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Background: In this study, we sought to identify a criterion for the intermediate-risk grouping of patients with cervical cancer who exhibit any intermediate-risk factor after radical hysterectomy., Methods: In total, 2158 patients with pathologically proven stage IB-IIA cervical cancer with any intermediate-risk factor after radical hysterectomy were randomly assigned to two groups, a development group and a validation group, at a ratio of 3 : 1 (1620 patients:538 patients). To predict recurrence, multivariate models were developed using the development group. The ability of the models to discriminate between groups was validated using the log-rank test and receiver operating characteristic (ROC) analysis., Results: Four factors (histology, tumour size, deep stromal invasion (DSI), and lymphovascular space involvement (LVSI)) were significantly associated with disease recurrence and included in the models. Among the nine possible combinations of the four variables, models consisting of any two of the four intermediate-risk factors (tumour size ≥3 cm, DSI of the outer third of the cervix, LVSI, and adenocarcinoma or adenosquamous carcinoma histology) demonstrated the best performance for predicting recurrence., Conclusion: This study identified a 'four-factor model' in which the presence of any two factors may be useful for predicting recurrence in patients with cervical cancer treated with radical hysterectomy.

Background: The objective of this study is to construct a preoperative nomogram predicting lymph node metastasis (LNM) in early-cervical cancer patients., Methods: Between 2009 and 2012, 493 early-cervical cancer patients received hysterectomy and pelvic/para-aortic lymphadenectomy. Patients who were diagnosed during 2009-2010 were assigned to a model-development cohort (n=304) and the others were assigned to a validation cohort (n=189). A multivariate logistic model was created from preoperative clinicopathologic data, from which a nomogram was developed and validated. A predicted probability of LNM<5% was defined as low risk., Results: Age, tumour size assessed by magnetic resonance imaging, and LNM assessed by positron emission tomography/computed tomography were independent predictors of nodal metastasis. The nomogram incorporating these three predictors demonstrated good discrimination and calibration (concordance index=0.878; 95% confidence interval (CI), 0.833-0.917). In the validation cohort, the discrimination accuracy was 0.825 (95% CI, 0.736-0.895). In the model-development cohort, 34% of them were classified as low risk and negative predictive value (NPV) was 99.0%. In the validation cohort, 38% were identified as low risk and NPV was 95.8%. Integrating the model-development and validation cohorts, negative likelihood ratio was 0.094 (95% CI, 0.036-0.248)., Conclusion: A robust nomogram predicting LNM in early cervical cancer was developed. This model may improve clinical trial design and help physicians to decide whether lymphadenectomy should be performed.

Background: To compare the long-term survival outcomes between laparoscopic radical hysterectomy (LRH) and open radical hysterectomy (ORH)., Method: We matched patients with stage IA2 to IIA cervical cancer with known risk factors for recurrence who underwent ORH and LRH., Results: Compared with ORH (n = 263), LRH (n = 263) did not have higher risks of recurrence [hazard ratio (HR) = 1.28; 95% confidence interval (CI) 0.62-2.64] or death (HR = 1.46; 95% CI 0.62-3.43). Even in patients with tumors >2 cm in diameter, the risks of recurrence (HR = 0.82; 95% CI 0.31-2.16) or death (HR = 1.01; 95% CI 0.35-2.95) were not higher for LRH than for ORH. The LRH and ORH group had 5-year recurrence-free survival rates of 92.8% and 94.4%, respectively (P = 0.499). LRH resulted in significantly lower estimated blood loss (379.6 versus 541.1 ml, P < 0.001) and shorter postoperative hospital stay (12.5 versus 20.3 days, P < 0.001). Intraoperative complication rates were similar in the two groups (6.8% versus 5.7%, P = 0.711), but postoperative complication rate was lower in the LRH than in the ORH group (9.2% versus 21%, P < 0.001)., Conclusion: LRH is an oncologically safe alternative to ORH and was associated with fewer postoperative complication and earlier recovery.

