Biomedical subjects

K C Podratz

Publications and source records attributed to K C Podratz.

At least 73 records · Page 4Linked to original sources

PubMed1994

Cervical cancer complicated by pregnancy: episiotomy site recurrences following vaginal delivery.

OBJECTIVE: To determine the optimal diagnostic and therapeutic modalities relevant to episiotomy site recurrence of cervical cancer after vaginal delivery. METHODS: Records from the past 30 years were reviewed to identify patients treated at the Mayo Clinic with episiotomy site recurrence of cervical cancer complicated by pregnancy with vaginal delivery. RESULTS: Four patients with episiotomy site recurrence of squamous cell carcinoma of the cervix were treated primarily at the Mayo Clinic. These cervical cancers were originally diagnosed at delivery or in the immediate postpartum period and were treated by radical hysterectomy. Episiotomy site recurrences were detected less than 12 weeks after surgery in three patients and at 2 years in one patient. Three patients have died of recurrent cancer and one is disease-free at 1 year. CONCLUSIONS: Careful screening and examination of cervical abnormalities during pregnancy is required. The primary cancer was not diagnosed until delivery or postpartum in all patients who developed episiotomy site recurrences. If vaginal delivery is elected in a patient with cervical cancer, perineal inspection becomes critical. Including other cases reported in the literature, six of nine with stage IB disease were diagnosed with episiotomy site recurrence within 12 weeks of primary therapy. Consideration should be given to colposcopy of the episiotomy site or random biopsy in these women preoperatively to rule out occult implantation, and this site warrants careful postoperative surveillance.

Adult↗

PubMed1993

Comparison of loss of heterozygosity patterns in invasive low-grade and high-grade epithelial ovarian carcinomas.

Loss of heterozygosity (LOH) studies were performed to investigate the genetic differences which separate low-grade (LG), high-grade (HG), and borderline epithelial ovarian carcinomas. Fresh tumor samples and blood were obtained from 58 patients (20 LG, 34 HG, and 4 borderline tumor specimens) undergoing surgery for ovarian carcinoma at Mayo Clinic. Tumors were graded using a modified Broder's classification with invasive grades 1 and 2 considered LG, invasive grades 3 and 4 considered HG, and tumors with no evidence of stromal invasion classified as borderline. Polymorphism analysis was performed using 76 restriction fragment length polymorphisms and variable number of tandem repeats and 59 microsatellite markers representing all chromosome arms. Chromosome arms 6p, 17p, 17q, and 22q were found to be frequently lost in LG as well as HG tumors. Chromosome arms 13q and 15q were lost to a significantly greater extent in HG tumors compared to LG neoplasms (P = 0.003 and P = 0.08, respectively). Conversely, 3p loss was seen more frequently with LG tumors (P = 0.02). The majority of LG tumors (65%) did not show frequent LOH in the allelotype analysis. In fact, a subset of 7 (7 of 20) LG tumors accounted for 76% of the total allelic loss in the LG category. These tumors showed LOH almost identical to that of the HG neoplasms. Borderline tumors showed a low rate of allelic loss. There were no common events found between borderline and invasive tumors. Our data suggest that most HG tumors and a subset of LG tumors share genetic alterations at putative tumor suppressor genes detected by LOH studies. Chromosome 6 and 17 losses appear to be early events while 13q and 15q losses appear to be critical late events. However, a majority of LG tumors appear to develop as a consequence of an alternative mechanism(s) which is not detected by LOH studies. Possibilities include: (a) inactivation of tumor suppressor genes without LOH; (b) dominant negative gene(s) in which only one allele requires mutation; and (c) changes in dominant acting oncogenes. This unidentified phenomenon may be operative in borderline tumors as well.

Alleles↗

PubMed1993

Human epithelial ovarian cancer allelotype.

