Biomedical subjects
Publications and source records attributed to K G Huang.
Traditionally, most women with cervical stump cancer underwent radiation therapy, as radical surgery was considered difficult. Given our success performing laparoscopic-assisted radical vaginal hysterectomy, we modified that technique to treat two women with carcinoma of the cervical stump. At follow-up of 14 and 17 months, respectively, both patients were free of recurrence.
PURPOSE: To compare the efficacy of neoadjuvant chemotherapy (NAC) followed by radical hysterectomy with that of radiotherapy (R/T) for bulky early-stage cervical cancer. PATIENTS AND METHODS: Women with previously untreated bulky (primary tumor >/= 4 cm) stage IB or IIA non-small-cell carcinoma of the uterine cervix were randomly assigned to receive either cisplatin 50 mg/m(2) and vincristine 1 mg/m(2) for 1 day and bleomycin 25 mg/m(2) for 3 days for three cycles followed by radical hysterectomy (NAC arm) or receive primary pelvic radiotherapy only (R/T arm). The ratio of patient allocation was 6:4 for the NAC and R/T arms. Women with enlarged para-aortic lymph nodes on image study were ineligible unless results of cytologic or histologic studies were negative. RESULTS: Of the 124 eligible patients, 68 in the NAC arm and 52 in the R/T arm could be evaluated. The median duration of follow-up was 39 months. Thirty-one percent of patients in the NAC arm and 27% in the R/T arm had relapse or persistent diseases after treatment, and 21% in each group died of disease. Estimated cumulative survival rates at 2 years were 81% for the NAC arm and 84% for the R/T arm; the 5-year rates were 70% and 61%, respectively. There were no significant differences in disease-free survival and overall survival. CONCLUSION: NAC followed by radical hysterectomy and primary R/T showed similar efficacy for bulky stage IB or IIA cervical cancer. Further study to identify patient subgroups better suited for either treatment modality and to evaluate the concurrent use of cisplatin and radiation without routine hysterectomy is necessary.
BACKGROUND: The purpose of this study was to investigate pretreatment variables that could predict prognosis and to evaluate the impact of postoperative adjuvant therapy on the outcomes of patients with Stage IB or II cervical carcinoma with or without pelvic lymph node metastases. METHODS: Eight hundred ninety-one patients with Stage IB or II cervical carcinoma who underwent radical hysterectomy and bilateral pelvic lymphadenectomy as primary treatment at a single institution were analyzed. Potential prognostic variables were studied. RESULTS: Among the variables that could be assessed before treatment, depth of cervical stromal invasion (determined by magnetic resonance imaging), clinical stage, tumor size, grade of differentiation, and DNA index (determined by flow cytometry) were independent predictors of outcome in multivariate analysis using a Cox regression model. Three distinct prognostic groups (low, intermediate, and high risk) were defined using these variables. Five-year recurrence free survival (RFS) rates for the low, intermediate, and high risk groups were 94.6%, 82.7%, and 62.3%, respectively (P = 0.0001), and overall survival (OS) rates were 98.4%, 84.5%, and 68.7%, respectively (P = 0.0001). Among patients with pelvic lymph node metastases who were free of parametrial extension, those who received postoperative chemotherapy or chemoradiotherapy had significantly better RFS (P = 0.017) and OS (P = 0.043) than those who received no adjuvant therapy. Among patients without pelvic lymph node metastases but at high risk of recurrence, those who received adjuvant radiotherapy had significantly better RFS (P = 0.015) and marginally improved OS (P = 0.087) compared with those who received no adjuvant therapy. CONCLUSIONS: A model containing assessable pretreatment variables for predicting the prognoses of patients with early stage cervical carcinoma was formulated. Subsets of patients for whom postoperative chemotherapy or radiotherapy might be beneficial were identified. The data from this retrospective review may be useful when future prospective trials of the treatment of early stage cervical carcinoma are designed.
