Result of the implementation of multidisciplinary teams in rectal cancer.

AIM: In 2003 colorectal multidisciplinary teams (MDTs) were established in all major Danish hospitals treating colorectal cancer. The aim was to improve the prognosis by multidisciplinary evaluation and decision about surgical and oncological treatment, based on medical history, clinical examination, imaging, histology and comorbidity. The present study evaluates the effect of the introduction of colorectal MDTs on 1 August 2004 in two Danish hospitals. METHOD: A retrospective cohort study was conducted comparing the outcome during the last 3 years before introduction of MDTs with the first 2 years after (the MDT cohort). The national colorectal cancer database, with follow-up recorded by the National Patient Registry in September 2010 was used. The end-points included the incidence of preoperative radiochemotherapy offered according to the national guidelines, R0/R1/R2 resection, postoperative mortality, local recurrence, distant recurrence and over-all and disease-free survival. RESULTS: Eight hundred and eleven patients were diagnosed with primary rectal cancer in Hvidovre and Bispebjerg hospitals between 1 May 2001 and 31 August 2006. The frequency of preoperative MRI scans increased in the MDT cohort and perioperative mortality decreased. More metachronous distant metastases were found in the MDT cohort but there was no difference in overall survival. CONCLUSION: There was an improved postoperative mortality but no other potential benefits for the patients were seen after the implementation of colorectal MDTs.

Sessile serrated polyps of the colorectum are rare in patients with Lynch syndrome and in familial colorectal cancer families.

Whereas the generally accepted carcinogenesis pathway of the microsatellite instabile high (MSI-H) colorectal carcinoma (CRC) involves the traditional adenoma in patients with Lynch syndrome, a serrate pathway involving serrate adenomas (SA) and sessile serrate polyps (SSP) characterize the sporadic MSI-H counterpart. Recent studies have, however, challenged such simple one-pathway models, inviting the consideration of alternative, unexpected pathways. Here, the issue as to the possible role of SSP, primarily in the context of Lynch syndrome, but also in subjects from familial CRC families (FCF) is addressed. Polyps coded as hyperplastic polyps (HP) from subjects with Lynch syndrome and FCF enrolled in the HNPCC-register at the Hvidovre University Hospital as well as adenomas from this population were retrieved and reviewed for features of SSP. Ninety-eight polyps coded as HP and 41 polyps coded as adenoma from 14 individuals with Lynch syndrome as well as 17 individuals from FCF constituted the study material. Seven of the 98 polyps coded as HP displayed histological features that, to varying extent, deviated from the traditional HP (THP), yet, merely two of these, both from the FCF, were considered examples of probable SSP. None of the 41 cases coded as adenoma possessed a morphology that qualified as SSP. The prevalence of SSP was not increased as compared to the background population and thus, this serrated lesion does not appear to play a tumorigenic role in Lynch syndrome, nor in FCF.

Endothelial cell nitric oxide synthase in peritumoral microvessels is a favorable prognostic indicator in premenopausal breast cancer patients.

Nitric oxide (NO) is involved in tumor cell apoptosis and has additional effects on tumor blood flow, immune responses, and angiogenesis. We, therefore, studied endothelial cell NO synthase (ecNOS) protein expression in a retrospective series of 118 patients with primary invasive breast cancer. Immunocytochemically stained paraffin sections were used for determining the frequency of (a) tumor cells, (b) intratumoral microvessels, and (c) peritumoral microvessels that were positive for ecNOS. A high density of ecNOS positive microvessels in the normal tissue surrounding the tumor (measured by the variable PEMVD) was associated with significantly better recurrence-free and overall survival. The prognostic significance was observed in a representative series of premenopausal patients and was independent of other factors, including lymph node status. The counting procedure was highly reproducible and correlated to stereological measurements but was influenced by heterogeneity of the tissue samples. Analyzing two sections per patient improved the discriminative power by reducing the influence of tissue heterogeneity and produced highly significant results (recurrence-free survival, P < 0.001; overall survival, P < 0.0001). Immunoreactive ecNOS in microvessels is an independent prognostic factor in breast cancer and may reflect a mechanism of endothelial defense against invasion by tumor cells. Individual variations in ecNOS may be related to environmental, hormonal, and genetic factors and could represent a therapeutic target.

HIV infection and breast-feeding: policy implications through a decision analysis model.

