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Biomedical subjects

J P Geisler

Publications and source records attributed to J P Geisler.

At least 19 recordsLinked to original sources

Heat shock protein 27 in the placentas of women with and without severe preeclampsia.

BACKGROUND: Although not fully understood, heat shock proteins (HSP) are well known stress response proteins. The purpose of this analysis was to determine whether staining for HSP27 was different between placentas from pregnancies complicated by severe pre-eclampsia with intrauterine growth restriction (IUGR) as compared to controls. METHODS: Sterile placental tissue was collected from ten women whose pregnancies were complicated by severe preeclampsia with IUGR and from ten women with uncomplicated by severe pre-eclampsia with IUGR and from ten women with uncomplicated term pregnancies. The tissue was then stained for HSP27. RESULTS: The median age of the patients was 27 years (mean 27, range 17-37). The median estimated gestational age at delivery was 38 weeks (mean 37, range 29-41). Overall 12 of 20 placentas stained positively for HSP27 (nuclear and/or cytoplasmic). Eight of ten placentas from women with pre-eclampsia and IUGR stained positively for HSP27 (p = 0.046). CONCLUSION: HSP27 staining of the placenta is twice as common in patients with severe preeclampsia as compared to patients with normal term gestations. These preliminary results warrant the inauguration of a similar but larger study to examine the significance of these findings.

Adolescent↗

HSP27 in patients with ovarian carcinoma: still an independent prognostic indicator at 60 months follow-up.

OBJECTIVE: Heat shock protein 27 (HSP27) is produced in response to pathophysiologic stress in animal cells. The authors have previously shown that HSP27 is an independent prognostic indicator in patients with ovarian carcinoma. The present study was performed to see whether HSP27 remained an independent prognostic indicator with longer follow-up. METHODS: One hundred and three consecutive patients with epithelial ovarian carcinoma were studied. Slides were prepared from fresh tissue. HPS27 staining was performed as previously described. Patient records were examined for FIGO stage, grade, histology, level of cytoreduction and survival. RESULTS: One hundred and three patients were followed for a mean of 60 months. Twenty patients had FIGO Stage I disease, four Stage II, 59 Stage III, and 20 Stage IV. Immunohistochemical (IHC) staining for HSP27 was not related to histologic grade, level of cytoreduction or histologic subtype. A statistically significant decrease in HSP27 staining was found to correlate with increased FIGO stage (p = 0.008). Using cox-regression analysis, HSP27 staining (p = 0.025), stage (p = 0.0012), and level of cytoreduction (p < 0.0001) were independent predictors of survival in these patients. CONCLUSION: Cox-regression analysis found HSP27 to be an independent indicator of prognosis and survival in patients with ovarian carcinoma who had longer follow-up. Decreased HSP27 staining was related to decreased survival. This study confirms the authors' earlier report on the importance of HSP27 as a prognostic indicator in ovarian carcinoma.

Adenocarcinoma, Clear Cell↗

Evaluation of DNA methylation in the human genome: why examine it and what method to use.

PURPOSE: Since its discovery 50 years ago, DNA methylation has been found to be an important part of gene regulation. Newer methods of analysis over the last decade have helped further the understanding of this epigenetic phenomenon. The purpose of this article is to describe current methods of analysis and discuss advantages and disadvantages of each and their possible roles in gynecologic malignancies. RESULTS: The methods for analysis of DNA methylation are divided into two major categories: 1) methods which utilize chemical methods or restriction enzymes to differentially cleave at cytosine versus 5-methylcytosine sites, 2) methods which utilize sodium bisulfite (NaHSO3) to specifically convert unmethylated cytosines to uracil (thymine after PCR). This recently developed method appears to be more sensitive and allows the investigator to specifically delineate the study site(s). CONCLUSION: DNA methylation is important in the human genome. Its role in tumorigenesis is just beginning to be understood. While relying upon newly designed methods of analysis, further understanding of this epigenetic phenomenon and its role in gene expression and tumorigenesis will be forthcoming.

DNA Methylation↗

Chemotherapy for ovarian cancer: an evidence-based approach.