OBJECTIVE: The aim of this study was to evaluate the specimen adequacy and the histological interpretation of loop conization for microinvasive cervical carcinoma. METHODS: We retrospectively reviewed the histopathological findings of the original cone specimens together with the final hysterectomy specimens in patients with microinvasive carcinoma of the cervix. From 1990 to 1995, 63 consecutive patients with microinvasive carcinoma of the cervix were included in the study, of which 35 patients underwent loop conization and 28 underwent cold-knife conization. All patients had a hysterectomy. RESULTS: The mean width, depth, and cone volume of the conization specimens were 2.44 cm, 2.15 cm, and 3.96 cm3, respectively, in the loop group versus 2.3 cm, 2.35 cm, and 4.38 cm3 in the cold-knife group. No significant differences were seen between the two groups. The application of loop conization was completed in a single slice in 27 patients (77.1%) and multiple slices by the loop in 8 (22.9%), in spite of the attempt to perform conization in a one-pass application when possible. In assessing these cone specimens microscopically, the rate of transection of tissue was significantly higher in the loop cone than in the cold-knife cone (17.1% versus 0%, P = 0.02). Because of transection of tissue and misorientation, pathologic determination of the depth and width of stromal invasion was undetermined in two loop cone specimens compared with none in the cold-knife cones. CONCLUSION: Our study suggests that cold-knife conization is a preferred method in assessing microinvasive carcinoma of the cervix if multiple applications of loop conization are inevitable.
OBJECTIVE: In order to understand the prognostic factors of placental site trophoblastic tumors (PSTT), we performed a MEDLINE search for cases from 1976 through 1998 and report three cases. MATERIALS AND METHODS: The patients' age at presentation, antecedent pregnancies, and responses to treatment were analyzed according to the extent of disease, disease status after treatment, and survival in 88 cases. RESULTS: Patients with disease extending outside the uterus at presentation had a median latency of 24 months between the antecedent pregnancy and presentation of PSTT, which was significantly longer than that of 12 months in those with disease confined to the uterus. Patients with metastatic diseases were 3 years older than patients with diseases confined to the uterus and had a higher incidence of term delivery as their antecedent pregnancy. The outcomes of patients with FIGO stage I-II disease after hysterectomy were excellent, while those with FIGO stage III-IV diseases had a 30% survival. Although initial partial responses to chemotherapy were observed in some patients, only 5 patients achieved a complete remission and 3 of these 5 received a combination of etoposide, methotrexate, and actinomycin-D, alternating with cyclophosphamide and vincristine. CONCLUSION: FIGO stage is the most important prognostic factor, and complete removal of all lesions provided good outcomes in PSTT patients. For those with unresectable tumors, combination chemotherapy showed a high response rate, but only a few achieved a complete response.
OBJECTIVE: This study was undertaken to investigate prognostic factors in patients with recurrent cervical carcinoma who had undergone a primary radical hysterectomy and pelvic lymphadenectomy. STUDY DESIGN: A retrospective analysis of 177 patients with recurrent cervical carcinoma after radical hysterectomy and pelvic lymphadenectomy for stage IB to II disease at a single institution was performed to evaluate clinicopathologic parameters, time to recurrence, pattern of failure, use of salvage therapy, and survival after recurrence. RESULTS: The 5-year survival rate from diagnosis of recurrence in this series was 10.1%. Survival after recurrence was significantly decreased in patients with pelvic lymph node metastasis at primary surgery and adenocarcinoma-adenosquamous carcinoma histologic type. Patients with extravaginal recurrences receiving chemoradiation for recurrent cervical carcinoma had significantly better outcomes than those receiving radiation alone. Six patients who had a distant relapse at a sole site had prolonged survival after salvage therapy, which was accomplished by chemoradiation, surgery plus radiotherapy, or surgery alone. CONCLUSIONS: Our results demonstrate the benefit of adding chemotherapy to radiotherapy in the treatment of recurrent cervical carcinoma. Salvage multimodality treatment should be offered to selected patients who have isolated relapse at a single distant site.
Clinical complete response (CR) to chemotherapy is not uncommon in small cell carcinoma. To understand its pathologic response, we conducted a phase II trial with neoadjuvant chemotherapy followed by hysterectomy in patients with small cell cervical cancer and reviewed all reported cases receiving neoadjuvant chemotherapy followed by hysterectomy through a MEDLINE search. From December 1993 to December 1997, the enrolled patients were treated with two to three courses of vincristine, adriamycin and cyclophosphamide alternating with cisplatin and etoposide (VAC/PE) before hysterectomy. Another three courses of chemotherapy were added after surgery. A total of seven patients was enrolled. Clinical CR was observed in six patients, but microscopic residual tumor was present in all. Lymphatic permeation, scattered residual tumor clusters and residual superficial invasive adenocarcinoma over the cervix presented in five cases, and another had a metastatic pelvic node with no residual cervical tumor. Three of these seven patients have been alive with no evidence of disease for 16.2, 45.2 and 56.6 months, respectively. The other four died from disease 10.3-23.6 months after diagnosis. These findings indicate the discrepancy between clinical and pathologic responses in small cell cervical cancer after chemotherapy and emphasize the necessity of local treatment.
