Clinical outcomes of patients with adenocarcinoma in situ of the cervix treated by conization.

OBJECTIVE: To describe the clinical outcomes of histologically confirmed adenocarcinoma in situ (AIS) of the cervix treated with cervical conization. MATERIALS AND METHODS: A retrospective chart review of patients with histologically confirmed AIS from July 1998 to February 2011 included 52 patients. The rates of residual disease in subsequent excisions, the clinical recurrence rate, the average disease-free interval, and risk of progression to adenocarcinoma were described. The clinical outcomes of patients treated with cold knife cone (CKC) and loop electrosurgical excisional procedure (LEEP) were compared. RESULTS: Fifteen LEEPs and 37 CKC procedures were performed as initial treatment and 26 patients (50%) had positive margins. There was no significant difference in rate of positive margins between LEEP and CKC (40% vs. 54%, respectively. p = 0.55). LEEPs and CKCs resulted in similar volumes of cervical tissue resected (4.98 cm3 vs. 5.04 cm3, p = 0.40). Of patients with positive margins, ten underwent immediate hysterectomy, six underwent a second cone biopsy, seven were managed expectantly, and four were lost to follow up. Residual AIS was found in 47% (eight of 17) of repeat cone biopsy and hysterectomy specimens performed for positive cone margins. Of the 26 patients with negative cone margins, no residual or recurrent disease was found after an average follow-up of 32 months. CONCLUSIONS: A positive surgical margin was associated with residual disease in 47% of patients with AIS treated with conization. No patient with negative cone margins had recurrent or progressive disease. Cervical conization with negative margins appears to be a safe treatment option for patients with AIS but requires further investigation. CKC and LEEP were equally efficacious treatments in our study population.

Role of surgical staging and adjuvant treatment in uterine serous carcinoma.

PURPOSE OF INVESTIGATION: This study evaluates the association of clinical and pathologic characteristics of patients with uterine serous carcinoma (USC) with disease recurrence. MATERIALS AND METHODS: Surgically-staged patients with USC at a single institution were identified and clinical and pathologic variables were compared. RESULTS: Of the 51 patients included in this analysis, 75% percent received adjuvant chemotherapy, 51% received radiation therapy, and 47% received both. After a median follow-up of 33 months, 42% of patients had disease recurrence. On multivariable analysis, positive pelvic lymph nodes were associated with a shorter interval between surgery and recurrence: 13.6 months progression-free survival (PFS) with positive vs 17.2 months with negative lymph nodes (p = 0.05). Patients with early-stage disease who did not receive any adjuvant treatments had a significantly greater risk of disease recurrence (44.4% vs 7.70%, p = 0.043). CONCLUSION: In this population of surgically-staged patients with USC, pelvic lymph node metastases were predictive of a shorter PFS.

Lymphatic ascites following pelvic and paraaortic lymphadenectomy procedures for gynecologic malignancies.

OBJECTIVE: Lymphatic ascites is an unusual complication in patients with cancer. In the gynecologic oncology patient population, the most common etiology is operative lymph node dissection. The purpose of this study was to explore the incidence, presenting symptoms, methods of diagnosis and treatment modalities utilized for lymphatic ascites in patients undergoing lymph node dissection for gynecologic cancers. METHODS: This observational study retrospectively reviewed the charts of patients who underwent lymphadenectomy as part of the surgical management for a gynecologic cancer. Patients that developed postoperative lymphatic ascites between January 2000 and December 2010 were included for analysis. Data extracted from the medical records included tumor pathology, number of harvested lymph nodes, postoperative course, method of diagnosis and treatment. RESULTS: From a total of 300 surgical staging procedures, 12 patients with lymphatic ascites were identified (4%). The most common reported symptom was leakage of clear fluid per vagina (7, 58%), followed by abdominal distension (4, 33%). The median interval from surgery to development of symptoms was 12.5 days (range 0-22 days). 5 patients had complete resolution of symptoms with dietary modifications alone while 7 patients required paracentesis. The median time from surgery to resolution of symptoms was 44 days (range 9-99). CONCLUSION: Lymphatic ascites is an under recognized and infrequently reported postoperative complication. Although it usually resolves spontaneously or with conservative management without sequelae, this condition can significantly prolong postoperative recovery and cause patient discomfort. To our knowledge this is the largest group of patients undergoing gynecologic surgical staging procedures to be reviewed for the occurrence of lymphatic ascites.

