing in vitro, the combined procedure appears to be the best method in patients scheduled to undergo diagnostic laparoscopy.

Human peritoneal macrophages possess two populations of IgG Fc receptors

To characterize the binding properties of the Fc receptors on human macrophages, the binding of radiolabeled human IgG 1 to peritoneal macrophages was assessed. Cells were obtained at the time of diagnostic laparoscopy from women undergoing evaluation of infertility. Macrophages bound on the average more IgG 1 monomer than monocytes but the avidity with which both types of cells bound IgG 1 monomer was comparable. By contrast, macrophages bound much more IgG 1 dimers than monocytes. Scatchard plots of the binding of dimer to monocytes were linear, but plots of binding to macrophages were markedly curvilinear. This curvilinearity was not an artifact of extensive ligand internalization or catabolism by cells, since 80% of binding was reversible and there was very little catabolism of ligand in the medium. Assuming that the observed curvilinearity was due to the presence of two independent subpopulations of receptors, an objective estimate for the number of receptors per cell and of the avidity with which each subpopulation bound IgG 1 dimer was obtained using a previously described computer program (Scatfit). The analysis of the binding of dimer to macrophages from six donors suggested the presence of 42,000 ± 33,000 high avidity receptors per cell which bind IgG 1 dimer with a mean K aof 2.7 × 10 9 M −1 and 218,000 ± 127,000 low avidity receptors which bind the same ligand with a K a, of 1.1 × 10 7 M −1. ADCC of IgG antibody-coated sheep red blood cells mediated by macrophages was less readily inhibited by soluble IgG 1 monomer than ADCC mediated by peripheral blood monocytes. This provides further evidence for the presence of low avidity receptors which bind monomeric IgG 1 poorly and also suggests that these sites are functionally active in triggering antibody-dependent immune clearance.