A retrospective review on atypical glandular cells of undetermined significance (AGUS) using the Bethesda 2001 classification

OBJECTIVE: The Bethesda system for reporting cervicovaginal cytologic diagnoses was recently revised in 2001. Pathologists are required to report not only whether the smear favors neoplastic changes, but also the origin of the abnormal cells. In this study, archival smears were reviewed to evaluate the usefulness of the new classification. METHODS: Smears having atypical glandular cells taken between January 1995 and December 1997 were reviewed and subclassified according to the revised Bethesda classification. Case records were then reviewed and cases with discrepancies between the cytological evaluation and corresponding final histological diagnoses were further reviewed. RESULTS: There were 138 smears reviewed. The mean age of the patients was 47 (range, 18 to 78). Thirty-four smears favored neoplasia and 104 favored "NOS" ("not otherwise specified"). Sixty smears favored endocervical origin and 78 endometrial origin. Forty-three patients (31%) had significant pathologies, including 12 (8.7%) patients with high-grade CIN, 2 (1.4%) with low-grade CIN, 5 (3.6%) with HPV infection, 7 (5.1%) with carcinoma of the corpus, 1 (0.7%) with cervical adenocarcinoma in situ, 4 (2.9%) with adenocarcinoma of the cervix, 3 (2.2%) with endometrial hyperplasia, and 5 (3.6%) with carcinoma of the ovary. Two (1.4%) patients had double primary female genital malignancies and 2 patients (1.4%) had extragenital malignancies. Significant correlation was found between smears "favor neoplasia" and a final diagnosis with significant pathology (chi(2) test, P < 0.05). Significant association was found between AGC favored endocervical origin and a final diagnosis with cervical diseases (chi(2) test, P < 0.05). Four of the 43 patients who had significant pathologies had lesions found during their subsequent visits and all of them had cervical smears classified as AGC "favor neoplasia". CONCLUSION: AGC found on cervical smears are an indication for early and intensive investigation.     

Quality of life in women treated with neoadjuvant chemotherapy for advanced ovarian cancer: a prospective longitudinal study

OBJECTIVE: The purpose was to examine the outcomes of patients with advanced ovarian cancer treated with neoadjuvant chemotherapy, with a special emphasis on the patients' quality of life (QOL). METHODS: Seventeen patients with advanced ovarian cancer were treated with neoadjuvant chemotherapy based on the extent of disease on computer tomography. All patients received combined platinum/paclitaxel chemotherapy. Debulking surgery was performed after three cycles or six cycles of chemotherapy, depending on the response to the chemotherapy. Patients' QOL was studied over time using European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30 and was then compared with that of patients treated with conventional treatment in the previous cohort. RESULTS: The response rate to chemotherapy assessed at three cycles was 82.4%. The rate of optimum debulking to residual disease less than 2 cm after chemotherapy was 76.9%, and 38.5% had no gross residual disease after surgery. The median overall survival was 22.9 months. The median disease-free interval was 13.3 months. The overall QOL improved after chemotherapy and this continued to improve up to 12 months. The other functional scales also showed improvements over time, apart from the initial transient deterioration in the role functioning and cognitive functioning at 3 months after chemotherapy. Patients treated with neoadjuvant chemotherapy seem to have better but statistically insignificant difference in QOL parameters than patients treated conventionally. CONCLUSION: Neoadjuvant chemotherapy is an alternative treatment for patients with advanced ovarian cancer in whom the chance of optimal cytoreduction is low. The patients' overall quality of life and functional status improve after neoadjuvant chemotherapy.     

Coexisting epithelioid trophoblastic tumor and choriocarcinoma of the uterus following a chemoresistant hydatidiform mole

The epithelioid trophoblastic tumor is an unusual type of trophoblastic tumor. Herein, we describe a patient with coexisting epithelioid trophoblastic tumor and choriocarcinoma in the uterus. The patient had a history of hydatidiform mole with recurrent elevation of human chorionic gonadotrophin level that is resistant to chemotherapy. Histopathologic and immunohistochemical examination showed distinctive differences between the 2 trophoblastic tumors. The development of epithelioid trophoblastic tumor may be related to the persistence of locally invasive disease, which was unresponsive to chemotherapy. The patient responded well to surgery. The presence of an epithelioid trophoblastic tumor should be considered in chemoresistant gestational trophoblast tumor.     

