ABSTRACT
OBJECTIVE: Rapamycin analogs have reproducible but modest efficacy in endometrial cancer (EC). Identification of molecular biomarkers that predict benefit could guide clinical development. METHODS: Fixed primary tissue and whole blood were collected prospectively from patients enrolled on GOG 248. DNA was isolated from macro-dissected tumors and blood; next-generation sequence analysis was performed on a panel of cancer related genes. Associations between clinical outcomes [response rate (RR) 20%; progression-free survival (PFS) median 4.9months] and mutations (PTEN, PIK3CA, PIK3R1, KRAS, CTNNB1, AKT1, TSC1, TSC2, NF1, FBXW7) were explored. RESULTS: Sequencing data was obtained from tumors of 55 of the 73 enrolled pts. Mutation rates were consistent with published reports: mutations in PTEN (45%), PIK3CA (29%), PIK3R1 (24%), K-RAS (16%), CTNNB1 (18%) were common and mutations in AKT1 (4%), TSC1 (2%), TSC2 (2%), NF1 (9%) and FBXW7 (4%) were less common. Increased PFS (HR 0.16; 95% CI 0.01-0.78) and RR (response difference 0.83; 95% CI 0.03-0.99) were noted for AKT1 mutation. An increase in PFS (HR 0.46; 95% CI 0.20-0.97) but not RR (response difference 0.00, 95% CI -0.34-0.34) was identified for CTNNB1 mutation. Both patients with TSC mutations had an objective response. There were no statistically significant associations between mutations in PIK3CA, PTEN, PIK3R1, or KRAS and PFS or RR. CONCLUSIONS: Mutations in AKT1, TSC1 and TSC2 are rare, but may predict clinical benefit from temsirolimus. CTNNB1 mutations were associated with longer PFS on temsirolimus.
Subject(s)
Endometrial Neoplasms/genetics , Megestrol Acetate/administration & dosage , Mutation , Sirolimus/analogs & derivatives , Tamoxifen/administration & dosage , Class I Phosphatidylinositol 3-Kinases , Endometrial Neoplasms/drug therapy , Endometrial Neoplasms/mortality , Female , Humans , PTEN Phosphohydrolase/genetics , Phosphatidylinositol 3-Kinases/genetics , Prospective Studies , Proto-Oncogene Proteins c-akt/genetics , Sirolimus/administration & dosage , Sirolimus/therapeutic use , Tuberous Sclerosis Complex 1 Protein , Tumor Suppressor Proteins/geneticsABSTRACT
OBJECTIVES: To determine the response, toxicities, and progression free survival of a regimen of temsirolimus with or without hormonal therapy in the treatment of advanced, or recurrent endometrial carcinoma. BACKGROUND: Preclinical evidence suggested that blockade of the PI3K/AKT/mTOR pathway might overcome resistance to hormonal therapy. METHODS: We performed a randomized phase II trial of intravenous temsirolimus 25mg weekly versus the combination of weekly temsirolimus with a regimen of megestrol acetate 80 mg bid for three weeks alternating with tamoxifen 20mg bid for three weeks in women with recurrent or metastatic endometrial carcinoma. RESULTS: There were 71 eligible patients who received at least one dose of therapy with 21 of these treated on the combination arm which was closed early because of an excess of venous thrombosis, with 5 episodes of deep venous thrombosis (DVT) and 2 pulmonary emboli. There were three responses observed in that arm (14%). A total of 50 eligible patients were treated on the single agent arm with 3 episodes of DVT and 11 responses (22%). Response rates were similar in patients with prior chemotherapy (7 of 29; 24%) and those with no prior chemotherapy (4 of 21; 19%). Two of four patients with clear cell carcinoma responded. CONCLUSIONS: Adding the combination of megestrol acetate and tamoxifen to temsirolimus therapy did not enhance activity and the combination was associated with an excess of venous thrombosis. Temsirolimus activity was preserved in patients with prior adjuvant chemotherapy.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Endometrial Neoplasms/drug therapy , Sirolimus/analogs & derivatives , Adult , Aged , Aged, 80 and over , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Disease-Free Survival , Drug Administration Schedule , Endometrial Neoplasms/metabolism , Endometrial Neoplasms/pathology , Female , Humans , Immunohistochemistry , Megestrol Acetate/administration & dosage , Megestrol Acetate/adverse effects , Middle Aged , Neoplasm Metastasis , Neoplasm Recurrence, Local/drug therapy , Neoplasm Recurrence, Local/metabolism , Neoplasm Recurrence, Local/pathology , Sirolimus/administration & dosage , Sirolimus/adverse effects , Sirolimus/therapeutic use , Tamoxifen/administration & dosage , Tamoxifen/adverse effectsABSTRACT
