First trimester screening for pre-eclampsia in Chinese pregnancies: case-control study.

OBJECTIVE: To assess the potential of screening for pre-eclampsia (PE) in a Chinese population. DESIGN: Case-control study. SETTING: Teaching hospital in Hong Kong. POPULATION: A total of 3330 women having a viable singleton pregnancy attending first-trimester Down-syndrome screening. METHODS: Mean arterial pressure (MAP), bilateral uterine artery pulsatility index (UtA-PI), and placental growth factor (PlGF) were measured. Screening markers were transformed to multiples of the gestational median (MoM) and adjusted for maternal and pregnancy characteristics. MoM distributions in PE and non-PE pregnancies were compared with published expected values. PE screening performance was assessed using area under receiver operating curves (AUROC). MAIN OUTCOME MEASURES: PE detection rate. RESULTS: A total of 30 (0.9%) women developed either early (<34 weeks) or late (≥34 weeks) onset PE. MAP was dependent on maternal BMI, UtA-PI on fetal crown rump length, uterine artery peak systolic velocity (UtA-PSV) on maternal age and gestation, and PlGF on gestation in non-PE pregnancies. MoM distributions determined using published Fetal Medicine Foundation models deviated significantly from one for both MAP (P < 0.0001) and PI (P < 0.0001), but not PlGF (P = 0.52) in non-PE pregnancies, whilst PlGF MoM distributions in those who developed early as opposed to late onset PE were significantly higher (P = <0.05). AUROC for any PE using multiple markers was 0.72 (95% CI: 0.64-0.81) with detection rates of 72 and 55% for early and late PE, respectively, for a 10% false positive rate. CONCLUSION: Detection rates for PE in our Chinese population were lower than the expected 90-95% even after adjusting MoM for local women's characteristics. FUNDING: General Research Fund (Project number 470513). TWEETABLE ABSTRACT: Pre-eclampsia screening in the Chinese population had detection rates lower than previously published results.

Triplet pregnancy with fetal reduction: experience in Hong Kong.

INTRODUCTION: Triplet and higher-order multiple pregnancies are well known to be associated with increased adverse outcomes. This study reviewed the perinatal outcomes in women with a triplet pregnancy who underwent fetal reduction versus expectant management at a university hospital in Hong Kong. METHODS: This was a retrospective review of triplet pregnancies at Prince of Wales Hospital in Hong Kong from 1 January 2008 to 30 September 2014. Women carrying a triplet pregnancy were classified as having had expectant management, fetal reduction to twins, or fetal reduction to a singleton. Maternal and pregnancy characteristics were compared. Outcome measures included fetal loss, gestational age at delivery, birth weight, neonatal survival rate, neonatal death, neonatal complications, and need for and length of neonatal intensive care unit stay. RESULTS: A total of 52 triplet pregnancies were identified. One pregnancy that was lost to follow-up and one that was terminated were excluded. The majority of pregnancies (84%) were the result of assisted reproductive technology. Fetal reduction was performed in 26 (52%) pregnancies, of which 22 were reduced to twins and four to a singleton. The mean gestations at delivery were 32.6, 35.2, and 39.6 weeks in the expectant management, fetal reduction to twins, and fetal reduction to a singleton groups, respectively. Significantly more pregnancies with expectant management resulted in a preterm birth. All pregnancies with fetal reduction to a singleton resulted in a term birth. A higher mean birth weight, lower neonatal death rate, and reduced need for admission to and length of stay in the neonatal intensive care unit were observed in the fetal reduction groups. CONCLUSIONS: Approximately 50% of women with a triplet pregnancy in Hong Kong elected to undergo fetal reduction. This was associated with a significant reduction in extreme preterm delivery and associated morbidity and mortality.

Randomized trial of anaesthetic interventions in external cephalic version for breech presentation.

