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Karl C Podratz

Publications and source records attributed to Karl C Podratz.

51 records · Page 3Linked to original sources
PubMed2003

Long-term follow-up of women with ovarian cancer after positive second-look laparotomy.

OBJECTIVE: Previous reports indicate that cytoreduction and salvage therapy with P32 or whole abdominal radiation may improve survival in patients with positive findings at second-look laparotomy (SLL). The aim of this investigation was to determine whether these findings held true with extended follow-up and a larger patient cohort. METHODS: From 1977 (the year platinum-based chemotherapy was introduced to our institution) to 1989, 150 patients had persistent disease at SLL. Relevant clinical information was extracted through retrospective chart review. RESULTS: One hundred forty-five patients were followed until death, with a median follow-up of 15.4 years for the 5 living patients. Median actuarial survival from the time of SLL was 18 months. Tumor grade (P = 0.003) and pre- and post-SLL tumor size (P < 0.0001) were significant determinants of survival by univariate analysis. Patients with microscopic disease or those with < or =1 cm disease rendered microscopic at SLL had improved survival relative to those with < or =1 cm and macroscopic disease following SLL (P = 0.03) (median survivals of 3.3, 2.5, and 1.4 years, respectively). In contrast, median survival of those with >1 cm disease cytoreduced to microscopic disease was no different than those with macroscopic residual, even if < or =1 cm (1.3 and 1.0 years, respectively). After adjusting for tumor size, salvage treatment was not a significant predictor of survival. CONCLUSION: With long-term follow-up there was no suggestion that the type of salvage therapy (e.g., P32 or WART) influenced survival. Rather, low-grade disease and low tumor burdens following cytoreduction were associated with improved survival on multivariate analysis.

Aged↗
PubMed2003

Hepatic resection for metachronous metastases from ovarian carcinoma.

OBJECTIVE: Hepatic resection for recurrent ovarian carcinoma is controversial because of the paucity of relevant published data. The principles of cytoreduction before chemotherapy suggest that resection of measurable liver lesions in properly selected patients would be beneficial. To determine the effect of resection of metachronous liver metastases on morbidity and survival, we reviewed our experience with this treatment. METHODS: Medical records were reviewed retrospectively for all patients who had anatomic hepatic resection for metachronous parenchymal liver metastases from ovarian carcinoma (epithelial or malignant mixed Müllerian tumors) at Mayo Clinic from 1976 to 1999. RESULTS: We identified 26 patients (median age at hepatic resection, 62 years; range, 39-75 years) who had hepatic resection requiring complete segmentectomies or more extensive hepatic surgery for recurrent ovarian carcinoma. Cytoreduction was optimal (extrahepatic and hepatic residual disease <or=1 cm) in 21 patients and suboptimal in 5. No intraoperative or postoperative deaths occurred. Aside from blood loss requiring transfusion of more than 4 units of erythrocytes in 4 patients, only two complications were noted: one superficial wound infection and one small-bowel perforation that required reoperation. The overall median disease-related survival was 26.3 months after hepatic resection; 18 patients (69%) died of disease at a median of 14.6 months (range, 5.0-41.3 months). However, 8 patients (31%) were alive at median follow-up of 33.2 months (range, 3.6-49.6 months). Factors significantly associated with improved disease-related survival were consistent with known prognostic factors associated with cytoreductive surgery, including more than 12 months since original diagnosis (27.3 vs 5.7 months, P = 0.004) and less than or equal to 1 cm of residual disease after hepatic resection (27.3 vs 8.6 months, P = 0.031). CONCLUSIONS: We present evidence that hepatic resection can be performed with minimal surgical morbidity and mortality by surgical teams trained in the procedures. Because of the disease-related survival advantage afforded women by optimal cytoreductive surgery, parenchymal liver metastases should not preclude secondary cytoreductive surgical efforts.

Adult↗
PubMed2003

Endometrial cancer: predictors of peritoneal failure.

