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Biomedical subjects

W Chapman

Publications and source records attributed to W Chapman.

At least 19 recordsLinked to original sources

Continuous treatment of Barrett's oesophagus patients with proton pump inhibitors up to 13 years: observations on regression and cancer incidence.

BACKGROUND: There is little evidence that treatment of patients with Barrett's oesophagus with proton pump inhibitors over periods up to 6 years results in major regression of Barrett's oesophagus. AIM: To determine if longer periods of treatment with proton pump inhibitors lead to significant regression of Barrett's oesophagus, and to determine the incidence of oesophageal adenocarcinoma in the proton pump inhibitor-treated patients. METHODS: We analysed prospectively-collected data on Barrett's oesophagus patients treated with proton pump inhibitors for 1-13 years. RESULTS: 188 patients with Barrett's oesophagus and intestinal metaplasia, were treated for 1-13 years with a proton pump inhibitor (966 years of treatment; mean 5.1 years). No change in length was seen during treatment but 48% of patients developed squamous islands (25% after 1-3 years; 100% at 12-13 years). Squamous islands correlated with treatment duration and male sex but not with proton pump inhibitor dose or patient age. Six patients developed dysplasia and three males developed adenocarcinoma during treatment (cancer incidence 0.31%). CONCLUSIONS: Proton-pump inhibitor treatment over 1-13 years does not shorten the Barrett's oesophagus segment but squamous islands appear in many patients. The incidence of oesophageal adenocarcinoma was low in these proton pump inhibitor-treated patients compared with published series.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Altruistic living donors: evaluation for nondirected kidney or liver donation.

A program was established within our regional procurement organization to permit evaluation of altruistic living donors (LD) interested in nondirected kidney or liver segment donation prior to transplant center referral. During the initial 30 months of program operations, 731 donor inquiries were received of which 131 individuals called back after review of mailed information materials. Forty-seven candidates initiated and 19 completed the evaluation process. Seven underwent donation to include six kidneys and one liver segment, five are actively pending donation, five were excluded from donation following transplant center evaluation and two took no further action after their intended liver recipients received deceased donor (DD) transplants. Psychological evaluation of these 19 candidates found them to be free of psychopathology, highly cooperative and self-directed. They did not exhibit attention-seeking or religious motivations for their actions. All seven donors and recipients continue to do well postoperatively. This evaluation program has made possible large-scale screening and education of prospective altruistic LD within the general population and also provides a unique opportunity to further our understanding of those individuals interested in living-nondirected donation.

Adult↗

Syndrome and outbreak detection using chief-complaint data--experience of the Real-Time Outbreak and Disease Surveillance project.

This paper summarizes the experience of the Real-Time Outbreak and Disease Surveillance (RODS) project in collecting and analyzing free-text emergency department (ED) chief complaints. The technical approach involves real-time transmission of chief-complaint data as Health Level 7 messages from hospitals to a regional data center, where a Bayesian text classifier assigns each chief complaint to one of eight syndrome categories. Time-series algorithms analyze the syndrome data and generate alerts. Authorized public health users review the syndrome data by using Internet interfaces with timelines and maps. Deployments in Pennsylvania, Utah, Atlantic City, and Ohio have demonstrated feasibility of real-time collection of chief complaints. Retrospective experiments that measured case-classification accuracy demonstrated that the Bayesian classifier can discriminate between different syndrome presentations. Retrospective experiments that measured outbreak-detection accuracy determined that the classifier's performance was adequate to support accurate and timely detection of seasonal disease outbreaks. Prospective evaluation revealed that a cluster of carbon monoxide exposures was detected by RODS within 4 hours of the presentation of the first case to an emergency department.

Algorithms↗

Removing a barrier to computer-based outbreak and disease surveillance--the RODS Open Source Project.

