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L Anderson

Publications and source records attributed to L Anderson.

At least 109 records · Page 6Linked to original sources

Prognostic significance of BCL-2 expression and bcl-2 major breakpoint region rearrangement in diffuse large cell non-Hodgkin's lymphoma: a British National Lymphoma Investigation Study.

The Bcl-2 protein is capable of preventing apoptosis, and in vitro evidence suggests a role in drug resistance. It is expressed and the gene is rearranged in a proportion of cases of large-cell non-Hodgkin's lymphoma (NHL), but the clinical significance of these findings is controversial. The purpose of this study was to determine the influence of both Bcl-2 expression and major breakpoint region (MBR) bcl-2 rearrangement in a large cohort of prospectively accrued patients with intermediate-grade B-cell NHL treated in a standardized manner. All patients with Working Formulation F, G, or H NHL treated with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy in British National Lymphoma investigation studies between July 1974 and April 1992 were considered for this study if the appropriate paraffin blocks were available. Paraffin sections from the diagnostic specimen were analyzed for evidence of MBR rearrangement using a polymerase chain reaction-based method, and for Bcl-2 expression using immunohistochemistry. Failure to achieve complete remission (CR), relapse, death from NHL, and deaths from all causes were used as end points to measure CR rate, actuarial relapse rate, actuarial survival from NHL, and actuarial overall survival. One hundred sixty-one suitable patients were identified and tested for the bcl-2 MBR translocation, with 27 (17%) found to be positive; 153 of these patients were tested with immunocytochemistry, and 84 (55%) showed evidence of Bcl-2 expression. For patients who achieved CR from the initial treatment, the relapse rate was significantly higher in those with Bcl-2 expression than in those without. In addition, multivariate analysis identified Bcl-2 expression as the only factor significantly related to relapse rate in the subjects measured. The cause-specific survival for NHL in the series as a whole was significantly lower in patients with Bcl-2 expression than in those without. MBR status had no significant influence on any of the outcome measures, but the number of MBR-positive patients was relatively small, and larger studies are required. In conclusion, in Working Formulation F, G, and H NHL of B-cell type, expression of Bcl-2 protein predicted independently for relapse.

Adult↗

Feasibility study of the treatment of primary unresectable carcinoma of the pancreas with 103Pd brachytherapy.

PURPOSE: The purpose of this study was to assess the feasibility of 103Pd brachytherapy in the management of primary unresectable carcinoma of the pancreas. METHODS AND MATERIALS: Between August 1988 and January 1992, 11 patients with biopsy-proven primary unresectable adenocarcinoma of the pancreas were treated with 103Pd brachytherapy during laparotomy. The median age was 66 (range 57-70). The most common presenting symptoms were weight loss (eight patients), pain (six patients), and nausea/vomiting (four patients). Less common symptoms were jaundice (two patients), early satiety (two patients), and ascites (one patient). All patients underwent laparotomy and surgical staging. Eight patients had T3N0M0 disease, two patients had T3N1M0 disease, and one patient had T3N1M1 disease. The surgical procedure performed was biliary bypass in six patients, biopsy only in four patients, and gastric bypass in one patient. The average tumor dimension was 4.0 cm. The median activity, matched peripheral dose (MPD) and implanted volumes were 95.3 mCi, 124.4 Gy, and 33 cm3, respectively. The median initial dose rate was 0.21 Gy per hour. Five patients received postoperative external beam radiation therapy (median 45 Gy) and seven patients received chemotherapy postoperatively. The median follow-up was 7 months (range 1-19). RESULTS: The median survival for the entire group of patients was 6.9 months. Ten of 11 patients have died, with 1 patient presently alive and receiving chemotherapy for metastatic disease to the liver, but without local progression radiographically. Five of 11 patients (45%) were locally controlled, defined as either a complete response or freedom from progression at the site of the implant as evaluated by computed tomography scan. In the other six patients, the median time to local progression was 6.9 months. Five patients developed distant metastases (four liver, one subcutaneous nodule). Two patients failed in regional sites (one omentum, one paraaortic lymph node). Four of 11 patients (36%) developed acute postoperative complications that included one gastric outlet obstruction, one duodenal perforation, and two with sepsis. One of 11 patients (9%) developed a late complication of radiation enteritis 5 months after implantation. The median survival for patients experiencing complications was 1.7 months as compared to 8.4 months for the patients who did not develop a complication (p = 0.10). Pain relief was obtained in five out of six (83%) of the patients presenting with pain for a median duration of 24 weeks. Local control did not appear to be related to the MPD, dose rate, implanted volume, treatment with external beam irradiation, or the use of chemotherapy. Patients were more likely to develop a complication if the MPD was greater than 115 Gy (four out of six patients) as compared to those whose MPD was less than 115 Gy (one out of five patients) (p = 0.12). CONCLUSIONS: Because there was no improvement in median survival over conventional modalities, and the complication rate was high; we do not recommend 103Pd brachytherapy as a component of the treatment of unresectable adenocarcinoma of the pancreas.