OBJECTIVES: (1) To develop a comprehensive decision analysis model to compare mortality associated with HIV transmission from breast-feeding with the mortality from not breast-feeding in different populations and (2) to perform sensitivity analyses to illustrate critical boundaries for guiding research and policy. METHODS: Using a decision tree, mortality rates were estimated for all children, children born to mothers infected during pregnancy, and children born to mothers who were uninfected at delivery. Given various assumptions about child mortality rates, relative risks of mortality among children who are not breast-fed compared with those who are (R), rates of HIV transmission from breast-feeding, HIV prevalence, and HIV incidence, scenarios were created and sensitivity analysis used to delineate critical boundaries. RESULTS: Our model shows that only in situations where R is approximately < or = 1.5 and HIV incidence/prevalence is high (prevalence > 10%, incidence > 5%) would universal breast-feeding result in equal or higher mortality compared with non-breast-feeding. Among populations in many developing countries, where there is a high relative risk of mortality if breast-feeding is not practiced, if R > 3, overall mortality is almost always lower among children who are breast-fed, even by HIV-infected mothers. In situations where maternal HIV status is known, the decision whether to breast-feed is largely dependent on the magnitude of additional mortality risk if the child is not breast-fed. The model illustrates the importance of distinguishing between population and individual recommendations. CONCLUSIONS: Based on available data, the model supports current World Health Organization and Centers for Disease Control recommendations on HIV infection and breast-feeding. Given the importance of breast-feeding and the global impact of HIV infection, more research is needed, especially to clarify the range of HIV transmission rates from breast-feeding and to expand specific assessments of relative risks for different areas of the world.

PIP: HIV/AIDS specialists have developed and applied 3 different scenarios to a comprehensive decision analysis model to estimate mortality rates for children of mothers infected with HIV during pregnancy and for children of mothers who were not infected with HIV during delivery. Scenario I represents Central Africa where HIV prevalence and incidence are high. Some scenario I assumptions are HIV prevalence in pregnant women of 30% and proportion of initially uninfected women who become infected after delivery during lactation (d) of 6%. Scenario II is a population where HIV epidemic is rather recent (e.g., some parts of Asia). Its assumptions are HIV prevalence of 5%, and s is 2%. Scenario III symbolizes high-risk populations in North America and Western Europe (HIV prevalence and s = 1%). The scenarios also consider child mortality rates and relative risks (RRs) of mortality of breast fed children and those who were not breast fed. Universal breast feeding would effect equal or higher mortality than non-breast feeding, when the RR of mortality is no more than 1.5 and HIV prevalence/incidence is high (high prevalence = 10% and high incidence = 5%). In developing countries, where the RR of mortality is high if children are not breast fed (RR 3), breast fed children have almost always lower child mortality than those who are not breast fed, regardless of HIV infection status. The decision to breast feed when the HIV status is known depends greatly on the degree of an additional mortality risk if an infant is not breast fed. The model substantiates WHO and CDC recommendations: HIV-positive women in the UK and the US should not breast feed, while those in developing countries with high RR of child mortality should breast feed. Additional research would define the range of HIV transmission rates from breast feeding and increase specific assessments of RRs for various parts of the world.

Medullary carcinoma of the breast. Prevalence and prognostic importance of classical risk factors in breast cancer.

In an earlier study of 235 breast cancers with medullary features, we concluded from a multivariate Cox regression analysis that only four histopathological features contained significantly positive prognostic information. In the present study, continuing our work on the same population base, we used these histological characteristics (predominantly syncytial growth pattern, no tubular component, diffuse stromal infiltration with mononuclear cells and sparse necrosis (< 25%), as diagnostic criteria for medullary carcinoma of the breast (MC). We found a significantly better prognosis for patients with MC than those with non-medullary carcinoma (NMC) or infiltrating ductal carcinoma (IDC). All tumours in the MC group were grade II or III (96% grade III). A significantly different distribution of general risk factors such as lymph node status, invasion, steroid receptor status, and menopausal status, was found between the group of MC and the control group of IDC grades II + III. Further, general risk factors, which are found to be of major prognostic importance in IDC, had little prognostic impact in MC. We found MC to be biologically unique, and patients with MC have a better than average prognosis compared to that of IDC. We propose a new histological definition of MC, but stress that prospective studies have to be performed.

Medullary carcinoma of the breast, prognostic importance of characteristic histopathological features evaluated in a multivariate Cox analysis.