INTRODUCTION: Computer-based outbreak and disease surveillance requires high-quality software that is well-supported and affordable. Developing software in an open-source framework, which entails free distribution and use of software and continuous, community-based software development, can produce software with such characteristics, and can do so rapidly. OBJECTIVES: The objective of the Real-Time Outbreak and Disease Surveillance (RODS) Open Source Project is to accelerate the deployment of computer-based outbreak and disease surveillance systems by writing software and catalyzing the formation of a community of users, developers, consultants, and scientists who support its use. METHODS: The University of Pittsburgh seeded the Open Source Project by releasing the RODS software under the GNU General Public License. An infrastructure was created, consisting of a website, mailing lists for developers and users, designated software developers, and shared code-development tools. These resources are intended to encourage growth of the Open Source Project community. Progress is measured by assessing website usage, number of software downloads, number of inquiries, number of system deployments, and number of new features or modules added to the code base. RESULTS: During September--November 2003, users generated 5,370 page views of the project website, 59 software downloads, 20 inquiries, one new deployment, and addition of four features. CONCLUSIONS: Thus far, health departments and companies have been more interested in using the software as is than in customizing or developing new features. The RODS laboratory anticipates that after initial installation has been completed, health departments and companies will begin to customize the software and contribute their enhancements to the public code base.

Disease Outbreaks↗

Assessment of tumor cell repopulation after chemotherapy for advanced ovarian cancer: pilot study.

BACKGROUND: Repopulation of clonogenic tumor cells appears to increase during fractionated radiation treatment and is recognized as an important factor affecting local control. Given the longer intervals between cycles and longer total duration of treatment, the impact of repopulation is likely to be greater after chemotherapy. METHODS: We assessed tumor cell repopulation with the proliferative marker Ki-67 in 21 patients with ovarian carcinoma who received initial chemotherapy. Paraffin slides were evaluated from the diagnostic biopsy and from tumor obtained at debulking surgery after chemotherapy. Immunohistochemistry using the MIB-1 antibody was performed on the paired samples and analyzed with a digital imaging device linked to a color camera mounted on a transmitted-light microscope. The ratio of Ki-67 positive to all nuclei was used as a proliferative index and compared for pre- and postchemotherapy specimens. RESULTS: All patients received platinum-based chemotherapy and most showed a response to treatment. The median duration between last chemotherapy and debulking surgery was 33 days (range, 22-50 days). Four (19%) of 21 patients showed an increased proliferative index after chemotherapy, and the remainder showed a decrease (n = 12) or no significant change (n = 5). CONCLUSIONS: Our results did not suggest an increase in proliferation of tumor cells after this type of chemotherapy in the majority of patients with ovarian cancer.

Antineoplastic Agents↗

How important is removal of the parametrium at surgery for carcinoma of the cervix?

OBJECTIVES: The aims of this study were (1) to determine the incidence and factors predictive for pathologic parametrial involvement in clinical stage IA1/2 and IB1 cervical cancer after radical surgery and (2) to identify a population at low risk for pathologic parametrial involvement. METHODS: All patient information was collected prospectively and extracted from a cervical cancer radical surgery database. Selection criteria for surgery were generally based upon tumor size, with the cutoff for surgery between 3 and 4 cm. Parametrial involvement (PI) was defined as either positive parametrial lymph nodes (PMLN) or malignant cells in the parametrial tissue (PT) (including lymphovascular channels) by either contiguous or discontiguous spread. Statistical analysis included the chi2 test, the Wilcoxon rank test, and the Mantel-Haentzel test. RESULTS: Between July 1984 and January 2000, 842 patients underwent radical surgery for clinical stage IA1/2 and IB1 cervical cancer at our center. Forty-nine patients (6%) had positive pelvic lymph nodes. Thirty-three patients (4%) had pathologic PI, 8 in the PMLN and 25 in the PT (none had both). PI was associated with older age (42 vs 40 years, P < 0.04), larger tumor size (2.2 vs 1.8 cm, P < 0.04), higher incidence of capillary-lymphatic space invasion (85% vs 45%, P = 0.0004), tumor grades 2 and 3 (95% vs 65%, P = 0.001), greater depth of invasion (18.0 vs 5.0 mm, P < 0.001), and pelvic lymph node metastases (44% vs 5%, P < 0.0001). The incidence of PI in patients with tumor size < or =2 cm, negative pelvic lymph nodes, and depth of invasion < or =10 mm was 0.6%. CONCLUSION: Pathologic parametrial involvement in clinical stage IA1/2 and /IB1 cervical cancer is uncommon. Acknowledging that almost all patients with pelvic lymph node metastases and a high proportion of patients with tumor invasion >10 mm will receive adjuvant radiation regardless of the radicality of surgery, a population at low risk for pathologic parametrial involvement can be identified. These patients are worthy of consideration for studies of less radical surgery performed in conjunction with pelvic lymphadenectomy.

Adult↗

Changes in the demographics and perioperative care of stage IA(2)/IB(1) cervical cancer over the past 16 years.

