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PubMed1994

Conservative therapy for microinvasive carcinoma of the uterine cervix.

The purpose of this study was to evaluate conservative therapy for microinvasive carcinoma (MIC) of the cervix. Large contact Nd-YAG laser conization (laser cone) with contact vaporization using contact probes was performed on 90 cases of MIC and 21 cases of early invasive carcinoma (early IC), with long-term postoperative follow-up for patients at Osaka Medical College, Osaka, Japan. The cure rates of MIC and early IC were 96.7 and 80.9%, respectively. The rates of incomplete excision and true residuation in cases with MIC were 17.8 and 10.0% and those in cases with early IC were 76.2 and 19.0%. Therefore, the spontaneous cure rate following incomplete excision of MIC and early IC was 43.7 and 75.0%. Hysterectomy was performed, for various indications, after cone in 5 patients (5.6%) with MIC, none of the patients with IC of less than 3 mm, 2 (22.2%) of the patients with IC of 3.1 to 5 mm, and 7 patients (87.5%) whose IC was 5.1 mm or more in depth. Combining the data from our department and those in the literature collected an incidence of lymph node metastasis of 0.15% for MIC and of 1.13% of IC of less than 5 mm. In conclusion, conservative therapy is indicated for MIC, and the contact laser cone with contact vaporization is considered to be an excellent therapeutic conservative method.

Adult↗
PubMed1994

Adenoma malignum of the uterine cervix detected by imaging methods in a patient with Peutz-Jeghers syndrome.

Adenoma malignum of the uterine cervix in a 25-year-old Japanese woman with Peutz-Jeghers syndrome (PJS) is described. A cervical multicystic mass was detected by CT scan, sonography, and MR imaging. These imaging findings strongly suggested the presence of adenoma malignum in spite of normal Pap smear, colposcopy, and cervical biopsy reports. Radical hysterectomy, bilateral salpingo-oophorectomy, pelvic lymphadenectomy, and para-aortic lymph node biopsy were performed after confirmation of adenoma malignum by conization. Both ovaries showed multicentric sex cord tumor with annular tubules. She is alive and well with no evidence of disease 23 months after surgery. Imaging methods including sonography, CT scan, and MR imaging may be useful aids in detecting the presence of adenoma malignum, especially in patients with PJS.

Adenoma↗
PubMed1994

Conservative surgical treatment in cervical cancer with 3 to 5 mm stromal invasion in the absence of confluent invasion and lymph-vascular space involvement.

We have previously reported that simple hysterectomy is adequate therapy for microinvasive carcinoma of the cervix with less than 3 mm stromal invasion (Yajima, A., et al, Am. J. Obstet. Gynecol. 135, 685-688, 1979). However, whether it is possible to effectively treat patients with deeper stromal invasion remained in question. A policy for surgical treatment in patients with 3 to 5 mm invasion has not been standardized. Although radical hysterectomy is usually performed, some authors insist that patients with 3 to 5 mm invasion can be safely treated conservatively. Patients treated with conservative surgery should be carefully assessed because cases with confluent invasion or lymph-vascular space invasion have a greater potential for lymph node metastasis and carry a worse prognosis. Conservative treatment in this study was limited to patients with microinvasive carcinoma with 3 to 5 mm invasion, stage IB occult patients (classified by the FIGO 1973 staging system). The patients were preoperatively diagnosed with either carcinoma in situ or microinvasive carcinoma, and treated by conservative surgery (conization, simple hysterectomy, or extended hysterectomy). Twenty-two patients with 3 to 5 mm invasion but without additional risk factors, i.e., confluent invasion or lymph-vascular space involvement, were followed without postoperative radiation therapy. All patients survived except one (who died of an intercurrent disease) and there were no signs of recurrence of serious surgical complications. The present study with stage IB "occ" subjects suggests that conservative therapy rather than radical hysterectomy can be used in a very carefully selected subset of patients, i.e., in cases with 3 to 5 mm microinvasive carcinoma without additional risk factors, such as confluent invasion and lymph-vascular space invasion.

Carcinoma in Situ↗
PubMed1995

Independent clinical factors which correlate with failures in diagnosing early cervical cancer.

