Biomedical subjects

L I Muderspach

Publications and source records attributed to L I Muderspach.

30 records · Page 2Linked to original sources

PubMed1996

Residual disease in the uterus after preoperative radiotherapy and hysterectomy in stage IB cervical carcinoma.

Sixty-one patients with FIGO IB cervical cancer treated with planned preoperative radiotherapy (dose to point A: 52-93 Gy, mean 73 Gy) and hysterectomy from 1969 to 1993 were retrospectively reviewed. Patient characteristics and treatment parameters and their association with residual tumor in the hysterectomy specimen were analyzed. Glandular (adenocarcinoma and adenosquamous) tumors were smaller than squamous tumors: 6/11 (55%) were < 6 cm in diameter, versus 12/50 (24%) squamous tumors (p = 0.03). Glandular tumors had a higher incidence of residual disease: 10/11 (91%) versus 24/50 (48%) (p = 0.01). There was no association between presence of pathologic residual disease in the hysterectomy specimen and tumor size, morphology (endophytic vs. exophytic), patient age, dose to point A, time to deliver radiotherapy, or interval between radiotherapy and hysterectomy. Overall 34/61 (56%) patients had residual disease in their hysterectomy specimens after planned preoperative radiotherapy. There were significantly more glandular tumors than squamous tumors with residual disease, even though glandular tumors were a group of smaller tumors.

Adenocarcinoma↗

PubMed1995

The role of endocervical curettage at cervical conization for high-grade dysplasia.

OBJECTIVE: To quantify the risk of invasive cancer above the location where the conization specimen was taken in patients with an endocervical curettage (ECC) positive for dysplasia at conization for high-grade cervical intraepithelial neoplasia (CIN), and to determine if any pathologic features may influence this risk. METHODS: The charts of 104 patients who underwent cervical conization for high-grade dysplasia followed by repeat conization or hysterectomy at Los Angeles County + University of Southern California Women's Hospital between January 1986 and December 1992 were reviewed retrospectively. Patients with invasive cancer or glandular dysplasia on the initial conization were excluded. The ECC performed immediately after conization biopsy (conization ECC) was benign in 63 patients and contained dysplasia in 41. All available conization ECC specimens that contained dysplasia were evaluated for volume of dysplasia and degree of cytologic atypia. Fisher exact test was used for statistical comparison between and within groups. RESULTS: Invasive cancer was not present in any patients in the benign ECC group but was present in nine (22%) patients in the dysplasia group (P < .0001); five of these patients had microinvasion (no more than 3 mm of stromal invasion and no lymph-vascular space involvement) and four had frank invasion. Comparison of patients with involved endocervical margins revealed that none of 37 patients in the benign ECC group versus eight of 27 patients in the dysplasia group had invasive cancer (P < .0005). All patients with invasion were 35 years or older and all patients with frank invasion were 50 years or older. Neither volume nor cytologic grade of dysplasia in the ECC was predictive of invasion in the residual cervix. CONCLUSIONS: An ECC at conization positive for dysplasia is an important predictor of invasion in the residual cervix of patients whose conization reveals high-grade intraepithelial neoplasia and should be routinely performed. Women 50 years or older with both a positive endocervical margin and conization ECC should undergo repeat conization before further therapy. Women under 50 years of age should undergo repeat conization if fertility is not desired; otherwise, close follow-up is necessary to exclude the presence of an invasive lesion in the residual cervix.

Adult↗

PubMed1995

Insulin-like growth factor binding proteins in a natural pre-ovulatory follicle from a woman with polycystic ovary syndrome.

Insulin-like growth factor binding protein (IGFBP) concentrations in the follicular fluid of ovarian follicles have been shown to correlate with dominance and atresia. IGFBP-2 and IGFBP-4 are increased in atresia, and IGFBP-3 is decreased in dominant follicles. The purpose of this study was to compare the IGFBP concentration in follicular fluid from a natural pre-ovulatory follicle of a woman with polycystic ovarian syndrome (PCOS) with other PCOS follicles and dominant follicles from normally cycling women. Follicular fluid was collected from 5-7 mm diameter follicles and a natural pre-ovulatory follicle from women with PCOS, and healthy and atretic follicles from normal women. The IGFBP profiles were analysed using Western ligand blotting. The IGFBP concentrations in the 5-7 mm diameter follicles from the polycystic ovaries containing a pre-ovulatory follicle were similar to those in follicles from other women with PCOS, and comparable with androgenic cohort follicles from normal women. In particular, the IGFBP-2 and IGFBP-4 concentrations were elevated significantly compared with the oestrogenic cohort follicles. The concentrations of all IGFBP detected in the follicular fluid from the PCOS pre-ovulatory follicle were significantly less than those of the 5-7 mm diameter follicles from the same subject. The IGFBP concentrations were within the range of normal dominant follicles, and IGFBP-2 and IGFBP-3 were at the lower end of the normal range. The results indicate that the PCOS pre-ovulatory follicle contained a normal pattern of IGFBP expression even though the other follicles exhibited a pattern typical of PCOS. These data support the hypothesis that decreased concentrations of IGFBP, in particular IGFBP-3, may be involved in selection of the dominant follicle, and that when a spontaneous pre-ovulatory follicle develops in PCOS, the underlying cause of the polycystic ovaries is not resolved but the rest of the ovary remains polycystic.