To determine which chromosomes and chromosomal regions contain putative tumor suppressor genes important for human epithelial ovarian cancer, we performed loss of heterozygosity (LOH) studies on 37 primary epithelial ovarian tumors. Using 70 polymorphic markers, we examined all chromosome arms (excluding acrocentric arms) on all specimens. Our findings show a high frequency of LOH for the following chromosome arms: 5q (43%); 6p (62%); 6q (57%); 7p (36%); 8p (40%); 9q (54%); 13q (56%); 14q (47%); 15q (36%); 17p (81%); 17q (76%); 18q (43%); 21q (36%); and 22q (71%). When separated into low and high grade tumors, there were statistically significant differences of LOH for the following chromosome arms: 6p (29% versus 70%); 13q (0% versus 72%); 17p (33% versus 90%); and 17q (29% versus 87%). No statistically significant difference was found between different histological subtypes. The average fractional allelic loss for low grade tumors was 0.17 versus 0.40 for high grade and 0.35 for all tumors. In an effort to more specifically localize common regions of molecular genetic deletion, we examined the following chromosomes in greater detail: chromosome 13 (5 markers); chromosome 17 (8 markers); and chromosome 6 (8 polymorphic markers). No tumor showed deletion of only a portion of chromosome 13. When any informative marker for chromosome 13 showed loss, all markers showed loss. Similarly, the tumors of most patients demonstrated LOH of all informative markers that map to chromosome 17; however, regional deletion of 17p markers was observed in 3 tumors. Twelve tumors demonstrated regional deletions of portions of chromosome 6. These tumors suggest that at least 2 regions of chromosome 6 are important for ovarian epithelial carcinogenesis. One region appears to be on distal 6q and a second region is near the centromere of chromosome 6 proximal to the HLA locus.

Alleles↗

PubMed1993

Second-look operation in ovarian cancer.

BACKGROUND: Although second-look laparotomy (SLL) remains the hallmark method for determining disease status after completion of adjuvant therapy, the inclusion of reassessment surgery in the treatment scheme of ovarian carcinoma has been challenged. Given the absence of prospective analyses addressing this issue, justification for continued use of SLL must demonstrate benefits regardless of the outcome of the procedure. RESULTS: In the absence of residual disease, either the recurrence rate after SLL should be acceptably low or the outcome should permit identification of specific groups that would benefit from consolidation therapy. The characteristics associated with a significant risk for recurrence after a negative SLL include patient age, histologic grade, and the amount of residual disease after the primary cytoreduction operation. The postoperative benefits of positive SLL findings must be manifested in enhanced survival rates after secondary cytoreduction surgery, salvage therapy, or both. Recent evidence suggests that tumor reduction during SLL and contemporary salvage methods favorably influence specific subgroups of patients. CONCLUSIONS: The criteria for continued use of SLL in advanced epithelial ovarian cancer should include the availability of (and preferably prospective clinical trials for) both consolidation and salvage therapy to which all patients with ovarian cancer optimally would be afforded access.

Female↗

PubMed1993

Intraoperative radiation therapy in gynecologic cancer: the Mayo Clinic experience.

Nineteen patients with recurrent and two patients with locally advanced gynecologic malignancies received intraoperative radiation therapy (IORT) with electrons at the Mayo Clinic. Fourteen of the patients also received external beam irradiation. Actuarial local control with or without central control at 5 years was 71%, and actuarial control within the IORT field (central control) was 80%. The distant metastases rate at 5 years was 47%. Actuarial 2- and 5-year overall survival was 58 and 33%, respectively, and disease-free survival was 47 and 40%, respectively. Patients with microscopic disease had significantly higher 5-year disease-free and overall survival (70 and 67%, respectively). In summary, IORT in combination with maximum debulking surgery with or without external beam therapy in patients with paraaortic or pelvic sidewall recurrences of gynecologic malignancies appeared to improve long-term local control and survival. The addition of hyperthermia or hypoxic sensitizers may be a consideration to further improve local control in patients with gross residual disease. The high incidence of distant metastasis warrants the search for effective systemic chemotherapy. IORT-related toxicity was acceptable.

Adult↗

PubMed1993

The proto-oncogene c-fms is overexpressed in endometrial cancer.

