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Biomedical subjects

A W Kennedy

Publications and source records attributed to A W Kennedy.

At least 19 recordsLinked to original sources
PubMed2000

2-5A antisense directed against telomerase RNA produces apoptosis in ovarian cancer cells.

OBJECTIVE: RNase L is converted to an active form upon binding short 2',5'-oligoadenylates (2-5A). To direct RNase L to an RNA target, 2-5A is attached to an antisense oligonucleotide (2-5A antisense). This chimera can be directed against telomerase-an RNA-protein complex that elongates telomeric DNA and is involved in cellular immortalization. Our objective is to investigate the effect of 2-5A antisense by targeting telomerase RNA (hTR) in the ovarian cancer cell line, HEY-1B. METHODS: Baseline RNase L levels and telomerase activities were measured in both HEY-1B and normal ovarian epithelial cells (NOE). Cells were treated daily with chimeric oligonuclotides (ODN) directed against four different hTR sites, or control ODNs including nonchimeric antisense, 2-5A fused to a mismatched sequence, or inactive 2-5A fused to antisense. At 48 h, apoptosis was evaluated using the TUNEL assay. After six daily ODN administrations, telomerase activity was redetermined, and at 7 days viability counts were obtained. RESULTS: Both cell lines expressed similar levels of RNase L. Hey-1B displayed telomerase activity while NOE did not. After 7 days of transfection, 2-5A antisense ODNs caused profound cell death in the HEY-1B cells, but not in the NOE cells. This effect was seen regardless of hTR target site, and ODN controls showed no significant decrease in cell viability in either cell line. HEY1B cells treated with 2-5A antisense against hTR showed a decrease in telomerase activity and a profound induction of programmed cell death. CONCLUSIONS: The results suggest that 2-5A antisense directed against telomerase RNA results in apoptotic cell death in ovarian cancer cells, but not normal ovarian epithelial cells. The 2-5A antisense strategy may hold a considerable advantage over the conventional antisense approach in targeting cancer-causing genes.

Adenine Nucleotides↗
PubMed2000

Safety and efficacy of adjuvant single-agent ifosfamide in uterine sarcoma.

PURPOSE: The role of adjuvant therapy for completely resected uterine sarcoma continues to be debated. Previous chemotherapy trials have shown little, if any, advantage over surgery alone, with significant added toxicity. To our knowledge, the current study is the first to evaluate adjuvant ifosfamide in completely resected uterine sarcomas. METHODS: Between 1992 and 1999, 13 consecutive patients with completely resected moderate- to high-grade uterine sarcoma received three cycles of adjuvant ifosfamide (1.5 g/m(2)/day x 3 days, repeated every 28 days). Mesna was given 30 min prior to infusion. Postinfusion mesna was administered to 10 of the patients in the outpatient setting utilizing a subcutaneous infusion pump. The remaining 3 patients received traditional intravenous mesna at 4 and 8 h after infusion. RESULTS: The median follow-up of the patient population was 26 months. For early-stage patients (n = 10), the 2-year progression-free survival was 60%, with a median of 26 months. The 2-year overall survival was 100%, dropping to 67% at 3 years. Early-stage patients showed an advantage in both progression-free and overall survival. Early-stage patients with mixed müllerian tumor (MMT) had a significantly longer time to progression that those with leiomyosarcoma (LMS) (2-year progression-free survival of 100% versus 33%; P = 0.019). Three patients required dose reduction secondary to grade 2-3 toxicities (neutropenia x2, nausea and vomiting x1). All significant toxicity was eliminated with dose reduction. CONCLUSIONS: Adjuvant ifosfamide appears to be safe and well tolerated in patients with completely resected uterine sarcoma. It can easily be given in the outpatient setting if mesna is administered via a subcutaneous pump. Our data, consistent with previous studies in advanced sarcoma, suggest a potentially greater role for ifosfamide in MMT than in LMS.

Adult↗
PubMed2000

Evaluation of plasma lysophospholipids for diagnostic significance using electrospray ionization mass spectrometry (ESI-MS) analyses.