BACKGROUND: This study was designed to determine whether screening for high-risk human papillomaviruses testing could improve the detection of cervical dysplasia and cancer in assistance with conventional Papanicoloau (Pap) smears. METHODS: The study was based on 114 patients with abnormal Pap smears referred for colposcopy from Feb. 1997 to Dec. 1997. The presence of high-risk human papillomavirus (HPV) DNA was determined with the Hybrid Capture method (including HPV types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, and 68). Cytologic examination by Papanicolaou smear was based on the Bethesda system and cervical biopsy was done via colposcopy. RESULTS: Cytologic examination demonstrated high-grade squamous intraepithelial lesions (HSIL) in 24 patients with HPV positive (75%), low-grade squamous intraepithelial lesions (LSIL) in 38 with 61% HPV positive, and atypical squamous cells of undetermined significance (ASCUS) in 52 with 37% HPV positive. Among patients with a cytologic diagnosis of borderline abnormalities (ASCUS or LSIL), those with who were HPV positive were significantly more likely to have cervical dysplasia (both p < 0.05). The sensitivity of combined HPV assay and/or cytology for detection of noninvasive precursor (91%) was significantly greater than those of cytology (68%) or HPV assay (81%) alone. CONCLUSION: The addition of the hybrid capture high-risk HPV DNA assay to cytologic examination of cervical smears appears to increase the sensitivity of cervical screening. Our findings suggest that HPV DNA may be a useful adjunct marker for early detection of cervical dysplasia in women with minimally abnormal Pap smears (ASCUS/low-grade SIL).
BACKGROUND: Small cell carcinoma of the uterine cervix is an uncommon tumor associated with high mortality even among patients with early stage disease. The role of adjuvant chemotherapy after surgery has been suggested by regimens used for small cell lung carcinoma. During the years 1980-1997, 19 cases in which various adjuvant chemotherapies were given after hysterectomy were reported in the literature published in English. METHODS: Adjuvant chemotherapy was administered consecutively to 23 patients with Stage Ib-II small cell cervical carcinoma who had been primarily treated with radical hysterectomy and had adequate bone marrow, renal, and hepatic functions. A combination of vincristine, doxorubicin, and cyclophosphamide alternating with cisplatin and etoposide (VAC/PE) was administered to 14 patients during the years 1988-1996 according to a prospective study protocol. A combination of cisplatin, vinblastine, and bleomycin (PVB) was administered to 8 patients, and another regimen was administered to 1 patient during the years 1984-1988. Prognostic factors were evaluated by analyzing both the data on these 23 patients and the pooled data on the cases retrieved from the literature and our own files. RESULTS: Ten of the 14 patients who received VAC/PE had no evidence of disease during a median follow-up of 41 months, whereas 3 of the 9 who received PVB or another regimen survived. Of the 10 patients who died of their disease, all died of distant metastasis within 10 months after recurrence. Meta-analysis of the pooled data showed that 68% of patients who received regimens containing VAC or PE survived, whereas 33% of patients who received regimens not containing VAC/PE survived (P = 0.0078, log rank test). Seventy percent of patients with no lymph node metastasis at hysterectomy and 35% with lymph node metastasis survived (P = 0.05). All patients who died of disease had extrapelvic metastasis. CONCLUSIONS: Chemotherapies containing VAC or PE are favorable regimens for patients with early stage small cell cervical carcinoma after radical hysterectomy.
BACKGROUND: Lymph node metastasis is established as a poor prognostic factor in cervical carcinoma patients undergoing primary surgery. However the optimal postoperative therapy for node-positive patients remains to be defined. MATERIALS AND METHODS: To determine the role of adjuvant therapy in stage Ib-IIa cervical carcinoma patients who had pelvic node metastases after radical hysterectomy, a single institutional randomized controlled trial with factorial design, comparing concurrent chemo-radiotherapy (CT + RT) versus chemotherapy (CT) or radiotherapy (RT) alone was conducted. Study endpoints included site of recurrence, time to recurrence, relapse-free and overall survivals, and toxicity of treatment. RESULTS: At a median follow-up of 61 months, the 6-year relapse-free and overall survival rates of the 39 patients entered into this trial were 78.2% and 85.2%, respectively. This trial was prematurely closed due to suboptimal accrual and protocol violation. It is inconclusive regarding the efficacy of CT because of the limitation of the sample size and the imbalance of prognostic features by actual treatment. A model for risk group classification of patients with stage Ib-II cervical carcinoma with pelvic node metastases from a retrospective analysis was validated by this prospective cohort. The results of this failed trial suggest that adjuvant CT alone seemed comparable to RT alone or CT + RT in survival but was associated with significantly less morbidity. CONCLUSION: It is warranted to consider a CT alone arm in comparison with either observation or CT + RT according to risk of recurrence in future prospective trials. However, this important issue can only be addressed by a large multicenter trial.