Although cytoreductive surgery is the most influential factor in treatment for ovarian cancer, chemotherapy is needed for almost all patients diagnosed with this disease. The mainstay of chemotherapy is platinum. Different platinum compounds are used for different histologies, and different combinations are used for different histologies also. We will present the data so that each reader can understand the knowledge behind chemotherapy decisions.

Antineoplastic Agents↗

Malignant mixed mullerian tumor of the ovary and bilateral breast cancer: an argument for BRCA3, or a coincidental cluster of unconnected cancers?

OBJECTIVES: Malignant mixed mullerian tumors (MMMTs) of the ovary are a rare, aggressive subtype of ovarian cancer without a clear relationship to familial breast-ovarian cancer syndromes. CASE: We present the case of a woman with bilateral breast cancers who subsequently developed a stage IIIc MMMT of the ovary. The patient had a first-degree female relative with breast and ovarian cancer (not MMMT), as well as second- and third-degree female relatives each with bilateral breast cancers. BRCA1 and BRCA2 sequencing of germline DNA revealed no evidence of a heritable mutation. CONCLUSIONS: Ovarian MMMTs may be a hallmark of breast/ovarian cancer secondary to genetic risk independent of classic BRCA1/2 pathways.

Breast Neoplasms↗

p21 and p53 in ovarian carcinoma: their combined staining is more valuable than either alone.

BACKGROUND: Mutations in p53 are the most common genetic alterations in human malignancies. Expression of its protein product has been linked to decreased survival rate in ovarian carcinoma. Less is known about the importance of p21 expression. The purpose of this study was to determine the value of the combination of p21 and p53 expression in patients with epithelial ovarian malignancies. METHODS: One hundred three consecutive patients with epithelial ovarian carcinoma were studied using snap-frozen tissue specimens. Immunohistochemical staining utilizing the pAb1801 monoclonal antibody to p53 and NCL-WAF-1 monoclonal antibody to p21 was performed. Image analysis was used to determine whether nuclear staining for either antibody was present. In addition to p21 and p53, International Federation of Gynecology and Obstetrics stage, grade, histology, level of cytoreduction, and DNA index were analyzed as prognostic factors. Univariate and multivariate analyses was performed. RESULTS: One hundred three patients were observed for more than 5 years. Immunohistochemical staining for p21 and p53 were significantly inversely related (P = 0.041). Among the patients whose tumors showed p21 staining but no p53 staining, there were no recurrences and all patients were alive at 5-year follow-up. The 5-year survival rate for these patients was significantly better than for the patients with other combinations of p21/p53 staining (P < 0.0001). The DNA index between these 2 groups was not significantly different (P = 0.057). Multivariate analysis shows the combination of p21 and p53 (P = 0.013) staining to be more valuable as a prognostic indicator than either p53 (P = 0.015) or p21 (P = 0.5) alone. CONCLUSIONS: This study confirms the importance of the combination of p21 and p53 nuclear staining in patients with ovarian carcinoma. Cox regression analysis revealed combination of p21 positive and p53 negative to be a better independent indicator of prognosis and survival in patients with ovarian carcinoma than either p21 or p53 alone.

Carcinoma↗

Ovarian cancer BRCA1 mutation detection: Protein truncation test (PTT) outperforms single strand conformation polymorphism analysis (SSCP).

Recent studies have shown that the BRCA1 tumor suppressor gene plays a role in the development of both hereditary and sporadic ovarian cancer. Since several different mechanisms may give rise to tumor gene defects, a better understanding of these mechanisms may identify BRCA1 as an attractive therapeutic target in ovarian cancer. Sequencing this large gene is not practical on a population-wide basis. The optimal screening strategy is yet to be determined. The purpose of our study is to compare two common screening techniques: the protein truncation test (PTT) and single strand conformational polymorphism analysis (SSCP). Ninety-four patients with epithelial ovarian cancer and available snap-frozen tissue were screened for BRCA1 mutations by both PTT (five individual PCR reactions with complete translation of the product in the TNT System (Promega, Madison, WI)) and SSCP (41 individual PCR reactions covering the entire coding sequence). All abnormal results were confirmed by sequencing. A paired peripheral blood DNA sample was utilized to determine if the sequence abnormality was a germline mutation. Twenty-three mutations in BRCA1 were found in 22 patients (14 germline, eight somatic, one unknown) including four novel mutations: E489X, 3558delT, 3871delGTCT, del exon 7-10. Although the predictive value of a negative test was close for the two methods (PTT 99.1%, SSCP 99.8%), the comparison of positive predictive value overwhelmingly favored PTT (100.0%, vs. 26.4%, respectively). The specificity for PTT was 100.0% while the sensitivity was 82.6%. While for SSCP, the specificity was 99.0% and the sensitivity was only 60.9%. The concordance rate for the two screening tests was 88.9%. Only SSCP can detect missense mutations. PTT is a superior screening test for truncating BRCA1 mutations that are expected to be of clinical significance.

