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K C Podratz

Publications and source records attributed to K C Podratz.

At least 37 records · Page 2Linked to original sources
PubMed1999

Modified radical hysterectomy in the treatment of early squamous cervical cancer.

OBJECTIVE: The aim of this study was to evaluate the results of modified radical hysterectomy in the treatment of early cervical cancer. MATERIAL AND METHODS: A retrospective chart review of 56 patients with stage I (IA in 35, IB in 21) squamous cervical carcinoma treated with modified radical hysterectomy and followed for a minimum of 5 years (mean, 12 years; range, 5.1-29) was conducted. All pathology slides were reviewed for tumor size, grade, depth of invasion, and lymph-vascular permeation. RESULTS: The mean depth of invasion was 0.5 cm (range, 0.1-2.5 cm), and the mean tumor size was 1.1 cm (range, 0.1-7 cm). Only 3 patients (5.4%) had positive nodes. None of the patients with tumors 2 cm or less in size had positive nodes, whereas 33.3% of the patients with tumors more than 2 cm in size had positive nodes. A recurrence developed in 2 patients (5-year recurrence rate of 3.6%). There were 10 deaths during the entire follow-up period, but only 2 were related to cervical cancer. The disease-specific and overall 5-year survival rates were 96.4 and 94.6%, respectively. The disease-specific 5-year survival rate was 100% among the 47 patients with tumors 2 cm or less and 75% for the 9 patients with tumors larger than 2 cm. Univariate analysis identified stage, lymph node status, and tumor size as statistically significant prognostic factors for overall survival. Tumor grade, lymph-vascular permeation, and depth of invasion (1-3 mm vs >3 mm) were not statistically significant for overall survival. CONCLUSIONS: Modified radical hysterectomy appears to be effective surgical therapy for patients with squamous cervical carcinoma 2 cm or less in size.

Adult↗
PubMed1999

Acute pancreatitis after gynecologic and obstetric surgery.

OBJECTIVE: Our goal was to evaluate the prevalence and comorbidity of acute postoperative pancreatitis after gynecologic and obstetric surgery. STUDY DESIGN: We reviewed the Mayo Medical Center surgical database (January 1953-January 1997) to identify all confirmed cases of acute pancreatitis occurring within the standard 6-week postoperative convalescence after obstetric and gynecologic surgical procedures. Pancreatitis as a result of concurrent pancreatic or biliary surgery was excluded. Pertinent clinical data were reviewed. RESULTS: Eleven cases of postoperative pancreatitis were identified, with an overall incidence of 1 in 17,000 surgical procedures. Postoperative pancreatitis was more common after obstetric surgery. Identifiable risk factors were noted in 45% of cases, with occult cholelithiasis the predominant factor. Presenting signs and symptoms were primarily epigastric pain, oliguria, and ileus. Significant morbidity or mortality was noted in 27% of the cases. CONCLUSIONS: Acute postoperative pancreatitis is a rare complication after gynecologic and obstetric surgery. Signs and symptoms of pancreatitis are nonspecific in the postoperative setting. Prompt diagnosis and supportive therapy are essential to minimize morbidity and mortality.

Acute Disease↗
PubMed1999

Serum sErbB1 and epidermal growth factor levels as tumor biomarkers in women with stage III or IV epithelial ovarian cancer.