BACKGROUND: Successful external cephalic version (ECV) for breech presenting fetus reduces the need for Caesarean section (CS). We aimed to compare the success rate of ECV with either spinal anaesthesia (SA) or i.v. analgesia using remifentanil. METHODS: In a double-phased, stratified randomized blinded controlled study we compared the success rates of ECV, performed under spinal anaesthesia (SA), i.v. analgesia (IVA) using remifentanil or no anaesthetic interventions. In phase I, 189 patients were stratified by parity before randomization to ECV, performed by blinded operators, under SA using either hyperbaric bupivacaine 9 mg with fentanyl 15 µg, i.v. remifentanil infusion 0.1 µg kg min(-1), or Control (no anaesthetic intervention). Operators performing ECV were blinded to the treatment allocation. In phase 2, patients in the Control group in whom the initial ECV failed were further randomized to receive either SA (n=9) or IVA (n=9) for a re-attempt. The primary outcome was the incidence of successful ECV. RESULTS: The success rate in Phase 1 was greatest using SA [52/63 (83%)], compared with IVA [40/63 (64%)] and Control [40/63 (64%)], (P=0.027). Median [IQR] pain scores on a visual analogue scale (range 0-100), were 0 [0-0] with SA, 35 [0-60] with IVA and 50 [30-75] in the Control group (P<0.001). Median [IQR] VAS sedation scores were highest with IVA [75 (50-80)], followed by SA, [0 (0-50)] and Control [0 (0-0)]. In phase 2, 7/9 (78%) of ECV re-attempts were successful with SA, whereas all re-attempts using IVA failed (P=0.0007). The incidence of fetal bradycardia necessitating emergency CS within 30 min, was similar among groups; 1.6% (1/63) in the SA and IVA groups and 3.2% (2/63) in the Control group. CONCLUSIONS: SA increased the success rate and reduced pain for both primary and re-attempts of ECV, whereas IVA using remifentanil infusion only reduced the pain. There was no significant increase in the incidence of fetal bradycardia or emergency CS, with ECV performed under anaesthetic interventions. Relaxation of the abdominal muscles from SA appears to underlie the improved outcomes for ECV.

Maternal hepatitis B surface antigen status and incidence of pre-eclampsia.

The relationship between chronic hepatitis B virus (HBV) infection with atherosclerosis and cardiovascular disorders remains unclear, and the impact of maternal HBV infection on the development of pregnancy-induced hypertension (PIH) and pre-eclampsia (PE) is also controversial. This retrospective cohort study was conducted to examine the relationship between maternal hepatitis B surface antigen (HBsAg) status with PIH and PE in singleton pregnancies that delivered at 24 weeks of gestation and beyond. Among the 86 537 cases in the cohort, 10% were HBsAg positive, and overall 2.0% had PIH, of whom 56.3% developed PE. HBsAg-positive women had higher weight and body mass index (BMI), but lower incidences of advanced age, nulliparity, PIH (1.6% vs 2.0%, P = 0.007) and PE (0.8% vs 1.1%, P = 0.005). On multiple logistic regression analysis adjusting for the effects of nulliparity, advanced age, high BMI, and underlying renal, cardiac and autoimmune diseases, HBsAg carriage was associated with significantly reduced incidence of PIH (aOR 0.79, 95% CI 0.66-0.95) and PE (aOR 0.71, 95% CI 0.56-0.91). Our results indicate that maternal HBsAg carriage is independently associated with reduced PE. As chronic HBV infection alters the immune response of the individual, our observation could be related to enhanced maternal immunotolerance of the foetus and hence a reduction in the incidence of PE. The implications of our findings on the long-term health outcome of the infected women, from cardiovascular morbidity to malignancies, warrant further studies.

Maternal HBsAg status and infant size--a Faustian bargain?

Information on the impact of maternal hepatitis B virus (HBV) infection on pregnancy outcome is conflicting. Some studies reported an association with increased infant birthweight, which could be interpreted as advantageous to pregnancy. A retrospective study was performed to compare birthweight outcome between 6261 and 55,817 singleton pregnancies in mothers screened positive and negative for hepatitis B surface antigen (HBsAg), respectively. The HBsAg positive women were younger, had higher body mass index (BMI) and incidence of overweight, but less gestational weight gain, and were associated with increased macrosomia (birthweight ≥4000 g) in mothers <35 years (odds ratio, OR, 1.28), BMI ≥25 kg/m(2) (OR 1.24), without gestational diabetes mellitus (GDM, OR 1.19), and in male infants (OR 1.18). It was also associated with increased large-for-gestational age (LGA, birthweight >90th percentile) infants in nulliparas (OR 1.13), age <35 years (OR 1.12), BMI ≥25 kg/m(2) (OR 1.19), with (OR 1.36) and without (OR 1.09) GDM, and in male infants (OR 1.13). When the effects of high BMI, advanced age, GDM, and male infants were controlled for, positive HBsAg was significantly associated with macrosomic (adjusted odds ratio, aOR, 1.15) and LGA (aOR 1.11) infants. In view of the latest findings on the association between high infant birthweight with increased risk of obesity, diabetes mellitus, and various forms of malignancies from childhood to adulthood, further studies are warranted to determine if maternal hepatitis B infection would impact adversely on the long-term health of the offspring through its effect on increasing birthweight.