OBJECTIVES: The aim of this study was to determine whether there have been any significant changes in the demographics and perioperative care of FIGO stage IA(2)/IB(1) cervical cancer over the past 16 years and, if so, to quantify them. METHODS: Since July 1984, all patients with FIGO stage IA(2)/IB(1) cervical cancer undergoing radical surgery by members of our division have been entered into a prospective database. Selection for surgery has been unchanged over the past 16 years. Since March 1994 and November 1996, one surgeon has performed radical vaginal trachelectomy and laparoscopic assisted radical vaginal hysterectomy, respectively. Statistical analysis used Spearman's correlation analysis, the proportional hazards regression model of Cox, and the Mantel-Hanzel test was performed. Due to the number of statistical analyses, statistical significance was defined as P < 0.01. RESULTS: Eight hundred sixty-four patients have undergone radical surgery (784 radical hysterectomy, 42 radical vaginal trachelectomy, 32 radical vaginal hysterectomy, 6 radical abdominal trachelectomy) for FIGO stage IA(2)/IB(1) carcinoma of the cervix by members of our division since 1984. There have been no changes in the median age (40 years), tumor size (2.0 cm), incidence of capillary lymphatic space involvement (47%), or positive pelvic lymph nodes (6%) over the past 16 years. The median Quetelet index (24.6), depth of tumor invasion (squamous cell carcinomas only) (6.0 mm), and proportion of patients with comorbid conditions (17%) have increased over time (P = 0.001, P = 0.003, and P < 0.001, respectively). Pathologically, there has been an increase in the proportion of adenocarcinomas (28%) and a decrease in the proportion of grade 3 tumors (28%) (P < 0.001 and P < 0.001, respectively). The median operating time (2.8 h), hospital stay (7.0 days), blood loss (600 cc), allogeneic blood transfusion (23%), postoperative infections (13%), and noninfectious complications (6%) have all decreased (P < 0.001, P < 0.001, P < 0.001, P < 0.001, P < 0.001, and P = 0.002, respectively). There has been no change in the incidence of positive surgical margins (3%), adjuvant radiation (13%), or recurrence-free survival (2 and 5 years, 94 and 90%, respectively) after a median follow-up of 45 months. CONCLUSION: Despite no substantive changes in the selection criteria for surgery and the small time interval studied (16 years), almost all indices of operative and postoperative morbidity analyzed have decreased significantly. These changes have occurred without an increase in the use of adjuvant radiation or decrease in recurrence-free survival. Although little progress has been made in the cure rates associated with surgical management of FIGO stage IA(2)/IB(1) cervical cancer during this time interval, it appears that the morbidity of surgery has decreased.

Adenocarcinoma↗

Intratumoral sickling in a patient with cervix cancer and sickle trait: effect on blood flow and oxygenation.

BACKGROUND: Sickle trait affects approximately 8% of the black population in the United States and up to 40% of individuals in some parts of tropical Africa, but rarely causes clinically significant illness. This report provides the first conclusive evidence that erythrocytes in patients with sickle trait may sickle in the microvasculature of solid tumors, leading to impaired perfusion and hypoxia. CASE: A black woman who was sickle trait positive presented with stage IIIB squamous cell carcinoma of the cervix. A biopsy showed extensive intravascular sickling of erythrocytes. An aspirate of blood obtained directly from the tumor also showed numerous sickled cells. A peripheral blood smear was normal. Direct measurement of oxygen tension using the Eppendorf electrode revealed the tumor to be markedly hypoxic, with 93% of a total of 142 individual oxygen reading <5 mm Hg. CONCLUSIONS: Erythrocytes in patients with sickle trait may sickle in the microvasculature of solid tumors and contribute to reduced blood flow and the development of hypoxia. Hypoxia is a strong independent prognostic factor in patients with cervix cancer, and further study is needed to evaluate the impact of intratumoral sickling on long-term outcome.