Adult↗

PubMed1995

Differentiation of benign and malignant adnexal masses: relative value of gray-scale, color Doppler, and spectral Doppler sonography.

OBJECTIVE: The purpose of this study was to evaluate prospectively the relative usefulness of color Doppler, spectral Doppler, and gray-scale sonography in differentiating benign from malignant adnexal masses. SUBJECTS AND METHODS: A total of 170 adnexal masses in 161 patients were classified prospectively as suggestive of or not suggestive of malignant tumor on the basis of gray-scale morphology, internal flow versus peripheral or no flow, and spectral Doppler pulsatility, as measured by a pulsatility index (PI) threshold of 1.0 and a resistive index (RI) threshold of 0.4. RESULTS: Surgical pathology revealed 123 benign masses and 46 malignant masses. One malignant mass was confirmed by cytologic evaluation of ascitic fluid. On gray-scale analysis, 46 of the 47 malignant masses were classified as suggestive of tumor, and 76 of the 123 benign masses were classified as not suggestive of tumor (sensitivity, 98%; specificity, 62%; negative predictive value [NPV], 99%; and positive predictive value [PPV], 50%). The use of internal color flow as a predictor of malignant tumor yielded a sensitivity of 77%, a specificity of 69%, an NPV of 89%, and a PPV of 49%. The PI and RI values were significantly lower (p < .0001) in malignant masses than in benign masses, although the values overlapped considerably. For a PI of less than 1.0, sensitivity was 67%, specificity was 66%, NPV was 83%, and PPV was 46%. For an RI of less than 0.4, sensitivity was 24%, specificity was 90%, NPV was 73%, and PPV was 50%. CONCLUSION: In our series, a gray-scale prediction of benignity was reliable (NPV = 99%), and a prediction of malignancy was unreliable (PPV = 50%). Internal color flow was not useful as a predictor of malignancy (PPV = 49%). Although the absence of internal or peripheral color flow suggested benignity (NPV = 94%), only 17 (16 benign) of the masses (about 10%) had no flow. Spectral Doppler analysis with RI and PI was not useful, as no reliable discriminatory value with both high sensitivity and high specificity could be found for either parameter because of the overlap in values obtained for benign and malignant masses.

Adnexal Diseases↗

PubMed1994

Microsatellite instability in sporadic endometrial carcinoma.

BACKGROUND: Recent studies have demonstrated ubiquitous somatic microsatellite mutations in some cancers of the colon, endometrium, stomach, and pancreas. PURPOSE: Our purpose was to characterize the frequency and nature of this replication error (RER) or mutator phenotype in sporadic endometrial carcinoma. METHODS: Formalin-fixed, paraffin-embedded normal and tumor tissues from 45 patients with sporadic endometrial cancer were screened for the RER phenotype at three microsatellite loci. To further characterize when these alterations were acquired relative to clonal expansion, the sizes of the altered microsatellites in different tumor and normal regions were determined using selective UV radiation fractionation. Approximately 150-300 histologically defined cells on stained tissue sections were covered with small ink dots, and UV irradiation was used to destroy the DNA of cells not covered by ink. Undamaged DNA from seven to 25 spots per section were extracted, then analyzed at the Mfd27, Mfd41, and Mfd47 microsatellite loci and also at the c-K-ras gene locus with individual polymerase chain reactions. Radioactively labeled amplified DNAs were analyzed by electrophoresis and autoradiography. Fisher's exact test and the logrank test were used for statistical analysis. RESULTS: The RER positive (RER+) phenotype was detected in nine (20%) of 45 sporadic endometrial carcinomas. The topographic tissue distributions of the altered microsatellites revealed clues to their pathogenesis. The RER+ phenotype was homogeneously present in the primary tumors and their metastases and was absent from adjacent normal and hyperplastic endometrium. The altered microsatellites were predominantly the same sizes throughout five tumors but demonstrated greater intratumor heterogeneity in three tumors. In one case, the primary tumor was stable but its metastasis was unstable. Mutant c-K-ras alleles were significantly more frequent in RER+ (56%) than in RER negative (RER-) (14%) tumors (P = .0165) and appeared to be acquired after the RER+ phenotype in one tumor. There were no significant clinical differences between the RER+ and RER- tumors. CONCLUSIONS AND IMPLICATIONS: The RER+ phenotype is frequently present in sporadic endometrial cancers and is expressed before and during clonal expansion. The underlying mutator mutations are probably heterogeneous, since the RER+ phenotypes were diverse. The absence of altered microsatellites in adjacent normal endometrium demonstrates that the expression of the RER+ phenotype is limited to neoplastic tissue. The bulk of the microsatellite alterations appeared to be acquired prior to clonal expansion, suggesting that expression of the underlying genomic instability contributes to, and is not a consequence of, transformation.