Intrapleural injection of OK-432 as the primary in-utero treatment for fetal chylothorax.

Chylothorax is a rare congenital condition associated with significant perinatal mortality and morbidity. Previous treatments with repeated thoracocentesis or thoracoamniotic shunting were technically demanding, and associated with significant procedure-related complications and neonatal complications. Here we report the first successful case in Hong Kong treated by a simple and effective intervention, namely pleurodesis with OK-432, in a fetus presenting at 20 weeks of gestation with bilateral pleural effusion.

Comparison of first-trimester contingent screening strategies for Down syndrome.

OBJECTIVE: To assess the relative performance of a multi-stage first-trimester screening protocol for fetal Down syndrome. METHODS: Data from 10,767 women who underwent combined ultrasound and biochemistry (BC) screening in the first trimester were reanalyzed using a contingent model approach. Amongst the 10,854 fetuses with known outcome, 32 had Down syndrome, 232 had other abnormalities and 10,590 were unaffected. Nuchal translucency (NT), BC and combined (NT-BC) gestational age-specific risks were calculated for each individual using The Fetal Medicine Foundation risk calculation algorithms (Mixture Model and Biochemistry). Individual patients were categorized as at low, high or intermediate risk according to one of the following three strategies. In 'Strategy-NT-BC' initial screening was performed using both NT and BC. In 'Strategy-BC' initial screening was undertaken using maternal serum markers followed by NT assessment in those with an intermediate risk (1 : 51 < risk

Which ultrasound or biochemical markers are independent predictors of small-for-gestational age?

OBJECTIVES: To investigate which ultrasound or biochemical markers in both the first and the second trimesters are the best predictors for fetal growth and small-for-gestational age (SGA). METHODS: This was a prospective study of 619 Chinese women with a singleton pregnancy. At 11 to 13 + 6 weeks, fetal crown-rump length (CRL), placental volume (PlaV), uterine artery pulsatility index (UtA-PI), and the maternal serum levels of pregnancy-associated plasma protein-A (PAPP-A) and free beta-human chorionic gonadotropin (beta-hCG) were measured. Fetal biparietal diameter, femur length, abdominal and head circumference, PlaV and UtA-PI were then measured at 18-22 weeks. All markers were transformed to gestational age-specific Z-scores or multiples of the median (MoM). Birth weights were also transformed to Z-scores using the individualized gestational age-related optimal weight based on a locally derived nomogram. The relationship between all markers and the customized birth weight were examined, and their predictive powers for SGA were examined by regression analysis. RESULTS: Univariate analysis revealed that all markers except free beta-hCG correlated with birth weight Z-score. After multiple linear regression analysis, only PlaV, UtA-PI and CRL in the first trimester, and PlaV and UtA-PI in the second trimester, stood out as independent markers. Logistic regression analysis showed that PlaV was the only independent first-trimester predictor of SGA, and in the second trimester both PlaV and UtA-PI were independent predictors. The sensitivity of these first- and second-trimester markers in predicting SGA were 41% and 45%, respectively, at a false-positive rate of 20%. Combining them did not significantly improve prediction of SGA. CONCLUSIONS: Among the various known ultrasound and biochemical markers, only the first-trimester PlaV and the second-trimester PlaV plus UtA-PI are independent predictors for SGA.

First-trimester fetal nasal bone length in an ethnic Chinese population.

OBJECTIVES: To determine reference ranges of fetal nasal bone length (NBL) in a Chinese population and to assess the value of NBL measurement in screening for chromosomal defects in the first trimester. METHODS: In this prospective study the fetal profile was examined and the fetal NBL and crown-rump length (CRL) were measured in Chinese women presenting with singleton pregnancies for first-trimester screening for aneuploidy between January 2004 and June 2007. Screening was performed on the basis of nuchal translucency (NT) measurement and maternal serum free beta-human chorionic gonadotropin and pregnancy-associated plasma protein-A levels. RESULTS: NBL was measured in 7543 fetuses, of which 7517 were euploid. The best fit equation for median NBL in euploid fetuses in relation to CRL was: NBL (mm) = 0.4593 + (0.0186 x CRL(mm)). The NBL for gestational age (GA, in days) was given by the equation NBL(mm) = 0.2392 + (0.0027 x GA). There was no correlation between log(10)(NBL multiples of the median (MoM)) and log(10)(NT MoM) in unaffected pregnancies (r = - 0.009; P = 0.43). Only two of the 11 cases with trisomy 21 had an NBL outside the 5(th) or 95(th) centiles of the reference range for euploid fetuses. CONCLUSION: Reference ranges for NBL in a Chinese population suitable for screening for aneuploidy between 11 and 13 + 6 weeks' gestation have been derived. The NBL in Chinese fetuses is similar to that of other ethnic groups. However, unlike the determination of presence vs. absence of the nasal bone, NBL measurement is unlikely to further improve screening for aneuploidy.