OBJECTIVE: To determine which patients with near midline lesions may safely undergo unilateral groin dissection based on clinical exam and lymphoscintigraphy (LSG) results. METHODS: Patients participating in GOG-173 underwent sentinel lymph node (SLN) localization with blue dye, and radiocolloid with optional LSG before definitive inguinal-femoral lymphadenectomy (LND). This analysis interrogates the reliability of LSG alone relative to primary tumor location in those patients who had an interpretable LSG and at least one SLN identified. Primary tumor location was categorized as lateral (>2cm from midline), midline, or lateral ambiguous (LA) if located within 2cm, but not involving the midline. RESULTS: Two-hundred-thirty-four patients met eligibility criteria. Sixty-four had lateral lesions, and underwent unilateral LND. All patients with LA (N=65) and midline (N=105) tumors underwent bilateral LND. Bilateral drainage by LSG was identified in 14/64 (22%) patients with lateral tumors, 38/65 (58%) with LA tumors and in 73/105 (70%) with midline tumors. At mapping, no SLNs were found in contralateral groins among those patients with LA and midline tumors who had unilateral-only LSGs. However, in these patients groin metastases were found in 4/32 patients with midline tumors undergoing contralateral dissection; none were found in 27 patients with LA tumors. CONCLUSION: The likelihood of detectable bilateral drainage using preoperative LSG decreases as a function of distance from midline. Patients with LA primaries and unilateral drainage on LSG may safely undergo unilateral SLN.
Subject(s)
Carcinoma, Squamous Cell/diagnostic imaging , Carcinoma, Squamous Cell/surgery , Lymph Nodes/diagnostic imaging , Lymph Nodes/surgery , Vulvar Neoplasms/diagnostic imaging , Vulvar Neoplasms/surgery , Carcinoma, Squamous Cell/pathology , Female , Humans , Lymph Node Excision/methods , Lymph Nodes/pathology , Lymphoscintigraphy/methods , Prospective Studies , Sentinel Lymph Node Biopsy/methods , Vulvar Neoplasms/pathologyABSTRACT
OBJECTIVE: To estimate activity and safety of trabectedin 1.5 mg/m2 IV over 24 hours every 3 weeks (1 cycle) in uterine leiomyosarcoma. METHODS: Patients with chemotherapy naive, advanced, persistent or recurrent uterine leiomyosarcoma, acceptable organ function and PS≤2 were eligible. A two-stage design was utilized. Three responses were required in the first stage to initiate the second stage; the target sample size was 40 for the combined stages. If the true response rate was 10%, the study design provided a 95% chance of correctly classifying the treatment as "inactive." Conversely, if the true response rate was 30%, then the average probability of correctly classifying the treatment as active would be 90%. RESULTS: Twenty patients were eligible and evaluable. The median number of cycles was 10 (123 total cycles, range 2-29). The number of patients with partial responses was 2 (10%; 95% confidence interval of 1.2%-31.7%). Response durations were 3.3 and 5.7 months. Ten patients had stable disease (50%). The median progression-free survival (PFS) and overall survival were 5.8 months and greater than 26.1 months (median not reached), respectively. Observed grade 3/4 toxicity included: neutropenia 16/20 (1 infection); thrombocytopenia 3/20; metabolic 3/20; anemia, gastrointestinal and vascular 1/20 each. There were no treatment related deaths nor cases of liver failure. CONCLUSIONS: Although a second stage of accrual was not indicated based on the overall response rate, the drug was well tolerated.