Phase I trial of ixabepilone plus pegylated liposomal doxorubicin in patients with adenocarcinoma of breast or ovary.

BACKGROUND: Ixabepilone is a semisynthetic epothilone B analogue that is active in taxane-resistant cell lines and has shown activity in patients with refractory breast and ovarian cancer. We carried out a phase I trial of ixabepilone plus pegylated liposomal doxorubicin (PLD) in patients with advanced taxane-pretreated ovarian and breast cancer. METHODS: Patients with recurrent ovarian or breast carcinoma received PLD every 3 or 4 weeks plus five different dose schemas of ixabepilone in cohorts of three to six patients. RESULTS: Thirty patients received a total of 142 treatment cycles of the PLD-ixabepilone combination. The recommended phase II dose and schedule of ixabepilone was 16 mg/m(2) on days 1, 8, and 15 plus PLD 30 mg/m(2) given on day 1, repeated every 4 weeks. Hand-foot syndrome and mucositis were dose limiting when both ixabepilone and PLD were given every 3 or 4 weeks. Objective responses were observed in 3 of 13 patients (23%) with breast cancer and 5 of 17 patients (29%) with ovarian cancer. CONCLUSION: Ixabepilone may be safely combined with PLD, but tolerability is highly dependent upon the scheduling of both agents. This combination demonstrated efficacy in patients with breast and ovarian cancer and merits further evaluation in these settings.

A case of mesothelioma masquerading pre-operatively as ovarian cancer and brief review of the literature.

BACKGROUND: Malignant peritoneal mesothelioma (MPM) can masquerade as an ovarian epithelial neoplasm, with very similar presenting clinical symptoms and imaging findings. The gold standard in differentiating between these two diagnoses lies in tissue pathology. CASE REPORT: This is a case of MPM that was initially misdiagnosed as ovarian cancer based on family history, imaging, and surgical findings. Tissue diagnosis preoperatively would have changed the planned procedure. Retrospectively, after the diagnosis of MPM, the patient was found to have had an indirect exposure to asbestos through her father. CONCLUSIONS: This case highlights the importance of keeping a broad differential when diagnosing ovarian malignancies, collecting both family and social histories (including screening for exposure to asbestos), and the benefit of obtaining tissue diagnosis when MPM is suspected.

Postoperative high dose-rate intravaginal brachytherapy combined with external irradiation for early stage endometrial cancer: a long-term follow-up.

PURPOSE: To evaluate the long-term control of disease and cure rate, complications, second malignancy, and survival of early-stage endometrial cancer patients treated with surgery, high dose-rate brachytherapy, and external beam radiation therapy. METHODS AND MATERIALS: From 1969 through 1979, 300 patients with clinically staged Stage I-II endometrial cancer underwent total abdominal hysterectomy and bilateral salpingo-oopherectomy, followed by high dose-rate intravaginal radiation, 7 Gy x 3 to 0.5 cm from the mucosal surface, using a remote afterloading technique. External beam radiation therapy, 40 Gy to midplane in 4 weeks, was delivered to high risk patients through AP/PA and lateral fields. RESULTS: The patients were followed for 5-24 years (median 12). The actuarial progression-free survival rate was 96.6%. Post-treatment grade 1-2 actuarial complication rate was 9.5%, including cystitis (4.5%), vaginal stenosis (2.5%), proctitis (1.5%), vaginal necrosis (0.5%), and partial bowel obstruction (0.5%). Neither grade 3-4 complications nor additional late complications were observed in any of our patients. Relapse rate was only 3.7%, of which 45.5% were local, 45.5% were distant, and 9% were mixed. All the patients with relapse were postmenopausal, age range of 58-77 years, with tumor grade 2-3 in 64%. Second primary cancer rate was 12.8% (mostly breast and colon). Factors that were associated with improved prognosis were young age, premenopausal, low grade, no extrauterine disease, and a histology of adenocarcinoma (adenocarcinoma with squamous metaplasia). CONCLUSION: High dose rate intravaginal radiation therapy combined with surgery and external beam radiation therapy achieved a high cure rate small number of minor complications. No long-term treatment-related complications were noted in any of the patients. This treatment combination may be safely applied to patients with early stage endometrial cancer.

Mucinous adenocarcinoma of the endometrium with intestinal differentiation: a case report.