Cluster significance testing using the bootstrap

Many of the statistical methods currently employed to analyze fMRI data depend on a response template. However, the true form of the hemodynamic response, and thereby the response template, is often unknown. Consequently, cluster analysis provides a complementary, template-free method for exploratory analysis of multidimensional fMRI data sets. Clustering algorithms currently being applied to fMRI data separate the data into a predefined number of clusters (k). A poor choice of k will result in erroneously partitioning well-defined clusters. Although several clustering algorithms have been successfully applied to fMRI data, techniques for statistically testing cluster separation are still lacking. To address this problem we suggest a method based on Fisher's linear discriminant and the bootstrap. Also introduced in this paper is a measure based on the projection of multidimensional data from two clusters onto the vector, maximizing the ratio of the between- to the within-cluster sums of squares. The resulting one-dimensional distribution may be readily visualized and used as a heuristic for estimating cluster homogeneity. These methods are demonstrated for the self-organizing maps clustering algorithm when applied to event-related fMRI data.     

Dose-Tumor Response for Carcinoma of Cervix: An Analysis of 594 Patients Treated by Radiotherapy

This is a retrospective study of 594 histologically proven carcinomas of the uterine cervix treated with radiotherapy alone between January 1970 and December 1986. The age of this group of patients ranged from 22 to 86 years, and the median age was 57 years. There were 544 (91.6%) patients with squamous carcinoma and 36 (6.1%) with adenocarcinoma. There were 24 (4.0%) patients who were treated by two sessions of intracavitary brachytherapy only using intrauterine tandem and vaginal ovoids; 513 (86.4%) patients received whole pelvis irradiation followed by two sessions of brachytherapy at 1-week intervals, with or without additional boost to the parametrium. The dose to point A ranged from 40 to 100.9 Gy for the patients with stage IB to IIIB disease. The 5- and 10-year survival for stages IB, IIA, IIB, IIIA, and IIIB were 90.0, 82.1, 72.0, 50.0, 51.5, and 86.9, 71.0, 67.5, 41.7, and 46.9%, respectively. There was no long-term survivor for stage IV disease; the median survivals for patients with stages IVA and IVB were 15.2 and 9.3 months, respectively. Dose response was demonstrated for stages IIB and III tumors; dose to point A greater than 85 Gy was associated with better central control (P = 0.0036 and 0.0234, respectively). However, further increase in dose to point A beyond 85 Gy was not associated with improvement in central control (P = 0.3128 and 0.3394, respectively, for stages IIB and III). It was also found that the occurrences of rectosigmoid and bladder complications were correlated with the rectal and point A dose. Thus, for these patients, there is no need to increase the dose to point A beyond 85 Gy so that the risk of radiation sequelae can be cut down.     

Circulating Epstein-Barr virus DNA in serum of patients with lymphoepithelioma-like carcinoma of the lung: a potential surrogate marker for monitoring disease.

PURPOSE: The purpose of this work was to study the sera of patients with lymphoepithelioma-like carcinoma (LELC) of the lung for circulating EBV DNA. EXPERIMENTAL DESIGN: Prospectively collected serum samples from five female patients with advanced, inoperable LELC of the lung were measured for free circulating EBV DNA using a quantitative PCR technique. EBV-encoded small RNA (EBER)-1 was assayed in serial serum samples of three of the five patients, either from the start or during the initial phase of chemotherapy/radiotherapy until their terminal event or last follow-up. There was only a single-point sample for analysis in the fourth and fifth patients. Six other patients with LELC of the lung were also retrospectively identified, and their sera were tested for EBER-1 at either the first visit plus the last follow-up visit (n = 2), the first visit only (n = 2), or the last follow-up visit only (n = 2). RESULTS: Prospectively collected serum samples from five patients and retrospectively collected serum samples from two patients who had clinical disease at initial serum measurement showed detectable levels of EBER-1. Retrospectively collected serum samples from four patients with no clinical disease had negative sera. There is consistent correlation between the clinical response to treatment and subsequent clinical course of LELC and serum EBER-1 levels in the three prospective patients with longitudinal serum monitoring. CONCLUSIONS: This study shows for the first time that free EBV DNA can be detected in the serum of patients with LELC of the lung and further suggests the feasibility of its use for monitoring response to therapy in advanced cases.     

Concurrent chemotherapy-radiotherapy compared with radiotherapy alone in locoregionally advanced nasopharyngeal carcinoma: progression-free survival analysis of a phase III randomized trial.