Epithelial ovarian cancer (EOC) has a high mortality rate, which is due primarily to the fact that early clinical symptoms are vague and nonspecific; hence, this disease often goes undetected and untreated until in its advanced stages. Sensitive and reliable methods for detecting earlier stages of EOC are, therefore, urgently needed. Epidermal growth factor (EGF) is a ligand for EGF receptor (ErbB1); this receptor is the product of the c-erbB1 proto-oncogene. ErbB1 overexpression is common in human ovarian carcinoma-derived cell lines and tumors, in which overexpression is thought to play a critical role in tumor etiology and progression. Furthermore, ErbB1 overexpression is associated with disease recurrence and decreased patient survival. Recently, we have developed an acridinium-linked immunosorbent assay that detects a approximately 110-kDa soluble analogue of ErbB1, ie., sErbB1, in serum samples from healthy men and women (A. T. Baron, et al., J. Immunol. Methods, 219: 23-43, 1998). Here, we demonstrate that serum p110 sErbB1 levels are significantly lower in EOC patients with stage III or IV disease prior to (P < 0.0001) and shortly after (P < 0.0001) cytoreductive staging laparotomy than in healthy women of similar ages, whereas EGF levels are significantly higher than those of age-matched healthy women only in serum samples collected shortly after tumor debulking surgery (P < 0.0001). We observe that the preoperative serum sErbB1 concentration range of advanced stage EOC patients barely overlaps with the serum sErbB1 concentration range of healthy women. In addition, we show that serum sErbB1 and EGF levels changed temporally for some EOC patients who were surgically debulked of tumor and who provided a second serum sample during the course of combination chemotherapy. Finally, we observe a significant positive association between sErbB1 and EGF levels only in serum samples of EOC patients collected prior to cytoreductive surgery (correlation coefficient = 0.61968; P = 0.0027). These data suggest that epithelial ovarian tumors concomitantly affect serum sErbB1 and EGF levels. In conclusion, these data indicate that serum sErbB1 and EGF (postoperative only) levels are significantly different between EOC patients and healthy women and that altered and/or changing serum sErbB1 and EGF levels may provide important diagnostic and/or prognostic information useful for the management of patients with EOC.

Acridines↗
PubMed1998

A sandwich type acridinium-linked immunosorbent assay (ALISA) detects soluble ErbB1 (sErbB1) in normal human sera.

The epidermal growth factor receptor (ErbB1) is overexpressed in various human tumor-derived cell lines and neoplasms, where it is believed that receptor dysregulation plays a role in oncogenic transformation and tumor progression. In addition to the ErbB1 holoreceptor, numerous studies demonstrate that cells synthesize soluble or secreted forms of ErbB1, i.e., sErbB1. Overexpression of ErbB1 in a variety of tumors has led us to hypothesize that sErbB levels also may be altered during oncogenesis, tumor progression, and/or metastasis; and that these molecules may be useful tumor biomarkers. To address this hypothesis we have developed an acridinium-linked immunosorbent assay (ALISA) specific for the extracellular domain of ErbB1 that can be used to quantify the levels of sErbB1 molecules in body fluids and conditioned culture media. This assay can also detect full-length ErbB1 in cell and tissue extracts. Our ALISA is characterized by high sensitivity (intra-assay LLD < 1 fmol/ml), a broad linear range (approximately 1 to 4000 fmol/ml), and good reproducibility (CVs < 10%). Specificity experiments show that this ALISA detects p170 ErbB1 and soluble forms of ErbB1 that embody extracellular subdomains I through IV, but not forms of sErbB1 lacking subdomain IV. Our ALISA does not detect full-length ErbB2, ErbB3, or ErbB4; or p105 soluble ErbB2. We report that serum sErbB1 levels of healthy women (median = 3716 fmol/ml), ranging in age from 43 to 76 years, differ significantly from those of healthy men (median = 24,512 fmol/ml), ranging in age from 25 to 79 years. Additional analyses do not indicate that serum sErbB1 levels change with age in either healthy men or women. Immunoprecipitation experiments show that monoclonal antibodies specific for extracellular epitopes of ErbB1 completely neutralize the detection of sErbB1 in normal human sera by ALISA. Finally, we show by immunoprecipitation and Western immunoblot analyses with monoclonal antibodies specific for the extracellular domain of ErbB1 that normal human female and male sera contain a approximately 110-kDa protein. We conclude that our ALISA is measuring the relative levels of this p110 sErbB1 analog in normal human sera. Our ALISA, therefore, should be useful for measuring the levels of ErbB1 and sErbB1 molecules in tumor biopsy specimens and body fluids, respectively, and for determining whether sErbB1, like ErbB1, is a useful tumor biomarker.

Acridines↗
PubMed1998

Increased risk for cancer in patients with the Peutz-Jeghers syndrome.