We previously reported that lysophosphatidic acid (LPA) represents a potential biomarker for ovarian and other gynecologic cancers. To further improve the accuracy and potentially increase the sensitivity and specificity of the assay, we developed an electrospray ionization mass spectrometry (ESI-MS)-based method to analyze LPA and related lysophospholipids. LPA, lysophosphatidylinositol (LPI), lysophosphatidylserine (LPS), and lysophosphatidylcholine (LPC) could be detected with high sensitivity (in low pmol range) using this method. Standard curves were established for quantitative analysis. LPA and closely related lysophospholipids isolated from thin-layer chromatography (TLC) plates were analyzed directly by ESI-MS. This ESI-MS-based assay allows simultaneous detection and quantitation of all different species of LPAs and LPIs in a sample over a range of at least 5-300 pmol. Moreover, this test was at least 50 times more sensitive when a multiple reaction monitoring (MRM) mode was used. Using these protocols in a limited set of analysis, we found that both LPA and LPI were elevated in patients with ovarian cancer.

Adolescent↗
PubMed1999

Plasmacytoma of the ovary: a case report and literature review.

BACKGROUND: Ovarian plasmacytomas are a unique and unusual presentation of extramedullary plasmacytomas (EMP). A report of the seventh such case is presented with review of the previous six cases. METHODS: Surgical and medical staging were performed on the present case. The literature is reviewed. RESULTS: EMP involving the ovary is usually large at the time of presentation, more likely involving the left side, and without evidence of disseminated disease. As in other plasma cell dyscrasia, IgG paraprotein is more frequently involved. CONCLUSION: Adjuvant treatment for ovarian plasmacytomas is not clearly established; however, if complete surgical resection is achieved and no evidence of multiple myeloma is found, observation should be strongly considered.

Female↗
PubMed1999

The use of paclitaxel and platinum-based chemotherapy in uterine papillary serous carcinoma.

OBJECTIVE: Uterine papillary serous carcinoma (UPSC) is an aggressive malignancy with a histologic appearance and pattern of spread that resembles that of papillary serous adenocarcinoma of the ovary. The current standard therapy for advanced ovarian cancer, cisplatin or carboplatin plus paclitaxel, results in high objective response rates for that tumor. This regimen has thus far not been evaluated in UPSC. METHODS: Twenty-four patients with UPSC treated with platinum-based chemotherapy and paclitaxel were retrospectively evaluated. Eighteen patients received these agents in the adjuvant setting (n = 9) or for disease persistent after initial surgical management (n = 9). Eleven patients received one or more courses of this drug combination for recurrent disease, 5 of whom had prior exposure in the initial setting. RESULTS: Mean follow-up was 35 months (range 6-72+). A median progression-free interval (PFI) of 30 months (range 8-61+) was seen in patients treated in the adjuvant setting. Objective response, indicated by normalization of an elevated prechemotherapy CA125 level, was seen in 8 of 9 patients treated for residual disease after initial surgery (median PFI of 13 months, range 5-38+). Objective response of both measurable and/or evaluable disease was seen in 7 of 11 patients treated for recurrent disease (median PFI of 9 months, range 4-18). Six patients had retreatment with one or both agents and 4 responded a second time. Overall, the regimen was well tolerated. CONCLUSION: Paclitaxel and platinum-based chemotherapy has demonstrated activity in UPSC with acceptable toxicity. These results merit further investigation of the possible role of these agents in patients with this aggressive histologic subtype.

Aged↗
PubMed1999

Survival probability in ovarian clear cell adenocarcinoma.