Adult↗

PubMed1994

Early mutational activation of the c-Ki-ras oncogene in endometrial carcinoma.

Endometrial carcinoma is theorized to arise from a series of somatic mutations which alter benign endometrium to progressively less differentiated histological lesions. One genetic alteration implicated in the carcinogenesis of endometrial cancer is the mutational activation of the c-Ki-ras oncogene. This study characterizes the frequency and the topographical distribution of activated c-Ki-ras alleles in endometrial carcinoma. Sixty formalin-fixed, paraffin-embedded endometrial cancer specimens were screened for point mutations at codons 12 and 13 of the c-Ki-ras oncogene by polymerase chain reaction and allelic specific oligomer dot-blot hybridization. c-Ki-ras mutations were identified in nine of 60 (15%) tumor specimens. Five cases resulted in G to A transitions, three in G to T transversions, and one in a G to C transversion. These nine mutant tumors were analyzed by selective UV radiation fractionation and polymerase chain reaction for the presence of activated c-Ki-ras alleles in cell populations of various histological phenotype. In eight tumors, c-Ki-ras mutations were uniformly present in the carcinoma cells. One tumor exhibited heterogeneous mutational activation, with mutant c-Ki-ras alleles detected in only grade 2 carcinoma cells but not grade 1 carcinoma cells. c-Ki-ras mutations were present in adjacent hyperplasia with atypia but absent from hyperplasia without atypia. With rare exception, c-Ki-ras activation appears to be an early oncogenic event since it is homogeneously present in premalignant and malignant endometrial tissues.

Adenocarcinoma↗

PubMed1994

Death from anaphylaxis to cisplatin: a case report.

A patient with a history of ovarian carcinoma that had responded well to cisplatin was treated with platinum agents for a recurrence. She had a seizure while receiving carboplatin and was switched to cisplatin. The patient was premedicated with antihistamines and steroids. After approximately 400 micrograms of cisplatin she went into anaphylactic shock and could not be resuscitated. The reported frequency of hypersensitivity reactions to cisplatin is between 1 and 20%. Premedication with steroids and antihistamines, single-agent chemotherapy, and slow rate of infusion are of help in preventing these reactions. All of these precautions were unsuccessful in preventing refractory anaphylaxis in this patient.

Anaphylaxis↗

PubMed1994

The significance of positive margins in loop electrosurgical cone biopsies.

OBJECTIVE: To determine the interpretability and significance of the endocervical margins of cervical cone biopsy specimens removed by the loop electrosurgical excision procedure (LEEP). METHODS: Loop electrosurgical cervical conization was performed on 57 women with biopsy-confirmed, high-grade dysplasias in whom the extent of the lesion could not be determined by colposcopic visualization. Internal endocervical margins of the resected specimens were marked with ink by the operating physician and evaluated microscopically by the pathologist. Endocervical curettage (ECC) was done in all instances, and all subjects were followed for 1 year after the procedure. RESULTS: Histologic evaluation of the inked endocervical margins was possible for all 57 resected specimens and was in no instance hindered by thermal artifact. In 19 patients, dysplasia was present in the inked core margin, the ECC, or both. Each patient had re-excisions of the endocervical area; 12 of the 19 (63%) had dysplasia in the specimen. Of 12 cases in which dysplasia was present in both the endocervical margin and the ECC, nine had residual dysplasia. Two of four patients with positive margins but a negative ECC had residual dysplasia, but only one of three patients with a negative endocervical margin and a positive ECC showed residual dysplasia. In the 38 patients with negative inked margins and a negative ECC, there was only one instance of dysplasia demonstrated during the 1-year follow-up period. CONCLUSION: Endocervical margins of cone biopsies removed by LEEP can be accurately assessed pathologically and can help predict the presence of persistent dysplasia.

Adult↗

PubMed1993

Spinal cord compression in metastatic cervical cancer.