Aged↗

The expression of gonadotropin-releasing hormone and its receptor in endometrial cancer, and its relevance as an autocrine growth factor.

The presence of a direct extra-pituitary action of gonadotropin-releasing hormone (GnRH) via specific receptors in endometrial cancer (EC) has been suggested as an explanation for the therapeutic effect of GnRH analogue (GnRHa) in recurrent disease. We have sought the expression of the GnRH peptide and functional GnRH receptor (GnRH-R) in human tissues and cell lines to investigate the possibility of an autocrine growth regulation mechanism. Using reverse transcription-PCR, differing GnRH mRNA transcripts were detected in two EC cell lines (Ishikawa and HEC-1A), a choriocarcinoma (JEG3) cell line, and tissues from endometrium and placenta. However, secretion of immunoreactive GnRH could be detected by RIA in only 1 of 10 EC tissues in primary culture, and in none of the cell lines. Low levels of GnRH-R mRNA expression were found in the same cells, which were only detectable by reverse transcription-PCR and Southern blotting of the PCR product. In radioligand binding assays using GnRHa goserelin, no pituitary-like, high-affinity GnRH binding sites could be found in either EC cell lines or tissues. Low affinity binding (Kd = 1.0 - 3.1 x 10(-7)M) was detected in three of eight (37%) EC tissues. Furthermore, receptor signal transduction measurements carried out in these cells showed no increases in either total inositol phosphate, cyclic AMP production, or cytosolic Ca2+ in response to either GnRH or GnRHa. Finally, no effect of either GnRH or GnRHa on the growth of EC cell lines was detected in vitro, under estrogen-free conditions, assessed by DNA content. Our data suggest that although there is a potential for autocrine activity for GnRH in EC as judged by the presence of mRNA for peptide and receptor, no functional receptor activity could be detected in vitro. Alternative mechanisms should be studied to explain the in vitro action of GnRHa.

Animals↗

Single-dose methotrexate for the treatment of ectopic pregnancy: Northwestern Memorial Hospital three-year experience.

OBJECTIVE: Our purpose was to evaluate the effectiveness of single-dose intramuscular methotrexate in the treatment of ectopic pregnancies by physicians in the Department of Obstetrics and Gynecology of Northwestern Memorial Hospital and to compare the results with those of previously published studies. STUDY DESIGN: A retrospective chart review was performed of 50 patients with ectopic pregnancies treated with single-dose methotrexate according to the protocol of Stovall et al. from January 1992 to February 1995. RESULTS: The mean pretreatment level of beta-human chorionic gonadotropin was 1896.4 +/- 2399 mlU/ml. Only 32 women (64%) were successfully treated with a single dose of methotrexate. An additional 7 women required a second or third injection. The combined success rate for medical management of ectopic pregnancy with one to three doses of methotrexate was 78% (39 women). Pretreatment beta-human chorionic gonadotropin levels were significantly lower in women who responded to single-dose therapy than in those who required either two or three doses or who had failure of medical management (p = 0.0011). The mean time to resolution of beta-human chorionic gonadotropin was 26.5 +/- 17 days. Higher pretreatment levels correlated with longer resolution time (r = 0.83, p < 0.001). Eleven women (22%) with failure of medical management required surgery. CONCLUSIONS: In our series single-dose methotrexate was only 64% successful. Women with a pretreatment beta-human chorionic gonadotropin level >5000 mlU/ml had a greater probability of requiring either surgical intervention or multiple doses of methotrexate. The potential for emergency surgery remains an important risk.