In this study of 136 breast cancers with medullary features (MC), registered in the Danish Breast Cancer Cooperative Group (DBCG) from 1982 to 1987, we confirmed the prognostic importance of a new definition of medullary carcinoma of the breast (MC newdef) which was recently proposed by us, deduced from a previous study of a corresponding tumour material (DBCG 77-82). However, the individual histological criteria did not have the same prognostic importance as in our previous study, although prognostic trends were the same. To further improve and validate the diagnostic criteria, we combined the two populations and performed a multivariate Cox regression analysis. In the final Cox model, four histological parameters retained positive prognostic importance: (1) predominantly syncytial growth pattern, (2) no tubular component, (3) diffuse stromal infiltration with mononuclear cells and (4) sparse necrosis. We propose that these criteria are emphasized in the histological diagnosis of medullary carcinoma of the breast.

Campylobacter pylori detected by indirect immunohistochemical technique.

An immunohistochemical assay for staining C. pylori is described. The method is compared with cultivation of C. pylori and observation of campylobacter-like organisms (CLOs) in hematoxyline-eosine (HE) stained sections. Eighteen biopsies from which C. pylori was cultivated but not seen in HE stained sections and three culture negative biopsies with CLOs seen in HE stained sections were selected from 331 biopsies including 113 culture positive biopsies. There were agreements between cultivation of C. pylori and CLOs seen in HE stained sections in the remaining 310 biopsies. Fourteen of the 18 and one of the three biopsies were found positive by the immunohistochemical assay. In addition 21 culture-positive control biopsies and one of 18 culture-negative control biopsies were also found positive. When the immunohistochemical assay was compared with cultivation the predictive value of positive result is 93% and of negative result 89%. By this method we were able to detect single organisms and no cross-reactions to other curved bacteria on the gastric epithelium were observed.

Extraorbital giant cell angiofibroma.

A number of intriguing fibrovascular mesenchymal proliferations with benign or low grade malignant potential have recently been described. Giant cell angiofibroma was introduced as an entity by Dei Tos et al. in 1995 and initially considered to be a lesion of the orbit. We describe an extraorbital example, indicating that giant cell angiofibroma is not confined to the orbit. Immunologically, giant cell angiofibroma is positive for CD 34, bcl-2 and vimentin, and negative for epithelial and muscle markers, and S-100. The tumor shares several morphological and immunological properties with giant cell fibroblastoma and solitary fibrous tumor, yet it features a histology sufficiently characteristic to allow its categorization as a separate entity. The recommended treatment is complete but conservative excision. Metastases have not been reported.

The prognostic importance of syncytial growth pattern in medullary carcinoma of the breast.

The histopathological criteria for medullary carcinoma of the breast (MC) used by most pathologists today were delineated by Ridolfi et al. in 1977. The prime criterion is: "A predominantly syncytial growth pattern", predominantly being defined as including 75% or more of the tumour. However, no indication has been given as to why this limit was set at 75%. The present study analyzes the prognostic importance of the extent of syncytial growth in a population of 102 breast cancers with medullary features. Generally, we find a positive prognostic influence of an extensive syncytial growth. The prognostic importance of setting the limit for predominantly syncytial growth at 90% and at 75%, respectively, is evaluated. This comparative study provides no basis for changing the definition of predominantly syncytial growth pattern.

The Helicobacter (Campylobacter) pylori-colonized duodenal mucosa and gastric metaplasia.

Biopsies were obtained from non-ulcerated sites of the duodenum from 100 dyspeptic patients. Helicobacter (Campylobacter) pylori was cultivated from 19 of these biopsies. Active chronic duodenitis (ACD) was found in 17 biopsies and more than 5% gastric metaplasia in 20 biopsies. H. pylori as well as ACD occurred with a significantly increased frequency when more than 5% gastric metaplasia was found in the duodenal biopsies. H. pylori on metaplastic tissue without ACD was, however, seen in two cases. H. pylori was cultivated from 9% and ACD was found in 5% of the biopsies with less than 5% gastric metaplasia. Gastric metaplasia in the duodenum was found significantly more frequently in patients with endoscopic duodenitis or duodenal ulceration than in patients with normal endoscopy. No association between gastric metaplasia in the duodenum and gastric pH or serum antibodies against H. pylori was seen. This study indicates that there is an established, but not exclusive, connection between gastric metaplasia and the colonization of the duodenum by H. pylori, the most important role being played by the antral gastric mucosa rather than the duodenum.