OBJECTIVE: To assess determinants of peritoneal failure in endometrial cancer patients after definitive primary treatment. METHODS: Of 599 patients with endometrial cancer who had primary surgery at our institution during the decade before 1994, 131 had relapse. We defined "peritoneal failure" as relapse when it occurred in the upper abdomen or involved the pelvic peritoneum (or both). Mean follow-up was 72.8 months. RESULTS: Peritoneal failure was detected in 37 of 599 (6%) patients and represented 28% of identified failures. Stage IV disease, cervical stromal invasion, adnexal involvement, myometrial invasion >50%, primary tumor diameter >2 cm, positive peritoneal cytology, lymph node metastasis, histologic grade 3, nonendometrioid histologic subtype, absence of associated hyperplasia, and lymphovascular invasion correlated significantly (P < 0.01) with peritoneal failure. However, on regression analysis, only stage IV disease (P < 0.001, relative risk [RR] = 7.53), nonendometrioid histologic subtype (P = 0.02, RR = 3.01), and cervical stromal invasion (P = 0.04, RR = 2.83) were independent predictors of peritoneal failure. Because 22 of 37 (59%) peritoneal failures were in patients with stage IV disease, we considered separately the 545 patients with stage I-III disease. On regression analysis, nonendometrioid histologic subtype (P < 0.001, RR = 11.58), positive peritoneal cytology (P = 0.009, RR = 6.72), lymph node metastasis (P = 0.02, RR = 5.10), and cervical stromal invasion (P = 0.04, RR = 3.10) were independent predictors of peritoneal failure. Of the 38 patients in whom at least two of these four predictors were positive, 26% had peritoneal failure at 5 years, compared with 1% of the 507 patients who had none or only 1 predictor (P < 0.001). CONCLUSION: Patients with stage IV disease and those with stage I-III disease and at least two of the four independent predictors (nonendometrioid histology, positive peritoneal cytology, cervical stromal invasion, and lymph node metastasis) would be candidates for new therapeutic trials incorporating surgical and adjuvant treatment targeting the entire abdominal cavity.

Adult↗
PubMed2003

Soluble epidermal growth factor receptor (sEGFR/sErbB1) as a potential risk, screening, and diagnostic serum biomarker of epithelial ovarian cancer.

Epithelial ovarian cancer (EOC) is the leading cause of death from gynecologic malignancies in the United States, for which risk assessment, screening, and diagnostic tests are needed. We have shown previously that women with stage III/IV EOC have lower serum p110 sEGFR/sErbB1 (Soluble Epidermal Growth Factor Receptor) concentrations than healthy women. Here, we show that serum p110 sEGFR/sErbB1 is the product of a 3-kb EGFR/ERBB1 alternate transcript. We report that serum sEGFR concentrations in stage I/II and stage III/IV EOC patients are significantly lower than in healthy women, and that serum sEGFR concentrations are not associated with disease stage or tumor grade. Logistic regression models show that: (a) lower serum sEGFR concentrations are associated significantly with a greater risk of EOC; (b) the risk associated with lower serum sEGFR concentrations is reduced by older age or menopause; and (c) age- or menopausal status-specific cutoff values for sEGFR concentration are appropriate. Receiver operating characteristic curves indicate that: (a) serum sEGFR concentrations are more effective in discerning stage III/IV than stage I/II EOC cases from healthy women; and (b) sEGFR concentrations have an 89% probability of correctly discerning EOC patients from healthy women when accounting for effect modification by age. By maintaining a test specificity of approximately 95% across strata of age or menopausal status with appropriate cutoff values, we observe that sEGFR concentrations are most useful for detecting stage I/II (sensitivity: 64-67%) and stage III/IV (sensitivity: 75-81%) EOC in young, premenopausal women. We conclude that serum sEGFR concentrations warrant additional investigation in the risk assessment, early detection, and/or diagnosis of EOC.

Adult↗
PubMed2002

Predictors of lymphatic failure in endometrial cancer.

OBJECTIVE: The aim of this study was to identify determinants of lymphatic failure in patients with endometrial cancer after definitive primary treatment. METHODS: We observed 142 relapses in endometrial cancer patients who had primary surgery at our institution during the decade before 1994. We defined lymphatic failure as a relapse occurring on the pelvic sidewall (PSW), para-aortic area (PAA), or other node-bearing area (i.e., groin, axilla, supraclavicular, mediastinal). Mean follow-up was 72.8 months. RESULTS: We observed 44 instances of lymphatic failure--6 on the PSW only, 16 in the PAA only, 12 concomitantly in the PAA and on the PSW, and 10 confined in other node-bearing areas. By univariate analysis, body mass index > or = 30 kg/m(2), para-aortic lymph node biopsy, cervical stromal invasion (CSI), positive adnexa, myometrial invasion >50%, primary tumor diameter >2 cm, positive peritoneal cytology, positive lymph nodes (pelvic and/or para-aortic), radiotherapy, grade 3 tumor, nonendometrioid histology, and lymph--vascular invasion (LVI) significantly (P < or = 0.05) correlated with lymphatic failure. However, on Cox regression analysis, only LVI (P < 0.01, relative risk [RR] = 4.27), nodal involvement (P = 0.02, RR = 3.43), and CSI (P = 0.049, RR = 2.26) were independent predictors of lymphatic failure. Moreover, lymph node metastases (P = 0.01, RR = 19.82) and CSI (P = 0.050, RR = 3.57) independently predicted failure on the PSW, and only lymph node involvement (P < 0.01, RR = 10.15) predicted relapse in the PAA. CONCLUSION: LVI, positive lymph nodes, and CSI were the strongest predictors of lymphatic failure in endometrial cancer (31% of patients with at least one of the above three variables had a failure at 5 years). Patients with none of the above three factors had an extremely low (<1%) risk of lymphatic failure.