Medians and correction factors for biochemical and ultrasound markers in Chinese women undergoing first-trimester screening for trisomy 21.

OBJECTIVE: To establish normative values and distribution parameters of first-trimester maternal serum free beta-human chorionic gonadotropin (beta-hCG), pregnancy-associated plasma protein-A (PAPP-A) and fetal nuchal translucency (NT) thickness in Chinese women and to examine the effects of covariates on their levels. METHODS: Maternal serum free beta-hCG, PAPP-A and fetal NT were measured in 9762 women presenting for first-trimester combined screening for Down syndrome at 11 to 14 weeks of gestation. Individuals' markers were converted to multiples of the median (MoM) using expected medians estimated by performing a weighted regression analysis. Multivariate regression analysis was performed to assess the influence of maternal weight, parity, ethnicity, chorionicity in twin pregnancies, smoking, insulin-dependent diabetes and mode of conception on individual marker MoM levels. RESULTS: Both free beta-hCG and PAPP-A median values demonstrated an exponential relationship with gestational age in days. Multivariate regression analysis indicated that free beta-hCG MoM was statistically significantly dependent on maternal weight (P < 0.0001) and chorionicity in twin pregnancy (both monochorionic and dichorionic P < 0.0001), that PAPP-A MoM was dependent on maternal weight (P < 0.0001), parity (P < 0.0001), chorionicity in twin pregnancy (both monochorionic and dichorionic P < 0.0001) and mode of conception (P = 0.002), and that fetal NT-MoM was dependent on maternal weight (P = 0.0006) and mode of conception (P = 0.012). CONCLUSION: Normative values have been generated to allow conversion of NT, free beta-hCG and PAPP-A to their MoM equivalents and correction factors have been determined to adjust for maternal and pregnancy characteristics for use in ethnic Chinese women undergoing first-trimester screening for aneuploidy.

De novo 16p13.11 microdeletion identified by high-resolution array CGH in a fetus with increased nuchal translucency.

OBJECTIVE: We investigated the application of high-resolution microarray-based comparative genomic hybridisation (array CGH) on a fetus showing increased nuchal translucency (NT). DESIGN: Case study. SETTING: Tertiary referral obstetrics unit. SAMPLE: Pregnant woman attended the antenatal clinic. METHODS: Conventional karyotyping and genetic test was carried out for the alpha-globin gene. High-resolution array CGH using the high-density 244K Agilent microarray was performed on fetal blood sample by cordocentesis to investigate the possibility of any genomic imbalance. MAIN OUTCOME MEASURES: Detection of chromosomal abnormality. RESULTS: Karyotyping analysis showed 46,XY. Molecular genetic diagnosis confirms the fetus has Hb-H constant spring disease but cannot explain the increased NT to 3.2 mm. Array CGH analysis discovered a 1.32-Mb microdeletion on chromosome 16p13.11. Deletion at 16p13.11 has been implicated to predispose to autism and/or mental retardation. Baby was delivered at 40 weeks of gestation, and follow up was carried out at 3 months of age without sign of mental retardation/developmental delay. CONCLUSIONS: This case study demonstrated that array CGH can accurately calibrate the size and identify de novo interstitial chromosome imbalances. However, the presence of chromosome copy variants with unknown clinical significance currently limits its wider scale application in prenatal diagnosis and needs further investigations.

Prediction of birth weight by fetal crown-rump length and maternal serum levels of pregnancy-associated plasma protein-A in the first trimester.