Blood Flow Velocity↗

p53 Alteration and chromosomal instability in prostatic high-grade intraepithelial neoplasia and concurrent carcinoma: analysis by immunohistochemistry, interphase in situ hybridization, and sequencing of laser-captured microdissected specimens.

p53 mutation has been shown to be associated with chromosomal instability (CI) in many human dysplastic and neoplastic lesions. However, the precise role of p53 in the pathogenesis of prostate carcinoma (Pca) is unknown. Topographic analysis of p53 alteration using immunohistochemistry (IHC) was performed on 35 archived prostatectomy specimens containing Pca foci; high-grade prostate intraepithelial neoplasia (HPIN) foci intermingled with cancer (HPINI) and situated away (HPINA). Specimens from 2 patients were topographically genotyped using laser capture microdissection, PCR amplification, and direct sequencing of p53 exons 5-9. CI was evaluated in the same tissue foci by interphase in situ hybridization (IFISH) using centromere probes for chromosomes 7, 8, and Y. p53 immunoreactivity was found in 20%, 17%, 0, and 0 in Pca, HPINI, HPINA, and benign epithelium, respectively. p53 molecular analysis in the specimens examined confirmed the IHC findings. IFISH revealed numerical chromosomal alterations in keeping with CI in 71% and 25% of p53+ and p53- Pca, respectively (P =.1), 67% and 0 of p53+ and p53- HPIN, respectively (P <.02), and in 27% and 0 of HPINI and HPINA, respectively. We concluded that p53 mutation is an early change in at least a subset of Pca. HPINI foci tend to have higher overall p53 immunoreactivity and CI than HPINA. The presence of p53 mutation in HPIN was associated with the presence of CI as determined by IFISH. Our study also provided additional evidence in support of the concept that HPIN might be the earliest precursor of cancer. Furthermore, our studies identify genomic similarities in HPINI and Pca, implying that carcinoma may arise from progression of certain HPIN foci that most likely harbor p53 mutation and/or more CI.

Aneuploidy↗

Attenuation and activation characteristics of steel and tungsten and the suitability of these materials for use in a fast neutron multileaf collimator.

A computer controlled multileaf collimator (MLC) is being designed to replace the multirod collimator (MRC) at present used to shape the d(48.5) + Be neutron beam from the Harper Hospital superconducting cyclotron. The computer controlled MLC will improve efficiency and allow for the future development of intensity modulated radiation therapy with neutrons. The existing MRC uses tungsten rods, while the new MLC will use steel as the leaf material. In the current study the attenuation and activation characteristics of steel are compared with those of tungsten to ensure that (a) the attenuation achieved in the MLC is at least equivalent to that of the existing MRC, and (b) that the activation of the steel will not result in a significant change in the activation levels within the treatment room. The latter point is important since personnel exposure (particularly to the radiation therapy technologists) from induced radioactivity must be minimized. Measurement of the neutron beam attenuation in a broad beam geometry showed that a 30 cm thick steel leaf yielded 2.5% transmission. This compared favorably with the 4% transmission obtained with the existing MRC. Irradiation of steel and tungsten samples at different depths in a 30 cm steel block indicated that the activation of steel should be no worse than that of tungsten.

Biophysical Phenomena↗

Endometrial evaluation with transvaginal US and hysterosonography in asymptomatic postmenopausal women with breast cancer receiving tamoxifen.

PURPOSE: To determine performance characteristics of transvaginal ultrasonography (US) and hysterosonography for diagnosing endometrial abnormality in asymptomatic postmenopausal women with breast cancer receiving tamoxifen. MATERIALS AND METHODS: The authors prospectively examined 138 women receiving tamoxifen by using transvaginal US, hysterosonography, and office hysteroscopy. The combined hysteroscopic-histopathologic diagnosis was the reference standard. Sensitivity, specificity, positive and negative predictive values, and likelihood ratios of transvaginal US and hysterosonography were calculated. RESULTS: All 138 women underwent transvaginal US; 104, successful hysterosonography; and 117, successful hysteroscopy. Uterine abnormality was present in 47 (40.2%) of 117 women: 45 with polyps and two with submucosal fibroids. Receiver operating characteristic curve analysis revealed 6 mm to be the optimal endometrial thickness cutoff for diagnosing endometrial abnormalities. When a thickness greater than 6 mm or a focal endometrial finding was considered abnormal, transvaginal US had a sensitivity of 85.1% and a specificity of 55.7%. In 92 women who completed transvaginal US, hysterosonography, and hysteroscopy, hysterosonography was more specific (79.2%; P =.008) but not significantly more sensitive (89.7%; P =.508) than transvaginal US. When women with abnormal transvaginal US findings were further examined with hysterosonography, the sequential combination of transvaginal US and hysterosonography was more specific (77.1%) than transvaginal US alone (P <.001), without a significant decrease in sensitivity (78.7%; P =.25). CONCLUSION: In asymptomatic postmenopausal women receiving tamoxifen, 6 mm is the optimal endometrial thickness cutoff for diagnosing endometrial abnormalities with transvaginal US. Further examination with hysterosonography can improve specificity by reducing the high false-positive rate of transvaginal US.