Adult↗
PubMed2002

Assessment of prognostic factors in stage IIIA endometrial cancer.

OBJECTIVE: The objective of this study was the assessment of prognostic factors in stage IIIA endometrial cancer. METHODS: Between 1984 and 1993, 51 patients with stage IIIA endometrial cancer received definitive treatment at our institution. Thirty-seven patients had positive peritoneal cytologic findings only (stage IIIA1), and 14 had adnexal or uterine serosal involvement (USI) (stage IIIA2). Median follow-up of surviving patients was 82.5 months. RESULTS: The 5-year disease-related survival (DRS) and recurrence-free survival (RFS) were 88 and 73%, respectively. RFS was 79% in patients with stage IIIA1 disease, compared with 57% in patients with stage IIIA2 disease (P = 0.04). However, DRS did not significantly differ between stages IIIA1 and IIIA2. In the 37 patients with stage IIIA1 tumors, histologic grade 3, nonendometrioid histologic subtype, and lymphovascular invasion (LVI) significantly predicted a poor prognosis, with extraabdominal sites of failure (P < 0.05). Of the 22 patients who had stage IIIA1 disease with endometrioid histologic subtype and without LVI, none had recurrence [17 had whole abdominal irradiation (WAR) or intraperitoneal injection of (32)P, 2 had pelvic external radiotherapy (PRT)]. By contrast, of the 15 patients with either nonendometrioid histologic subtype or LVI, 9 (60%) had recurrence and 7 (47%) died of disease (12 had WAR or (32)P). An extraabdominal component was present in 7 of the 9 recurrences observed in this subgroup. Among the 14 patients with stage IIIA2 tumors (6 had WAR, 6 had PRT), those with USI had a 5-year DRS of 83% and a rate of extraabdominal failure of 83%, compared with 100 and 12.5% in patients without USI (P < 0.05). CONCLUSION: Patients with stage IIIA endometrial cancer who have endometrioid tumors, no LVI, and positive peritoneal cytologic findings as the only sign of extrauterine disease have an excellent prognosis. Nonendometrioid histologic subtype, LVI, and USI are strong predictors of distant failures and poor prognosis. Patients with either of these histologic factors should be considered candidates for systemic adjuvant therapy.

Adult↗
PubMed2002

Stage IIIC endometrioid corpus cancer includes distinct subgroups.

OBJECTIVE: Because stage IIIC corpus cancer is a heterogeneous substage, the outcomes of patients with stage IIIC disease were assessed according to the extent of extrauterine disease. METHODS: From 1984 through 1993, 51 patients with surgical stage IIIC corpus cancer were treated at our institution; 5 patients had tumors with nonendometrioid histologic features and were excluded from the analyses. Of the 46 patients with endometrioid carcinoma, 22 had lymph nodes as the only site of extrauterine disease (stage IIIC(0)) and 24 also had peritoneal cytologic, uterine serosal, adnexal, or vaginal involvement or a combination of these (stage IIIC(ab)). The mean number of lymph nodes removed was 18 pelvic and 8 aortic nodes. Median follow-up for surviving patients was 84 months. RESULTS: Patients with stage IIIC(0) cancer had a 5-year cause-specific survival (CSS) of 72% and a 5-year recurrence-free survival (RFS) of 68%, and those with stage IIIC(ab) had a CSS of 33% and an RFS of 25% (P < 0.01). Of the 22 patients with stage IIIC(0) endometrioid cancer, 21 had adjuvant radiotherapy (1 also received chemotherapy) and 1 was not treated. Relapse occurred in 7 (32%) patients, with only 1 having an initial failure component outside the node-bearing areas (lung). Of the 24 patients with stage IIIC(ab) cancer, 16 received adjuvant radiotherapy (1 had concomitant chemotherapy), 2 had chemotherapy, 4 had hormonal therapy, and 2 were not treated. We observed 16 recurrences (67%). Of the 14 patients with known initial sites of failure, 9 had an extranodal failure component. CONCLUSION: Assessment of CSS, RFS, and sites of relapse suggests that FIGO surgical stage IIIC endometrioid corpus cancer includes two distinct and readily separable subgroups: (1) stage IIIC(0), nodal involvement only, and (2) stage IIIC(ab), nodal plus cytologic, uterine serosal, adnexal, or vaginal involvement, or a combination of these. Our results also suggest that different treatment strategies are needed for these subgroups.