OBJECTIVE: The aim of this study was to evaluate the 5-year survival probability (SP) of patients treated for ovarian clear cell adenocarcinoma (OCCA) at a single tertiary institution and to compare it to the 5-year SP of patients with other histologic subtypes of epithelial ovarian cancer. METHODS: Sixty-four patients with pure OCCA treated at the Cleveland Clinic Foundation from 1981 to 1996 were retrospectively identified and clinical information was abstracted. All histologic materials were reviewed by a single gynecologic pathologist. SP was calculated by the Kaplan-Meier method. SPs for OCCA patients were compared to that of other high-grade epithelial ovarian cancer patients in the gynecologic tumor registry. Cox proportional hazards modeling was used to identify varibles associated with decreased SP. RESULTS: The FIGO stages of OCCA study patients were Stage I, 31 (50%), Stage II, 6 (10%), Stage III, 17 (27%), and Stage IV, 8 (13%) (2 patients unstaged). Forty-four patients had no gross residual cancer at the completion of initial surgery while 9 patients had </=1 cm diameter residual and 10 had >1 cm residual. Forty-five (73%) received postoperative chemotherapy. The median follow-up for surviving patients is 97 months (range 38 to 209 months). The overall 5-year SP of OCCA patients is 50% with limited disease (Stages I and II) patients having a 5-year SP of 72% versus 17% 5-year SP in patients with advanced disease (P < 0.001). FIGO stage was most predictive of outcome. The overall 5-year SP of OCCA patients (50%) differed significantly (P < 0.05) from that of other ovarian cancer registry patients (30%). OCCA patients with limited cancer survived similarly to registry patients (72 vs 72%) as did patients with advanced OCCA compared with registry patients (17 vs 22%). CONCLUSIONS: When controlled for grade and stage, the overall survival with OCCA is identical to that of other high-grade epithelial ovarian cancers. Factors that account for the better overall survival of OCCA patients are more favorable disease stage, younger age, and improved debulking status.

Adenocarcinoma, Clear Cell↗
PubMed1999

Screening for gynecologic cancer.

Screening for cervical cancer with the Pap test has significantly reduced mortality from the disease. Although screening for ovarian and endometrial cancer is desirable, suggested strategies have not demonstrated efficacy. For the present time, educating patients with regard to the symptoms associated with these diseases and prompt evaluation of women who present with these symptoms helps limit unnecessary diagnostic delay.

Endometrial Neoplasms↗
PubMed1999

Human papillomavirus typing and the reduction of cervical cancer risk.

Minor cervical cytologic abnormalities are common, but knowing which low-grade lesions will progress to cervical cancer--and therefore deserve biopsy and excision--is difficult. Since some human papillomavirus (HPV) types are strongly associated with cervical cancer, HPV typing may be a means of determining which patients with minor abnormalities require biopsy and treatment and which need only follow-up smears. This paper reviews the association between cervical cancer and HPV infection, the pathogenesis of HPV infection, the utility of HPV typing in training patients with a diagnosis of atypical squamous cells of undetermined significance, and the prospects for the development of an HPV vaccine.

Female↗
PubMed1998

Lysophosphatidic acid as a potential biomarker for ovarian and other gynecologic cancers.

CONTEXT: Lysophosphatidic acid (LPA) has been shown to stimulate proliferation of ovarian cancer cells and is present in the ascitic fluid of patients with ovarian cancer. OBJECTIVES: To determine whether elevated levels of LPA are present in plasma from patients with ovarian cancer and other gynecologic malignancies compared with healthy controls and to evaluate whether an elevated LPA plasma level may be a biomarker for these diseases. DESIGN: A research assay was used to measure total LPA levels in plasma from healthy women and women with different diseases. All LPA assays and comparison of LPA levels and CA125 (an ovarian cancer biomarker) levels were performed by observers blinded to patient status or group. SETTING: The Cleveland Clinic Foundation. PARTICIPANTS: A convenience sample of 48 healthy control women, 48 women with ovarian cancer, 36 women with other gynecologic cancers, 17 women with benign gynecologic diseases, 11 women with breast cancer, and 5 women with leukemias. MAIN OUTCOME MEASURES: Total LPA levels in plasma samples from patients and controls. RESULTS: Patients in the ovarian cancer group had significantly higher plasma LPA levels (mean, 8.6 micromol/L; range, 1.0-43.1 micromol/L) compared with the healthy control group (mean, 0.6 micromol/L; range, <0.1-6.3 micromol/L) (P<.001). Elevated plasma LPA levels were detected in 9 of 10 patients with stage I ovarian cancer, 24 of 24 patients with stage II, III, and IV ovarian cancer, and 14 of 14 patients with recurrent ovarian cancer. Of 36 patients with other gynecologic cancers, 33 also showed higher LPA levels(mean, 14.9 micromol/L; range, <0.1-63.2 pmol/L), compared with healthy controls (P<.001). Elevated plasma LPA levels were detected in 5 of 48 controls and 4 of 17 patients with benign gynecologic diseases and in no women with breast cancer or leukemia. In comparison, among a subset of patients with ovarian cancer, 28 of 47 had elevated CA125 levels, including 2 of 9 patients with stage I disease. CONCLUSIONS: Plasma LPA levels may represent a potential biomarker for ovarian cancer and other gynecologic cancers. However, these findings are preliminary and require confirmation in larger studies.

