Tung V. Dinh

Circulating Serum Levels of Cytokines and Angiogenic Factors in Patients with Cervical Cancer

Progression of cervical cancer is associated with excessive circulating levels of cytokines, which are known to be modulators of tumor angiogenesis. The concentrations of cytokines and growth factors were assayed using enzyme-linked immunosorbant assays in the serum of 61 women in various stages of cancer [stage 0 (n = 6), stage I (n = 15), stage II (n = 15), stage III (n = 15), and stage IV (n = 10)] and of 20 healthy control subjects. Our results indicated that b-FGF and TNF-beta levels were significantly elevated in stage I, and serum levels of TGF-beta and IL-7 were elevated in stages II-IV of invasive carcinoma. Our experimental subjects had significantly increased serum levels of IL-6, GM-CSF, and angiogenin in stages I-IV of cervical cancer, and TNF-alpha serum levels were elevated in all stages of invasive carcinoma. The serum levels of IL-8 and IL-10 were elevated only in stages II-III, and the levels of IL-2 were elevated in stages III-IV. The serum levels of IL-1 alpha and IL-1 beta remained unaltered in all stages of cancer progression. Progression of cervical cancer is associated with increased serum levels of angiogenin, IL-2, IL-6, IL-7, IL-8, IL-10, b-FGF TNF-alpha, TGF-beta, TNF-beta, and GM-CSF during different stages, all of which have the potential to be angiogenic amplifiers.

Three-dimensional endothelial-tumor epithelial cell interactions in human cervical cancers

SummaryThe purpose of this study is to understand the multicellular interaction between tumor epithelial (TEC) and human umbilical vein endothelial cells (HUVEC). The development of in vitro systems in which to coculture these cells as multicellular aggregates is very critical. Cell lines were established from cervical tumor cells (n=6) and two from HUVEC (n=2) and they were cultured as three-dimensional (3-D) multicellular-cultures using Cytodex-3 microcarrier beads in the rotating wall vessel (RWV). After a 240-h incubation, TEC and HUVEC proliferated exponentially to 4.2×107 and 2.2 × 107 cells/ml, respectively, without requiring a feeder layer; in contrast to the two-dimensional (2-D) cultures that average about 8 × 106 cells/ml. Phase contrast microscopy indicated formation of 3-D aggregates that varied in size from 0.5 to 5 mm. The size of the aggregates (1–5 mm, 6⊋ash;14 microcarriers) increased over time; however, the number of aggregates (0.5–1 mm, 2–5 microcarriers) decreased over a long-term incubation (240 h) because the cells merged to form large clumps. Maximum aggregation was observed with TEC at 120 h and HUVEC at 96 h. The culture of TEC in the absence of HUVEC produced minimal differentiation in contrast to cocultures. The TEC and HUVEC as cocultures in RWV proliferated at an accelerated rate (1.3 × 107 cells/ml, 96 h). The TEC-HUVEC coculture presented tubular structures penetrating the tumor cell masses, forming aggregates larger in size than the monocultures and typically with greater cell mass and number. The cells were viable (trypan blue exclusion) and metabolically active (glucose utilization) until 240 h. These data suggest that RWV provides a new model that allows us to investigate the regulatory factors that govern tumor angiogenesis.

Necessity of endocervical curettage in colposcopy

The use of endocervical curettage was evaluated in 200 patients undergoing colposcopy, biopsy, endocervical curettage, and conization. It is suggested that endocervical curettage be performed only in cases of satisfactory colposcopy, since patients with unsatisfactory colposcopy should undergo conization.

Human papillomavirus type 16 found in primary transitional cell carcinoma of the Bartholin's gland and in a lymph node metastasis

We report a case of primary transitional cell carcinoma of the Bartholins gland and its lymph node metastasis that contained HPV 16 sequences by polymerase chain reaction. The physical state of HPV 16 DNA in the primary cancer was investigated by Southern blot analysis which showed the presence of the episomal form of viral DNA. Our findings of HPV 16 DNA in the transitional cell carcinoma of the Bartholins gland and its metastasis would indicate that both tumors arose from a single clonal event, thus providing evidence that the HPV 16 may have an oncogenic potential in this rare malignancy even in the episomal state.

Management of cervical intraepithelial neoplasia during pregnancy: a simplified and cost-effective approach.