BRCA1 Protein↗

Radical hysterectomy in the elderly female: a comparison to patients age 50 or younger.

BACKGROUND: Longevity in the United States is increasing, therefore the knowledge of whether radical surgery can be performed on patients over age 65 with acceptable morbidity and mortality is increasingly important. A retrospective study of elderly patients undergoing radical hysterectomy was performed with a comparison to a younger cohort. METHODS: A retrospective case study of all patients over 65 years of age having undergone a radical hysterectomy for cervical cancer in one practice of gynecologic oncology was performed. Each patient was matched with two patients age 50 or younger having undergone a similar operation during the same year. No patients between July 1, 1965, and March 31, 1998, were knowingly excluded. All patients were analyzed for preexisting medical conditions, length of postoperative stay, morbidity, and postoperative mortality. RESULTS: Sixty-two patients over age 65 having undergone a radical hysterectomy and pelvic lymphadenectomy were found. These patients were matched with 124 patients age 50 or younger having undergone a radical hysterectomy during the same calendar year. No differences in operative morbidity (minor, P > 0.57; major, P > 0.93) or mortality (no deaths in either group) were found. Patients age 65 or older had more comorbidities prior to surgery than the younger cohort (minor, P < 0.001; major, P < 0.001). The mean postoperative hospital stay was significantly longer in the older cohort (P = 0.005). CONCLUSIONS: Radical hysterectomy is a safe surgical procedure in a select population of patients 65 and over. No differences in operative mortality or morbidity were found when compared to a cohort of patients age 50 or younger. However, hospital stay was longer in the older cohort.

Adult↗

Papillary serous carcinoma of the uterus: increased risk of subsequent or concurrent development of breast carcinoma.

OBJECTIVE: Some women with endometrial cancer may be at increased risk for developing breast cancer. The histologic type of endometrial cancer associated with synchronous or subsequent breast cancer has not been clearly established. Our purpose was to determine if a certain histologic type of endometrial cancer was associated with an increased risk of synchronous or subsequent breast cancer. METHODS: The University of Iowa Hospitals and Clinics tumor registry was queried to ascertain all patients with the diagnosis of uterine cancer from January 1, 1983, to December 31, 1994. Statistics were performed utilizing SPSS for Windows version 9.0 (SPSS Inc., Chicago, IL), including Student's t tests and chi(2) tests. RESULTS: Five hundred ninety-two patients had endometrial adenocarcinoma during the study period. Five hundred thirty-six women had endometrioid adenocarcinoma, 23 women had papillary serous carcinoma (UPSC), 21 women had adenosquamous carcinoma, 10 women had clear-cell carcinoma, and 1 woman each had mucinous or squamous carcinoma. Twelve patients had previously been diagnosed with breast carcinomas. Twenty-five patients were diagnosed with breast cancer either concurrently or subsequent to their diagnosis of endometrial cancer. Synchronous or subsequent breast cancers developed in 3.2% of patients with endometrioid carcinoma and in 25% of patients with UPSC (P < 0.001). CONCLUSION: Patients with UPSC have an increased risk of development of breast cancer as compared to patients with endometrioid adenocarcinoma of the uterus.

Aged↗

Tumor markers and molecular biological markers in gynecologic malignancies.