Background: this study investigated the outcomes after radical hysterectomy according to tumor size divided by 2-cm interval in patients with International Federation of Obstetrics and Gynecology stage IA2-IIA cervical cancer., Patients and Methods: a total of 1415 patients were eligible for participation in the study and were retrospectively analyzed. Patients were divided into four groups according to tumor size (i.e. ≤ 2, 2-4, 4-6 and >6 cm). The relationships between tumor size and other clinicopathologic risk factors, the probability of adjuvant therapy, survival parameters, recurrence-free survival (RFS) and overall survival (OS) were analyzed., Results: the incidence of intermediate- and high-risk factors gradually increased with increasing tumor size. Adjuvant therapy was required in 13.6%, 34.0%, 56.7% and 92.9% of patients with tumor sizes of ≤ 2, 2-4, 4-6 and >6 cm, respectively (P < 0.001). The risks of recurrence and death gradually increased with increasing tumor size, after adjusting for other significant prognostic factors in multivariate analysis (P < 0.001 and < 0.001, respectively). Even in patients with no intermediate- or high-risk factors, tumor size was a significant predictor of RFS and OS (P < 0.001 and < 0.001, respectively). Immediate surgical parameters did not significantly differ according to tumor size., Conclusions: tumor size divided by a 2-cm interval was an independent prognostic factor and correlated well with other risk factors and with the need for adjuvant therapy.

Background: To determine the prognostic factors and treatment outcomes of patients with early-stage adenocarcinoma (AdCa) of uterine cervix who underwent radical hysterectomy (RH)., Methods: Patients with early-stage squamous cell carcinoma (SCCa) of the uterine cervix who underwent RH were compared with patients with AdCa by multivariate analysis., Results: A total of 1218 patients were eligible, of which 996 (81.8%) had SCCa and 222 (18.2%) had AdCa. In multivariate analysis, parametrial involvement and lymph node metastasis were significant factors for both recurrence-free survival(RFS) and overall survival (OS) of patients with AdCa, whereas age, tumour size, parametrial involvement and lymph node metastasis were significant factors for both RFS and OS of patients with SCCa. After adjusting for significant prognostic factors, patients with AdCa had significantly poorer RFS (odds ratio (OR)=2.07, 95% confidence interval (CI)=1.37-3.12, P=0.001) and OS (OR=2.56, 95% CI=1.65-3.96, P<0.001) than patients with SCCa. Recurrence outside the pelvis was more frequent in AdCa than in those with SCCa (75 vs 57.8%, P=0.084)., Conclusion(s): Although RH is still acceptable for treatment of patients with AdCa, a more effective systemic adjuvant therapy is required.

Background: To estimate safety and efficacy of radical parametrectomy (RP) and radiation therapy (RT) or concurrent chemoradiation therapy (CCRT) for patients with occult invasive cervical cancer found after simple hysterectomy., Materials and Methods: We retrospectively evaluated outcomes in 147 patients with occult invasive cervical cancer., Results: Forty-eight patients with IA1 lesions (IA1 group) did not receive further treatment. Of the 99 patients with IA2-IIA lesions, 26 received no definitive treatment (observation group), 44 received RT or CCRT (RT/CCRT group), and 29 underwent RP (RP group). After a median follow-up of 116 months (range 3-235 months), recurrent disease was observed in 0%, 34.6%, 6.8%, and 0% of patients in the IA1, observation, RT/CCRT, and RP groups, respectively. In the RT/CCRT group, treatment was delayed due to severe diarrhea in 4 patients (9%) and 12 patients (27%) had late complications related to RT requiring further management (including two surgical interventions). Five patients in the RP group (17%) experienced perioperative complications which were easily managed, intraoperatively or conservatively. Late complications were not observed in the RP group., Conclusion: Although RP and RT/CCRT had similar therapeutic efficacy, the lower rate of late complications observed with RP makes it preferable to RT/CCRT.