Antineoplastic Agents, Hormonal↗

Comparison of human papillomavirus DNA testing and repeat Papanicolaou test in women with low-grade cervical cytologic abnormalities: a randomized trial. HPV Effectiveness in Lowgrade Paps (HELP) Study No. 1 Group.

BACKGROUND: Results of cervical cytology screening showing atypical squamous cells of undetermined significance (ASCUS) or low-grade squamous intraepithelial lesions (LSIL) indicate risk for high-grade cervical intraepithelial neoplasia (CIN 2 or 3). In a community-based randomized trial we compared the test performance of human papillomavirus (HPV) DNA testing with that of 6-month repeat Papanicolaou (Pap) test in detecting histologically confirmed CIN 2 or 3. METHODS: We randomly assigned 212 women aged 16-50 years with ASCUS or LSIL on cervical cytology screening to undergo either immediate HPV DNA testing or a repeat Pap test in 6 months. Cervical swabs for the HPV DNA testing and the Pap smears were obtained by their family physicians. We tested the swabs for oncogenic HPV using the Hybrid Capture II assay (Digene Corp., Beltsville, Md.). Community-based pathologists examined the Pap smears. All women were referred for colposcopy by their family physicians. Two gynecological pathologists assessed the histology findings. We calculated test performance in women who completed the trial using CIN 2 or 3 as the reference standard. RESULTS: A total of 159 women completed the study. Compared with HPV DNA testing, which detected 87.5% (7/8) of the cases of CIN 2 or 3, repeat Pap smear showing high-grade intraepithelial neoplasia (HSIL) detected 11.1% (1/9) of cases (p = 0.004), and repeat Pap smear showing ASCUS, LSIL or HSIL detected 55.6% (5/9) (p = 0.16). Corresponding specificities were 50.6%, 95.2% (p = 0.002) and 55.6% (p = 0.61). Loss to follow-up was 17.1% in the HPV test group and 32.7% in the repeat Pap group (p = 0.009). Given the 7 cases of CIN 2 or 3 detected by HPV testing and the 5 cases detected by the repeat Pap smear, the incremental cost of HPV testing was calculated to be $3003 per additional case of CIN identified. INTERPRETATION: HPV DNA testing was more costly but was associated with significantly less loss to follow-up. It may detect more cases of CIN 2 or 3 in women with low-grade cytologic abnormalities.

Adolescent↗

Comparison of self-collected vaginal, vulvar and urine samples with physician-collected cervical samples for human papillomavirus testing to detect high-grade squamous intraepithelial lesions.

BACKGROUND: Certain types of human papillomavirus (HPV) in cervical samples are strongly associated with squamous intraepithelial lesions (SIL) and invasive cervical carcinoma. We determined and compared the test characteristics of testing for HPV with samples obtained by patients and with samples obtained by their physicians. METHODS: In a consecutive series of women referred to a colposcopy clinic at a teaching hospital because of abnormalities on cervical cytologic screening, 200 agreed to collect vulvar, vaginal and urine samples for HPV testing. The physician then collected cervical samples for HPV testing, and colposcopy, with biopsy as indicated, was performed. Presence of HPV was evaluated using the hybrid capture II assay (Digene Corp., Silver Spring, Md.) with a probe cocktail for 13 carcinogenic types. Cervical specimens were also tested for HPV by polymerase chain reaction and hybridization with type-specific probes. Cervical smears for cytologic examination were obtained from all women. RESULTS: High-grade lesions (high-grade squamous intraepithelial lesions [HSIL], equivalent to cervical intraepithelial neoplasia [CIN] grade 2 or 3, and adenocarcinoma) were found in 58 (29.0%) of the 200 women. Carcinogenic types of HPV were detected in the self-collected vaginal samples of 50 (86.2%) of these 58 women, in the self-collected vulvar samples of 36 (62.1%) and in the self-collected urine samples of 26 (44.8%). Carcinogenic types of HPV were detected in the cervical samples collected by physicians for 57 (98.3%) of these 58 women. The remaining 142 women (71.0%) had normal findings or low-grade squamous intraepithelial lesions (LSIL, CIN grade 1). Test results were negative or noncarcinogenic types of HPV were detected in the self-collected vaginal samples of 76 (53.5%) of these 142 women, in the self-collected vulvar samples of 89 (62.7%) and in the self-collected urine samples of 99 (69.7%). The sensitivity for self-collected samples ranged from 44.8% to 86.2%, and the specificity from 53.5% to 69.7%. For the samples collected by physicians, the sensitivity was 98.3% and the specificity 52.1%. The self-sampling methods were generally acceptable to the women: 98.4% of respondents (126/128) deemed urine sampling acceptable, 92.9% (118/127) found vulvar sampling acceptable, and 88.2% (112/127) found vaginal sampling acceptable. INTERPRETATION: Self-collection of samples for HPV testing was acceptable to women attending a colposcopy clinic for investigation of suspected cervical lesions and shows sufficient sensitivity to warrant further evaluation as a screening test for cervical cancer prevention programs.