Recent studies have shown that macrophage colony-stimulating factor and its receptor c-fms protein are significantly overexpressed in endometrial and ovarian cancers. In the present study, we analyzed the steady-state levels of c-fms mRNA in benign and malignant endometrial tissues by Northern and slot blot analyses. The relative levels of c-fms mRNA were quantified by using a hybridization signal for each sample on Northern blot analysis. Slot blot analysis was used to further quantitate the relative increase in c-fms mRNA in malignant specimens compared to benign specimens. Correlation of c-fms expression in the endometrial cancers was made with traditional prognostic indicators. Secretory endometrium had low levels of c-fms mRNA, whereas the endometrial cancers had the highest levels. Proliferative and hyperplastic endometrium values were intermediate. Comparative assessment of c-fms expression in endometrial cancer relative to other prognostic factors demonstrated greater expression of c-fms in specimens from patients with abnormal DNA ploidy, high-grade lesions, and possibly extrauterine metastases. Our study confirms the overexpression of c-fms in endometrial cancer and demonstrates a positive correlation between the steady-state mRNA levels of c-fms and other select adverse prognostic indicators.

Endometrial Neoplasms↗

PubMed1993

Absence of prohibitin gene mutations in human epithelial ovarian tumors.

Multiple loss of heterozygosity (LOH) studies of ovarian cancers have found a high incidence of chromosome 17 loss in these tumors. Several authors have suggested that the region commonly deleted encompasses 17q12-21. In addition, this region has recently been reported to be linked to the familial breast/ovarian cancer syndrome. Recently the human prohibitin gene was mapped to region 17q12-22. Prohibitin causes arrest of DNA synthesis by fibroblast and HeLa cells and prohibitin shows significant homology to a gene (Cc) thought to be important for the regulation of development of Drosophila melanogaster. These findings have led many to consider the prohibitin gene a potential tumor suppressor gene. In addition, sequence analysis of exon 4 of human prohibitin gene revealed mutations in 4 of 23 sporadic breast carcinomas. Because of the proposed function for prohibitin, its alterations in breast cancers, and the fact that its location on 17q falls within a commonly deleted region in ovarian cancers, we have undertaken an analysis of the sequence of prohibitin in epithelial ovarian cancers. Using several polymorphic DNA probes, we identified 20 epithelial ovarian tumors which demonstrated LOH for the region that contains the prohibitin gene. To evaluate whether mutations of prohibitin may be important in ovarian carcinogenesis, we have sequenced exons 4 and 5 of this gene using the technique of genomic amplification with transcript sequencing. Only normal exon 4 and 5 sequence was observed among the 20 tumors screened. These results demonstrate that this region of the prohibitin gene is not mutated in epithelial ovarian cancers and suggest that the prohibitin gene does not play a role in ovarian carcinogenesis. Sequencing of further exons and introns are needed to confirm this latter hypothesis.

Base Sequence↗

PubMed1993

Deoxyribonucleic acid analysis facilitates the pretreatment identification of high-risk endometrial cancer patients.

OBJECTIVE: Our purpose was to assess the proficiency with which cytometrically determined deoxyribonucleic acid variables from pretreatment curettage specimens identify patients at high risk for extrauterine disease or posttreatment relapse. STUDY DESIGN: Flow cytometrically determined deoxyribonucleic acid ploidy, S-phase fraction, deoxyribonucleic acid index, and proliferative index were assessed in 140 paraffin-embedded curettage specimens containing endometrial carcinoma. RESULTS: Although clinical staging identified only 19% of patients with advanced disease, 46% of surgical stages III and IV were aneuploid, 69% had an S-phase fraction > or = 9%, and 69% had a proliferative index > or = 14%. Documented recurrences and cancer-related deaths correlated with nondiploid patterns (29% of 140, 50% of recurrences, 54% of deaths), S-phase fraction > or = 9% (41% of 140, 67% of recurrences, 75% of deaths), and proliferative index > or = 14% (45% of 140, 73% of recurrences, 79% of deaths). Deoxyribonucleic acid index (< 1.5 vs > 1.5) provided additional stratification of aneuploid tumors (p < 0.01). Multivariate analysis identified the proliferative index as the most cogent independent prognostic factor (p < 0.01). CONCLUSION: Deoxyribonucleic acid ploidy and proliferative activity in pretreatment curettage specimens identified the majority of patients at high risk for extrauterine metastasis and relapses.

Adult↗

PubMed1992

Long-term survival and sequelae after surgical management of invasive cervical carcinoma diagnosed at the time of simple hysterectomy.