Subject(s)
Antineoplastic Agents, Alkylating/therapeutic use , Dioxoles/therapeutic use , Leiomyosarcoma/drug therapy , Neoplasm Recurrence, Local/drug therapy , Tetrahydroisoquinolines/therapeutic use , Uterine Neoplasms/drug therapy , Adult , Aged , Aged, 80 and over , Antineoplastic Agents, Alkylating/adverse effects , Dioxoles/adverse effects , Disease-Free Survival , Drug Administration Schedule , Female , Humans , Infusions, Intravenous , Leiomyosarcoma/pathology , Middle Aged , Neoplasm Recurrence, Local/pathology , Prospective Studies , Survival Rate , Tetrahydroisoquinolines/adverse effects , Trabectedin , Uterine Neoplasms/pathologyABSTRACT
OBJECTIVE: To evaluate the safety and efficacy of canfosfamide in combination with pegylated liposomal doxorubicin (PLD) in platinum-resistant ovarian cancer (OC). METHODS: Patients with platinum-refractory or -resistant (primary or secondary) OC were randomized to receive canfosfamide at 1000 mg/m² and PLD at 50 mg/m² intravenously or PLD alone at 50 mg/m2 intravenously on day 1 every 28 days until tumor progression or unacceptable toxicity. The primary end point was progression-free survival (PFS). Other end points were objective response rate and safety. The study was originally planned for 244 patients. The trial was temporarily placed on hold after 125 patients were randomized while the results of another trial were being reviewed and the sponsor decided not to resume enrollment. The interim analysis became the final analysis. RESULTS: The median PFS was 5.6 months for canfosfamide + PLD (n = 65) versus 3.7 months for PLD (n = 60) (hazards ratio, 0.92; P = 0.7243). A preplanned subgroup analysis showed that 75 patients with platinum-refractory or primary platinum-resistant OC had a median PFS of 5.6 months for canfosfamide + PLD versus 2.9 months for PLD (hazards ratio, 0.55; P = 0.0425). Hematologic adverse events were 66% on the canfosfamide + PLD arm versus 44% on the PLD arm, manageable with dose reductions. Nonhematologic adverse events were similar for both arms. The incidence of palmar-plantar erythrodysesthesia and stomatitiswas lower on canfosfamide + PLD(23%, 31%, respectively) versus (39%, 49%, respectively) on PLD. CONCLUSIONS: Overall median PFS showed a positive trend but was not statistically significant. The median PFS in the platinum-refractory and primary platinum-resistant OC patients was significantly longer for canfosfamide + PLD versus PLD. Canfosfamide may ameliorate the palmar-plantar erythrodysesthesia and stomatitis known to be associated with PLD. Further study of this active well-tolerated regimen in platinum-refractory and primary platinum-resistant OC is planned. This study was registered at www.clinicaltrials.gov: NCT00350948.
Subject(s)
Antineoplastic Agents/therapeutic use , Doxorubicin/analogs & derivatives , Glutathione/analogs & derivatives , Ovarian Neoplasms/drug therapy , Polyethylene Glycols/administration & dosage , Adult , Aged , Aged, 80 and over , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Doxorubicin/administration & dosage , Female , Glutathione/administration & dosage , Humans , Middle Aged , Platinum Compounds/therapeutic use , Survival Analysis , Treatment Outcome , Young AdultABSTRACT
Multiple myeloma is a plasma cell malignancy, which grows in the bone marrow (BM). The major population of cells in the BM is represented by neutrophils and they can form neutrophil extracellular traps (NET). Here, we investigated whether multiple myeloma cells induce NET formation and whether targeting this process would delay multiple myeloma progression. We demonstrated that murine and human multiple myeloma cells stimulate citrullination of histone H3 and NET formation by neutrophils and that this process is abrogated by pharmacological targeting of peptidylarginine deiminase 4 (PAD4) with a novel-specific small molecule inhibitor BMS-P5. Administration of BMS-P5 to multiple myeloma-bearing mice delays appearance of symptoms and disease progression. Taken together, our data demonstrate that targeting PAD4 may be beneficial for treatment of multiple myeloma.