Adult↗
PubMed1998

Analysis of allelic imbalance on chromosome 17p13 in stage I and stage II epithelial ovarian cancers.

OBJECTIVES: To determine whether there is evidence for allelic imbalance (AI) on chromosome 17p13 in early-stage epithelial ovarian tumors. METHODS: Studies of allelic imbalance were performed on 29 stage I or stage II epithelial ovarian cancers using 5 short tandem repeat polymorphic markers (STRPs) on chromosome 17p13 by polymerase chain reaction (PCR) amplification. RESULTS: Sixteen of 29 (55%) tumors showed AI at one or more loci, including 7 of 29 (24%) tumors that showed distinct regions of AI. AI at p53 was present in only 9 of 25 (36%) informative tumors. A region of AI, defined by marker D17S654, close to candidate genes OVCA1 and OVCA2, was identified distal to p53 and occurred in 11 of 23 (48%) informative tumors. This region of AI also extended more distal to this locus, and included marker D17S695 where AI occurred in 11 of 26 (42%) informative tumors. Microsatellite instability was observed in 2 of 29 tumors. CONCLUSIONS: This study supports the presence of at least one tumor suppressor gene on chromosome 17p13 distal to p53 that is involved in the early development of epithelial ovarian cancer. This study also suggests that the molecular analysis of early-stage epithelial ovarian cancers can provide important information on the genetic etiology of ovarian cancers.

Alleles↗
PubMed1998

Experience with platinum-paclitaxel chemotherapy in the initial management of papillary serous carcinoma of the peritoneum.

OBJECTIVE: The objective of this study was to assess the activity and toxicity of combination platinum-paclitaxel chemotherapy in the initial management of patients with papillary serous carcinoma of the peritoneum (PSCP). METHODS: Patients initially treated at The Cleveland Clinic Foundation (CCF) for PSCP with platinum-paclitaxel combination chemotherapy regimens were identified and clinical information was abstracted by chart review. Toxicity data, progression-free survival, and overall survival were determined. RESULTS: Thirty-eight patients (36 Stage IIIC and 2 Stage IV) were identified. All chemotherapy was administered as outpatient infusions. All patients received paclitaxel (135 or 175 mg/m2) and 12 received cisplatin and 26 carboplatin. Two hundred thirty-two cycles were administered, with only three (1.3%) episodes of grade 3 toxicity and no grade 4 toxicity. Ninety-two percent of patients experienced at least a 50% reduction in their CA-125 levels and 55% experienced a greater than 90% reduction. Median progression-free survival (Kaplan-Meier) was 15 months and median overall survival was 40 months. Survival for optimally debulked patients (median not yet reached with median follow-up of 24 months) was significantly better than for suboptimally debulked patients (median 32.8 months) (P = 0.012). CONCLUSION: Platinum-paclitaxel chemotherapy regimens have substantial utility in the initial management of PSCP patients. The toxicity profile is modest. Carboplatin or cisplatin in conjunction with paclitaxel is the current first-line recommended chemotherapy for PSCP.