From 1956 to 1988, 27 women (median age, 60 years) found to have occult invasive carcinoma of the cervix at total hysterectomy underwent radical reoperation consisting of radical parametriectomy, upper vaginectomy, and pelvic lymphadenectomy. Residual disease was present at reexploration in 4 (15%) of the 27 patients: in the pelvic lymph nodes in 2, in the parametrium in 1, and in the vagina and a para-aortic node in 1. All patients were followed a minimum of 18 months; there were no deaths within 3 months of operation. However, 2 (7%) of the 27 patients developed ureterovaginal fistulas. Recurrent disease was observed in 6 (22%) of the patients: 2 had successful salvage procedures, and 4 died of disease, all within 4 years of reoperation. Recurrence correlated with the presence of residual disease at reoperation and with nonsquamous histologic findings. At a median follow-up of 8.4 years, 23 of the 27 patients were alive and disease-free. The 5-year absolute survival estimate (Kaplan-Meier) was 82%. Radical reoperation can be performed safely in selected patients who have early-stage invasive carcinoma of the cervix at the time of total hysterectomy with the expectation of an acceptable rate of long-term disease-free survival.

Adenocarcinoma↗

PubMed1992

HER-2/neu expression: a major prognostic factor in endometrial cancer.

The HER-2/neu oncogene encodes for a specific cell-surface glycoprotein similar to the human growth factor receptor. An analysis of 247 patients with endometrial cancer treated between 1979 and 1983 was performed using an immunoperoxidase technique on paraffin-embedded tissue samples to detect HER-2/neu overexpression. Specimens were graded blindly with regard to HER-2/neu staining intensity. Overexpression of HER-2/neu was identified as strong in 37 patients (15%), mild in 144 (58%), and none in 66 (27%). The 5-year progression-free survival was 56% for the strong, 83% for the mild, and 95% for the nonstaining groups. The strong (P < 0.0001) and the mild (P = 0.028) staining groups were distinct from the nonstaining group in predicting progression-free survival. Likewise, strong overexpression was associated with a poor (51%) overall survival (P < 0.0001). Multivariate analysis revealed that intense overexpression had independent significance in predicting progression-free (P = 0.0003) and overall survival (P < 0.0001). In stage I patients (203), the 5-year progression-free survival was 62% for the strong and 97% for the nonstaining groups (P = 0.0007). This retained independent significance when subjected to multivariate analysis (P = 0.0017). Other significant stage I prognostic factors in multivariate analysis included DNA ploidy, histologic subtype, and histologic grade but not depth of invasion.

Endometrial Neoplasms↗

PubMed1992

Proliferating cell nuclear antigen in epithelial ovarian cancer: relation to results at second-look laparotomy and survival.

We determined the proliferative index (PI) of 92 previously untreated advanced epithelial ovarian cancers using PCNA/cyclin immunostaining and image analysis quantitation. In this retrospective study, there was a relationship between tumor PI and 5-year survival. For patients with a tumor PI greater than the median, the estimated 5-year survival was 44%; for patients with a tumor PI below the median, the estimated 5-year survival was 15% (P = 0.003). This may partly reflect sensitivity to chemotherapy, as those patients with more rapidly proliferating tumors were more likely to achieve a pathologic complete response to platinum-based therapy.

Adult↗

PubMed1992

Flow-cytometric DNA analysis of stages IB and IIA cervical carcinoma.

The prognostic significance of flow-cytometric DNA analysis was assessed in 375 stages IB and IIA squamous cell carcinoma patients treated with radical hysterectomy and lymphadenectomy at the Mayo Clinic between 1956 and 1985. Paraffin-embedded samples containing at least 20% tumor were dewaxed, rehydrated, stained with propidium iodide, and analyzed. Among 344 assessable samples, 136 (40%) were diploid and 208 (60%) were nondiploid (26 tetraploid, 158 aneuploid, and 24 polyploid). Diploid cases were further subclassified: 25 high proliferative phase (HPP) (S+G2M greater than 20%) and 111 low proliferative phase. No significant correlation was noted between DNA diploid patterns and stage, tumor size, grade, or histotype, but HPP diploid tumors had a significantly higher risk of nodal metastasis. With a mean follow-up period of 150 months, 62 patients died of disease. No significant difference was observed in survival rates (SR) between diploid and nondiploid tumors, but the subset of HPP diploid tumors had a prognosis significantly worse than that of any other group (P less than 0.01). Other significant variables included nodal metastases, parametrial extension, age, and clinical stage. While ploidy patterns did not assign additional risk to node-positive lesions, HPP diploid tumors in node-negative patients were associated with a significantly lower SR. Multivariate analyses in node-negative patients demonstrated that stage, histologic subtype, and HPP diploid patterns retained prognostic independence.