Adenocarcinoma↗

Combined preoperative chemotherapy and radiation for locally advanced rectal carcinoma.

To determine the efficacy of combined preoperative chemotherapy and radiation therapy for locally advanced rectal carcinoma and the rate of sphincter conservation, a retrospective survey of 39 patients with locally advanced rectal carcinoma treated with various 5-fluorouracil- and leukovorin-based chemotherapy regimens and radiation prior to surgery in a single institution was reviewed. Toxicity, local control and survival were evaluated and compared to previous studies with similarly staged patients. Long-term follow-up was available on 35 patients. The actuarial local failure was 5.7% while the actuarial 5-year survival was 87%. The mortality rate was low (2.5%) and the rate of long-term serious complications acceptable (11.4%). Combined preoperative chemotherapy and radiation provided excellent local regional control despite the poor prognostic factors associated with size, fixation, and the initial advanced tumor stage with acceptable morbidity. In addition, patients with tumors located in the lower third of the rectum may be able to undergo sphincter-sparing surgery. Although the median follow-up is relatively short (32.4 months), the results are in accordance with previous studies of neoadjuvant combined chemotherapy and radiation for locally advanced rectal carcinoma in terms of local and distant control.

Anal Canal↗

Treatment of early epithelial ovarian cancer with chemotherapy and abdominopelvic radiotherapy: results of a prospective treatment protocol.

PURPOSE: To test the hypothesis that the combination of adjuvant chemotherapy and abdominopelvic radiation (APRT) improves the outcome of patients with early ovarian cancer compared to treatment with APRT alone. METHODS AND MATERIALS: Between 1991 and 1994, 93 patients with Stage I to III, optimally cytoreduced, invasive, epithelial ovarian cancer were treated with sequential chemotherapy and APRT. Treatment was assigned using a prognostic classification that was derived from previous cohorts of patients. Low-risk patients (n = 9) received APRT alone, intermediate-risk patients (n = 66) received two courses of cisplatin followed by APRT, and high-risk patients (n = 18) received 6 courses of cisplatin and cyclophosphamide followed by APRT. RESULTS: Disease recurred in 22 patients, and was confined to the pelvis or abdomen in 15. Nine patients died and the remainder were alive with disease after receiving salvage chemotherapy. The 3-year disease-free and overall survivals were 78% and 91%, respectively. The prognostic classification used to assign treatment was the only factor that predicted disease-free survival (83% and 59% at 3 years for low/intermediate- and high-risk patients, respectively; p = 0.03). There was no detectable difference in outcome between the present series and an historical control group treated with APRT alone. Treatment was well tolerated and only 2 patients (2.5%) developed serious complications. CONCLUSION: APRT is an effective adjuvant treatment for carefully selected patients with early ovarian cancer. The addition of chemotherapy as used in this study to APRT does not significantly improve outcome compared to APRT alone.

Adult↗

Radiotherapy for the treatment of metastatic granulosa cell tumor in the mediastinum: a case report.

OBJECTIVE: We report a case of metastatic ovarian granulosa cell tumor in the mediastinum with a 2-year disease-free interval after treatment with radiotherapy and review the literature regarding the use of radiotherapy in recurrent and metastatic granulosa cell tumor. METHODS: The patient's medical records, histological slides, and radiological films were reviewed. The pertinent references were obtained using a Medline search and cross-references. RESULTS: A patient with Stage 1A granulosa cell tumor developed a recurrence in the retroperitoneum 10 years after initial surgery. She was treated with chemotherapy followed by surgical resection. She subsequently developed metastatic tumor in the mediastinum which responded completely to radiotherapy. She has remained disease free for 2 years since the completion of radiotherapy. CONCLUSION: Radiotherapy is a treatment option that should be considered in localized recurrent or metastatic granulosa cell tumor that is not amenable to surgery as it can potentially control the disease for several years.