Mucinous differentiation of endocervical type has been well documented in endometrial carcinoma. However, we describe an unusual case of adenocarcinoma of the endometrium showing diffuse histological, immunohistochemical, and ultrastructural evidence of intestinal differentiation. Although intestinal differentiation has been described in mesodermally derived tissues including endocervix, ovary, and urinary tract, it has not been reported in normal endometrium. One previous case has been reported showing this pattern in endometrial carcinoma. Possible histogenetic mechanisms of this pattern are discussed.

Septic pulmonary embolism complicating a central venous catheter.

Bacteremia is a recognized complication in patients with indwelling central venous catheters. More recently pulmonary embolism in such patients has also been described. Despite abundant clinical experience with these devices, to our knowledge, septic pulmonary embolism has not been reported in adult patients. This case illustrates such a complication.

Endometrial cancer after menopausal use of estrogens.

The incidence of endometrial cancer has increased rapidly during recent years, paralleling the increased postmenopausal use of estrogens. The relation of endometrial cancer to disease conditions in which estrogens are elevated and three case-control epidemiologic studies suggest the likelihood of a cause-and-effect relation between estrogen use and endometrial cancer. These studies and New York State Cancer Registry data further suggest that the incidence will continue to rise in coming years. A thorough reevaluation of the medical indications for estrogen replacement therapy is urgently needed. Women with long-term exposure to estrogens should have periodic cancer screening examinations.

Symptoms of ovarian cancer.

OBJECTIVE: To examine the symptoms of ovarian cancer in patients compared with symptoms experienced by healthy women using a case-control design. METHODS: Cases (n = 168) were women with ovarian cancer diagnosed at two hospitals in New York between 1994 and 1997 who were interviewed shortly after diagnosis. They were compared with healthy women (n = 251 controls) from the community. Women were asked about the prevalence, duration, and constancy of eight symptoms and about use of three types of medications in the 6 to 12 months before diagnosis (cases) or interview (controls). RESULTS: Nearly all the cases (93%) reported at least one symptom, compared with 42% of controls. The most common symptoms among cases were: unusual bloating, fullness, and pressure in the abdomen (71%); unusual abdominal pain or lower back pain (52%); and lack of energy (43%). The proportions of controls reporting these symptoms were 9, 15, and 16%, respectively, resulting in odds ratios and 95% confidence intervals of 25.3 (15.6, 40.9), 6.2 (4.0, 9.6), and 3.9 (2.5, 6.1), respectively, for these symptoms. Bloating, fullness, and pressure was of more recent onset among cases than controls (4.9 months compared with 7.6 months, P =.01). There were only minor differences in reported symptoms between cases with early and later stage disease. CONCLUSION: Unusual bloating, fullness, and pressure, abdominal or back pain, and lack of energy are prominent symptoms in women with ovarian cancer and distinguish them from controls. Information on symptoms may make women and physicians more aware of changes associated with ovarian cancer.

Estrogen and progestin binding in cytosols of ovarian adenocarcinomas.

Because a few ovarian adenocarcinomas respond favorably to endocrine therapy, we tested the hypothesis that some ovarian adenocarcinomas have functional similarity with sex-hormone-sensitive endometrial and breast tumors. Cytosols from 23 ovarian adenocarcinomas and 27 control tissues were examined for receptorlike estrogen and/or progestin binding. Eight of 16 primary ovarian adenocarcinomas had estrogen and/or progestin receptorlike components; among the metastases tested, one third retained estrogen binding. No correlations were found between binding characteristics and histopathologic grade. The presence of estrogen binding in a lung lesion helped confirm recurrent ovarian disease. Estrogen binding occurred in specimens from women with no histories of exposure to exogenous estrogen. Because tamoxifen and nafoxidine could inhibit estradiol binding, it is likely that antiestrogens will prove beneficial against some ovarian cancers.

The stilbestrol child.

PIP: There have been over 100 cases reported of clear cell carcinoma in young girls, most of whose mothers received diethylstilbestrol during pregnancy. Other nonsteroidal synthetic estrogens, such as dienestrol and hexestrol, have also been implicated. Dose and duration of therapy varied widely in the cases. Until these cases of vaginal and cervical clear cell carcinoma are understood, patients who took nonsteroidal synthetic estrogens during pregnancy must be examined thoroughly, stained and biopsied when necessary, and followed carefully with frequent pelvic examinations. In fact, carcinoma of the vagina should be considered as a possibility in every case of irregular vaginal bleeding in young girls; vaginal examination should be performed in order to exclude such a possibility. A follow-up program in the clinic at Emory University is described. The program involves a complete pelvic examination, a Pap smear, an application of Schiller's stain to the vagina and cervix, and routine follow-up treatment at regular intervals.^ieng

An easy, fast technique for making immediate surgical obturators.