Objective: To report the results of laparoscopic radical trachelectomy (LRT) with respect to surgical, oncological and reproductive outcomes., Design: Retrospective analysis., Setting: University of Ulsan College of Medicine, Asan Medical Centre, Seoul, Korea., Sample: Thirty-two consecutive patients who wish to preserve fertility with early stage cervical cancer., Methods: Demographic, clinicopathologic, surgical, and follow-up data were obtained from patients' medical records. All patients agreed to telephone interviews to assess their menstrual and obstetrical outcomes., Main Outcome Measures: Surgical parameters, perioperative complication, disease-free survival, overall survival, return and pattern of menstruation and pregnancy rate., Results: Thirty-two consecutive patients who wish to preserve fertility with early stage cervical cancer were offered LRT. In five patients, the planned LRT procedures were abandoned during the operations because of lymph node metastasis or parametrial involvement on frozen section. The mean age was 29 years (range, 22-37 years). The mean tumour size was 1.7 cm in diameter (range, 0.4-3.5 cm). The mean operating time was 290 min (range, 120-520 min) and the mean estimated blood loss was 332 ml (range, 50-1000 ml). Perioperative transfusion was required in six patients. There were no perioperative complications requiring further management. After a median follow-up time of 31 months (range, 1-58 months), there was one recurrence and death from disease. Regular menstruation returned in 24 patients. Six patients attempted to conceive, and three succeeded., Conclusions: Laparoscopic radical trachelectomy may be a safe and useful alternative to radical hysterectomy for women with early cervical cancer who want to preserve their fertility.

Purpose: To investigate clinicopathologic findings of patients with small cell carcinoma of the uterine cervix (SCCUC), and evaluate their prognosis., Methods: We retrospectively reviewed the medical records of 20 patients with histologically confirmed SCCUC treated between October 1996 and December 2004 at Asan Medical Center, Korea. The review included demographic data, pathologic findings, treatments, and outcomes., Results: Of 1,358 invasive cervical carcinoma, the incidence of SCCUC was 1.5%. Median age was 45.5 years. The clinical stages were Ib in 11, IIa in two, IIb in one, IIIa in one, IIIb in one, IVa in three and IVb in one. Fourteen patients underwent radical hysterectomy. Ten patients are alive and nine show no evidence of disease. Median overall survival was 77.0 months and 5-year overall survival rate was 50%. There was significant difference in overall survival with FIGO stage and tumor mass size., Conclusion: Advanced FIGO stage and tumor mass size are poor prognostic factors for overall survival in patients with SCCUC. Even though SCCUC is a highly aggressive neoplasm, early diagnosis and combined therapeutic modalities may lead to longer survival in some patients.

Objective: To determine human leukocyte antigen (HLA)-G and interleukin (IL)-10 expression and the relationship between HLA-G expression and clinicopathologic features in patients with cervical cancer., Method: Tissue samples were obtained from 40 patients with cervical cancer and 15 control patients with a normal cervix. Quantitative real-time RT-PCR for mRNA and western blot analysis for protein expression were used., Result: Both HLA-G and IL-10 mRNA expression in cervical cancer tissues was significantly greater than normal controls (P<0.001, P=0.005). Protein expression of HLA-G and IL-10 in the cancer group was also significantly greater than in the controls (P<0.001, P=0.021). There was an inverse relationship between FIGO stage and HLA-G mRNA expression (P=0.046)., Conclusion: HLA-G and IL-10 might play an important role in cancer progression of the cervix. High HLA-G mRNA expression may be related to early carcinogenesis since it was associated with early-stage cervical cancer.

Aim: Cyclins are a family of regulatory proteins that play a key role in controlling the cell cycle. Abnormalities of cell cycle regulators, including cyclins and cyclin dependent kinases, have been reported in various malignant tumors. This study was undertaken to quantitatively detect cyclin B1 and D1 in cervical cancer., Methods: A quantitative real-time reverse transcription polymerase chain reaction and Western blot assay were used to analyze the expression of cyclin B1/D1 mRNA and proteins, respectively, in fresh invasive cervical cancer (n = 41) and normal cervical tissues (n = 10)., Results: There was significantly greater cyclin B1 expression in invasive cervical cancer than in normal cervical tissue (P = 0.019). However, cyclin D1 expression was not significantly different. A Western blot assay yielded similar results., Conclusion: Our results were consistent with the concept that up-regulation of cyclin B1 expression occurred in cervical cancer and an aberrant expression of cyclin B1 might play an important role in cervical carcinogenesis.