Gynecologic oncology is a rapidly growing field due to constant advances in immunohistochemistry and molecular biology. This review serves as an overview of new studies promoting the use of tumor markers and molecular biological prognostic factors in malignancies affecting women. The majority of studies focus on either endometrial or ovarian carcinoma. Other gynecologic malignancies (cervical, vulvar, and vaginal carcinoma) have a much smaller representation in the world literature. Multiple new markers were examined over the last year. We conclude that although some markers show promise as potential new consensus prognostic indicators, more work is needed to confirm results and clarify any existing discrepancies.

Biomarkers, Tumor↗

p53 and bcl-2 in epithelial ovarian carcinoma: their value as prognostic indicators at a median follow-up of 60 months.

OBJECTIVE: p53 is the most common tumor suppressor gene involved with human malignancies. Mutations in p53 are present in approximately 50% of human malignancies. bcl-2 is a protooncogene. Expression of its protein product is related to better prognosis in several malignancies. METHODS: One hundred and three patients with epithelial ovarian carcinoma were studied. Immunohistochemical staining using the pAb1801 monoclonal antibody to p53 and the anti-bcl-2 124 monoclonal antibody to bcl-2 was performed. Image analysis was used to measure percentage positive nuclear area staining of mutant p53. In addition to bcl-2 and p53, FIGO stage, grade, histology, and level of cytoreduction were analyzed as prognostic factors. Univariate as well as Cox regression analysis was performed. RESULTS: One hundred and three patients were followed for a mean of 60 months. Twenty patients had FIGO stage I disease, 4 stage II, 59 stage III, and 20 stage IV. Immunohistochemical staining for mutant p53 was not significantly related to DNA index (P = 0.99) but was related to increasing FIGO stage (P < 0.001) and increasing histologic grade (P = 0.039). Using Cox regression analysis, increased mutant p53 staining was an independent predictor of survival in these patients (P = 0.0032), along with stage (P < 0. 0001) and level of cytoreduction (P < 0.0001). Although by itself bcl-2 was not an independent prognostic indicator (P = 0.18), the combination of p53 and bcl-2 was independently predictive of survival (P = 0.038). CONCLUSION: This study confirms the authors' earlier report on the importance of p53 as a prognostic indicator of survival in ovarian carcinoma. Cox regression analysis reveals mutant p53 staining to be a better independent indicator of prognosis and survival in patients with ovarian carcinoma than the combination of bcl-2 and p53.

Adult↗

Docetaxel extravasation causing significant delayed tissue injury.

PURPOSE: Docetaxel is a relatively new taxane that has not been associated with significant tissue injury after extravasation. We present a case of a patient who had grade 4 tissue toxicity after extravasation of docetaxel infused through a peripheral intravenous site. CASE REPORT: A 71-year-old female was being treated for recurrent ovarian cancer with docetaxel and carboplatin. Shortly after the docetaxel infusion began, she experienced docetaxel extravasation into the dorsum of her left hand. The infusion was halted, and then the administration was continued in a peripheral intravenous site in the other upper extremity. Erythema was noted by the patient on the dorsum of her left hand 6 days after infiltration. The following day, the patient noted severe pain, decreased function, and blistering along with increased erythema. The patient presented to the gynecology oncology clinic 11 days after the extravasation injury occurred. Conservative management was undertaken, and over the next 4 weeks the patient had resolution of the skin changes and full return of function. CONCLUSION: Docetaxel can cause significant delayed tissue injury if extravasation occurs.

Aged↗

The great imitator: miliary peritoneal tuberculosis mimicking stage III ovarian carcinoma.

PURPOSE: To report a case of peritoneal tuberculosis initially mistaken at the time of surgery for metastatic ovarian carcinoma. CASE REPORT: A 31-year-old Filipino female was found to have increasing abdominal pain, ascites, early satiety, increasing abdominal girth and bilateral complex masses. Diagnostic laparoscopy revealed the presence of > 4 liters of ascites, a frozen pelvis secondary to what appeared to be bilateral ovarian carcinomas, along with miliary seeding of the entire anterior abdominal wall, omentum, small bowel and small bowel mesentery, right and left diaphragmatic surfaces, and hepatic surface. Frozen section, at the time of laparotomy, revealed necrotizing granulomas most consistent with disseminated tuberculosis that was confirmed at the time of final pathologic review and culture. CONCLUSION: Peritoneal tuberculosis can be mistaken for widely metastatic ovarian carcinoma at time of surgery.