Radiation-associated angiosarcoma of the small bowel. A case of multiploidy and a fulminant clinical course. Case report.

Angiosarcoma developing in unusual sites such as the gastrointestinal tract is not uncommonly associated with a known eliciting factor. Thus, among hitherto reported cases of angiosarcoma of the small bowel, five were radiation-associated. One additional example of ileal angiosarcoma induced by therapeutic irradiation of endometrial carcinoma is herein reported as a reminder of this causal association. DNA analyses of the primary growth as well as the metastatic deposits showed at least four aneuploid cell clones indicating genetic instability. This observation corresponds to the consistently poor prognosis of radiation-associated angiosarcoma of the small bowel.

The histopathology of human gastric mucosa inhabited by Helicobacter heilmannii-like (Gastrospirillum hominis) organisms, including the first culturable case.

The aim was to determine the prevalence of Helicobacter heilmannii-like organisms in human gastric biopsies and the associated histology compared with that of Helicobacter pylori-bearing gastric biopsies. Furthermore, the feasibility of culturing H. heilmannii was examined. A consecutive series of 727 gastric biopsies from 650 patients were prospectively scrutinized for H. heilmannii. Their distribution pattern was recorded as well as the affiliated morphology of the gastric mucosa. Additional biopsies from some of the patients were examined microbiologically. Four cases (0.6%)(95% confidence intervals: 0.01-1.2%) of the examined material harboured H. heilmannii. The bacterial burden was graded as sparse in three cases, moderate in one case. The distribution pattern was patchy; thus, in no case did all biopsies from one endoscopy comprise H. heilmannii. Adhesion to epithelial cells was infrequent. A mild gastritis, active in three cases, characterized all biopsies. Lymphoid aggregates occurred in biopsies from three patients. Micropapillary tufting of the epithelial layer and intestinal metaplasia were not apparent. Culture studies proved successful in the one of the four cases assayed. In conclusion the morphology of H. heilmannii-bearing mucosa deviates from that of H. pylori-associated mucosa by the absence of epithelial damage in the former. This observation can in part be explained by the predominant location of H. heilmannii at a distance from the epithelium in contrast to the conspicuous H. pylori adhesion to epithelial cells, coupled with a usually low bacterial burden and patchy occurrence of H. heilmannii as opposed to the generally more heavy infestation with H. pylori.

Prevalence of antibodies against heat-stable antigens from Helicobacter pylori in patients with dyspeptic symptoms and normal persons.

Heat-stable antigens from Helicobacter pylori were investigated for the detection of serum IgG, IgA and IgM antibodies against H. pylori by an ELISA technique. Antibody titers against H. pylori were measured in 167 dyspeptic patients, of whom 96 were H. pylori positive confirmed by culture or microscopy, and in 482 controls (0-98 years). Increased IgG antibody titers were found significantly more often in dyspeptic patients with active chronic gastritis than in patients with normal morphology, as well as in H. pylori-positive patients as compared to H. pylori-negative patients, independent of the endoscopic findings. The heat-stable antigens were compared with acid glycine-extracted antigens and a high degree of concordance was found in the results obtained with the two antigen preparations. The differences in the IgA antibody titers against H. pylori between H. pylori-positive and H. pylori-negative dyspeptic patients were significant and may be useful to confirm a borderline IgG result. No differences were found in IgM antibody titer between H. pylori-positive and -negative patients. The greatest age-dependent increase in IgG and IgA antibody titers was found in children, and if a lower cut-off level is used for children than for adults, as has been proposed, the proportion of people with increased antibody titers against H. pylori would be almost constant from the age of between five and 10 years until the time between 61 and 80 years. Comparison of H. pylori IgG antibodies with IgG antibodies against Campylobacter jejuni and total antibodies against cytomegalovirus (CMV) showed a greater similarity between H. pylori and C. jejuni (R = 0.51) than between H. pylori and CMV (R = 0.22). This may possibly be caused by cross-reactions between H. pylori and C. jejuni. The H. pylori heat-stabile antigen seems not to be very different from other crude H. pylori antigens like acid glycine-extracted antigens, but purification and characterization of the antigens are needed to improve antibody assays.

Verrucous carcinoma of urinary bladder.