Adult↗

Prognostic factors for relapse and pelvic lymph node metastases in early stage I adenocarcinoma of the cervix.

OBJECTIVES: The aim of this study was to assess the prognostic significance of local tumor factors in predicting lymph node metastases and/or recurrence in early adenocarcinoma of the cervix. METHODS: Patients were selected from the prospective computerized cervical cancer database of the division of gynecologic oncology. All patients had radical surgery and pelvic lymph node dissection. The study population consisted of all patients with stage I adenocarcinoma having tumor thickness <10 mm. Pathology was re-reviewed to assess histological subtype, depth, volume, grade, and presence of capillary lymphatic space involvement. RESULTS: The study group consisted of 68 patients, with a mean age of 40 years. The median follow-up was 40 months (range 8-102 months). The median tumor depth and volume were 2.8 mm (range 0.3-8.0 mm) and 237 mm(3) (range 0.1-7996 mm(3)), respectively. Twenty-two patients had tumor volumes greater than 600 mm(3), and of these, 5 (23%) patients either had positive pelvic lymph nodes (2) or developed recurrent disease (3) (none node positive) at a median time of 49 months. In comparison, 46 patients (68%) had tumor volumes of less than 600 mm(3), none of whom had positive pelvic lymph nodes or developed recurrence (P<0.005). Only 1 of 20 patients with a depth of invasion <2 mm had a tumor volume >600 mm(3) in comparison to 21 of 48 patients with deeper invasion (P<0.002). CONCLUSION: The incidence of positive pelvic lymph nodes and/or recurrence in this patient population is very low. As all patients with metastatic disease or recurrence had tumor volumes >600 mm(3), volume of disease rather than depth of invasion may be the single most important prognostic factor for the above events. However, many more patients will have to be studied to confirm this.

Adenocarcinoma↗

Tumour proliferation and apoptosis in human uterine cervix carcinoma II: correlations with clinical outcome.

PURPOSE: The prognostic value of tumour proliferation and apoptosis measurements were studied prospectively in patients with carcinoma of the uterine cervix, relative to other established clinical factors. MATERIALS AND METHODS: The labelling index (LI) for bromodeoxyuridine was determined by flow cytometry (fc) and also by immunohistochemistry. Apoptosis was assessed histologically using morphological criteria. Patients were treated with radical radiation therapy (RT). RESULTS: The median/mean LI-fc were 6.7%/7.9% (range 1.52-3.9%). The median/mean apoptosis index (AI) were 1.0%/1.6% (range 0-6.8%). To date, 27 patients have died of disease, and the median follow-up for alive patients is 3.2 years (range 0.4-6.0 years). Among 64 patients who completely responded to treatment, 25 patients have relapsed (six pelvic, 17 distant and two pelvic and distant). In univariate analysis, the most significant factors for disease-free survival (DFS) were large tumour size (P=0.0001), low haemoglobin (P=0.01 ), LI-fc (DFS 67% for LI < 7%, 33% for LI > or = 7%, P=0.03), and T(pot) (DFS 66% for T(pot) > 5 days, 35% for T(pot) < or = 5 days, P=0.04) Stage, overall treatment time (OTT), S-phase fraction, ploidy, T(s), LI by histology, mitotic index, and AI were not significant. Multivariate analysis (Cox's model) showed that the only significant prognostic factors for DFS were tumour size and OTT. However, for small tumours (diameter < 6 cm), either a high LI-fc ( > or = 7%) or a high AI ( > 1%) was associated with poorer DFS, whereas patients with larger tumours (diameter > or = 6 cm) fared poorly regardless of LI-fc and AI. CONCLUSIONS: Tumour size was the most important prognostic factor in cervix carcinoma. Although none of the biologic parameters have independent prognostic significance when the effect of initial tumour size was taken into account, our data suggests that LI and AI may be useful in discriminating outcome for patients with smaller tumours when managed by radical RT. These findings support the hypothesis that rapidly proliferating tumours are less likely to be controlled with a conventional course of RT.

Analysis of Variance↗