Adolescent↗

Significance of the Banff borderline biopsy.

In the Banff classification of kidney transplant pathology the "borderline changes" category falls short of a diagnosis of mild acute rejection, with the recommendation that no treatment is a possible clinical approach. We reviewed the clinical course of patients whose renal allograft biopsies showed "borderline changes" to determine how often these histologic findings actually represented acute rejection. Between January 1992 and June 1994, 351 biopsy specimens were obtained from 170 renal allografts and graded according to the Banff criteria. Eighty-one biopsy specimens were classified as "borderline changes" (23%). Of these, 59 had Banff scores of i1, t1, and vO; the remaining 22 had scores of i2, t1, and vO (i = interstitial infiltrate, t = tubulitis, and v = vasculitis). Medical record review showed that nearly all the "borderline" biopsies had been performed because of an elevated creatinine (Cr; 78 of 81 [96%]), with a mean increase of 1.1 +/- 0.1 mg/dL (+/- SE) over baseline. Most of the patients with "borderline changes" and elevated Cr were treated for acute rejection (61 of 78 [78%]); some with pulse steroids alone (29 of 61 [48%]), the rest with antilymphocyte antibody (32 of 61 [52%]). Among all 61 patients with "borderline" biopsies treated for rejection, 26 had a complete response (43%), 17 had a partial response (28%), and 18 had no response (30%). Interpretation of these changes in Cr, however, was confounded by intercurrent conditions in 28 of the patients. A group of 33 patients was therefore identified in whom a "borderline changes" biopsy was obtained, who were treated for rejection, and in whom all other identifiable causes of elevated Cr other than possible acute rejection had been systematically eliminated from consideration. In this group the mean Cr was 2.0 +/- 0.1 mg/dL at baseline, 3.3 +/- 0.2 mg/dL at the time of biopsy, and 2.2 +/- 0.1 mg/dL 1 month after treatment (P < 0.001 Cr at biopsy v Cr 1 month later). Among these 33 patients, 19 had a complete response (58%), 10 had a partial response (30%), and four had no response (12%). Therefore, the Cr in 88% of the patients in this group was lower 1 month after treatment for rejection than it was at the time of the biopsy. Follow-up biopsies were performed within 1 month of the "borderline" biopsy in 24 cases; these showed "borderline changes" (five of 24 [21%]), mild acute rejection (eight of 24 [33%]), or moderate to severe acute rejection (11 of 24 [46%]). We conclude that in the clinical setting of deteriorating renal graft function with mild elevation of serum Cr, the "borderline changes" biopsy frequently represents acute rejection. Antirejection treatment is therefore appropriate in the majority of cases. The reader should bear in mind that the current study is retrospective, with no control group. The risk of loosely interpreting these data is that some patients will be treated without due cause. Banff "borderline changes" should be used as part of an algorithm, but not the sole criterion, for therapeutic decision making.

Biopsy↗

Pharmacokinetics, pharmacological and anti-tumour effects of the specific anti-oestrogen ICI 182780 in women with advanced breast cancer.