Adult↗
PubMed1997

p53 overexpression is not an independent prognostic factor for patients with primary ovarian epithelial cancer.

BACKGROUND: The clinical significance of p53 overexpression in patients with ovarian carcinoma is uncertain. Previous studies have yielded conflicting results and have been hampered by small patient populations, failure to account for other well-known prognostic variables in multivariate analysis, and failure to account for the grade of p53 overexpression. The aim of this study was to investigate the independent prognostic significance of p53 overexpression in patients with primary ovarian epithelial cancer (POEC). METHODS: Tumors obtained from 221 patients with primary ovarian epithelial cancer (POEC) (Stages I-IV) were studied for p53 overexpression semiquantitatively by immunohistochemical techniques. The median duration of follow-up of surviving patients was 7 years. The presence or absence and degree of p53 overexpression were correlated with the clinicopathologic features of the study population and overall survival. Survival curves were constructed according to the Kaplan-Meier method, and differences in survival were assessed with the log rank test. The prognostic significance of p53 overexpression for survival was assessed in a multivariate analysis with the Cox proportional hazards model. RESULTS: One hundred seven tumors (48.4%) exhibited p53 overexpression. The overexpression was graded as mild in 16.7% of cases, moderate in 5.9%, and strong in 25.8%. p53 overexpression was associated with advanced stage (P = 0.04), higher grade (P = 0.0003), serous histology (P = 0.0018), and patient age > 61 years (P = 0.013). In univariate analysis, p53 overexpression was a significant prognostic factor (P = 0.049 for any degree of overexpression, P = 0.03 for strong overexpression). However, in multivariate analysis, after adjustment for stage and size of residual tumor following cytoreductive surgery, p53 overexpression did not retain statistical significance. Survival curves for patients with different stages and grades of tumor differentiation did not demonstrate a difference in survival among patients with no p53 overexpression, compared with those who demonstrated any degree of p53 overexpression or compared with those who demonstrated strong p53 overexpression. CONCLUSIONS: p53 overexpression is not an independent prognostic factor for patients with primary ovarian epithelial cancer.

Adenocarcinoma↗
PubMed1997

p53 and HER-2/neu overexpression in ovarian borderline tumors.

OBJECTIVE: To study p53 and HER-2/neu expression in borderline ovarian tumors (BLOT) by assessing their frequency, coexpression, and relationship to histologic type, FIGO stage, tumor recurrence, and survival. METHODS: Forty-two patients with confirmed BLOT (25 serous, 13 mucinous, and 4 seromucinous) were followed for 1.5 to 14 years (mean, 6.3). Thirty (71%) patients had FIGO stage I and 12 (29%) had FIGO stage III disease. Paraffin-embedded sections from the 42 BLOT, 5 normal ovaries, and 10 benign ovarian cystadenomas were stained using monoclonal antibodies against human p53 (DAKO-p53, DAKO, Denmark) and HER-2/neu (C-erB-2, Triton, Parkway, CA). Positive staining was semiquantitated depending on the number of positively stained tumor cells. p53 and HER-2/neu overexpressions were correlated to each other, to histologic subtype, stage, tumor recurrence, and survival. RESULTS: None of the patients had tumor recurrence. The 5- and 10-year disease-free survival was 100%. None of the normal ovaries or ovarian cystadenomas demonstrated overexpression of p53 or HER-2/neu. Ten (24%) BLOT demonstrated overexpression of p53 and 9 (21%) demonstrated overexpression of HER-2/neu. HER-2/neu overexpression was significantly greater in stage III than in stage I tumors (P = 0.0157). Seromucinous BLOT demonstrated significantly greater p53 overexpression compared with other histologic subtypes (P = 0.030). Coexpression of p53 and HER-2/neu occurred in 4 patients (9.5%). There was no significant correlation between the overexpression of p53 and HER-2/neu (P = 0.180) and no significant relationship between p53 and HER-2/neu overexpression and the presence of microinvasion, ability to perform optimal cytoreductive surgery, tumor recurrence, or survival. CONCLUSIONS: p53 and HER-2/neu overexpression occurred in about 20-25% of BLOT overall and more commonly in seromucinous and advanced stage tumors. Coexpression occurred in 9.5% of the cases with no significant correlation between the expression of p53 and HER-2/neu.