PURPOSE: Nasopharyngeal carcinoma (NPC) is highly sensitive to both radiotherapy (RT) and chemotherapy. This randomized phase III trial compared concurrent cisplatin-RT (CRT) with RT alone in patients with locoregionally advanced NPC. PATIENTS AND METHODS: Patients with Ho's N2 or N3 stage or N1 stage with nodal size > or = 4 cm were randomized to receive cisplatin 40 mg/m(2) weekly up to 8 weeks concurrently with radical RT (CRT) or RT alone. The primary end point was progression-free survival (PFS). RESULTS: Three hundred fifty eligible patients were randomized. Baseline patient characteristics were comparable in both arms. There were significantly more toxicities, including mucositis, myelosuppression, and weight loss in the CRT arm. There were no treatment-related deaths in the CRT arm, and one patient died during treatment in the RT-alone arm. At a median follow-up of 2.71 years, the 2-year PFS was 76% in the CRT arm and 69% in the RT-alone arm (P =.10) with a hazards ratio of 1.367 (95% confidence interval [CI], 0.93 to 2.00). The treatment effect had a significant covariate interaction with tumor stage, and a subgroup analysis demonstrated a highly significant difference in favor of the CRT arm in Ho's stage T3 (P =.0075) with a hazards ratio of 2.328 (95% CI, 1.26 to 4.28). For T3 stage, the time to first distant failure was statistically significantly different in favor of the CRT arm (P =.016). CONCLUSION: Concurrent CRT is well tolerated in patients with advanced NPC in endemic areas. Although PFS was not significantly different between the concurrent CRT arm and the RT-alone arm in the overall comparison, PFS was significantly prolonged in patients with advanced tumor and node stages.     

Placental site trophoblastic tumor: with features between an exaggerated placental site reaction and a placental site trophoblastic tumor

Chorionic villi, whose presence in cases of trophoblastic disease is normally used to exclude both a choriocarcinoma and placental site trophoblastic tumor (PSTT), were present in the initial uterine curettage specimen of a trophoblastic tumor. The lesion shared morphologic features of both an exaggerated placental site reaction and a PSTT. There was infiltration of the posterior wall of the uterus by small clusters and isolated cells which had a prominent affinity for vessels and resembled a usual placental bed reaction. There was, however, deep involvement of myometrium with extension to the cervix, and the condition persisted for 5 months after uterine evacuation. Because different treatment is entailed, identification of this lesion as a tumor of nonvillous trophoblast is also of great importance in a region where the more usual forms of trophoblastic disease represent a declining but not infrequent event. When products of gestation are examined, the possibility of a PSTT should be considered and the clinician alerted if there is a suggestion of excessive intermediate trophoblastic activity, regardless of the presence of chorionic villi. While this may result in the unnecessary followup of some cases, it would permit, with the aid of serial beta-hCG and HPL levels, the earlier detection of PSTTs.     

Serum squamous cell carcinoma antigen in the monitoring of radiotherapy treatment response in carcinoma of the cervix

In this study, squamous cell carcinoma antigen (SCC) was detected in 96 of 157 patients with squamous cell carcinoma of the cervix and the percentage of patients with raised SCC levels increased with the stage of disease (P less than 0.01). The use of serial SCC assays and cervical biopsy histology during the course of radiotherapy to predict tumor response to irradiation was assessed. In patients who were given external irradiation before intracavitary radium, a high SCC level or the presence of viable tumor cells in the biopsy was found to be of no predictive value. However, at completion of radiotherapy, i.e., after intracavitary radium application, patients with persistently high SCC levels had a significantly higher incidence of residual tumor than patients whose SCC levels returned to normal (P less than 0.01). In 60% of patients with a persistently high SCC level, viable tumor was found in the cervical biopsy at the end of radiotherapy. On the other hand, only 5.4% of patients whose SCC level returned to normal had residual tumor.     

Primary treatment with vincristine, dactinomycin, and cyclophosphamide in nondysgerminomatous germ cell tumor of the ovary

Thirty-three patients with malignant nondysgerminomatous germ cell tumors were treated with vincristine/dactinomycin/cyclophosphamide regimen. Thirty-two patients were suitable for analysis. The overall cure rate was 68.7%. This is comparable to the cure rate observed in the cisplatin/vinblastin/bleomycin regimen. The roles of second-look laparotomy in malignant germ cell tumor are discussed.