A seventy-five-year-old man with a four-month history of dysuria had a verrucous squamous carcinoma harbored within a bladder diverticulum. Whereas this low-grade malignancy occasionally develops in bilharzial specimens, its occurrence in schistosome egg-negative bladders is distinctly uncommon, having been the subject of only 1 previous case report.

Gastric mucosal cytokine responses in Helicobacter pylori-infected patients with gastritis and peptic ulcers. Association with inflammatory parameters and bacteria load.

Helicobacter pylori is an important pathogen in gastroduodenal inflammation and ulceration. Several mechanisms have been proposed to explain its role. We studied the cytokine production patterns in situ in gastric mucosal biopsies from H. pylori-positive and H. pylori-negative patients with dyspepsia. Immunohistochemistry with monoclonal antibodies was used. The study showed enhanced expression of interleukin (IL) -8, IL-10 and interferon-gamma (IFN-gamma) in H. pylori infection and a significant association was found between these cytokines and the following parameters: bacteria load, chronic inflammation and activity. These parameters were significantly correlated with the cell markers CD19 and CD56. The study indicates a dual effect of H. pylori on the Th1 response, i.e. a stimulation of the response verified by increased IFN-gamma and a feed-back verified by an increase of the counterinflammatory IL-10, which may dampen the inflammatory and cytotoxic effect of the Th1 response. Furthermore, the study confirms the connection between increase of IL-8 and inflammatory activity in gastric mucosa in H. pylori infection.

Development of a PCR-based technique for detection of Helicobacter pylori.

A primer-set was designed for specific detection of genes that encode for 16S rRNA of Helicobacter pylori, using direct polymerase chain reaction (PCR). The primers were selected in the hypervariable regions, derived from a complete small subunit 16S rRNA sequence of the reference strain H. pylori CCUG 17874. The primer-set amplified a 537 base pair (bp) sequence specifically from chromosomal H. pylori DNA. Amplification of purified chromosomal H. pylori DNA was achieved at concentrations as low as 1 femto gram (fg), equivalent to 5 bacteria. Furthermore, as few as 1 lysed H. pylori cell was detected by this PCR technique. The specificity of the primers was 100%, since purified chromosomal DNA was detected from all 32 various H. pylori isolates, whereas no other bacteria species were detected, whether related to Helicobacter or not. The 16S rDNA primers successfully detected H. pylori in antral biopsy specimens collected from infected patients.

Quantification of microvessel density of breast carcinoma: an assessment of the inter- and intraobserver variation.

The density profile of microvessels (MVD) has recently emerged as a prognostically independent morphological marker of various malignancies, including carcinoma of the breast. MVD-scoring may thus afford the pathologist the opportunity to identify subsets of early stage breast cancer patients, which may benefit from adjuvant therapy. Reproducibility studies are, however, mandatory. Fifty sections of invasive breast carcinoma, immunolabelled for Factor VIII-related antigen, were scored independently by two observers for the number of vessel-profiles (v-p) in the following manner: 1) 250 randomly selected high power fields (HPF) were scored by two analysts to evaluate the agreement of the counting per se; and 2) the hot spot(s), i.e. the zones considered the most vessel rich, in the 50 sections were identified and scored twice to evaluate the agreement on selecting hot spots. When the observers evaluated MVD in the very same 250 HPF a median deviation of 2 v-p (10%) was produced. The interobserver disparity was further accentuated when the participants independently had to identify the hot spots with a median deviation of 6 v-p (13%). Intraobserver variation was approximately equal to the interobserver discordance. Divergences were most conspicuous in fields with a complex vasculature. In conclusion the v-p scoring resulted in substantial inter- and intraobserver variation both in selecting hot spots and in performing the scoring per se. Alternative-scoring techniques, including strict stereological principles, should be considered in the morphological evaluation of angiogenesis.

False-negative frozen section of sentinel lymph node biopsy for breast cancer.

A prospective study is presented of frozen section examinations (FS) performed in parallel with 265 consecutive sentinel lymph node procedures (SLNP) over a 20-month period. The final pathological study included immunohistochemistry (IHC) for keratin if the haematoxylin-eosin (HE)-stained section was tumour free. FS correctly identified node-positive or node-negative axillae in 235 cases. In 28 SLNPs the final examination gave a positive result not detected in the FS, resulting in reoperation. In 21 of these false-negative (FN) cases micrometastases (MIM) were present. There were no false-positive cases, but in two cases of lobular carcinoma the findings in the FS were equivocal, the final reports recording metastases in one but not in the other. Lobular carcinoma and other less common subtypes of carcinoma were overrepresented, ductal carcinoma not otherwise specified (NOS) being less likely to affect the FN findings.