Adult↗

Immunohistochemical staining of the mismatch repair gene, hMSH2, and survival in patients with ovarian carcinoma.

OBJECTIVE: hMSH2 is a mismatch repair gene. The protein of this gene can be demonstrated by immunohistochemical methods. The authors wanted to analyze whether the percent of positive nuclear area staining of the hMSH2 protein correlated with survival in patients with ovarian carcinoma. METHODS: One hundred and two patients with epithelial ovarian carcinoma were studied. Slides were prepared from snap frozen tissue. Quantification of staining and DNA index were performed using image analysis. In addition to hMSH2, FIGO stage, grade, histology, and level of cytoreduction were analyzed as prognostic factors. RESULTS: Mean follow-up was 64 months and median was 59 months. Nineteen patients had stage I cancers, 4 stage II, 59 stage III, and 20 stage IV. Optimal cytoreduction was accomplished in 71% of patients. hMSH2 staining was significantly higher in better differentiated tumors (p=0.006), but there was no difference in staining among the FIGO stages (p=0.43). Cox regression analysis revealed FIGO stage (p=0.0005), level of cytoreduction (p=0.006) and hMSH2 staining (p=0.016) to be independent predictors of survival in patients with ovarian carcinoma. CONCLUSION: The hMSH2 protein can be demonstrated by immunohistochemical methods and quantified by image analysis. hMSH2 staining was shown to be an independent prognostic indicator of survival in patients with ovarian carcinoma.

Adult↗

Successful laparoscopic treatment of an abdominal pregnancy in the posterior cul-de-sac.

PURPOSE: To describe the laparoscopic treatment of a first trimester abdominal pregnancy found in the cul-de-sac between the right uterosacral ligament and the rectum. CASE REPORT: A 32-year-old female presented to the emergency department with abdominal pain beginning a few hours prior to presentation. The serum betahCG level was 543 mIU/ml. An ultrasound examination revealed an empty uterus, bilateral normal fallopian tubes, and a large quantity of fluid in the pelvis. Secondary to patient symptoms, laparoscopy was performed. After the pelvis was irrigated to remove blood and clot, bilaterally normal fallopian tubes and ovaries were found. Further laparoscopic examination revealed an abdominal pregnancy implanted on the peritoneum between the right uterosacral ligament and the rectum. Hydrodissection was used to help elevate the peritoneum away from adjacent structures, and the products of conception were removed laparoscopically. CONCLUSION: In select first trimester patients with abdominal pregnancies, laparoscopic management can be performed.

Adult↗

A study of heat shock protein 27 in endometrial carcinoma.

OBJECTIVE: Heat shock protein 27 (HSP27) is a relatively small protein produced in response to pathophysiologic stress. The purpose of this study was to determine prospectively whether HSP27 was associated with known prognostic factors in patients with endometrial carcinoma. METHODS: One hundred fifty-three consecutive patients with endometrial carcinoma were studied. Slides were prepared from fresh tissue. HSP27 was analyzed using a semiquantitative measurement. Patient records were examined for FIGO stage, grade, depth of myometrial invasion, histology, lymphovascular space invasion, time to recurrence, and survival. RESULTS: The mean follow-up was 53 months (median 56 months, range 30-68 months). Endometrioid tumors showed significantly higher HSP27 staining than nonendometrioid tumors (P = 0.005). Patients alive at the conclusion of this study had significantly higher mean HSP27 staining than patients who were deceased (P < 0.001). Logistic regression revealed HSP27 staining (P = 0.02), FIGO stage (P = 0. 014), and lymphovascular space invasion (P = 0.046) to be independently predictive of survival. CONCLUSION: HSP27 staining is significantly higher in endometrioid than nonendometrioid tumors. HSP27 staining is an independent prognostic indicator in patients with endometrial carcinoma, the most common gynecologic malignancy in the United States.

Adult↗