Carcinoma, Squamous Cell↗

PubMed1991

Stage I ovarian epithelial carcinoma: survival analysis following definitive treatment.

Between 1977 and 1986, 55 patients with surgical stage I ovarian epithelial carcinoma were managed in a definitive fashion, which included surgical staging and adjuvant therapy in 51 of 55 patients (93%) and second-look laparotomy. The mean follow-up time from the data of reassessment surgery was 94 months, allowing sufficient time to facilitate the identification of one or more subgroups of patients at risk of having persistent disease or developing a recurrence. Treatment failures were detected at second-look laparotomy in 6 patients (11%), and an additional 5 patients (9%) subsequently had recurrences after being declared free of disease at second-look reassessment. Analysis of pathologic variables identified grade and substage as important prognostic factors, with 8 of the 9 deaths (89%) being associated with Broders grade 3 or 4 and/or stage IC. Within the bivariate model consisting of patients harboring poorly differentiated (grade 3 or 4) stage IC lesions, 6 of 14 patients (43%) are dead from disease, yielding a long-term survival rate that at best approximates the survival rate associated with optimally reduced (microscopic residual) stage III patients subjected to contemporary adjuvant therapy and reassessment surgery. These data suggest that intensive therapy as utilized in advanced disease, including platinum-based chemotherapy, second-look laparotomy, and innovative salvage or investigational consolidation therapy, is equally applicable to this "high-risk" stage I group.

Antineoplastic Agents↗

PubMed1990

Identification of putative nonfunctional steroid receptors in breast and endometrial cancer.

A nuclear binding assay was developed for the purpose of having available a more predictive assay for hormone responsiveness in human cancers. The BNB assay identified specific and saturable steroid nuclear binding in human target tissues and human carcinomas. When the BNB assay was applied to a large set of breast and endometrial carcinomas, we speculate that nonfunctional receptors were detected in 20%-50% of the patients who were receptor-positive by the DCC assay. Lastly, as responsiveness to hormonal therapy in these cancer patients becomes known, the predictive value of the BNB assay can be established.

Biopsy↗

PubMed1990

Hormonal therapy in endometrial carcinoma.

Although hormonal agents have been used to treat endometrial cancer for nearly 30 years, response rates have remained essentially unchanged. Furthermore, objective response rates vary considerably from institution to institution, presumably because of differences in accepted response criteria and patient selection. The latter is particularly influenced by the distribution within the treated population of well-differentiated and poorly differentiated tumor histologic types. Nevertheless, the rapid attrition after hormonal therapy begins and the limited long-term salvage in nonselected patients with advanced primary or recurrent disease suggest primary nonresponsiveness or acquired tumor refractoriness to hormonal therapy. The determination of tumor progesterone receptor levels has made it easier to identify patients with sensitivity to such therapy. Recent investigations have shown favourable response rates (72%) after administration of progestational agents in patients with progesterone receptor-rich tumors. Similarly, responses have been reported with antiestrogens and combination progestin-antiestrogen therapy, recent laboratory observations having suggested potential benefit from sequential administration. Although these clinical and laboratory findings are encouraging, the limited duration of objective responses and the poor long-term survival rates continue to temper enthusiasm for routine hormonal therapy. Properly stratified (according to pathologic, biochemical, and clinical criteria), prospective, randomized, double-blind studies with more definitive end points, such as progression-free survival and overall survival, are mandatory to further evaluate the merits of various therapeutic regimens using gonadal hormones.

Carcinoma↗

PubMed1990

Evaluation of unfavorable histologic subtypes in endometrial adenocarcinoma.