We have assessed the pharmacokinetics, pharmacological and anti-tumour effects of the specific steroidal anti-oestrogen ICI 182780 in 19 patients with advanced breast cancer resistant to tamoxifen. The agent was administered as a monthly depot intramuscular injection. Peak levels of ICI 182780 occurred a median of 8-9 days after dosing and then declined but were above the projected therapeutic threshold at day 28. Cmax during the first month was 10.5 ng/ml-1 and during the sixth month was 12.6 ng ml-1. The AUCs were 140.5 and 206.8 ng day ml-1 on the first and sixth month of dosing respectively, suggesting some drug accumulation. Luteinising hormone (LH) and follicle-stimulating hormone (FSH) levels rose after withdrawal of tamoxifen and then plateaued, suggesting no effect of ICI 182780 on the pituitary-hypothalamic axis. There were no significant changes in serum levels of prolactin, sex hormone-binding globulin (SHBG) or lipids. Side-effects were infrequent. Hot-flushes and sweats were not induced and there was no apparent effect of treatment upon the endometrium or vagina. Thirteen (69%) patients responded (seven had partial responses and six showed "no change' responses) to ICI 182780, after progression on tamoxifen, for a median duration of 25 months. Thus ICI 182780, given by monthly depot injection, and at the drug levels described, is an active second-line anti-oestrogen without apparent negative effects on the liver, brain or genital tract and warrants further evaluation in patients with advanced breast cancer.

Aged↗

A randomised comparison of a third-generation regimen (PACEBOM) with a standard regimen (CHOP) in patients with histologically aggressive non-Hodgkin's lymphoma: a British National Lymphoma Investigation report.

A combination of cyclophosphamide, doxorubicin, vincristine and prednisolone (CHOP) has been a standard therapy for histologically aggressive non-Hodgkin's lymphomas for over 20 years, but several newer regimens, referred to as second or third generation, have been reported to give improved results in single-centre studies. Positive evidence from randomised trials has been lacking, and the British National Lymphoma Investigation therefore commenced a randomised comparison of CHOP vs a third-generation regimen, PACEBOM, in November 1987. A total of 459 eligible patients were entered into the trial: 226 in the CHOP arm and 233 in the PACEBOM arm. Overall, there was no significant difference in outcome between the two arms of the trial. In patients with stage IV disease there was an apparent improvement in survival for those treated with PACEBOM, but considerable caution must be exercised with such subgroup analysis.

Aged↗

Comparison of two methods to detect P-glycoprotein in patients with chronic lymphocytic leukaemia.

P-glycoprotein (Pgp) is a transmembrane protein associated with multiple drug resistance. Pgp can be detected by several monoclonal antibodies or its activity inferred by measuring drug uptake. We compared two methods for quantitating Pgp in 32 patients with chronic lymphocytic leukaemia. The monoclonal antibody 4E3, which recognizes an external epitope of Pgp, was detected by flow cytometry. Intracellular daunorubicin (DNR) accumulation was measured by flow cytometry in the presence (treated) and absence (control) of cyclosporin, an agent known to inhibit Pgp. Correlation between the degree of positivity on the drug uptake assay and Pgp detected by monoclonal antibody 4E3 was poor (r = 0.06). No association with previous drug exposure or lymphocyte doubling time and Pgp positivity was found in this series of patients. Poor correlation between assays might reflect a lack of sensitivity of the DNR uptake assay. Drug accumulation may be influenced by other cellular efflux pumps unrelated to Pgp, making the DNR assay non-specific.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

The ISHAGE guidelines for CD34+ cell determination by flow cytometry. International Society of Hematotherapy and Graft Engineering.