Objectives: To investigate whether pretreatment levels of serum squamous cell carcinoma antigen (SCCA) and urine polyamines can predict lymph node metastases in patients with early stage cervical carcinoma., Methods: Pretreatment measurement of serum SCCA and urine polyamine levels was carried out for 419 women. Of those women, 104 with stage IB and IIA cancer received radical surgery and had tumor size reassessed postoperatively., Results: The women had increased levels of serum SCCA (>2.0 ng/mL) and elevated urine polyamines (>45 micromol/g of creatinine) with advanced cancer stage (P<0.01). The median SCCA level was significantly higher in women with metastatic disease than that in those without lymph node involvement (3.9 vs. 1.1; P<0.01). Women with nodal involvement also had significantly higher median levels of urine polyamines than those without nodal disease., Conclusions: Pretreatment measurement of SCCA and urine polyamine levels may help in predicting lymph node metastases in women with early stage cervical carcinoma.

The purpose of this study was to compare the plasma levels of the anti-oxidant system and oxidative stress between a cervical neoplasia group and a normal control group and to investigate the relationship between the levels of micronutrients of antioxidant system and various clinicopathological parameters of cervical carcinoma. A cross-sectional sample of 180 women, including 90 normal controls, was recruited from November 2000 to January 2001. Plasma concentration of malondialdehyde (MDA) was spectrophotometrically measured as the parameter of lipid peroxidation. Plasma levels of antioxidant vitamins were analyzed with the help of reverse-phase, high-pressure liquid chromatography, whereas glutathione peroxidase activity was evaluated by using coupled enzyme procedure. While the activity of glutathione peroxidase and the plasma levels of antioxidant vitamins, such as lutein, beta-carotene, lycopene, and zeaxanthin, were all significantly lower, the concentration of MDA was significantly higher in women with cervical intraepithelial neoplasia (CIN) or invasive cervical cancer, compared to those of the normal control group. The status of the plasma antioxidant system showed no significant correlation with the prognostic factors of cervical cancer. These findings suggest a potential role of oxidative stress-induced lipid peroxidation and the impairment of the anti-oxidant system in the pathogenesis of CIN and carcinoma of the uterine cervix.

Granulocytic sarcoma (GS) is a rare manifestation of leukemia and has been reported in 3-5% of acute myelogenous leukemia (AML) patients. GS in the uterine cervix is very rare and is also called chloroma because of its greenish appearance. We present the case of a patient whose disease relapsed as chloroma of the uterine cervix after bone marrow transplantation (BMT). She remained in continuous complete remission for 2 years after allogeneic BMT. However, she visited the hospital because of painless vaginal bleeding. She was diagnosed as having chloroma by cervical smear and colposcopically directed biopsy of the cervix. Systemic chemotherapy was administered on the presumption that myelogenous leukemia had recurred as chloroma, and a good clinical response was achieved. We describe the first case of AML that relapsed as chloroma of the uterine cervix after complete remission of the AML, which had complete response to only systemic chemotherapy.

This study was designed to evaluate a series of patients who underwent surgical management due to cervical cancer stage IA1 fitting the 1995 FIGO definition. A total of 149 patients were followed from 3 years to 11.7 years with a median follow-up interval of 5 years. The cases with invasions of < or = 1 mm and > 1 mm but < or = 3 mm were noted in 89 (59.7%) and 60 (41.3%) patients, respectively. Lymphvascular space invasion was identified in five patients. In 49 patients, conization or nonradical hysterectomy was performed without pelvic lymph node dissection (PLND) and pelvic recurrence developed in one patient who had an extended hysterectomy. PLND was performed in 100 patients and the average number of lymph nodes examined per case was 26.5 +/- 10.1. None of the 100 patients had metastasis to the pelvic lymph node and recurrence. None of the 149 patients has died from recurrent disease. In conclusion, this study suggests that patients with cervical cancer stage IA1 have an extremely low risk of pelvic lymph node metastasis, very rarely recur, and present an excellent prognosis, so nonradical management that excludes PLND could be as effective as radical surgery in these patients.