A retrospective review of 388 patients who presented to the Mayo Clinic for treatment of endometrial carcinoma between 1979 and 1983 was performed and the surgical and pathologic observations were documented. An uncommon histologic subtype was detected in 52 patients (13%): 20 adenosquamous, 14 serous papillary, 11 clear cell, 7 undifferentiated. In contrast to the survival of patients with endometrioid lesions (92%), the overall survival in these patients was only 33%. Each of the individual abnormal histologic subtypes exhibited a survival of less than 50%. At the time of surgical staging, 62% of patients with unfavorable histologic subtypes had extrauterine spread of disease. Despite liberal utilization of postoperative adjuvant therapy in 42 of the 52 patients (81%), only 10% of these patients survived 5 years. Fifty-five percent had a component of recurrence outside of the abdominal/pelvic cavity. Subsequent treatment considerations should incorporate regimens addressing systemic and local tissue control.

Adenocarcinoma↗

PubMed1990

Effector function of lymphokine-activated killer cells and cytotoxic T lymphocytes in ovarian epithelial carcinoma.

From 20 patients with ovarian carcinoma (4 with stage I and 16 with stage III disease), we obtained peripheral blood mononuclear cells (MNC) from each, tumor-associated MNC from 9, and ascitic MNC from 6. These cells were stimulated with interleukin 2 (IL-2), and radioactive chromium-release cytotoxicity assays were used to evaluate the lymphokine-activated killer (LAK) activity against autologous tumor cells and two natural killer-resistant cell lines. The LAK response was consistently better with control peripheral blood MNC than with patient-derived MNC against all targets. However, within the ascitic MNC population, LAK activity against two cell lines (Daudi and OVCAR) was not statistically different from that of the control MNC. Phenotypic analysis of the ascitic MNC with monoclonal antibodies and flow cytometry revealed an activated population (IL-2 receptor-positive) characterized by predominantly monocytes/macrophages and T cells. In addition, the peripheral blood LAK activity for patients with stage I disease was statistically better against each target than that from patients with stage III disease. These results suggest an immunosuppressive effect directly related to tumor burden. Except perhaps for the ascitic MNC, autologous MNC do not appear to be effective LAK sources. Follow-up of the stage III patients revealed no difference in 2-year survival associated with in vitro LAK response.

Ascitic Fluid↗

PubMed1990

Peripheral nerve and ureteral tolerance to intraoperative radiation therapy: clinical and dose-response analysis.

Between April 1981 and July 1984, 51 patients received intraoperative radiation therapy (IORT) as a component of therapy for the management of primary or recurrent pelvic malignancies which were initially unresectable for cure. For these patients, curative surgical alternatives did not exist, or would have involved extensive procedures such as pelvic exenteration, distal sacrectomy, hemipelvectomy, or hemicorporectomy. The primary disease was colorectal in 38 patients. Treatment consisted of external beam radiation (range 3000 to 6890 cGy, median 5040 cGy), surgical debulking when feasible, and an intraoperative electron beam boost to the gross or microscopic residual disease (dose range 1000 to 2500 cGy, median 1750 cGy) utilizing 9-18 MeV electrons. The most common IORT associated toxicities were peripheral neuropathy and ureteral obstruction. None were life-threatening or fatal in severity. Of the 50 patients evaluable for neurotoxicity analysis, 16 (32%) developed peripheral neuropathy consisting of pain in 16 patients, numbness and tingling in 11, and weakness in 8. The pain, numbness and tingling resolved in about 40% of patients, while weakness resolved in only 1 of 8. Sixteen ureters were initially unobstructed by tumor at the time of IORT. Of these, 10 (63%) subsequently showed evidence of obstruction and hydronephrosis. The development of neurotoxicity was more common at IORT doses of 1500 cGy or more versus 1000 cGy. Ureteral obstruction with hydronephrosis occurred more frequently at IORT doses of 1250 cGy or more compared to 1000 cGy. There was no relationship between the likelihood of developing complications and the total external beam dose. The observed dependence of human nerve toxicity primarily on the IORT dose is consistent with data generated from animal experiments.

Colorectal Neoplasms↗