The increased use of Peripheral Blood Stem Cells (PBSC) to reconstitute hematopoiesis in autotransplant and, more recently, allotransplant settings has not been associated with a consensus means to quality control the PBSC product. Since the small population of cells that bear the CD34 antigen are thought to be responsible for multilineage engraftment, graft assessment by flow cytometric quantitation of CD34+ cells should provide a rapid, reliable, and reproducible assay. Unfortunately, although a number of flow cytometric assays for CD34 enumeration have been described, the lack of a standardized method has led to the generation of widely divergent data. Furthermore, none of these assays has been validated as to interlaboratory reproducibility and suitability for widespread clinical application. In early 1995, the International Society of Hematotherapy and Graft Engineering (ISHAGE) established a Stem Cell Enumeration Committee, the mandate of which was to validate a simple, rapid, and sensitive flow cytometric method to quantitate CD34+ cells in peripheral blood and apheresis products. We also sought to establish its utility on a variety of flow cytometers in clinical laboratories and its reproducibility between transplant centers. Here, we describe the four-parameter flow methodology adopted by ISHAGE for validation in a multicenter study in North America.

Antigens, CD34↗

Phase I/II study of concomitant irradiation and carboplatin for locally advanced carcinoma of the uterine cervix: an interim report.

The outcome of women treated with either definitive irradiation alone or in combination with cisplatin-based chemotherapy for locally advanced (>IIb) squamous cell carcinoma of the cervix has been disappointing. To improve upon our reported results with irradiation alone, a trial using irradiation plus carboplatin chemotherapy was designed for these patients. Twenty-seven women with unresectable squamous cell carcinoma of the uterine cervix were referred to our institution between July 1991 and September 1994. Seven of these patients were enrolled in a phase I/II protocol combining concurrent irradiation and carboplatin chemotherapy. Megavoltage irradiation was used to deliver 45-50.4 Gy to the pelvis (and paraaortic chain when nodes were involved) through a multiple-field technique followed by the application of Fletcher-Suit-Delclos tandem and ovoids to boost the point A dose to 85 Gy. Chemotherapy consisted of intravenous carboplatin (60 mg/m2) administered in conjunction with irradiation to a total dose of 300 mg/m2. The enrolled patients consisted of six women with stage IIIb disease and one with stage IIa with concomitant paraaortic adenopathy. All seven patients enrolled in the study completed the planned course of treatment and tolerated the treatment without severe acute morbidities. No dose modifications were required for the radiation therapy regimen. For one patient, a dose of carboplatin was withheld to allow recovery from thrombocytopenia. The overall response rate was 100% (four complete response, three partial response). The combination of concurrent irradiation (pelvic or pelvic + paraaortic fields) and carboplatin chemotherapy can be safely administered to patients with locally advanced squamous cell carcinoma of the cervix. The treatment is well tolerated and is associated with a high rate of response. Longer follow-up will be necessary to assess the durability of response. In the meantime, we have elected to escalate the dose of carboplatin (90 mg/m2) in the hope of increasing the rate of complete response without incurring unacceptable toxicity.

Adult↗

Carbamazepine trial for Lesch-Nyhan self-mutilation.

Anticonvulsants may reduce the self-mutilation of acquired sensory neuropathy, and one report described sensory neuropathy in an older patient with Lesch-Nyhan syndrome. We performed nerve and muscle biopsies on four patients with Lesch-Nyhan syndrome and initiated an uncontrolled pilot trial to see if carbamazepine would reduce the self-mutilation in these patients. All of the boys had clinical features typical of Lesch-Nyhan syndrome, and the diagnosis was confirmed in each by enzyme analysis. No specific abnormalities were identified in either nerve or muscle. Nevertheless, self-mutilation and the need for constant restraint diminished in all four patients, though in one the effect was only transient. Two patients had increased self-mutilation when carbamazepine was stopped, then improved a second time when treatment was restarted. Sensory neuropathy was not confirmed, so any effect of carbamazepine is likely to be on the central nervous system.

Adolescent↗

Intracellular mechanisms triggering gonadotrophin secretion.