Our aim was to identify independent factors that correlated with colposcopically directed biopsy's reliability as a method for diagnosing early cervical cancer. One hundred ninety-one of a total of 2265 patients who had colposcopic examinations because of abnormal Papanicolaou smears were included in this study. These patients had all undergone a hysterectomy after being diagnosed as having cervical intraepithelial neoplasia grade III by colposcopically directed biopsy. By univariate analysis, old age (P = 0.0195), achievement of menopausal status (P = 0.0046), large lesion size (P = 0.0021), and unsatisfactory colposcopy (P = 0.0017) were found to be associated with the nondiagnosis of early cervical cancer. However, multivariate analysis using stepwise logistic regression revealed that large lesion size (P = 0.003) and unsatisfactory colposcopy (P = 0.0008) were the only independent factors that correlated with nondiagnosis. Our findings indicate that in order to reach a clear-cut diagnosis, cases with either unsatisfactory colposcopy or satisfactory colposcopy with large lesions (despite a lack of histologic evidence of invasions) should undergo a diagnostic conization.

Adult↗
PubMed1996

Microinvasive cervical carcinoma and cervical intraepithelial neoplasia: biologic significance and clinical implications of 72-kDa metalloproteinase immunostaining.

OBJECTIVE: The immunohistochemical expression of 72-kDa metalloproteinase was evaluated in cervical intraepithelial neoplasia (CIN) and microinvasive carcinoma, with the aim to define a relationship between 72-kDa metalloproteinase expression and neoplastic invasiveness, useful to identify subsets of intraepithelial lesions with higher risk of progression. MATERIALS AND METHODS: Cervical bioptic samples were obtained consecutively from 54 women who attended our Colposcopic Service from January 1993 to July 1993 because of abnormal pap smear, suspicious for cervical dysplasia and/or human papillomavirus infection. After written consent, 29 women with CIN were included in the study. All women with CIN 3 lesion underwent conization; in 21 women with mild or moderate cervical dysplasia, we did not perform any medical or physical treatment but followed them longitudinally at close interval. After 12 months, the clinical evolution was classified as spontaneous remission, persistence, or progression depending on the absence or presence of lesion and/or HPV infection in colposcopy, histology, and polymerase chain reaction findings. In the study we also included surgical specimens from 10 women with microinvasive squamous carcinoma who underwent primary radical surgery. Seventy-two kilodalton metalloproteinase positivity was immunohistochemically stained on serial sections by using the avidin-biotin complex technique (Vector Laboratories, Burlingame, CA) and expressed as percentage of cells per 10(3) counted neoplastic cells. RESULTS: Cytoplasmatic positive 72-kDa metalloproteinase immunostaining was significantly higher in microinvasive cervical carcinomas than in CIN lesion (Student's t test; P < 0.001). Considering only cervical intraepithelial neoplasias, a significant increase in 72-kDa metalloproteinase immunostaining was observed with CIN degree increasing (one-way analysis of variance; P = 0.002). No correlation was found between 72-kDa metalloproteinase immunostaining and HPV infection and lesion size defined by quadrants of the cervix involved with colposcopically evident dysplasia. By analyzing 72-kDa metalloproteinase positivity, regressive dysplasia showed low values of 72-kDa metalloproteinase immunostaining (median 1.2%, range 0.5-1.8%), while persistent (median 2.6%, range 1.9-3.6%) and progressive lesions (median 4.6%, range 2.3-6.9%) presented a significantly higher positivity (one-way analysis of variance; P < 0.001). DISCUSSION: In conclusion, the 72-kDa metalloproteinase expression is related to invasive potential with a significant increase in staining positivity in microinvasive carcinomas; 72-kDa metalloproteinase is detectable in cervical dysplasia, and it is related to the severity of cellular atypia. A clinical implication of 72-kDa metalloproteinase immunostaining seems to be indicated, by analyzing the differences in 72-kDa metalloproteinase positivity rates between regressive and persistent or progressive disease.

Adult↗
PubMed1997

Villoglandular adenocarcinoma of the cervix: a report of three cases and review of the literature.