Adolescent↗
PubMed1997

Serum CA-125 measurements > 65 U/mL. Clinical value.

OBJECTIVE: To review the prevalence of various conditions associated with serum CA-125 values > 65 U/mL, to calculate the odds ratios of different ranges of high CA-125 in predicting cancer and to study the effect of menopause and the presence of a mass on the predictive value of high serum CA-125. STUDY DESIGN: A retrospective review of the diagnoses in 313 consecutive women seen at the Cleveland Clinic Foundation whose serum CA-125 was > 65 U/mL was performed. Statistical analysis was performed using crosstabulation, chi 2, Fisher's exact test and the odds ratio. RESULTS: In patients with serum CA-125 > 65 U/mL, gynecologic cancers, nongynecologic cancers and non-malignant conditions constituted 74.3%, 10.2% and 13.1% of diagnoses, respectively. In patients with serum CA-125 > or = 1,000 U/mL, the same conditions were responsible for 89%, 7% and 3% of diagnoses, respectively. Endometriosis and metastatic breast cancer were the most common benign condition and nongynecologic cancer associated with serum CA-125 > 65 U/mL. The presence of an abdominopelvic mass significantly increased the risk of malignancy (P < .00005). Approximately 90% of patients with CA-125 > 65 U/mL and no mass had nonmalignant disease. The diagnoses of serum CA-125 values > 65 U/mL varied significantly in premenopausal versus postmenopausal patients. Postmenopausal patients had a higher incidence of gynecologic (P = .002) and nongynecologic (P = .0008) cancers and lower incidence of benign conditions (P < .0005). The odds ratio that CA-125 levels were associated with cancer increased as the level of CA-125 increased. The odds ratio of malignant versus benign disease was significantly higher in post-menopausal patients for all intervals of CA-125 levels until the level of > or = 1,000 U/mL was reached. CONCLUSION: In patients seen at a tertiary center, serum CA-125 measurements > 65 U/mL were associated with nonmalignant conditions in 13% of patients. Although higher serum CA-125 levels were more associated with gynecologic malignancies, no level of CA-125 occurred exclusively with gynecologic cancers. In postmenopausal patients with serum CA-125 values > 65 U/mL and in patients with serum CA-125 values > 65 U/mL and an abdominopelvic mass, subspecialty consultation should be considered before proceeding to surgery.

Adult↗
PubMed1996

Ovarian papillary serous tumors of low malignant potential (serous borderline tumors). A long-term follow-up study, including patients with microinvasion, lymph node metastasis, and transformation to invasive serous carcinoma.

BACKGROUND: The clinical outcome of patients with ovarian serous tumors of low malignant potential (LMP) remains controversial, especially for those with extraovarian disease. We retrospectively reviewed our experience to study this question further, to assess the safety of conservative management of patients with limited disease, and to determine whether exophytic ovarian surface tumor was predictive of tumor recurrence. METHODS: The clinical and pathologic records of 76 patients with ovarian serous LMP tumors accessioned at the Cleveland Clinic Foundation from 1979 to 1990 were reviewed. International Federation of Gynecology and Obstetrics (FIGO) staging was retrospectively assigned, follow-up information obtained, and clinicopathologic correlations made. RESULTS: An exophytic ovarian surface component was present in 39 of 76 patients (51%). Stage II or III disease was present in 28 of 74 staged patients (38%). Follow-up information was available on 66 patients, ranging from 8 to 264 months (mean, 99 months). Twenty-five patients of 66 patients with follow-up information (38%) received adjuvant therapy. Only 1 patient (1.5%) developed progressive disease; she died of widespread invasive serous carcinoma. Two of 18 conservatively managed patients (11%) developed "recurrent" disease, including 1 patient with a second primary serous LMP tumor of the preserved ovary and 1 patient with an incidentally discovered microscopic serosal implant. There were no other recurrences in the study group, which included four patients with stromal microinvasion and one with lymph node involvement. CONCLUSIONS: The long term outcome of serous LMP tumors is extremely favorable. Exophytic ovarian surface tumor did not serve as a predictor for subsequent peritoneal implants. Conservative surgical management in young patients with localized disease is supported and the use of adjuvant therapy in the initial management of patients with advanced tumors is further questioned.