Subject(s)
Antineoplastic Agents/pharmacology , Enzyme Inhibitors/pharmacology , Extracellular Traps/drug effects , Multiple Myeloma/drug therapy , Protein-Arginine Deiminase Type 4/antagonists & inhibitors , Animals , Apoptosis , Cell Proliferation , Extracellular Traps/enzymology , Female , Humans , Male , Mice , Mice, Inbred C57BL , Multiple Myeloma/enzymology , Multiple Myeloma/pathology , Tumor Cells, Cultured , Xenograft Model Antitumor AssaysABSTRACT
To isolate circulating tumor cells (CTC) from women with advanced cervical cancer and estimate the impact of CTCs and treatment on overall survival and progression-free survival (PFS). A total of 7.5 mL of whole blood was drawn pre-cycle 1 and 36 days post-cycle 1 from patients enrolled on Gynecologic Oncology Group 0240, the phase III randomized trial that led directly to regulatory approval of the antiangiogenesis drug, bevacizumab, in women with recurrent/metastatic cervical cancer. CTCs (defined as anti-cytokeratin+/anti-CD45- cells) were isolated from the buffy coat layer using an anti-EpCAM antibody-conjugated ferrofluid and rare earth magnet, and counted using a semiautomated fluorescence microscope. The median pre-cycle 1 CTC count was 7 CTCs/7.5 mL whole blood (range, 0-18) and, at 36 days posttreatment, was 4 (range, 0-17). The greater the declination in CTCs between time points studied, the lower the risk of death [HR, 0.87; 95% confidence interval (CI), 0.79-0.95)]. Among patients with high (≥ median) pretreatment CTCs, bevacizumab treatment was associated with a reduction in the hazard of death (HR, 0.57; 95% CI, 0.32-1.03) and PFS (HR, 0.59; 95% CI, 0.36-0.96). This effect was not observed with low (< median) CTCs. CTCs can be isolated from women with advanced cervical cancer and may have prognostic significance. A survival benefit conferred by bevacizumab among patients with high pretreatment CTCs may reflect increased tumor neovascularization and concomitant vulnerability to VEGF inhibition. These data support studying CTC capture as a potential predictive biomarker.
Subject(s)
Neoplastic Cells, Circulating/pathology , Uterine Cervical Neoplasms/diagnosis , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Biomarkers, Tumor , Disease Management , Female , Humans , Kaplan-Meier Estimate , Middle Aged , Molecular Targeted Therapy , Prognosis , Treatment Outcome , Uterine Cervical Neoplasms/etiology , Uterine Cervical Neoplasms/mortality , Uterine Cervical Neoplasms/therapyABSTRACT
PURPOSE: The primary objective was to determine if vaginal cuff brachytherapy and chemotherapy (VCB/C) increases recurrence-free survival (RFS) compared with pelvic radiation therapy (RT) in high-intermediate and high-risk early-stage endometrial carcinoma. PATIENTS AND METHODS: A randomized phase III trial was performed in eligible patients with endometrial cancer. Eligible patients had International Federation of Gynecology and Obstetrics (2009) stage I endometrioid histology with Gynecologic Oncology Group protocol 33-based high-intermediate-risk criteria, stage II disease, or stage I to II serous or clear cell tumors. Treatment was randomly assigned between RT (45 to 50.4 Gy over 5 weeks) or VCB followed by intravenous paclitaxel 175 mg/m2 (3 hours) plus carboplatin (area under the curve, 6) every 21 days for three cycles. RESULTS: The median age of the 601 patients was 63 years, and 74% had stage I disease. Histologies included endometrioid (71%), serous (15%), and clear cell (5%). With a median follow-up of 53 months, the 60-month RFS was 0.76 (95% CI, 0.70 to 0.81) for RT and 0.76 (95% CI, 0.70 to 0.81) for VCB/C (hazard ratio, 0.92; 90% confidence limit, 0.69 to 1.23). The 60-month overall survival was 0.87 (95% CI, 0.83 to 0.91) for RT and 0.85 (95% CI, 0.81 to 