Villoglandular adenocarcinoma of the cervix is a distinct histologic type of cervical cancer. Fewer than 60 cases have been reported in the literature. Previous reports suggest that, due to the highly favorable prognosis of this rare histologic type of cervical cancer, conservative surgical therapy with cervical conization or extrafascial hysterectomy alone may be undertaken. In this series, three cases of villoglandular adenocarcinoma of the cervix are described. Preoperatively in each case, the cancer was confined to the cervix and histologic well-differentiated villoglandular adenocarcinoma of the cervix was confirmed. Extended hysterectomy was performed in all cases. In one case, residual invasive endocervical adenocarcinoma was noted. Careful review of the histologic characteristics of these tumors is needed when deciding if these patients can be managed with conservative therapy.

Adenocarcinoma↗
PubMed1997

The value of repeat Pap smear at the time of initial colposcopy.

OBJECTIVE: The objective was to determine if repeating a Pap smear at the time of an initial colposcopy has sufficient clinical benefit to justify its clinical and financial costs. METHODS: The records were reviewed of all patients who had an initial colposcopy at Queens Hospital Center between 1984 and 1995. Data were gathered regarding the referral cytology, the cytology done at the time of colposcopy, and the results of any biopsies which were taken. The terminology for cytology and histology done prior to 1989 was adjusted to the Bethesda classification system. A repeat Pap smear was defined as clinically valuable if it would have changed the patient's management, i.e., if it suggested more advanced disease than the referral Pap and that the disease was not identified on the colposcopically directed biopsy. RESULTS: Two thousand nine hundred sixty-nine records were reviewed. In 139 cases, no Pap smear was repeated at the time of colposcopy. Of the remaining 2830 women, only 1347 (47.6%) showed exact correlation between their referral Pap smear and the Pap done at the time of colposcopy. In another 1016 (35.9%), the Pap at colposcopy was within one grade of the referral Pap. In 312 women, the Pap at the time of colposcopy was a higher grade than the referral Pap. However, in 236, the higher grade of disease was detected by the colposcopically directed biopsy. Of the remaining 76 women, 58 had a normal biopsy, but their Pap at the time of colposcopy showed low-grade squamous intraepithelial lesions (44) or high-grade squamous intraepithelial lesions (HGSIL) (14). Seventeen others had a biopsy showing low-grade dysplasia while the Pap at the time of colposcopy showed HGSIL. In 1 patient, the repeat Pap showed malignant cells while the biopsy showed a high-grade lesion. Based on the triage protocols at our institution, this means that a repeat Pap at the time of colposcopy would have indicated a cone biopsy in 31 patients (1.1%) and more careful follow-up of another 44 patients (1.6%). Skipping the repeat Pap smear would not have resulted in any missed cancers. In our series of 2830 patients, the cost savings of skipping the repeat smear would have been $68,580 or $24.23 per patient. On a national level, skipping the repeat smear would save more than $24,000,000 annually. CONCLUSION: Using current triage protocols at our institution, repeating the Pap smear at the time of an initial colposcopy would have changed the management in 2.7% of patients and indicated a conization in only 1.1% of patients. It is doubtful that this justifies its cost and the potential detrimental effects on the colposcopic examination.

Adolescent↗
PubMed1998

Histology corresponding to mildly dyskaryotic smears--a study of 190 laser cone biopsied patients.

OBJECTIVES: The aim of the study was to evaluate the histological outcome of laser ring biopsies in patients with one or more smears showing cytological mild dyskaryosis where punch biopsies were not performed. The possibilities of predicting histological findings of CIN 2 and CIN 3 were analyzed. METHODS: The study comprised 190 laser ring biopsied patients with mildly dyskaryotic smears. Eighty-five patients were excluded from the initial 275 because of up- and downgrading of smears. Conization specimens and smears were reviewed by an experienced histopathologist and two experienced cytotechnicians. The histological findings were correlated to smear findings. RESULTS: Histologically, CIN 2 was found in 60 and CIN 3 in 45 patients (31 and 24%, respectively). The incidence of histological CIN 3 was higher in those with two or more mildly dyskaryotic smears and in those dyskaryotic smears lacking koilocytic change. Mildly dyskaryotic smears without endocervical cells indicated higher incidence of histological CIN 3. The fact that 36 of 96 CIN 2 and 3 lesions (38%) involved only 3 mm or less of the mucosa might be one important explanation for the absence of representative cells in the corresponding smears. CONCLUSIONS: Our study has shown that a mildly dyskaryotic smear is a strong indicator of CIN 2-3 histologically, especially in those cases without koilocytic cells and in those with repeatedly abnormal smears. The importance of inadequate sampling is indicated by higher incidence of histological CIN 3 in those with less than optimal smears. These findings are some of the factors to be taken into account when planning treatment strategies for this group of patients.