The demands for surgical obturators, both in numbers and time restraints, is ever increasing. A quick, simple method to provide these obturators by using the light-cured resins that are currently available is described.

HIV-related primary non-Hodgkin's lymphoma of the vulva.

We reported on a 25-year-old HIV-positive woman diagnosed with Ann Arbor Stage IEB primary extranodal immunoblastic lymphoma arising in the vulva. This is the first documented instance of an HIV-associated malignant lymphoma originating in the lower female genital tract, and only the 16th reported case of primary malignant lymphoma of the vulva. The nonspecific clinical presentation coupled with the unanticipated finding of lymphoma made diagnostic confirmation an arduous task, requiring weeks of persistence. The patient's disease was refractory to three courses of chemotherapy, but did respond to a brief palliative course of external beam irradiation prior to her demise 7 months after presentation. Our findings are presented, and 15 cases from the literature, the largest series to date, are discussed.

Perforation of the inferior vena cava by a recently inserted Greenfield filter.

The Greenfield filter is an effective device which provides protection against emboli to the lungs from the deep veins of the lower half of the body. Specific complications, such as perforation, may occur following the placement of caval filters. We report a case of inferior vena cava perforation by a Greenfield filter diagnosed at the time of surgery. With the increasing use of caval filter placement, specific complications such as this will be encountered.

Smoking, body weight, and early-stage endometrial cancer.

The effect of cigarette smoking on the risk of early-stage endometrial cancer was evaluated in a population-based case-control study of women aged 40 to 69 years from upstate New York. Two hundred women with early-stage endometrial cancer diagnosed between 1979 and 1981, and 200 matched community controls were interviewed in person and asked about smoking habits and other risk factors. Statistical analysis revealed a significant decline in relative risk with increased smoking (P less than 0.05). This effect strongly modified the well-known increase in risk with body weight. Among smokers risk did not increase with body weight, whereas among nonsmokers risk increased rapidly with body weight, especially among nonsmokers in whom the peripheral conversion of androgens was the primary source of serum estrogen. Despite this apparent reduced risk for endometrial cancer, smoking remains a major health hazard for women as well as men.

Analysis of sera from ovarian cancer patients for immune complexes.

In contrast to other malignancies, circulating immune complexes (CICS) are usually not detected by conventional assays in the sera of ovarian cancer patients. However, a polyethylene glycol (PEG) precipitation assay has been reported to detect putative CICS in ovarian cancer. To determine if CICS were indeed present, we analyzed sera from 12 women with ovarian cancer. All were negative for CICS by the Raji cell assay; 5 (42%) were positive by the PEG assay. However, the PEG precipitate did not possess characteristics of immune complexes. IgG in sera or in the precipitate sedimented in sucrose gradients solely at the same rate as 7S monomeric IgG. In addition, the precipitates were not able to activate the complement system and the four IgG subclasses were present in the same relative concentration as that found in normal serum. The results suggest that it is probably a misnomer to label the material detected in ovarian cancer sera by the PEG precipitation assay as CICS. Instead a non-immune interaction of IgG with other components, possibly membrane fragments, is probably being measured.

Antibodies to the neutral glycolipid asialo ganglio-N-tetraosylceramide: association with gynecologic cancers.