OBJECTIVE: To determine whether the first trimester crown-rump length (CRL), maternal serum levels of pregnancy-associated plasma protein A (PAPP-A) and free beta-human chorionic gonadotropin (fbeta-hCG) are independent predictors of birth weight. METHODS: This was an observational study over 1.5 years in Chinese patients who underwent first-trimester combined screening for Down syndrome in a University fetal medicine unit. After excluding cases with multiple pregnancies, congenital malformations and in-utero deaths, the relationship between fetal CRL (expressed as standardized Z-score (Z-CRL)), maternal PAPP-A and fbeta-hCG levels (expressed as log(10) of multiples of the median) and birth weight (Z-BW) were analyzed by Pearson's correlation test followed by multiple regression to check for their independency. The predictive power of the independent predictors for small-for-gestational age (SGA, defined as birth weight < 10(th) centile) was then assessed using receiver-operating characteristics (ROC) curves, and the likelihood ratios were derived. RESULTS: A total of 2760 cases were included. Z-CRL, log(10) PAPP-A(MoM), and log(10) fbeta-hCG were positively correlated with Z-BW (P < 0.0001), but only Z-CRL and log(10) PAPP-A(MoM) were independent predictors (P < 0.0001). The areas under the ROC curves of PAPP-A(MoM) and Z-CRL were 0.608 and 0.593, respectively (P < 0.0001). Likelihood ratios increased with decreasing PAPP-A(MoM) and Z-CRL, but were around 1 when the markers were at or above the mean. CONCLUSION: First-trimester CRL and PAPP-A are independent factors that influence final birth weight. The lower the PAPP-A and the smaller the CRL, the higher the risk of a fetus becoming SGA. However, their predictive powers are not sufficiently good for them to be used alone for SGA screening.

The role of laparoscopic surgery in the management of tubal prolapse: a 7 case series and literature review.

Fallopian tube prolapse is an unusual complication after hysterectomy. Different surgical options have been proposed, including abdominal, vaginal, and combined laparoscopic approaches, with partial or complete salpingectomy. This article presents experience in the management of 7 cases of fallopian tube prolapse with different surgical approaches according to the characteristics of the case. Additionally, 6 cases were reported in the English literature between 1960 and 2006 that required a second procedure after vaginal partial salpingectomy, and the causes of failure were reviewed. It is suggested that the choice between abdominal, vaginal, and combined laparoscopic approach with partial or complete salpingectomy in the management of prolapsed tubes must be decided individually, according to the patient's characteristics and the presenting symptoms. Laparoscopic surgery has a role in cases with dense intraperitoneal adhesions. It safely enables the mobilization of the prolapsed tube, allowing complete removal of the structure and resolution of symptoms.

Prediction of intrapartum Cesarean delivery for non-reassuring fetal status after a successful external cephalic version by a low pre-version pulsatility index of the fetal middle cerebral artery.

OBJECTIVE: To determine whether a pre-version Doppler assessment of fetal cerebral and umbilical blood flow can predict the ultimate need for intrapartum Cesarean delivery after a successful external cephalic version (ECV). METHODS: A prospective observational study on women undergoing ECV between 36 and 38 gestational weeks was performed over a 5-year period. The pulsatility index (PI) of the fetal middle cerebral artery (MCA) and umbilical artery, heart rate and amniotic fluid index were measured before ECV. Women who had successful ECV were then divided into three groups according to the mode of delivery: (1) vaginal delivery, (2) intrapartum Cesarean delivery for poor progress and (3) intrapartum Cesarean delivery for non-reassuring fetal status. The fetal blood flow parameters were compared between the groups. Potential predictors were further analyzed using receiver-operating characteristics curves. RESULTS: Of 174 women with successful ECV, 140 (80.5%) had vaginal delivery, 19 (10.9%) required emergency intrapartum Cesarean delivery for non-reassuring fetal status and 15 (8.6%) for poor progress. MCA-PI was significantly lower in the group with non-reassuring fetal status. MCA-PI is predictive of intrapartum Cesarean delivery (area under the curve = 0.68, P = 0.021). The sensitivity and specificity at a cut-off level of 1.4 were 62.5% and 76%, respectively, while at a cut-off level of 1.5 they were 68.8% and 63.5%, respectively. CONCLUSION: Intrapartum Cesarean delivery for non-reassuring fetal status after successful ECV is associated with a lower pre-version fetal MCA-PI.

An unusual case of bilateral ureteric obstruction after anterior colporrhaphy and vaginal hysterectomy for pelvic organ prolapse.

We report a case of bilateral ureteric obstruction after anterior colporrhaphy. The excessive folding of the bladder trigone after anterior colporrhaphy led to occlusion of both ureteric orifices.

Melanosomal proteins as melanoma-specific immune targets.