0.90) for VCB/C (hazard ratio, 1.04; 90% confidence limit, 0.71 to 1.52). Vaginal and distant recurrence rates were similar between arms. Pelvic or para-aortic nodal recurrences were more common with VCB/C (9% v 4%). There was no heterogeneity of treatment effect with respect to RFS or overall survival among clinical or pathologic variables evaluated. CONCLUSION: Superiority of VCB/C compared with pelvic RT was not demonstrated. Acute toxicity was greater with VCB/C; late toxicity was similar. Pelvic RT alone remains an effective, well-tolerated, and appropriate adjuvant treatment in high-risk early-stage endometrial carcinomas of all histologies.
Subject(s)
Carboplatin/therapeutic use , Endometrial Neoplasms/drug therapy , Endometrial Neoplasms/radiotherapy , Paclitaxel/therapeutic use , Pelvis/radiation effects , Radiotherapy, Adjuvant/methods , Vagina/radiation effects , Adult , Aged , Aged, 80 and over , Brachytherapy/methods , Carboplatin/pharmacology , Endometrial Neoplasms/pathology , Female , Humans , Middle Aged , Neoplasm Staging , Paclitaxel/pharmacology , Prospective Studies , Young AdultABSTRACT
OBJECTIVE: The purpose of this study was to determine whether age is a risk factor for perioperative and postoperative complications. STUDY DESIGN: This was a retrospective case-control study of 120 women over age 79 (group 1) compared with 1,497 younger patients 50-79 (group 2) undergoing major elective gynecologic surgery. RESULTS: Mean length of stay was 4.8 days for group 1, compared with 3.8 for group 2 (P = .018). Patients hospitalized longer than 1 week was higher (P < .01) among group 1. There were statistically significant increases in UTI, psychiatric events, pulmonary edema, respiratory failure, sepsis, and hypovolemic shock. No significant difference in mortality rate was noted (group 1: 0.83%, n = 1 vs group 2: 0.47%, n = 7). CONCLUSION: Although length of stay for the elderly is slightly increased, mortality and complication rates are comparable to younger patients with few exceptions. We conclude that age need not be the sole determinant in the decision to undergo major elective gynecologic surgery.
Subject(s)
Female Urogenital Diseases/surgery , Gynecologic Surgical Procedures , Postoperative Complications/epidemiology , Aged , Aged, 80 and over , Cardiovascular Diseases/epidemiology , Cellulitis/epidemiology , Comorbidity , Elective Surgical Procedures , Female , Female Urogenital Diseases/epidemiology , Gastrointestinal Diseases/epidemiology , Humans , Hysterectomy , Laparotomy , Length of Stay , Middle Aged , Retrospective Studies , Risk Factors , Shock/epidemiology , Thromboembolism/epidemiology , Treatment Outcome , Urinary Incontinence/surgery , Vulvar Diseases/surgeryABSTRACT
BACKGROUND: Endometrial carcinoma is the most common cancer of the female genital tract. Two histologic variants have been described: an estrogen-dependent form and a more aggressive, non-estrogen-dependent form, which includes uterine serous carcinoma. CASES: Two cases of uterine serous carcinoma were confined to an endometrial polyp without myometrial invasion and were widely metastatic. One patient presented with abdominal pain and constipation, while the other patient was asymptomatic. Both patients had elevated CA-125 levels. At the time of surgery, these patients were found to have extensive carcinomatosis and underwent surgical staging procedures that required bowel resections. Pathology showed metastatic disease originating in a small focus of serous adenocarcinoma at the tip of an endometrial polyp. Combination chemotherapy was planned; but 1 of the patients died prior to its initiation. CONCLUSION: These cases emphasize the aggressive nature of uterine serous carcinoma despite insignificant myometrial invasion.