All patients with bulky (> or =4 cm) Stage Ib or IIa cervical carcinoma treated at Chang Gung Memorial Hospital between August 1988 and December 1991 using a strategy of neoadjuvant chemotherapy with cisplatin, vincristine, and bleomycin and radical hysterectomy were reviewed. Fifty-nine evaluable patients received 1 to 3 courses of chemotherapy, and 51 underwent subsequent hysterectomy. The remaining 8 patients, not completing planned surgery, were treated with definitive radiotherapy. The overall clinical response rate was 81.4% (48/59) with 18.6% complete response. Clinical response to chemotherapy was not different by stage, histologic type, tumor size, level of squamous cell carcinoma antigen, or DNA ploidy. However, tumors with DNA indices (DI) greater than 1.3 were associated with higher clinical response rates than tumors with DI < or = 1.3 (P = 0.043). Histologically proven pelvic node metastases was noted in 18.5% (10/54) who had laparotomy. Concomitant pregnancy and more than one node metastases had significant adverse influence on recurrence and death. The 5-year survival rate of those patients who received hysterectomy was 80.3%, while only 1 of the 8 patients without hysterectomy survived. Of the 7 patients received hysterectomy despite clinical poor response, only 2 had node metastases and 3 died, whereas all the 4 patients deterred hysterectomy for poor response died. This study demonstrates the value of DNA flow cytometry in predicting chemosensitivity. However, with a DI cutoff at 1.3, only 29.2% patients could be selected. Further studies are necessary to find additional indicators that predict histological response to select better candidates for this approach and to determine optimal adjunctive treatment in case that poor prognostic features are found.
In 1991-1995 by using the Rieckmann in vitro micro-method, susceptibilities of Plasmodium falciparum to eight antimalarials in the China-Lao PDR and China-Myanmar border areas were tested. The resistant rates of P. falciparum to chloroquinine were 95.0%-100%; IC50 114-240nmol/l. P. falciparum resistant rates to amodiaquine resistance accounted for 83.5%-100%, IC50 52-72nmol/l. All cases were sensitive to quinine, IC50 470-608nmol/l. P. falciparum isolates from the Lao PDR frontier were highly sensitive to artesunate, dihydroartemisinin, and arteether. Resistant rates from other areas were 0-11%. P. falciparum from China-Myanmar and Lao PDR border areas were also sensitive to mefloquine, IC50 68-88nmol/l. A longitudinal survey of the sensitivity of P. falciparum in vivo on the China-Lao PDR border showed that the average defervescent time of falciparum malaria was treated by pyronaridine increased from 32.7 +/- 16.0 hours during 1984-85 to 56.2 +/- 27.4 hours in 1995; the recrudescence rate rose up from 15.2% to 37.5%. The results monitored in vitro showed that all cases assessed in 1988 for response to pyronaridine were sensitive, but 36.4% of cases had emerging resistance, IC50 increased from 13nmol/l to 40 nmol/l. The above results suggested that P. falciparum in these areas has expressed resistance to chloroquine and amodiaquine. However, the parasites are still sensitive to artemisinin, pyronaridine, mefloquine, quinine, but with a declining sensitivities.
BACKGROUND: The role of flow cytometric DNA analysis in predicting prognosis of patients with borderline malignant ovarian tumors has been controversial. METHODS: Fifty cases of patients with borderline malignant ovarian tumors were analyzed by histology and by flow cytometry on paraffin embedded tissue. Multiple tissue blocks and serial sections were analyzed for each tumor. The results of DNA analysis were correlated to clinicopathologic data. RESULTS: DNA aneuploidy was demonstrable in 4 cases (8%) when the most atypical section was analyzed. The overall rate of aneuploidy was 14% if additional blocks and serial sections were studied. Two patients died from tumor. One of the two patients had an initial diagnosis of Stage IIc mucinous borderline tumor with DNA indices (DI) of 1.12, 1.42, and 2.04. She had a recurrence in the contralateral ovary 1 year later (DI = 1.83), and a second frankly malignant recurrence diffusely in peritoneum (DI = 1.89). The other patient had an initial diagnosis of Stage IIIc mucinous borderline ovarian tumor with pseudomyxoma peritonei. DNA diploidy was obtained in all of the samples from the primary tumor. An aneuploid peak (DI = 1.28) was demonstrated in only one serial section of the peritoneal implants. Of the other 5 patients who had aneuploid histograms but were disease-free, the DNA indices were 1.35, 1.14/1.18, 1.15, 1.20, and 1.31 and were demonstrable only in either 1 or 2 of the blocks or unproven on serial sections. All patients with diploid-peridiploid tumors were alive and disease free. CONCLUSIONS: Reproducible DNA aneuploidy of high DI may be predicting a poor outcome, whereas the significance of inconsistently reproducible aneuploidy of low DI remains to be determined. Further studies of prospective DNA analysis with adequate sampling are necessary to define the role of flow cytometry in patients with borderline malignant ovarian tumors.