Pigmentation of our skin, hair and eyes is essential for photoprotection, embryological development, detoxification and protective/cosmetic coloration. A number of proteins important to the production of melanin within melanosomes have now been identified including enzymatic and structural proteins encoded at the murine albino, brown, pinkeyed-dilution, MART1, slaty and silver loci. Interestingly, many of those melanosomal proteins (including epitopes derived from tyrosinase, TRP1/gp75, silver/gp100 and MART1/melan-A) function in vivo as targets of humoral and cellular autoimmune responses directed specifically against normal or transformed melanocytes. These findings have provided new impetus to research on immune responses to melanoma and, perhaps more importantly, examining why they are insufficient to provide protection against tumour growth and what type of immune therapy can be designed to correct that. The melanosome must now be considered beyond its function in pigmentation, and assumes the role of a valuable source for specific immune targets for malignant melanoma.

Novel experimental approaches to melanoma diagnosis and therapy.

We have investigated the potential use of immune therapies on the growth of melanoma metastases in a new animal model that more closely approximates the clinical situation. We have found that significant benefits towards decreased metastatic growth and subsequent animal survival can be achieved by treatment of tumor-bearing mice with melanoma-specific monoclonal antibodies or alternatively, with various types of monovalent or polyvalent vaccines. The beneficial effects of those vaccines can be significantly enhanced by concomitant interleukin-2 therapy.

Characterization of cloned class I MHC-restricted, CD8+ anti-Meth A cytotoxic T-lymphocytes: recognition of an epitope derived from the Meth A gp110 tumor rejection antigen.

Meth A gp110 has been tentatively identified as a tumor rejection antigen. Following isolation of a class I major histocompatibility complex (MHC)-restricted, CD8+ anti-Meth A cytotoxic T-lymphocyte (CTL), we sought to determine whether the determinant recognized by this CTL was: (a) functional in tumor rejection of Meth A sarcoma; and (b) derived from Meth A gp110. Initially, we isolated an anti-Meth A CTL-resistant variant of Meth A sarcoma, Meth A4R, by immunoselection. The results of the subsequent analysis of Meth A4R cells showed the CTL-defined determinant as having a functional role in transplantation rejection of Meth A sarcoma. Walker et al. (Proc. Natl. Acad. Sci. USA, 89: 7915-7918, 1993) showed that the cationic lipid, N-[1-(2,3-dioleoyloxy)propyl]-N,N,N- trimethylammonium-methyl sulfate, mediated delivery of a recombinant glycoprotein into the cytosol of target cells, making it available for processing and presentation by class I MHC molecules. As a result, the cells were sensitized for cytolysis by a class I MHC-restricted CD8+ CTL, which recognized an epitope expressed by the glycoprotein. In a similar manner, we treated the SV40-transformed BALB/c cell line, SVBalb, which is relatively insensitive to cytolysis by the anti-Meth A CTL, with Meth A gp110 and N-[1-(2,3-dioleoyloxy)propyl]-N,N,N-trimethylammonium methyl sulfate. The sensitivities of the treated cells and control cell lines to the anti-Meth A CTL were then examined. The results of these experiments permit us to conclude that the determinant recognized by the anti-Meth A CTL line is derived from Meth A gp110.

Further studies of the therapeutic effects of murine melanoma-specific monoclonal antibodies.

The results presented here further characterize four murine monoclonal antibodies (mAb) that recognize melanoma-specific antigens (9B6, T97, 2-3-1 and 2-3-3). These melanoma-specific mAbs are of the IgG2b isotype and are significantly therapeutic when administered systemically against established pulmonary melanoma metastases. Here we show a consistent and significant inhibition of the growth of melanoma lung metastases by all four mAbs and the existence of a time 'window' at days 5-8 after tumor inoculation for optimal therapy. Since these mAbs were found not to be cytotoxic or cytolytic in vitro, we looked for host immune response regulation as being responsible for the therapeutic effects. Natural killer (NK) cells were implicated as one arm of the host immune system involved in this response since depletion of NK cells in vivo by alpha asialoGM1 or alpha NK1.1 antibodies partially abrogated the inhibitory effect of the mAbs. The observed antimetastatic effects could also be partially abrogated using antibodies directed against the T-cell subset surface markers, CD4+ and CD8+. Intramuscular melanoma tumor growth was also found to be suppressed by mAb 2-3-1, but only if administered in the area of tumor growth and only if multiple inoculations are administered over a 13-day period. The beneficial effect of mAb antimetastatic therapy was found to be useful against several syngeneic melanomas, including JB/MS, B16 and several sublines of the B16 F10 melanoma.