Phase IV study of the injection Norigest in Pakistan.

A field study of the injectable contraceptive, norethisterone enanthate (NET-EN), was conducted in family planning clinics in Sind and Punjab provinces of Pakistan, to determine the acceptability and feasibility of providing NET-EN in government family planning clinics staffed by Family Welfare Visitors (FWVs). A total of 2147 women were recruited to the study, of whom approximately three-fourths had never previously used contraception. The overall discontinuation rate at one year was 78 per 100 women; the most common reason for discontinuation was bleeding disturbances, including amenorrhea, although returning to the clinic too late for an injection also accounted for a substantial proportion of the discontinuations. Given adequate training, FWVs were shown to be capable of providing NET-EN in family planning clinics, including managing the bleeding disturbances common with this method of contraception. No pregnancies were reported, demonstrating that the method is highly effective when used in a usual family planning clinic situation.

Lipid and biochemical changes after low-dose oral contraception.

A randomized double-blind study of the metabolic effects of 2 low-dose combined oral contraceptives was carried out in Singaporean women. The subjects comprised 58 women randomly allocated to two treatment groups (29 each): norethisterone 1 mg/ethinyl estradiol 35 micrograms (NET/EE) or levonorgestrel 150 micrograms/ethinyl estradiol 30 micrograms (LNG/EE) and a control group of 23 women using intra-uterine devices (IUD). Blood samples were taken on admission and at 3 and 12 months after pills or insertion of IUDs. Fasting glucose levels were decreased while 2h glucose and triglyceride were increased throughout the treatment period in NET/EE group [corrected]. LNG/EE group only showed significant increase of 2h glucose at 12 months and decrease of LDL cholesterol at 3 months while total cholesterol was significantly suppressed at 3 and 12 months [corrected]. The atherogenic index, LDL/HDL cholesterol was significantly reduced by 12 months. Both groups had no change in hemoglobin, hematocrit and total protein levels but alkaline phosphatase, bilirubin and aspartate transaminase (SGOT) were suppressed. While NET/EE suppressed albumin significantly, this was not observed with LNG/EE group. However, these differences observed with use of each pill preparations, were not so obvious between treatment groups and control. Changes in total, HDL and LDL cholesterol and SGOT were not significantly different than the IUD group. Furthermore, except for 2h glucose, there was no increase in the number of abnormal parameters after treatment. On the contrary, there was a reduction of abnormal values in most liver function parameters. Thus, except for glucose intolerance, the observed changes in metabolic parameters may not constitute any clinical significance.(ABSTRACT TRUNCATED AT 250 WORDS)

PIP: This randomized double-blind study of the metabolic effects of two low-dose oral contraceptives was conducted in 58 randomly selected Singaporean women. Study subjects were divided into two treatment groups: 1) norethisterone 1 mg/ethinyl estradiol 35 mcg (NET/EE) or levonorgestrel 150 mcg/ethinyl estradiol 30 mcg (LNG/EE) were given to 35 women; 2) a control group of 23 women using IUDs. Blood samples were taken on admission and at 3 and 12 months after pills or insertion of IUDs. Findings demonstrate a significant decrease in mean fasting glucose and in 2-hour glucose loading, while triglycerides were increased throughout the treatment period in the NET/EE group. The LNG/EE group only showed significant suppression of the 2-hour glucose loading at 12 months and low-density lipoprotein/high-density lipoprotein (LDL/HDL) cholesterol was significantly reduced by 12 months. Both groups had no change in hemoglobin, hematocrit and total protein levels, but alkaline phosphatase, bilirubin and aspartate transaminase (SGOT) were decreased. Decreased albumin was observed in the NET/EE group, but not in the LNG/EE group. Changes in total HDL and LDL cholesterol and SGOT were not significantly different in the treatment group compared to the IUD group, except for the 2-hour glucose loading. There was no increase in the number of abnormal parameters after treatment. On the contrary, there was a reduction of abnormal values in most liver function parameters. Thus, except for glucose intolerance, the observed changes in metabolic parameters may not be of any clinical significance.