BACKGROUND: Some reports describe an increased risk for cancer in patients with the Peutz-Jeghers syndrome. OBJECTIVE: To characterize occurrences of cancer in a large cohort of patients with the Peutz-Jeghers syndrome. DESIGN: Retrospective cohort study. SETTING: Tertiary care center. PATIENTS: 34 patients with the Peutz-Jeghers syndrome identified from Mayo Clinic records from 1945 to 1996. MEASUREMENTS: Cases of cancer documented by chart review and telephone follow-up. RESULTS: 26 cases of noncutaneous cancer developed in 18 of the 34 patients: 10 cases of gastrointestinal cancer and 16 cases of extraintestinal cancer. With the use of SEER (Surveillance, Epidemiology, and End Results) data for comparison, the relative risk for cancer was 18.5 (95% CI, 8.5 to 35.2) in women with the Peutz-Jeghers syndrome and 6.2 (CI, 2.5 to 12.8) in men with the syndrome (P = 0.001). In women, the relative risk for breast and gynecologic cancer was 20.3 (CI, 7.4 to 44.2). CONCLUSIONS: The Peutz-Jeghers syndrome is associated with an increased risk for cancer. The relative risk for breast and gynecologic cancers is particularly high.

Adolescent↗
PubMed1998

Primary squamous cell cancer of the vulva: radical versus modified radical vulvar surgery.

OBJECTIVE: To evaluate the results of surgical therapy and to specifically compare radical and modified radical vulvar surgery relative to survival, recurrence, metastasis, and complications. METHODS: A retrospective review of 225 patients with primary squamous cell cancer of the vulva was performed. Clinical, pathologic, surgical, and follow-up data were collected from the patient records. All pathology slides were reviewed with a pathologist. Radical surgery included 134 patients treated by the Basset operation. Modified radical surgery accounted for 91 patients with vulvar excision alone (65) or with lymphadenectomy (26) via separate groin incisions. RESULTS: The 5-year recurrence rate was 14%. The overall and disease-free survival rates at 5 years were 76. 1 and 83.4%, respectively. There were no statistically significant differences between the two procedures regarding overall survival, disease-free survival, or the development of recurrence, even after adjusting for stage (P > 0.05). Patients undergoing radical vulvar surgery were more likely to develop surgical complications and sequelae than patients having modified radical surgery, even after adjusting for stage. CONCLUSIONS: Modified radical vulvar surgery is associated with decreased complications and 5-year overall and disease-free survival and recurrence rates similar to those of radical vulvar surgery.

Adult↗
PubMed1998

Cervical cancer in older women: a molecular analysis of human papillomavirus types, HLA types, and p53 mutations.

OBJECTIVE: The purpose of this study was to evaluate cervical cancers in older women to determine whether they differed from tumors in younger women with respect to human papillomavirus types, frequencies of p53 mutations, and presence of a proposed high-risk HLA-DR2 haplotype. STUDY DESIGN: Cervical tissue was obtained from women undergoing surgical treatment of in situ or invasive carcinoma of the cervix. Viral and genomic deoxyribonucleic acid was extracted. The presence of human papillomavirus deoxyribonucleic acid was detected by polymerase chain reaction amplification. Viral subtypes were assigned by means of a combination of type-specific amplification and automated sequencing of the L1 region. The presence of p53 mutations was evaluated by direct sequencing of exons 5 through 9. The HLA-DR locus was screened for the presence of the high-risk DRB1*1501 allele by means of selective polymerase chain reaction amplification followed by agarose gel electrophoresis of HLA-DR2 types. RESULTS: Tumors from 39 women 62 to 85 years old were analyzed. Tumors from 104 younger women formed a reference group. Human papillomavirus 16 was found in 41% and 54% and human papillomavirus 18 was found in 10% and 12% of the tissue samples from older and younger women, respectively. The overall distributions of human papillomavirus types did not differ statistically between the groups. One of the 25 older patients tested had a p53 mutation. This tumor also had a positive test result for human papillomavirus 18. The DR*1501 allele was present in 33% of the older patients and 28% of the younger patients. The expected frequency of this allele in white Americans is 19.8%. The increased frequency of this allele among both older and younger women with cervical cancer was statistically significant (P < .05). CONCLUSIONS: We hypothesized that cervical cancer in older women might differ from that in younger women with respect to human papillomavirus types, natural host immunity, or the frequency of nonviral origins of the cancer. The findings show, however, that tumors from older women are extremely similar to those from younger women with respect to the human papillomavirus types present and the infrequent occurrence of p53 mutations. In addition we found that an HLA-DR allele that is associated with a risk of cervical cancer in younger women is also associated with risk in older women. These findings are most consistent with a model similar to that in younger women but with an unusually long latency for the transforming effect of the virus in some hosts.