Subject(s)
Cystadenocarcinoma, Serous/etiology , Cystadenocarcinoma, Serous/pathology , Endometrial Neoplasms/pathology , Polyps/pathology , Uterine Neoplasms/etiology , Uterine Neoplasms/pathology , Abdominal Pain/etiology , Aged , Constipation , Cystadenocarcinoma, Serous/surgery , Fatal Outcome , Female , Humans , Neoplasm Invasiveness , Prognosis , Uterine Neoplasms/surgeryABSTRACT
Ten years ago, Georgia was lauded for dedicating a portion of tobacco settlement funds to the Georgia Cancer Coalition (GCC). The plan championed by then-Governor Roy E. Barnes was designed to make Georgia a leader in prevention, treatment, and research. This plan called for the expansion of clinical trials to ensure Georgians had access to the highest quality care based on the most current treatments and discoveries. As a result, oncologists in the state were engaged in a planning process that resulted in a shared vision to improve the quality of cancer care through research and the formation of a new organization: the Georgia Center for Oncology Research and Education.
Subject(s)
Biomedical Research/organization & administration , Medical Oncology/organization & administration , Neoplasms , Research Design , Biomedical Research/economics , Cooperative Behavior , Georgia , HumansABSTRACT
PURPOSE: To determine the safety of sentinel lymph node biopsy as a replacement for inguinal femoral lymphadenectomy in selected women with vulvar cancer. PATIENTS AND METHODS: Eligible women had squamous cell carcinoma, at least 1-mm invasion, and tumor size ≥ 2 cm and ≤ 6 cm. The primary tumor was limited to the vulva, and there were no groin lymph nodes that were clinically suggestive of cancer. All women underwent intraoperative lymphatic mapping, sentinel lymph node biopsy, and inguinal femoral lymphadenectomy. Histologic ultra staging of the sentinel lymph node was prescribed. RESULTS: In all, 452 women underwent the planned procedures, and 418 had at least one sentinel lymph node identified. There were 132 node-positive women, including 11 (8.3%) with false-negative nodes. Twenty-three percent of the true-positive patients were detected by immunohistochemical analysis of the sentinel lymph node. The sensitivity was 91.7% (90% lower confidence bound, 86.7%) and the false-negative predictive value (1-negative predictive value) was 3.7% (90% upper confidence bound, 6.1%). In women with tumor less than 4 cm, the false-negative predictive value was 2.0% (90% upper confidence bound, 4.5%). CONCLUSION: Sentinel lymph node biopsy is a reasonable alternative to inguinal femoral lymphadenectomy in selected women with squamous cell carcinoma of the vulva.
Subject(s)
Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/surgery , Lymph Nodes/pathology , Lymph Nodes/surgery , Sentinel Lymph Node Biopsy/methods , Vulvar Neoplasms/pathology , Vulvar Neoplasms/surgery , Aged , Aged, 80 and over , Female , Groin/pathology , Groin/surgery , Humans , Incidence , Lymph Node Excision , Lymphatic Metastasis , Middle Aged , Prospective StudiesABSTRACT
BACKGROUND: Rarely, excessively large, slow growing tumors are found to be malignant. One exception includes retroperitoneal tumors, which if considered a mass of pelvic origin, may be encountered by the gynecologic oncologist. CASE: A post-menopausal female was referred for evaluation of a huge mass thought to arise from the pelvis. The patient underwent exploratory laparotomy and had resected a 50x48x45 cm, 103.6 lb. liposarcoma arising from the right retroperitoneum. DISCUSSION: Rarely, large slow growing abdomino-pelvic masses may be malignant, and one should be prepared to perform an appropriate surgical resection. This case represents removal of the largest retroperitoneal liposarcoma reported.