As part of our efforts to define subpopulations at increased risk for gynecologic malignancies, sera from 145 women were obtained prior to diagnosis and analyzed for antibody to asialo ganglio-N-tetraosylceramide. This neutral glycolipid is present on the surface of thymocytes and natural killer cells, and asialo ganglio-N-tetraosylceramide antibody has been shown in animals to block natural killer cell activity and promote tumor cell proliferation. With the use of an enzyme-linked immunosorbent assay and with a value of 2 SD above the mean for healthy women designated as the boundary for a positive response, antibody to asialo ganglio-N-tetraosylceramide was detected in only one of 30 (3%) healthy women, none of 16 pregnant women, none of 18 women with benign masses, and two of 24 (8%) women with microbial infections. All of the above samples that contained antibodies were barely over the 2 SD limit. In marked contrast, 19 of 35 (54%) women with gynecologic malignancies had asialo ganglio-N-tetraosylceramide antibodies, with positive values ranging to greater than 10 SD above the control mean. Asialo ganglio-N-tetraosylceramide antibody was found in six of eight (75%) patients with cervical cancer, five of eight (63%) with endometrial cancer, and seven of 15 (47%) with ovarian cancer. Of the eight patients with Stage I gynecologic cancer at any site, five (62%) had asialo ganglio-N-tetraosylceramide antibodies. Four of 22 (18%) women with Hodgkin's disease also had antibodies, with values just exceeding 2 SD above control levels. The presence of these antibodies may contribute to an impaired immune surveillance system in these women and so increase their susceptibility to malignancy.

An epidemiologic case-control study of ovarian cancer and reproductive factors.

A population-based case-control study was conducted with 403 white, ovarian cancer patients, 20-79 years of age, who were diagnosed from October 1977 through February 1980 in 11 New York State counties. The study also included 806 controls who were matched to the cases by age, race, and county of residence. The contraceptive and reproductive patterns observed in this study suggest that infertility plays an important role in determining the relationship between reduced parity and gravidity and increased ovarian cancer risk. Ovarian cancer patients were less likely than controls to have ever used nonpermanent birth control methods (relative risk = 0.63, 95% confidence interval = 0.45-0.89), and they tended to practice contraception less often. A direct graded-response relationship was observed between ovarian cancer risk and the number of contraceptive-free years of marriage (chi 2 Linear trend = 5.911, p = 0.02). An inverse graded-response relationship was observed between gravidity and risk. This relationship persisted even after contraception was taken into account (chi 2 Linear trend = 13.002, p = 0.0003). Ovarian cancer risk was not found to be associated with an excess in reported fetal loss.

PIP: A population-based case control study was conducted with 403 white, ovarian cancer patients, ages 20-79, who were diagnosed from October 1977-February 1980 in 11 New York State counties. The study also included 806 controls who were matched to the cases by age, race, and county of residence. The contraceptive and reproductive patterns observed in this study suggest that infertility plays an important role in determining the relationship between reduced parity and gravidity and increased ovarian cancer risk. Ovarian cancer patients were less likely than controls to have ever used nonpermanent birth control methods (relative risk=0,63, 95% confidence interval=0.45-0.89), and they tended to practice contraception less often. A direct graded response relationship was observed between ovarian cancer risk and the number of contraceptive-free years of marriage (chi square linear trend=5.911, p=0.02). An inverse graded response relationship was observed between gravidity and risk. This relationship persisted even after contraception was taken into account (chi square linear trend=13.002, p=0.0003). Ovarian cancer risk was not found to be associated with an excess in reported fetal loss.

Infrared spectroscopy of exfoliated human cervical cells: evidence of extensive structural changes during carcinogenesis.

Infrared spectra were obtained from exfoliated cervical cells from 156 females, of whom 136 were normal, 12 had cervical cancer, and 8 had dysplasia. The spectra of the normal women, essentially identical, differed from those obtained from patients with either cancer or dysplasia. In malignant samples we noted (i) significant changes in the intensity of the glycogen bands at 1025 cm-1 and 1047 cm-1, the bands at 1082 cm-1 and 1244 cm-1, the C--O stretching band at 1155 cm-1, and the band at 1303 cm-1, (ii) significant shifts of the peaks normally appearing at 1082 cm-1, 1155 cm-1, and 1244 cm-1, and (iii) an additional band at 970 cm-1. Further study of several of these bands, including the pressure dependence of their frequencies, revealed that in the malignant cervical tissue there were extensive changes in the degree of hydrogen bonding of phosphodiester groups of nucleic acids and C--OH groups of proteins, as well as changes in the degree of disorder of methylene chains of lipids. The IR spectra of samples with dysplasia demonstrated the same changes with cancer samples, except that the changes were of lesser magnitude and the phosphodiester peak normally appearing at 1082 cm-1 did not shift. These spectroscopic changes appear to progress in tandem with the morphological changes that lead normal cervical epithelium to cancer through the premalignant stage of dysplasia. The diagnostic potential of IR spectroscopy is discussed.