Treatment results of 26 patients with squamous cell carcinoma (SCC) arising in mature cystic teratoma of the ovary were analyzed. Four nulliparous patients with stage Ia tumors underwent conservative salpingo-oophorectomy. Following surgery, 2 patients had successful pregnancies. The remaining 7 patients with stage Ia tumors were observed after hysterectomy and bilateral salpingo-oophorectomy. Fifteen patients with stage Ic-IV tumors underwent cytoreductive surgery followed by cis-platinum-based chemotherapy with or without sequential radiotherapy. The mean survival was 63.9 months. The overall actuarial disease-free survival at 2 years was 69%, and by stage was as follows: stage I, 100% (13/13); stage II, 100% (2/2); stage III, 30% (3/10); and stage IV, 0% (0/1). A significant difference in disease-free survival was noted in stage (P = 0.0001). Optimal versus suboptimal operation was associated with a median Kaplan-Meier survival of 65 months versus 34.8 months, with actuarial disease-free survival at 2 years of 60 and 0%, respectively (P = 0.0210). Our study shows that 67% (16/24) of the patients had SCC antigen levels exceeding 2 ng/ml, which by stage was as follows: stage I, 5/11 (45%); stage II, 1/2 (50%); stage III, 9/10 (90%); and stage IV, 1/1(100%). After completion of treatment, all 8 patients with recurrent lesions had reelevated SCC antigen levels in series SCC antigen monitoring. In conclusion, positive prognostic factors of disease-free survival were optimal cytoreduction and lower FIGO stage. We suggest that multimodality therapy, including aggressive cytoreduction followed by cis-platinum-based chemotherapy with or without sequential radiotherapy, is recommended. In addition, we suggest that serum SCC antigen monitoring may be helpful in early detection of cancer recurrence.
We report on a case of ureteral injury during laparoscopically radical hysterectomy to treat a patient with a stage IA2 carcinoma of the uterine cervix. The advantage of laparoscopically radical hysterectomy is the prevention of the identification and dissecting of the ureter from a vaginal approach, the main problem in the Schauta technique. However, ureteral injury may still occur while resecting the cardinal ligament without good visualization of the ureter during a vaginal procedure. Because the ureter was well identified and freed laparoscopically, a vaginal approach after uterine removal may be an option for treatment. Moreover, using the ureteral stent as a marker during a modified Schauta technique is helpful in the prevention of ureteral injury during laparoscopically assisted radical vaginal hysterectomy.
Clinical and histopathological features of 12 patients with malignant mixed müllerian tumor of the uterine corpus presenting to Chang Gung Memorial Hospital from January 1988 to September 1993 were retrospectively investigated. The age distribution ranged from 43 to 76 years with a median of 56, and post-menopausal bleeding was the most common symptom in these patients. There was 60% (6/10) of discrepancy in histologic diagnosis between the specimens of dilatation and curettage and that of hysterectomy. All patients received total hysterectomy and bilateral salpingo-oophorectomy, and 10 with retroperitoneal lymph node dissection. Nine patients received cisplatin based chemotherapy, one received radiation only, one received sequential chemotherapy and irradiation, and one underwent concurrent chemoradiation as adjuvant. Two-year survival in patients with stage I-II was 70% (95% C.I.: 34%, 100%) and that of stage III, 25% (95% C.I.: 0.67%). There was 42% (5 of 12) progression/recurrence rate, all developed within 2 years. An effective adjuvant chemotherapy after comprehensive surgery including a total abdominal hysterectomy, bilateral salpingo-oophorectomy and lymph node dissection may be needed for a satisfactory improvement in the patients' survival.
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