Aged↗
PubMed1997

Intraoperative radiation therapy in gynecologic cancer: update of the experience at a single institution.

PURPOSE: To update the Mayo Clinic experience with intraoperative radiation therapy (IORT) in patients with gynecologic cancer. METHODS AND MATERIALS: Between January 1983 and June 1991, 39 patients with recurrent or locally advanced gynecologic malignancies received intraoperative radiation therapy with electrons. The anatomical area treated was pelvis (side walls or presacrum) or periaortic nodes or a combination of both. In addition to intraoperative radiation therapy, 28 patients received external beam irradiation (median dose, 45 Gy; range, 0.9 to 65.7 Gy), and 13 received chemotherapy preoperatively. At the time of intraoperative radiation therapy and after maximum debulking operation, 23 patients had microscopic residual disease and 16 had gross residual disease up to 5 cm in thickness. Median follow-up for surviving patients was 43.4 months (range, 27.1 to 125.4 months). RESULTS: The 5-year actuarial local control with or without central control was 67.4%, and the control within the IORT field (central control) was 81%. The risk of distant metastases at 5 years was 52% (82% in patients with gross residual disease and 33% in patients with only microscopic disease postoperatively). Actuarial 5-year overall survival and disease-free survival was 31.5 and 40.5%, respectively. Patients with microscopic disease had 5-year disease-free and overall survival of 55 and 50%, respectively. Grade 3 toxicity was directly associated with IORT in six patients (15%). CONCLUSION: Patients with local, regionally recurrent gynecologic cancer may benefit from maximal surgical debulking and IORT with or without external beam irradiation, especially those with microscopic residual disease.

Adult↗
PubMed1997

Expression of nm23/nucleoside diphosphate kinase-A protein in endometrial carcinoma.

A metastatic tumor suppressor role for the nm23 gene product in breast carcinoma has been proposed. The biologic significance of nm23/NDP kinase-A (NDPK-A) expression in endometrial carcinoma remains undetermined. We sought to (1) characterize the pattern and intensity of nm23 protein expression in endometrial carcinoma and (2) assess the relationship between intensity/pattern of nm23 protein immunostaining and treatment response assessed by progression-free survival and survival to death. Formalin-fixed paraffin-embedded sections from 234 patients with endometrial cancer were immunostained with a mouse monoclonal IgG to nm23/NDPK-A protein. In most specimens of endometrial carcinoma (67.5%), nm23 expression was strongly upregulated. No association was found between either intensity (0 vs 1, 2, 3) or pattern (nuclear membrane vs cytoplasmic) of immunostaining and FIGO stage, ploidy status, histologic subtype, myometrial invasion, progression-free survival, or survival to death. Absence of nm23 staining (0 vs 1, 2, 3) was significantly associated with lower tumor grades (P = 0.02). For stage I patients, moderate to strong nm23 immunostaining intensity (2, 3) was associated with a trend toward diminished progression-free survival (P = 0.08). Our data imply a heterogeneity of nm23 protein expression and possible distinct biologic roles for nm23 in endometrial compared with breast or ovarian carcinoma.

Adult↗
PubMed1997

Overexpression of p34cdc2 protein kinase in epithelial ovarian carcinoma.