DNA copy number changes were studied by comparative genomic hybridization on 10 tumor specimens of squamous cell carcinoma of cervix obtained from Korean patients. DNA was extracted from paraffin-embedded sections after removal of non-malignant cells by microdissection technique. Copy number changes were found in 8/10 tumors. The most frequent changes were chromosome 19 gains (n=6) and losses on chromosomes 4 (n=4), 5 (n=3), and 3p (n=3). A novel finding was amplification in chromosome arm 9p21-pter in 2 cases. Gains in 1, 3q, 5p, 6p, 8q, 16p, 17, and 20q and losses at 2q, 6q, 8p, 9q, 10p, 11, 13, 16q, and 18q were observed in at least one of the cases.

Neoadjuvant chemotherapy prior to definitive radical surgery or radiotherapy may be effective in reducing tumor volume or clinical stage and may even enhance pelvic control and survival. However, there are significant limitations to the use of neoadjuvant therapy in the non-responder group. They include delayed total treatment course, the presence of drug resistant clones which result in accelerated tumor growth, and limited bone marrow reserve for subsequent definitive therapy. Thus, there is a need to identify parameters providing a more precise indication of the response to neoadjuvant chemotherapy in patients with invasive cervical cancer. From Jan. 1995 to Jan. 1996, neoadjuvant chemotherapy with 3 courses of cisplatin and vincristine was used in 32 patients with invasive cervical cancer (FIGO stage Ib to IIIb; tumor size greater than 2 cm). Prior to chemotherapy, quantitative tissue levels of epidermal growth factor receptor (EGFR) and c-erbB-2 oncogene protein were measured by using an enzyme-linked immunosorbent assay (ELISA). Tumor size was estimated before and after chemotherapy. Relations between oncoproteins and reductions of tumor size were evaluated. Tumor size prior to neoadjuvant chemotherapy did not show any correlation with either the concentrations of EGFR or c-erbB-2 oncoprotein. As well, the tumor reduction index did not manifest any correlation with EGFR, it did had an inverse linear correlation with the c-erbB-2 oncoprotein levels (Rs = -0.71, P < 0.05). The results of this study suggest that c-erbB-2 oncoprotein is associated with a reduced response to neoadjuvant chemotherapy in primary treatment of invasive cervical cancer and may be useful in directing therapeutic approaches.

Recent studies have revealed a new family of tumor suppressor genes that directly implicate aberrant cell cycle regulation in tumorigenesis. The general function of these gene products is that they prevent cell cycle progression by directly interfering with cyclin/cyclin-dependent kinase (CDK) activation. The importance of these genes is that they are potent inhibitors of CDK. Among these cell cycle inhibitors, p21(WAF1/CIP1) and p16 have been thoroughly studied. However, the role of p21(WAF1/CIP1) and p16 in the tumorigenesis of the uterine cervix has been poorly defined. We used immunohistochemical techniques to study the expression of these cell cycle inhibitors in formalin-fixed, paraffin-embedded cervical tissue to explore the relationship between cyclin/CDK inhibitors and cervical carcinoma. Cervical tissues were analyzed from 46 patients with cervical carcinoma, 30 cases with cervical intraepithelial neoplasia (CIN) and 22 control cases who underwent hysterectomy due to benign gynecologic disease at Yonsei University College of Medicine. All CDK inhibitors were strongly expressed in the reverse cell hyperplasia and koilocytes, whereas they revealed significantly decreased expression in neoplastic tissues (P < 0.05). P16 revealed higher expressions in cases associated with human papillomavirus (HPV) (t test, P < 0.05) than in cases lacking any type of HPV. Our results were consistent with the concept that underexpression of CDK inhibitors may play an important role in neoplastic transformation in cervical carcinoma., (Copyright 1998 Academic Press.)