Adult↗
PubMed1999

Prediction of recurrent and residual cervical dysplasia by human papillomavirus detection among patients with abnormal cytology.

To determine the discriminative capacity of human papillomavirus (HPV) DNA testing for recurrent and residual cervical dysplasia, 43 patients with abnormal cytology after treatment for cervical dysplasia were tested for the presence of HPV DNA by PCR. An endocervical curettage was performed in all patients for histological examination. Sixteen of the 43 patients showed moderate or severe dysplasia. The HPV test was positive in all 16 patients with recurrent or residual dysplasia and negative in 12 of the 27 patients without dysplasia. The sensitivity and specificity of the HPV test were 100 and 44%, respectively. The likelihood ratio of a positive HPV test was 1.8, whereas a negative HPV test had a likelihood ratio of 0.12. Testing for the presence of HPV has the potential to select patients without recurrent or residual cervical dysplasia who have an abnormal cytological smear. This may have clinical implications, since unnecessary diagnostic conizations may be avoided in patients with abnormal cytology after treatment for cervical dysplasia and a negative HPV test.

Adolescent↗
PubMed1999

Modified radical hysterectomy for early Ib cervical cancer.

A total of 39 patients with selected early Ib cervical cancer were treated with modified radical hysterectomy (MRH) and compared with 102 patients with nonbulky Ib cervical cancer treated with radical hysterectomy (RH). Postoperative voiding difficulty (15.4 vs 46%) and constipation (43.6 vs 74.5%) were significantly less after MRH than after RH. All patients with MRH were followed uneventfully and the 3-year survival rate is 100%. No recurrence or persistence of disease was noted. It is suggested that patients with exophytic squamous cell carcinoma of the cervix less than 2 cm in diameter and invading less than 10 mm, as diagnosed by conization, may be effectively treated with MRH, resulting in less morbidity.

Female↗
PubMed1999

The significance of ASCUS cytology in HIV-positive women.

OBJECTIVE: The aim of this study was to determine the incidence and severity of dysplasia associated with a cytologic diagnosis of atypical cells of undetermined significance (ASCUS) in women infected with the human immunodeficiency virus (HIV). METHODS: A cross-sectional analysis of cervical cytology, colposcopic impression, and cervical biopsy results was performed on 261 HIV-positive women diagnosed with ASCUS. The prevalence and grade of histologically documented cervical intraepithelial neoplasia (CIN) was determined. Patients with CD4 counts above and below 200 cells/mm(3) were compared using chi(2) analysis to determine any effect of worsening immunosuppression on the rates of associated dysplasia. RESULTS: Seven hundred sixty-one Pap smears were performed during the study period. Two hundred nine (27%) were diagnosed as ASCUS. All patients (pts) received colposcopic evaluation. The incidence of human papilloma virus (HPV) effect, low-grade CIN (I), and high-grade CIN (II, III, and carcinoma in situ) documented by cervical biopsy, cervical conization or endocervical curettings was 40, 17, and 15%, respectively. No cases of invasive cancer were found. These results are similar to those of previous cytohistologic studies of ASCUS in HIV-untested populations. There was no significant difference in frequency or severity of CIN in pts with severe immunosuppression (P = 0.4). CONCLUSION: A cytologic diagnosis of ASCUS in HIV-positive women identifies a group at significant risk for histologic abnormalities. The majority of pts will be diagnosed with HPV or low-grade CIN. HIV infection and severe immunosuppression do not appear to increase the frequency or severity of CIN associated with ASCUS. Given the 32% risk of associated CIN, all HIV-positive women with ASCUS cytology should undergo colposcopic evaluation.

Adult↗
PubMed2000

Recurrent invasive adenocarcinoma after hysterectomy for cervical adenocarcinoma in situ.