OBJECTIVE: To investigate the role of expression of p34cdc2 protein kinase in normal, benign, and malignant ovarian epithelium. MATERIAL AND METHODS: Tissue sections from 24 patients with epithelial ovarian carcinoma (EOC) along with 6 normal ovarian specimens and 12 benign cystadenomas were incubated with mouse IgG monoclonal antibody to human p34cdc2 protein kinase, followed by detection with use of a standard peroxidase-labeled streptavidin-biotin technique. Immunohistochemical staining was graded and compared. Clinical data were also reviewed. RESULTS: Normal surface epithelium and 10 of 12 benign cystadenomas failed to stain for p34cdc2 protein kinase. Of the 24 EOC specimens, however, 19 (79%) stained positively. The staining pattern or intensity was not associated with the histologic grade or surgical stage. CONCLUSION: Expression of p34cdc2 protein kinase is strongly up-regulated in most cases of EOC but not in normal epithelial ovarian tissue or in most cases of benign epithelial tumors evaluated. Therefore, it may be associated with early events in carcinogenesis. Redundant overexpression of cyclin-dependent kinases such as p34cdc2 may contribute to deranged cell cycle progression and proliferation of EOC. Observation of overexpression of p34cdc2 protein kinase in other malignant lesions suggests a common mechanism.

Adolescent↗
PubMed1996

Concordance of DNA ploidy pattern as measured by flow cytometry in primary, metastatic, and persistent ovarian carcinoma.

In an attempt to evaluate the stability of DNA content in ovarian carcinoma, 66 tumor specimens from 25 patients with stage III disease were analyzed by flow cytometry. For all patients, both primary tumor and omental metastasis were available, and for 16 patients the persistent tumor found at second-look operation was also available. The concordance of the tumor DNA content in the primary tumor and in the corresponding omental metastasis was 72%; the concordance in persistent tumor at second-look operation was 63%. When diploid and aneuploid tumors with very low DNA index were considered together, the concordance of the DNA content in primary and metastatic tumors reached 84%. According to our data, if DNA ploidy is used to differentiate patients with a favorable prognosis (DNA diploid and DNA aneuploid with low DNA index) from those with an unfavorable prognosis (DNA aneuploid with high DNA index), a 16% risk of misclassification appears unacceptable in prospective studies. Hence, the assessment of two specimens (preferably the primary lesion and a metastatic site) to determine the most abnormal DNA ploidy result would reduce the risk of underclassification of tumor.

DNA, Neoplasm↗
PubMed1996

Elevated nm23 protein expression is correlated with diminished progression-free survival in patients with epithelial ovarian carcinoma.

OBJECTIVES: The role of the candidate metastasis-suppressor gene nm23-H1 first characterized in breast cancer remains controversial, with both metastasis suppression and disease progression being linked to elevated nm23-H1 gene expression in different human tumor types. We sought to characterize (1) the pattern and intensity of nm23-H1/nucleoside diphosphate (NDP) kinase expression in human epithelial ovarian carcinoma (EOC) and (2) the relationship between nm23-H1/NDP kinase expression and tumor extent at diagnosis (FIGO stage) and response to treatment as defined by progression-free survival and actuarial survival. METHODS: Twenty-four patients with EOC aged 61.1 +/- 13.0 (mean +/- SD) years were followed for 614.0 +/- 289.7 days after a debulking procedure, cisplatin-based chemotherapy (19 of 24), and second-look laparotomy (9 of 24). After the primary debulking procedure, 63% of patients had no or microscopic residual disease. Overnight incubation of formalin-fixed tumor sections at 4 degree C with primary rabbit polyclonal IgG antibody to human nm23-H1/NDP kinase was followed by detection with standard ABC method. Nonimmune rabbit serum and normal breast tissue served as controls. Immunohistochemical staining was graded by a clinically blinded observer for intensity of staining (0, negative; 1, weak; 3, strong), pattern of staining (focal or diffuse), and histologic grade of tumor (1 through 4). RESULTS: Of the EOCs, 54% were histologic grade 3 or 4 and 58% were FIGO stage III; 88% (21 of 24) stained positively, and 18 of 21 stained strongly and 14 of 21 stained diffusely. No correlation was found between either intensity or pattern of nm23-H1/NDP kinase immunostaining and histologic grade. No correlation was found between either staining pattern or intensity and FIGO stage. There was a trend toward decreased actuarial survival with both focal pattern (P = 0.12, log-rank test) and strong intensity (P = 0.15, log-rank test) of nm23-H1 staining. Decreased progression-free survival was likewise correlated with focal nm23-H1/NDP kinase immunostaining pattern (P = 0.02, log-rank test) and strong intensity of nm23-H1/NDP kinase staining (P = 0.08, log-rank test). CONCLUSIONS: Expression of nm23-H1/NDP kinase is strongly upregulated in most EOCs. Redundant overexpression of nm23-H1/NDP kinase may contribute to deranged cell cycle progression and EOC proliferation. Pattern and intensity of nm23-H1/NDP kinase immunostaining of EOC tissue retrieved at primary operation may identify patients at risk for tumor progression and help guide treatment strategies. These findings suggest that nm23-H1 gene expression may have distinct if not opposite biologic functions in EOC and breast carcinoma.