The recently cloned GnRH receptor, a G-protein coupled receptor that spans the membrane seven times, plays a central role in the maintenance of normal reproductive events. In pituitary gonadotrophs, activation of the GnRH receptor stimulates a concert of intracellular signalling pathways. Phospholipase C stimulation generates inositol 1,4,5 trisphosphate and diacylglycerol, which release calcium and activate protein kinase C, respectively. After these primary signals, prolonged activation of protein kinase C arises from the continued production of diacylglycerol from additional signal transduction pathways. While characteristic calcium responses, involving specific calcium pools, are instrumental in triggering exocytosis, the precise role of protein kinase C activation is unclear. Key players within the exocytotic machinery are also elusive but may include a range of membrane, guanine nucleotide and calcium-binding proteins, inositol 1,4,5 trisphosphate receptors and the cell cytoskeleton. Cellular signalling is also important in determining pituitary responsiveness to GnRH, involving intracellular cross-talk between the GnRH, oestradiol and progesterone receptors.

Animals↗

GnRH-induced calcium mobilisation and inositol phosphate production in immature and mature rat ovarian granulosa cells.

In rat ovarian granulosa cells the effects of GnRH are determined by the state of granulosa cell development with mainly inhibitory actions in immature cells and stimulatory actions in differentiated mature cells. These developmentally related effects of GnRH may arise from changes in either one or more of the signal transduction pathways activated by GnRH. The present study therefore measured downstream signalling events associated with the activation of the phospholipase C (PLC) signal transduction pathway in both mature and immature rat ovarian granulosa cells. Results showed that GnRH produced similar total inositol phosphate and intracellular calcium ([Ca2+]i) responses in both immature and mature granulosa cells. In contrast to the biphasic GnRH-induced [Ca2+]i response in pituitary gonadotropes, stimulation of the endogenously expressed GnRH receptor in both immature and mature granulosa cells produced a prompt monophasic rise in [Ca2+]i. This calcium transient was abolished by pretreating either cell type with a potent GnRH receptor antagonist or the PLC inhibitor U73122, demonstrating a GnRH receptor-specific activation of PLC. Similarly, pretreatment of cells with the [Ca2+]i antagonists thapsigargin or cyclopiazonic acid abolished the GnRH-induced calcium transient, whereas EGTA and nifedipine, a voltage-operated calcium channel (VOCC) antagonist, had no effect. These results suggest that in either immature or mature granulosa cells GnRH mobilises calcium from thapsigargin/cyclopiazonic acid-sensitive [Ca2+]i stores but does not involve the influx of extracellular calcium through VOCCs. We conclude that GnRH-induced stimulation of the PLC signal transduction pathway is independent of the stage of granulosa cell maturity and that alternative mechanisms account for the opposite effects of GnRH on gonadotrophin-induced steroidogenesis in mature and immature rat granulosa cells in vitro.

Animals↗

Poorer prognosis in older patients with endometrial adenocarcinoma.

It has been suggested that there are two types of endometrial carcinoma: the first arises in younger women who have hyperestrogenism and has a favorable prognosis and the second occurs in older women, is not associated to estrogen stimulation, and has a poorer prognosis. This study examined the hypothesis that more aggressive carcinomas are found in older patients with no evidence of estrogen stimulation. A retrospective review of all patients (N = 82) with endometrial carcinoma diagnosed and treated at our institution between 1978 and 1990 was undertaken. The following data were analyzed: age at diagnosis, stage, race, histologic type, grade, depth of myometrial invasion, absence or presence of associated hyperplasia, and survival. The mean age of the patients was 64.8 years. Sixty (73%) of the 82 patients were considered estrogen-positive either because of obesity (body mass index > or = 27.3) or the use of unopposed exogenous estrogen. There were no statistically significant differences between estrogen-positive and estrogen-negative patients. Patients > or = 65 years had a 5-year survival of 60% compared with 74% for younger patients. There was a trend toward higher histologic grade among the older patients. Otherwise no statistically significant differences were found between these two groups. Estrogen-negative women > or = 65 years had the worst prognosis with a 5-year survival of 29%. As identified by other investigators, age at diagnosis is a significant indicator of prognosis in patients with endometrial carcinoma. In this series, thin, older (> or = 65 years) women who developed endometrial carcinoma had the worst prognosis.