Objectives To determine the cost-effectiveness of managing an abnormal Papanicolaou (PAP) smear during pregnancy with a single colposcopic exam and biopsies, followed by Pap smears in each subsequent trimester of pregnancy and 8 weeks postpartum. Materials and Methods We reviewed 84 pregnant women with cervical intraepithelial neoplasia (CIN) between 1983 and 1991, testing the accuracy of an initial biopsy and subsequent Pap smears, to follow the progression (or regression) of disease as determined by postpartum biopsy or Pap smears. Results In 26 women with CIN1, 2 (8%) progressed to CIN3. In 29 women with CIN2, 5 (17%) progressed to CIN3. Of 29 patients with CIN3, 20 (69%) remained at CIN3 and 2 (6%) progressed to microinvasive carcinoma postpartum, confirmed by conization. No invasive carcinoma was missed. The cost of colposcopy with biopsies and Pap smear is

Avoiding conization for inadequate colposcopy : Suggestions for conservative therapy

304, whereas cost of a Pap smear only is

CD-ROM versus standard text-based model for gynecologic operative procedures: a randomized controlled trial

30. Conclusions Single colposcopy with biopsies at the beginning of pregnancy and Pap smears during subsequent trimesters and postpartum should be adequate follow-up to prevent progression to invasive cancer and represents a significant cost savings.

Management of patients with positive margins after cervical conization.

OBJECTIVE To determine if conservative treatment can safely be offered to patients with cervical intraepithelial neoplasia (CIN) and inadequate colposcopic examination. STUDY DESIGN We reviewed the charts of 733 evaluable cone biopsies of the cervix performed for CIN at the University of Texas Medical Branch at Galveston from January 1981 to September 1990. RESULTS Of 371 conizations that indicated inadequate colposcopy, there were 62 cases that fulfilled all the following conditions: cytologic smear suggesting CIN 2 or less, negative endocervical curettage (ECC) and cervical colposcopic biopsy showing CIN 2 or less. Pathologic examination of the cone biopsy specimen in these 62 cases revealed no dysplasia in 29.0%, CIN 1 in 16.%, CIN 2 in 37.0%, 3 in 17.7%, and no microinvasive or invasive lesions. Pathologic examination of the cone specimens of 309 patients with any high-risk factor--smear suggesting CIN 3 or invasive disease, colposcopic biopsy showing CIN 3 or positive ECC--revealed no dysplasia in 11.9%, CIN 1 in 11.3%, CIN 2 in 16.8%, CIN 3 in 49.8%, microinvasive carcinoma in 5.5% and frankly invasive carcinoma in 4.5%. CONCLUSION Conservative therapy may be offered to patients with inadequate colposcopy, CIN 1-2 on both biopsy and cytology, and negative ECC without over-looking either invasive or microinvasive carcinoma. With these criteria, 16.7% of patients with an inadequate colposcopy in our study could have avoided cone biopsy.

Clinical and Molecular Responses in High-Grade Intraepithelial Neoplasia Treated with Topical Imiquimod 5%

Abstract Objective: To compare CD-ROM use with the standard text-based model ( TeLinde’s ) in the teaching of common gynecologic operative procedures to residents in the field of obstetrics and gynecology. Methods: In a randomized controlled trial, first-, second- and third-year residents in an obstetrics and gynecology department were randomized to receive either a CD-ROM that contains digitally edited surgical photographs with surgical text or a copy of the chapter of TeLinde’s that correlates with the operative procedure performed. The resident either viewed the CD-ROM or read the text model the evening before the surgery and then filled out a questionnaire afterward. Operations included TAH/BSO, TVH/BSO, cold knife conization, anterior colporrhaphy, perineorrhaphy, and Burch retropubic urethropexy. Helpfulness with indications, pelvic anatomy, understanding of techniques/methods, learning the names and uses of surgical instruments, and completing dictation were assessed in a rating system of 0 (not helpful) to 7 (extremely helpful). Results: During the study period, six residents completed questionnaires in both groups (CD-ROM, text group). The mean differences in resident evaluation of the surgical indications were 2.67 (Mann-Whitney rank sum, P = 0.0022); pelvic anatomy, 3.0 (Mann-Whitney rank sum, P = 0.0065); surgical techniques, 1.83 (Mann-Whitney rank sum, P = 0.0082); knowledge and use of instruments, 3.0 (Mann-Whitney rank sum, P = 0.0022); aid in completing surgical dictations, 3.167 (Mann-Whitney rank sum, P = 0.0022); and overall usefulness: 2.33 (Mann-Whitney rank sum, P = 0.0022). Conclusion: One of the biggest complaints from junior residents has been the lack of good photographs in traditional surgical textbooks. The residents in this study felt that the photographs shown on the CD-ROM better aided their knowledge of the indications, techniques, and surgical anatomy of the aforementioned procedures. We believe that the CD-ROM medium is underused and that it could provide better resident education, especially if combined with the traditional surgical textbook.