Allelic deletions involving the short arm of chromosome 3 (3p13-21.1) have been observed frequently in cervical carcinomas. Recently, a candidate tumor suppressor gene, FHIT (Fragile Histidine Triad), was cloned and mapped to this chromosomal region (3p14.2). Abnormal FHIT transcripts have been identified previously in a variety of tumor cell lines and primary carcinomas, although their significance and the molecular mechanisms underlying their origin remain incompletely defined. In addition, integration of human papillomavirus DNA has been identified at a fragile site (FRA3B) within the FHIT locus in cervical cancer. These observations motivated us to evaluate FHIT mRNA and protein expression in cervical cancer cell lines, primary cervical carcinomas, and normal tissues. Transcripts of the expected size and sequence were the predominant species identified by reverse transcription (RT)-PCR in cultured keratinocytes and all normal tissues evaluated. In contrast, aberrant FHIT transcripts were readily demonstrated in 6 of 7 cervical carcinoma cell lines and 17 of 25 (68%) primary cervical carcinomas. Northern blot analyses demonstrated reduced or absent FHIT expression in the cervical carcinoma cell lines, particularly those with aberrant RT-PCR products. Immunohistochemical analysis of Fhit expression in cervical tissues revealed strong immunoreactivity in nonneoplastic squamous and glandular cervical epithelium and marked reduction or loss of Fhit protein in 25 of 33 (76%) primary cervical carcinomas. In those cervical cancer cell lines and primary tumors with exclusively aberrant or absent FHIT transcripts by RT-PCR, Fhit protein expression was always markedly reduced or absent. The frequent alterations in FHIT expression in many cervical carcinomas, but not in normal tissues, suggest that FHIT gene alterations may play an important role in cervical tumorigenesis.

Retinoids are strong inhibitors of epithelial cancer promotion and progression in experimental carcinogenesis. Recently, therapeutic trials of retinoids have demonstrated activities in cervical cancer and precancerous lesion of cervix. Our purpose was to determine whether additional administration of 13-cis-retinoic acid would improve the treatment effect of neoadjuvant chemotherapy in patients with squamous cell carcinoma of the cervix. From January 1994 through January 1995, 40 patients with invasive cervical cancer were enrolled in this prospective study and randomized into the two groups. Group 1 had neoadjuvant chemotherapy alone and group 2 had neoadjuvant chemotherapy plus 13-cis-retinoic acid (RA) at a dosage of 1 mg/kg/day for 1 month. Patients in group 1 and group 2 were similar with respect to age, parity, clinical stage, and histological subtype. Therapeutic responses were compared using Fisher's exact test, Mann-Whitney test, and Wilcoxon signed-rank test. RA increased the complete response rate of neoadjuvant chemotherapy from 0% in group 1 to 5% in group 2. However, a difference of overall clinical response rate between the two groups was not evident. The drug toxicities in group 1 and group 2 included anemia in 30.0% and 23.7%, leukopenia in 6.7% and 15.2%, and hepatotoxicity in 6.7% and 6.8%, respectively. More frequent incidence of mucocutaneous side effects was seen in group 2 than group 1, but these side effects were mild and reversible. The clinical response rate achieved in this trial indicates that the combination of 13-cis-retinoic acid and neoadjuvant chemotherapy, at least when used on the schedule reported herein, is not superior to treatment of neoadjuvant chemotherapy alone for patients with squamous cell carcinoma of the cervix. However, a single patient achieved a complete response on this therapy, and the impact of such a treatment on survival needs to be explored.