Spinal cord compression secondary to metastatic cervical cancer may not be considered as a possible cause of neurologic symptoms by primary care physicians who do not often treat these patients. Delays in diagnosis and treatment may result in irreversible but potentially preventable neurologic changes. This report describes 5 cases of spinal cord compression in patients with metastatic cervical carcinoma, 2 of whom were previously undiagnosed with cervical cancer. These 2 patients represent 1.6% (2 of 121) of all new cervical cancer cases diagnosed during this time period. Two of 5 patients (40%) with spinal cord compression showed improvement following therapy by regaining the ability to walk, while none of the remaining patients had further acute deterioration of neurologic function. The mean survival of patients presenting with spinal cord compression from cervical cancer in this series was 4 months (maximum 6 months). This series illustrates the relative frequency with which spinal cord compression is seen in patients with a new diagnosis of invasive cancer. This diagnosis should be considered when evaluating neurologic complaints in known cervical cancer patients or any woman with apparent pelvic pathology. Rapid diagnosis and treatment of these lesions, while not likely to improve overall survival significantly, can improve function and alleviate symptoms.

Adult↗

PubMed1993

Myxoid leiomyosarcoma of the uterus.

BACKGROUND: A case of myxoid leiomyosarcoma of the uterus is presented. In contrast to 10 of the 11 previously published cases, our patient has a tumor with a high mitotic rate. CASE: The patient presented with a 2-month history of vaginal bleeding and a 20-week-size uterine mass. A total abdominal hysterectomy with bilateral salpingo-oophorectomy was performed. At the time of surgery, the tumor appeared well circumscribed. Microscopically, an infiltrative growth pattern, bizarre nuclei, and 30 abnormal mitotic figures per 10 high power fields were noted. The patient was treated with ifosfamide and mesna. After the fifth course of chemotherapy, a pelvic mass was palpated. Exploratory laparotomy demonstrated a large sidewall recurrence and upper abdominal metastases which were completely resected. The patient is currently being treated with combination chemotherapy consisting of vincristine, Adriamycin, and cyclophosphamide. CONCLUSION: Ten of the 11 previously reported cases of myxoid leiomyosarcoma had a low mitotic count. However, our patient has a high mitotic count in combination with an infiltrative growth pattern. Ifosfamide was ineffective as adjuvant chemotherapy and there was aggressive tumor growth while the patient was on this regimen.

Female↗

PubMed1993

Cervical cancer in pregnancy: reporting on planned delay in therapy.

OBJECTIVE: To report our experience with invasive carcinoma of the cervix during pregnancy, assessing maternal morbidity due to treatment delay and reporting maternal and fetal outcome. METHODS: Twenty-seven patients with invasive cervical cancer, who were pregnant at the time of diagnosis or treatment, were identified from review of morbidity and mortality statistics between January 1, 1980 and December 31, 1991. All medical records were examined retrospectively. RESULTS: The incidence of cervical carcinoma in our population was 1.2 cases per 10,000 pregnancies. Most patients had stage I lesions. The predominant histologic cell type was squamous cell carcinoma, followed by adenosquamous carcinoma and adenocarcinoma. Eight patients with stage Ia or Ib cervical cancer postponed therapy to optimize fetal outcome, with a mean diagnosis-to-treatment interval of 144 days (range 53-212). Nineteen patients elected immediate treatment, with a mean diagnosis-to-treatment interval of 17 days (range 2-42). Fetal outcome was uniformly good for the delayed-treatment group. Nine fetal deaths and two neonatal deaths occurred in the immediate-treatment group. All patients who delayed therapy are free of disease after a median follow-up of 23 months. CONCLUSION: Deliberate delay of therapy to achieve fetal maturity appears to be a reasonable option for patients with stage I cervical cancer complicating pregnancy.

Adenocarcinoma↗

PubMedDate not supplied

Endometrial cancer patients have a significant risk of harboring isolated tumor cells in histologically negative lymph nodes.

In this study, we examine the prevalence of finding isolated tumor cells (ITCs) in negative lymph nodes of endometrial cancer patients using immunohistochemistry. Seventy-six endometrial cancer patients with lymph nodes histologically negative for metastatic disease were examined. Nodal tissue sections were stained with anticytokeratin antibodies AE-1 and CAM 5.2. Nodes with single or groups of cells (two to four cells) < or =0.2 mm and showing cytokeratin reactivity were positive for ITCs. Findings were compared to features of the primary tumor and patient outcome. ITCs were present in 31 of 1712 lymph nodes. Fifteen (19.7%) patients had ITC-positive nodes. ITCs involved only pelvic nodes in nine cases, only para-aortic nodes in five cases, and pelvic and para-aortic in one case. Tumor in adnexa was the only pathologic feature associated with nodal ITCs (P= 0.0485). All 15 patients with nodal ITCs were alive at follow-up. One (6.7%) patient suffered recurrent disease but was alive at last encounter. Disease recurred in 5 (8.8%) of 57 patients without nodal ITCs. Two are alive without disease, two alive with disease, and one died from her cancer. In summary, a significant proportion of endometrial cancer patients have ITCs detected by immunohistochemistry in histologically negative regional lymph nodes.

Adult↗