Adult↗
PubMed2002

Surgical stage I endometrial cancer: predictors of distant failure and death.

OBJECTIVES: The objective was to analyze the effect of various histopathologic characteristics on prognosis in surgical stage I (node-negative) endometrial carcinoma. METHODS: During a 10-year period, 229 patients with stage I epithelial (all subtypes) endometrial cancer had hysterectomy and node dissection. Mean number of nodes harvested was 16.2 pelvic and 5.7 paraaortic. Median follow-up was 83 months. Sixty-seven patients (29%) received adjuvant radiotherapy. RESULTS: Five-year disease-related survival (DRS) was 95%, and 5-year relapse-free survival (RFS) 91%. We observed 7 (3%) isolated vaginal recurrences, 14 (6%) distant failures, and 1 (0.4%) simultaneous recurrence at both regional (pelvic sidewall) and distant sites. Only 1 of 7 patients (14%) with vaginal failure died of the disease (median follow-up of censored patients after failure was 110 months), compared with 10 of the 15 patients (67%) with distant failure. By univariate analysis, myometrial invasion (MI) >or= 66%, nonendometrioid histology, lymphovascular invasion, absence of associated hyperplasia, and tumor diameter >2 cm were significant predictors of poor prognosis with distant failure (P or= 66% as the only independent predictor of DRS (P < 0.001, relative risk [RR] = 12.44), RFS (P < 0.001, RR = 8.67), and distant failure (P < 0.001, RR = 24.89). Only 2% of patients with MI < 66% had distant failure and died of the disease at 5 years, compared with a 29% 5-year distant failure rate and a 22% 5-year death rate among patients with MI >or= 66%. CONCLUSION: Stage I (negative nodes) endometrial cancer patients with MI >or= 66% are at significant risk for distant failure and death and should be considered candidates for new randomized trials of adjuvant systemic therapy.

Adult↗
PubMed2002

Multimodal therapy including neoadjuvant methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) for stage IIB to IV cervical cancer.

OBJECTIVE: The purpose of this study was to determine the survival rates and toxicity levels that are associated with multimodal therapy (including neoadjuvant methotrexate, vinblastine, doxorubicin, and cisplatin [MVAC]) in patients with stage IIB to IVB cervical cancer. STUDY DESIGN: We retrospectively reviewed the cases of 49 patients who were treated between 1989 and 1997 with neoadjuvant MVAC for advanced cervical cancer. RESULTS: The clinical response rate was 90% (27 partial responders, 17 complete responders). Grade 3 or greater toxicity was mostly limited to neutropenia; no deaths were attributed to MVAC. Combined therapy after MVAC included operation in 34 patients (69%) and radiation in 41 patients (84%). Twenty-one patients (43%) had <2 cm residual tumor at histologic evaluation. Pelvic control was achieved in 86% of patients. Five-year disease-specific survival for patients with stage III disease was 60%. CONCLUSION: For patients with advanced cervical cancer, neoadjuvant MVAC had a high response rate (90%) and an acceptable toxicity level. Compared with historic control subjects, multimodal treatment may be associated with improved rates of pelvic control.

Adult↗
PubMed2002

Long-term survival of patients with advanced/recurrent carcinoma of cervix and vagina after neoadjuvant treatment with methotrexate, vinblastine, doxorubicin, and cisplatin with or without the addition of molgramostim, and review of the literature.