Adenocarcinoma↗

Safety, efficacy and cost of three cervical cytology sampling devices in a prenatal clinic.

OBJECTIVE: To evaluate and compare the safety, efficacy and cost of three cervical cytology sampling devices in pregnant women presenting for prenatal care to the obstetrics clinic, at Medical College of Pennsylvania Hospital. STUDY DESIGN: From September 7, 1993, to November 5, 1993, 61 cervical cytologic smears were obtained using the Cell-Sweep. From November 8, 1993, to January 7, 1994, 66 smears were obtained using the Ayre spatula/Cytobrush, and from January 10, 1994, to February 18, 1994, 55 smears were obtained using the Ayre spatula/cotton swab. The rate of smears with no endocervical component or with epithelial cell abnormality was determined for each group. The patients' medical records were reviewed retrospectively to determine complications occurring within two weeks of smear collection. RESULTS: Fifteen (25%) smears in the Cell-Sweep group, one (1.5%) in the Cytobrush group and nine (16%) in the cotton swab group were satisfactory but limited by absence of an endocervical component (P < .0006). None of the smears were unsatisfactory. Eleven (18%) smears in the Cell-Sweep group, eight (12%) in the Cytobrush group and nine (16%) in the cotton swab group revealed an epithelial cell abnormality (P = .643). For all three groups there was a low rate of spontaneous abortion, preterm spontaneous rupture of membranes or preterm labor occurring within two weeks of collection. There was no statistically significant difference in these complications between the three groups (P = .7). The Ayre spatula/cotton swab is the least expensive device. CONCLUSION: The Ayre spatula/cotton swab was the most satisfactory of the three methods tested for obtaining cervical cytology during pregnancy. It is safe and cost-effective and identifies the same proportion of epithelial cell abnormalities as the Ayre spatula/Cytobrush and the Cell-Sweep.

Abortion, Spontaneous↗

Clinical Significance of a cervical cytologic diagnosis of atypical squamous cells of undetermined significance. Favoring a reactive process or low grade squamous intraepithelial lesion.

OBJECTIVE: To define the clinical significance of qualifying the cytologic diagnosis of atypical squamous cells of undetermined significance (ASCUS) as favoring either a reactive process or a low grade squamous intraepithelial lesion (LSIL) in an effort to provide management guidelines. STUDY DESIGN: A total of 118 consecutive nonpregnant women with a cytological diagnosis of ASCUS favoring either a reactive process or LSIL were evaluated in our colposcopy clinic by repeat cervical cytologic smear, colposcopy and colposcopically directed biopsies and/or endocervical curettage, as indicated. RESULTS: Of the 58 patients evaluated for a smear of ASCUS, favoring a reactive process, 5 (8.6%) had cervical intraepithelial neoplasia (CIN) CIN 1 documented by biopsy. None had a high grade lesion. Twenty-six (45%) of the 58 patients who had a cytologic diagnosis of ASCUS favoring a reactive process had a repeat smear that was normal. None was found to have CIN. Of the 60 patients who had a cervical diagnosis of ASCUS favoring LSIL, 9 (15%) had CIN 1 or CIN 2. Nineteen (32%) of the 60 patients who had a cytologic diagnosis of ASCUS favoring LSIL had a repeat smear that was normal. One of these patients had CIN 1 on biopsy. The sensitivity of a repeat smear, in this limited series, after an initial smear of ASCUS favoring a reactive process is 100%, while it was 66% after an initial smear of ASCUS favoring LSIL. CONCLUSION: This study showed that in our laboratory a cytologic diagnosis of ASCUS favoring either a reactive process or LSIL is associated with a very low risk that the patient is haboring CIN. In the patient whose initial smear shows ASCUS favoring a reactive process, a repeat smear that is normal is reassuring. The patient whose smear shows ASCUS favoring LSIL probably requires further evaluation even in the presence of a normal repeat smear.

Adolescent↗