BACKGROUND: Unlike its squamous counterpart, therapy for cervical adenocarcinoma in situ with positive endocervical cone margin remains controversial. CASE: A 52-year-old gravida 2, para 1,0,1,1, presented with vaginal bleeding. Gynecologic history was significant for cervical cold knife conization with a positive endocervical margin and endocervical curettage with atypical endocervical cells. Repeat cone biopsy was considered unsafe given the large initial cone specimen. An extrafascial hysterectomy was performed 5 weeks later and pathology confirmed a disease-free cervix. Pap smear performed 1 year later was interpreted as recurrent adenocarcinoma but later downgraded to inflammation. Inspection and random biopsies of the vaginal cuff revealed only inflammation. Two subsequent Pap smears also returned inflammation. Seventeen months after the hysterectomy physical examination revealed a 2 x 3-cm smooth mass at the vaginal cuff. Biopsy revealed invasive adenocarcinoma. The patient underwent an upper vaginectomy followed by postoperative pelvic radiation. CONCLUSION: This case suggests that despite extrafascial hysterectomy for presumed adenocarcinoma in situ of the cervix, a residual focus could remain and present later as invasive adenocarcinoma.

Adenocarcinoma↗
PubMed2000

Connective tissue activating peptide III expression disappears progressively with increased dysplasia in human cervical epithelium.

OBJECTIVE: The aim of this study was to explore the possible involvement of CTAP-III in the development of cervical cancer as it progresses through several cervical intraepithelial neoplasia (CIN) stages. MATERIAL AND METHODS: Twenty-four cervical specimens were obtained by direct punch biopsy, conization, or hysterectomy. Diagnosis of CIN I to CIN III was based on standard morphological criteria in 12 specimens. Tissue specimens were also obtained from 4 normal uteri and 8 cases of invasive squamous cell cervical carcinoma. RT-PCR, using CTAP-III-specific primers, was used to identify CTAP-III mRNA and polyclonal antibodies, directed against the N-terminus of CTAP-III, for immunostaining of the CTAP-III protein. RESULTS: RT-PCR yielded amplified fragments in RNA derived from normal cervical tissue, while no PCR product was detected in the invasive cervical carcinoma tissue. The PCR product corresponded to a CTAP-III plasmid PCR product. Both tissues expressed the same amounts of GAPDH mRNA as the control for the integrity and equal amounts of the isolated RNA. In each of the 16 specimens of normal cervices and of CIN tissues, epithelial cells were stained with the anti-CTAP-III antibodies. In normal epithelium, CTAP-III staining was homogeneously distributed in all epithelial layers, except in the highly active and proliferating basal cells. CTAP-III was localized at the epithelial cell membrane or between adjacent epithelial cells in a granular, chain-like pattern of staining. In the CIN specimens, CTAP-III staining was no longer seen in the deep epithelial layers, consistent with the dysplastic appearance of the cells, and remained in the seemingly normal superficial epithelial layers. Cells of invasive cervical carcinoma did not stain for CTAP-III and were detected in endothelial cells of capillary blood vessels. CONCLUSION: The specific localization of CTAP-III between adjacent epithelial cells suggests a possible role of this chemokine in maintaining the normal architecture of epithelial tissues. Its progressive disappearance in increasingly severe CIN may be applied to distinguish between specific stages in the progression of cervical carcinoma.

Amino Acid Sequence↗
PubMed2001

Term delivery following conservative treatment for villoglandular papillary adenocarcinoma of the uterine cervix: report of a case and analysis of the literature.

BACKGROUND: Villoglandularpapillary adenocarcinoma (VPA) of the cervix is often indolent, and surgical treatment has a favorable outlook. Risk factors include depth of invasion, lymphovascular invasion, and the presence of other histologic types of cancer. CASE: An amputation of the cervical portio was required to satisfactorily resect a 2.5-cm ectocervical lesion in a 28-year-old nulligravida. A diagnosis of pure VPA with a depth of invasion less than 2 mm was established. During a subsequent pregnancy, second trimester ultrasound showed extreme effacement of her cervix and an abdominal cerclage was placed. The pregnancy continued until delivery of a healthy infant at 36 weeks. CONCLUSIONS: In cases of tumor invasion less than 3 mm, and in the absence of lymphovascular space involvement, extrauterine spread of pure VPA has not been described. When conservative treatment is planned, amputation of the cervical portio may be better suited than conization to the achievement of an adequate margin of resection. Cervical cerclage may be needed to offset the extensive cervical surgery.