A randomized phase III study was conducted to assess the addition of molgramostim (GM-CSF) to the combination of methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) in terms of response rate, progression-free survival, and survival in women with advanced, recurrent, or metastatic carcinoma of the cervix or vagina. Patients received four 4-week cycles of methotrexate 30 mg/m2 IV days 1, 15, 22; vinblastine 3 mg/m2 IV days 2, 15, 22; doxorubicin 30 mg/m2 IV day 2; and cisplatin 70 mg/m2 IV day 2 with or without GM-CSF 5 microg/kg every 12 hours subcutaneously days 3 to 12. They were then reevaluated for operability. Those who were not surgical candidates were offered additional chemotherapy until progression or toxicity. Those who were surgical candidates were offered surgical resection of remaining tumor followed by involved-field external beam irradiation to sites of no prior irradiation and intraoperative irradiation to sites of prior external beam irradiation. This trial closed after 36 eligible patients were entered because of poor accrual. Although more than 40% of patients on each arm received fewer than four cycles of MVAC, the clinical response rate was 78% (95% CI: 52-94%) and 50% (95% CI: 26-74%) for MVAC and MVAC + GM-CSF, respectively; the median time to progression was 10.2 and 11.8 months, respectively; and median survival was 13.8 and 16.0 months, respectively. Toxicity was substantial, with more than 40% experiencing grade III to IV leukopenia, and nearly 40% experiencing grade III to IV stomatitis. MVAC with or without GM-CSF support achieves high response rates in patients with advanced, recurrent, or metastatic cervical carcinoma despite dose reductions and deletions. Its progression-free survival and overall survival rates appear promising. These results need to be confirmed within a large randomized phase III clinical trial.

Adult↗
PubMedDate not supplied

Pathophysiology and palliation of inoperable bowel obstruction in patients with ovarian cancer.

Malignant bowel obstruction is the cause of death in the majority of women who die of ovarian cancer. Some patients are considered acceptable surgical candidates for relief of the obstruction. For many patients, however, lack of such surgical options has spawned a broad range of medical interventions, including palliative strategies to target pain and nausea and vomiting. This review discusses the general approach to patients with ovarian cancer and inoperable malignant bowel obstruction, with an emphasis on such palliative strategies.

Adrenal Cortex Hormones↗
PubMedDate not supplied

HER-2/neu overexpression and hormone dependency in endometrial cancer: analysis of cohort and review of literature.

BACKGROUND: Overexpression of HER-2/neu (HER) is associated with unfavorable prognoses in both endometrial and breast cancer. MATERIALS AND METHODS: To determine whether an association exists between HER expression and markers of hormone dependency in endometrial cancers, we subjected hysterectomy specimens from 125 patients to immunohistochemical staining for HER. HER was visually interpreted as negative/weakly positive (HER-) versus strongly positive (HER+). Estrogen receptor (ER) and progesterone receptor (PR) levels were quantitated on fresh tissue using a dextran-coated charcoal assay. RESULTS: HER+ was observed in 12% of endometrioid tumors and 22% of nonendometrioid tumors (p = 0.07). Mean ER and PR levels were 255 fmol/mg and 457 fmol/mg in endometrioid tumors, compared with 74 and 104 in nonendometrioid tumors (p < 0.01). Hyperplasia associated with the tumor was related to high levels of both ER and PR (p < 0.05), but not with HER expression. Age was significantly related to high levels of ER (p = 0.007). Both recurrence and death rates were significantly associated with low levels of ER and PR (p < 0.01). Mean ER and PR levels were 270 and 466 fmol/mg, respectively, in HER-tumors, compared with 95 (p = 0.14) and 138 fmol/mg (p = 0.02) in HER+ tumors. CONCLUSION: HER overexpression may be an important step in hormone-independent growth and proliferation in a subgroup of endometrial cancers.

Adult↗
PubMedDate not supplied

Role of bcl-2 in endometrioid corpus cancer: an experimental study.

BACKGROUND: Bcl-2 expression appears to be under hormonal control in normal endometrium and to correlate with hormone receptor status in endometrial cancer. The aim of this study was to assess bcl-2 expression in endometrial cancer. MATERIALS AND METHODS: Hysterectomy specimens from 125 patients with endometrial cancer were stained for bcl-2. Estrogen receptor (ER) and progesterone receptor (PR) levels were quantified with a dextran-coated charcoal assay. RESULTS: Bcl-2 expression correlated significantly with endometrioid histology and high levels of ER and PR (p < 0.05). For the entire population, bcl-2 expression was not significantly associated with the presence of extrauterine disease. However, when only patients with grade 1 or 2 endometrioid histology were considered, tumors with bcl-2 expression were significantly (p < 0.05) more likely to present with extrauterine disease than those not expressing bcl-2. CONCLUSION: Bcl-2-mediated inhibition of apoptosis may be important in the acquisition of molecular alterations and development of metastases in a subset of hormone-dependent endometrial cancers.

Carcinoma, Endometrioid↗