Subject(s)
Liposarcoma/diagnosis , Retroperitoneal Neoplasms/diagnosis , Diagnosis, Differential , Female , Humans , Liposarcoma/pathology , Liposarcoma/surgery , Middle Aged , Postmenopause , Retroperitoneal Neoplasms/pathology , Retroperitoneal Neoplasms/surgeryABSTRACT
BACKGROUND: Adenocarcinoma of the endometrium is the most common gynecologic malignancy in the United States, accounting for approximately 36,000 diagnoses of invasive carcinoma annually. The most common histologic type, endometrioid adenocarcinoma (EC), accounts for 75-80% of patients. The objective of this work was to estimate the prevalence of concurrent carcinoma in women with a biopsy diagnosis of the precursor lesion, atypical endometrial hyperplasia (AEH). METHODS: This prospective cohort study included women who had a community diagnosis of AEH. Diagnostic biopsy specimens were reviewed independently by three gynecologic pathologists who used International Society of Gynecologic Pathologists/World Health Organization criteria. Study participants underwent hysterectomy within 12 weeks of entry onto protocol without interval treatment. The hysterectomy slides also were reviewed by the study pathologists, and their findings were used in the subsequent analyses. RESULTS: Between November 1998 and June 2003, 306 women were enrolled on the study. Of these, 17 women were not included in the analysis: Two patients had unreadable slides because of poor processing or insufficient tissue, 2 patients had only slides that were not endometrial, the slides for 5 patients were not available for review, and 8 of the hysterectomy specimens were excluded because they showed evidence of interval intervention, either progestin effect or ablation. In total, 289 patients were included in the current analysis. The study panel review of the AEH biopsy specimens was interpreted as follows: 74 of 289 specimens (25.6%) were diagnosed as less than AEH, 115 of 289 specimens (39.8%) were diagnosed as AEH, and 84 of 289 specimens (29.1%) were diagnosed as endometrial carcinoma. In 5.5% (16 of 289 specimens), there was no consensus on the biopsy diagnosis. The rate of concurrent endometrial carcinoma for analyzed specimens was 42.6% (123 of 289 specimens). Of these, 30.9% (38 of 123 specimens) were myoinvasive, and 10.6% (13 of 123 specimens) involved the outer 50% of the myometrium. Among the women who had hysterectomy specimens with carcinoma, 14 of 74 women (18.9%) had a study panel biopsy consensus diagnosis of less than AEH, 45 of 115 women (39.1%) had a study panel biopsy consensus diagnosis of AEH, and 54 of 84 women (64.3%) had a study panel diagnosis of carcinoma. Among women who had no consensus in their biopsy diagnosis, 10 of 16 women (62.5%) had carcinoma in their hysterectomy specimens. CONCLUSIONS: The prevalence of endometrial carcinoma in patients who had a community hospital biopsy diagnosis of AEH was high (42.6%). When considering management strategies for women who have a biopsy diagnosis of AEH, clinicians and patients should take into account the considerable rate of concurrent carcinoma.
Subject(s)
Adenocarcinoma/epidemiology , Endometrial Hyperplasia/complications , Endometrial Hyperplasia/pathology , Endometrial Neoplasms/epidemiology , Adenocarcinoma/etiology , Adenocarcinoma/pathology , Adult , Aged , Aged, 80 and over , Biopsy , Endometrial Hyperplasia/diagnosis , Endometrial Hyperplasia/surgery , Endometrial Neoplasms/etiology , Endometrial Neoplasms/pathology , Female , Hospitals, Community/statistics & numerical data , Humans , Hysterectomy , Middle Aged , Patient Care Planning , Prevalence , Prospective Studies , Risk FactorsABSTRACT
BACKGROUND: We present a case of recurrent colon cancer detected by routine, annual Papanicolaou screening. CASE: A 59-year-old African American woman who had been treated for T2N0M0 (stage II, Dukes A) colon cancer 2 years before to presentation had a Pap smear showing a high-grade squamous intraepithelial lesion with a normal cervical biopsy result. Because of this discrepancy, a loop electrosurgical excision procedure and endocervical curettage were performed and showed atypical glandular cells suspicious for adenocarcinoma. Subsequent colonoscopy showed recurrent adenocarcinoma of the colon. The patient underwent an en-block total abdominal hysterectomy and anterior-perineal resection showing invasion of recurrent colon cancer into the uterus and cervix. CONCLUSION: In patients with a history of extrauterine adenocarcinoma, abnormal Pap screening may indicate recurrent or metastatic carcinoma.