Adenocarcinoma, Papillary↗
PubMed2001

FHIT (fragile histidine triad) gene analysis in cervical intraepithelial neoplasia.

OBJECTIVE: Recently a candidate tumor suppressor gene, FHIT (fragile histidine triad), was identified at chromosome 3p14.2. Abnormality of this gene has been observed in a variety of human tumors. Although aberrant FHIT transcripts in a substantial percentage of cervical cancer cell lines and primary cervical tumors were also noted, some other studies revealed different results. Therefore, its association with the development of cervical cancer is still debatable. Because allelic loss in chromosome 3p is also a frequent finding in cervical intraepithelial neoplasia (CIN), we compared the transcription pattern and expression of FHIT in the preinvasive cervical lesions and normal cervical epithelia to investigate its possible role in cervical carcinogenesis. METHODS: Thirty-five consecutive CIN lesions taken from conization specimens and 33 normal cervical epithelial tissues taken from hysterectomy for benign diseases were included in this study. Total RNA was extracted from the pathology-confirmed tissue samples and first-strand cDNA was synthesized. It was amplified using a nested reverse transcription polymerase chain reaction (RT-PCR) method. The PCR products were then subjected to subcloned sequence analysis. Paraffin blocks from all of the samples were selected and prepared for immunohistochemical study with an anti-FHIT polyclonal antibody. RESULTS: All the cDNAs of CIN and normal cervical epithelial tissues showed the expected size of RT-PCR product. However, 7 of the 35 (20%) CIN lesions and 5 of the 33 (15%) normal cervical epithelia also presented aberrant transcripts in addition to the normal-sized transcript of FHIT. Deletion of the cDNA segment covering exon 4 to exon 8 was the most frequent finding in the cases that showed abnormal FHIT transcripts. FHIT protein was intermediately or strongly expressed in most of the CIN lesions and normal squamous epithelia. However, reduced or absent FHIT expression was observed heterogeneously in the 7 CIN lesions and 5 normal cervices in which aberrant FHIT transcripts were detected. CONCLUSION: Because the normal-sized FHIT transcript was present robustly in all of the CIN lesions and the abnormal FHIT transcripts occurred with similar frequency and pattern in the CIN lesions and normal cervical tissues, we suggest that abnormal FHIT transcription might not be causal in the early process of cervical carcinogenesis.

Acid Anhydride Hydrolases↗
PubMed2002

Management of invasive carcinoma of the uterine cervix associated with pregnancy: outcome of intentional delay in treatment.

OBJECTIVE: To investigate patients with invasive cervical carcinoma associated with pregnancy, with special reference to the maternal and neonatal outcomes after planned treatment delay to improve fetal maturity. METHODS: The medical records of 28 patients with invasive cervical carcinoma diagnosed during pregnancy or within 1 month after pregnancy were retrospectively reviewed. RESULTS: Twenty-two patients (79%) had Stage I disease and 6 (21%) had Stage II or III disease. Tumor histology revealed squamous cell carcinoma in 27 cases and adenocarcinoma in 1. Twenty cases were diagnosed before 22 weeks gestation, 4 between 22 and 36 weeks, 1 after 36 weeks gestation, and 3 were diagnosed postpartum. In the immediate treatment group (n = 16), the diseases were Stage IA in 3 cases, IB in 7, and II or III in 6. In 11 patients, hysterectomy was performed after therapeutic abortion or with fetus in situ. In 2 patients, cesarean section was followed by hysterectomy or radiotherapy. Three patients diagnosed postpartum were treated with either hysterectomy or radiotherapy. Fifteen patients were free of disease during the follow-up of 27 to 114 months. In the delayed treatment group (n = 12), the diseases were Stage IA1 in 8 cases, IA2 in 1, IB1 in 2, and IB2 in 1 case. In 8 patients with Stage IA1 tumor, the treatment was deferred until term with a delay of 6 to 25 weeks, and hysterectomy or therapeutic conization was performed after delivery. In 4 patients with Stage IA2, IB1 or IB2 tumor, the treatment was postponed until after 30 weeks gestation with a delay of 6 to 15 weeks. No disease progression was documented. Cesarean delivery was followed by hysterectomy in these patients. All patients were free from disease during the follow-up of 70 to 156 months and their babies were well with no sequelae. CONCLUSION: Delay in treatment to allow for fetal maturity is safe in patients with early Stage I cervical carcinoma associated with pregnancy.