Increased expression of the epidermal growth factor receptor (EGFR) gene has been shown in a large number of tumors, generally indicating a more aggressive biological behavior of cancers than those with low or normal expression. The role of EGFR in the tumorigenesis of the uterine cervix has been poorly understood and controversial. In order to explore the relationship between EGFR status and cervical carcinoma, tissues were analyzed from 40 patients, each of whom had invasive cervical carcinoma prior to treatment, 20 patients with cervical intraepithelial neoplasia (CIN) and 10 control cases who underwent hysterectomy due to benign gynecological disease at Yonsei University College of Medicine. We measured EGFR with an enzyme-linked immunosorbent assay which was a sandwich type using a mouse monoclonal capture antibody and a rabbit antiserum as detector. Patients with invasive cervical cancer were found to have significantly higher median EGFR expression than either the patients with CIN (P = 0.002) or the control (P = 0.001), respectively. However, there was no significant difference in EGFR status between CIN and the control groups. Overexpression of EGFR was found in 29 of 40 (72.5%) invasive cervical cancers and in 5 of 20 (25%) CIN patients. In invasive cervical cancer, no significant difference in EGFR levels was noted when stratified according to age, menopausal status, histological cell type, or clinical stage. With regard to tumor size, lesions of 4 cm and larger had significantly higher receptor levels than those lesions under 4 cm (P = 0.003). Even though quantitative EGFR status did not correlate with other prognostic parameters except tumor size, our results were consistent with the concept that EGFR may play an important role in malignant transformation and tumorigenesis in cervical cancer.

One hundred and sixty-eight cases of cervical conization were performed for cervical intraepithelial neoplasia (CIN) in a 32-month study. The indications for conization were unsatisfactory colposcopic finding, abnormal epithelium that extended into the endocervical canal, a microinvasive cervical cancer, and significant discrepancy among cytology, colposcopy, and/or punch biopsy histology. In the early period of the study, conization was done by the cold-knife method (N = 107), whereas loop diathermy was used in the latter part of the study (N = 61). Both groups were similar in terms of age, indications for conization, and size of cervical cone specimens. Loop diathermy conization was done in a significantly shorter time (5.7 +/- 1.8 minute vs 15.2 +/- 6.1 minute)(P < 0.05) than cold-knife conization. However, the difference in the postoperative complications between loop diathermy(3.0%) and cold-knife conization(4.7%) was not significant. The incidence rate of residual CIN III lesions in the subsequent hysterectomy specimens, found by histological documentation on these specimens was 25.0 and 26.1 percent after loop diathermy and cold-knife conization respectively. These results suggest that loop diathermy is much easier to perform and a more time-conserving treatment modality than cold-knife conization in the management of patients with cervical intraepithelial neoplasia.

The 386 cases of invasive cervical carcinoma treated with radiotherapy alone were statistically analyzed to delineate the high risk factors (HRFs) associated with a significantly high treatment failure rate; they were (1) stages III-IV, (2) lesion greater than or equal to 4.0 cm, (3) small cell carcinoma or adenocarcinoma, (4) stages I-II with lesion greater than or equal to 4.0 cm, and (5) lymphographic evidence of nodal metastasis. Then, chemoradiotherapy (induction chemotherapy plus subsequent radiotherapy) was instituted to 113 invasive cervical carcinoma patients with at least one such HRF. Each patient received two to three cycles of induction chemotherapy at about 3-week intervals. For squamous cell carcinoma, cisplatin, 100 mg/m2 iv, was followed immediately by 5-fluorouracil, 1000 mg/m2, as a 24-hr iv infusion x 5 days. For adenocarcinoma, cisplatin, 70 mg/m2 iv, on Day 1 was followed by cytoxan, 250 mg/m2, on Day 2, and adriamycin, 45 mg/m2, on Day 3. Five-year survival of these patients according to each HRF, in the above order, was 69.1, 67.2, 68.1, 78.3, and 79.5% after chemoradiotherapy, all significantly higher than 57.4, 53.0, 54.5, 48.0, and 48.8% by radiotherapy alone. Drug toxicities such as leukopenia, hepatotoxicity, nephrotoxicity, and hypomagnesemia were seen in 46.5, 53.2, 47.1, and 55.4% of all cycles, respectively. The toxicities altered drug schedule in 191 (61.2%) ongoing induction chemotherapy cycles. Our cisplatin-based induction chemotherapy is considered an effective preradiotherapy adjunct that can reduce treatment failure in HRF-associated invasive cervical carcinoma.