Adolescent↗
PubMed1996

Adenocarcinoma in situ of the uterine cervix: management and outcome.

OBJECTIVE: To retrospectively review the management of adenocarcinoma in situ of the uterine cervix, to determine the outcome of conization versus hysterectomy, and to compare the results achieved by different methods of conization. METHODS: We performed a retrospective pathology and chart review of 46 patients with cervical adenocarcinoma in situ from January 1980 to October 1994. RESULTS: Nine patients were managed during the first half of the study period and 37 were managed in the second half. The mean age of patients was 38.4 years (range 25-72). Forty-five of 46 patients were diagnosed as a result of an abnormal Pap smear, although only 19 smears indicated adenocarcinoma in situ or other glandular abnormalities. Cold knife conization resulted in a 33% rate of positive margins for adenocarcinoma in situ compared to 50% for large loop excision of the transformation zone (LLETZ). Among 24 conservatively managed patients with negative conization margins, there have been 2 (8.3%) recurrences of adenocarcinoma in situ. Among patients not undergoing hysterectomy as definitive treatment, 1 of 18 (6%) patients undergoing cold knife conization recurred, compared to 4 of 14 (29%) managed with LLETZ, despite a 63.4-month shorter mean follow-up interval for the LLETZ patients. CONCLUSIONS: Cold knife conization is associated with a lower rate of recurrence of cervical adenocarcinoma in situ compared to LLETZ. We recommend cold knife conization for patients who are not treated with hysterectomy.

Adenocarcinoma↗
PubMed1996

Results of the clinical evaluation of atypical glandular cells of undetermined significance (AGCUS) detected on cervical cytology screening.

OBJECTIVE: To determine the clinical significance of and underlying pathology among patients with atypical glandular cells of undetermined significance (AGCUS) identified on cervical Pap smear screening. METHODS: The computerized files of the Cleveland Clinic Foundation cytology laboratory were searched from 1990 to 1994 to identify all patients with AGCUS. Patients with other significant cytologic diagnoses were considered separately from patients whose only significant finding was reported to be AGCUS. Retrospective chart review was completed to identify associated conditions and to record the results of the clinical evaluations of these patients. RESULTS: One hundred thirty-six patients were identified among the 68,368 (0.2%) specimens from this 5-year period in contrast to 3078 (4.5%) patients with atypical squamous cells (ASCUS). Mean patient age was 43.7 years (range 20-78). Among 77 patients without other significant cytologic findings in addition to AGCUS, without prior gynecologic cancer and who had a recorded gynecologic evaluation, 13 patients (17%) were diagnosed with the following lesions: two (3%) invasive cervical adenocarcinomas, three cervical adenocarcinomas in situ (4%), three grade 1 cervical intraepithelial neoplasms (CIN) (4%), four grade 2-3 CIN (5%), and one (1%) endometrial adenocarcinoma. Additionally, in subsequent follow-up examinations two patients were diagnosed with cervical adenocarcinoma in situ, one with invasive adenocarcinoma of the cervix and one with diffusely metastatic pancreatic cancer. CONCLUSIONS: AGCUS on cervical cytologic screening, even in the absence of other associated cytologic findings, is associated with substantial underlying uterine pathology including at least 4% (95% confidence interval (CI) 0.8%, 11.0%) invasive cancers and 13% (95% CI 6.4%, 22.6%) precancerous lesions. Cervical colposcopy, endocervical curettage, and endometrial biopsy are recommended for the complete evaluation of AGCUS.

Adenocarcinoma↗