Adult↗
PubMed1999

The Outcome of Patients with Breast Cancer Who Underwent Breast Conserving Treatment with or without Immediate Volume Replacement with Autogenous Tissue.

BACKGROUND: Breast conserving treatment (BCT) is accepted as an appropriate therapy for most patients with stage I and stage II breast cancer. However, BCT is associated with a relatively high incidence of local recurrence, and aesthetically unacceptable results occur in some patients. A novel method of immediate volume replacement using autogenous tissue has been developed to strike a balance between adequate excision and cosmesis. We determined the oncological outcome inpatients with breast cancer treated with wide excision, immediate volume replacement with autogenous tissue, and axillary dissection followed by radiotherapy. METHODS: One hundred fifty-three patients with TIS, stage I, II, or III breast cancer underwent wide excision and axillary dissection. The surgical margin ofexcised breast tissue was examined histologically during surgery. If involved, the breast tissue adjacent to the primary site was excised. When the margin of re-excision was positive, patients underwent modified radical mastectomy with or without breast reconstruction. After wide excision, immediate volume replacementwith autogenous tissue was perform-ed, unless the deformity was corrected by undermining and conization of the residual breast tissue. Postoperatively, all patients received breast irradiation. RESULTS: Eighteen patients underwent modified radical mastectomy. The surgical margin was negative in 132 of the 135 patients who underwent BCT. The crude local recurrence rate was 0.7% (1/135). Estimated overall and disease-free 5-year survival rates were 96% and 94%, respectively. CONCLUSION: Wide excision with tumor-free margins and axillary dissection followed by breast irradiation provides adequate local control in many patients with breast cancer. Immediate breast volume replacement with autogenous tissue mayavoid some unpleasant cosmetic results associated with extensive local resection. Our technique eliminates the need for mastectomy in selected patients.

Journal Article↗
PubMed2004

Phase I/II trial of immunogenicity of a human papillomavirus (HPV) type 16 E7 protein-based vaccine in women with oncogenic HPV-positive cervical intraepithelial neoplasia.

PURPOSE: Infection with oncogenic human papillomavirus (HPV) and HPV-16 in particular is a leading cause of anogenital neoplasia. High-grade intraepithelial lesions require treatment because of their potential to progress to invasive cancer. Numerous preclinical studies have demonstrated the therapeutic potential of E7-directed vaccination strategies in mice tumour models. In the present study, we tested the immunogenicity of a fusion protein (PD-E7) comprising a mutated HPV-16 E7 linked to the first 108 amino acids of Haemophilus influenzae protein D, formulated in the GlaxoSmithKline Biologicals adjuvant AS02B, in patients bearing oncogenic HPV-positive cervical intraepithelial neoplasia (CIN). METHODS: Seven patients, five with a CIN3 and two with a CIN1, received three intramuscular injections of adjuvanted PD-E7 at 2-week intervals. Three additional CIN1 patients received a placebo. CIN3 patients underwent conization 8 weeks postvaccination. Cytokine flow cytometry and ELISA were used to monitor antigen-specific cellular and antibody responses from blood taken before and after vaccine or placebo injection. RESULTS: Some patients had preexisting systemic IFN-gamma CD4+ (1/10) and CD8+ (5/10) responses to PD-E7. Vaccination, not placebo injection, elicited systemic specific immune responses in the majority of the patients. Five vaccinated patients (71%) showed significantly increased IFN-gamma CD8+ cell responses upon PD-E7 stimulation. Two responding patients generated long-term T-cell immunity toward the vaccine antigen and E7 as well as a weak H. influenzae protein D (PD)-directed CD4+ response. All the vaccinated patients, but not the placebo, made significant E7- and PD-specific IgG. CONCLUSIONS: The encouraging results obtained from this study performed on a limited number of subjects justify further analysis of the efficacy of the PD-E7/AS02B vaccine in CIN patients.

Adult↗