Subject(s)
Adenocarcinoma/diagnosis , Colorectal Neoplasms/diagnosis , Diagnostic Tests, Routine , Neoplasm Recurrence, Local/diagnosis , Papanicolaou Test , Uterine Neoplasms/diagnosis , Vaginal Smears , Adenocarcinoma/secondary , Carcinoma, Squamous Cell/diagnosis , Colonoscopy , Colorectal Neoplasms/pathology , Female , Humans , Middle Aged , Uterine Cervical Neoplasms/diagnosis , Uterine Neoplasms/secondary , Uterine Cervical Dysplasia/diagnosisABSTRACT
OBJECTIVE: The study analyzed morbidity and mortality rates among octogenarian and nonagenarian patients who underwent operations for gynecologic indications. STUDY DESIGN: A retrospective chart review was performed for patients, aged >or=80 years, who underwent gynecologic procedures between January 1, 1995, and September 30, 2000. Information obtained included a complete medical history, type of surgical procedure, length of hospital stay, and discharge disposition. Simple demographic statistics were used. RESULTS: Sixty-two patients (mean age, 83.6 years) were identified. Seventy-seven operative procedures, 49 major and 28 minor, were performed. All patients were discharged home, except 2, who were discharged to nursing homes. Sixteen patients, who underwent minor procedures, were discharged the same day, and 6 patients were admitted for "23" hour stays. There were 11 perioperative complications and no perioperative deaths. CONCLUSION: Successful gynecologic surgical outcomes with minimal morbidity are achievable in octogenarian patients and nonagenarian patients with optimization of co-medical conditions and careful perioperative treatment. Age should not be the sole determinant in the decision-making process.
Subject(s)
Genital Diseases, Female/mortality , Genital Diseases, Female/surgery , Gynecologic Surgical Procedures/standards , Age Factors , Aged , Aged, 80 and over , Female , Follow-Up Studies , Frail Elderly , Genital Diseases, Female/diagnosis , Geriatric Assessment , Gynecologic Surgical Procedures/trends , Humans , Length of Stay , Postoperative Complications/mortality , Retrospective Studies , Risk Assessment , Survival Analysis , Treatment OutcomeABSTRACT
OBJECTIVE: The purpose of this study was to assess survival and morbidity when completion hysterectomy follows radiation for bulky cervical cancer. STUDY DESIGN: This was a retrospective observational descriptive review that assessed the survival and morbidity of patients with bulky cervical cancer that was treated with radiation followed by completion hysterectomy between 1993 and 2002. Chemotherapy, external beam radiation, and brachytherapy data were collected. RESULTS: Fifty-five cases were reviewed. Fifty-three patients received brachytherapy. Twenty-nine patients underwent sensitizing chemotherapy. All patients had hysterectomies. There were 12 early postoperative complications (21.8%) and 10 late complications (19.6%). Eleven patients are dead of disease (21.6%); 3 patients are alive with disease (5.9%), and 37 patients are free of disease (72.5%). Four patients were lost to follow-up. Seven patients who are free of disease had residual cancer in the specimen at hysterectomy. CONCLUSION: Complications of combined therapy were comparable to radiation or radical hysterectomy alone. In cases in which an incomplete response to radiation and chemotherapy leaves potential residual carcinoma, adjuvant hysterectomy may be a reasonable treatment option.