Adolescent↗
PubMed1996

Adjuvant chemotherapy versus chemotherapy plus pelvic irradiation for high-risk cervical cancer patients after radical hysterectomy and pelvic lymphadenectomy (RH-PLND): a randomized phase III trial.

OBJECTIVE: To compare the clinical efficacy of adjuvant chemotherapy a lone vs chemotherapy plus whole pelvic radiation therapy (RT) on recurrence rates, patterns of recurrence, and survival of patients post-RH-PLND for cervical cancer at high risk for recurrence. METHODS: Prospective multicenter randomized Phase III trial. Patients with Stage IB-IIA cervical cancer undergoing RH-PLND were eligible. Risk factors include deep cervical invasion, tumor > or = 4 cm, parametrial involvement, nonsquamous histology, and/or pelvic lymph node metastasis. Chemotherapy consisted of cisplatin and bleomycin, alone or in combination with whole pelvic RT. Survival was determined by Kaplan-Meier estimate. RESULTS: Eighty-nine patients were entered from 1987 to 1994. Seventy-five patients had a Stage IB cancer and 14 patients had Stage IIA. Twenty-five patients had > or = 3 risk factors. Forty-four patients received chemotherapy alone vs 45 patients treated with chemotherapy and RT. Nineteen patients had recurrences and 16 patients have died. Nine of 44 (20%) patients receiving chemo alone recurred compared to 10/45 (22%) patients receiving chemo and RT (P=ns). Patterns of recurrence were statistically similar between the two treatment arms, even among the subgroup of patients with > or = 3 risk factors. Both regimens were well tolerated. CONCLUSION: CT + RT did not prove a superior adjuvant therapy for patients at high risk of recurrence after RH-PLND for early cervical cancer in this limited trial. Recurrence rates and patterns of recurrences (local, regional, or distant) were not influenced by the addition of RT.

Adult↗
PubMed1996

Prognostic value of p53 and proliferating cell nuclear antigen expression in endometrial carcinoma.

The degree of expression of p53 and proliferating cell nuclear antigen (PCNA) was measured in archival samples from 221 patients managed surgically for endometrial carcinoma between 1979 and 1983. With use of primary antibodies to the p53 protein (DO7) and PCNA (PC10), immunoperoxidase nuclear staining of paraffin-embedded tissue was performed. The computerized CAS200 Image Analysis System was used to determine the percentage of nuclear area stained. There was no evidence to conclude that progression-free survival differed with respect to PCNA expression. In contrast, intense p53 expression (66% or more nuclear area stained) was significantly associated with compromised progression-free survival both in the analysis of all stages (P < 0.001) and in the subset of patients with stage I disease (P < 0.001). Intense expression of p53 was significantly associated with other prognostic indicators, including stage, grade, depth of myometrial invasion, histologic subtype, cytologic findings, DNA ploidy, and HER-2/neu expression. Multivariate analysis identified four independent prognostic factors for progression-free survival in endometrial carcinoma: intense p53 expression, histologic subtype, DNA ploidy status, and HER-2/neu expression. When none of these four independent factors are present, the 4-year progression-free survival is 96%. In contrast, it is 63% when one or more of these factors are present (P < 0.001) and 40% when two or more factors are present (P < 0.001).

Adult↗