Colposcopy Directed Cone Biopsy and Endocervical Curettage as Management of Carcinoma in Situ of the Uterine Cervix

OBJECTIVE: The goal of this study was to evaluate the prognostic factors in relation with residual cervical intraepithelial neoplasia (CIN) in hysterectomized specimen of the patients diagnosed as carcinoma in situ of the uterine cervix (CIS) and underwent cone knife biopsies first. Also we investigated if colposcopically directed wide cone knife biopsy with endocervical curettage followed by electrocauterization could substitute for traditional hysterectomy as a conservative management of CIS. METHODS: Data were collected retrospectively from 169 patients who were diagnosed as CIS after colposcopy directed conization in Yonsei University Hospital from Jan 1997 to Dec 2001. The patients were divided into two groups, those who underwent colposcopically directed cone biopsy only (Group A) and those who received colposcopically directed cone biopsy and extrafascial abdominal hysterectomy (Group B). Pap smear, pelvic examination and punch biopsy of the uterine cervix according to symptoms and physical findings of the patients were performed for follow-up. Patient characteristics, histologic results and follow-up outcomes were compared using student t-test, x2 test, and logistic regression analysis. RESULTS: Among 169 patients, 82 (study group) received no further treatment while 87 (control group) were hysterectomized. 58 of control group showed residual CIN in colposcopically directed cone biopsy and 12 from these patients, residual CIN were found in hysterectomized specimen. Positive endocervical margin on conization was found as a significant predictor for residual disease after conization. Abnormal Pap smear results were reported in 10 patients of study group only, of whom 2 cases of CIN I, 8 cases cervicitis. CONCLUSION: The residual CIN in endocervical margin can predict whether hysterectomized specimen might contain residual CIN and no difference in life threatening prognosis existed between the patients received colposcopically directed cone biopsy only and hysteretomy, regardless of the residual CIN in cone biopsy margin. Based on these results, it is reasonable to choose expectant management over hysterectomy for treating CIS patients with marginal involvement.ope

Synchronous Coexpression of Epidermal Growth Factor Receptor and Cyclooxygenase-2 in Carcinomas of the Uterine Cervix - A Potential Predictor of Poor Survival

PURPOSE: To evaluate the potential of the new prognostic information gained by analyzing the coexpression of epidermal growth factor receptor (EGFR) and cyclooxygenase-2 (COX-2) in cervical cancer patients. EXPERIMENTAL DESIGN: Sixty-eight patients with International Federation of Gynecology and Obstetrics stage IIB squamous cell carcinoma of the uterine cervix, who underwent concurrent chemoradiotherapy between 1993 and 1996, were divided into the following four groups according to their immunoreactivities for EGFR and COX-2 in paraffin-embedded sections: (a). the EGFR-negative/COX-2-negative group (n = 11); (b). the EGFR-negative/COX-2-positive group (n = 8); (c). the EGFR-positive/COX-2-negative group (n = 27); and (d). the EGFR-positive/COX-2-positive group (n = 22). The clinical features, patterns of treatment failure, and survival data in the four groups were compared. RESULTS: Positive immunoreactivity for EGFR and COX-2 was observed in 49 of 68 (72%) and 19 of 68 (28%), respectively. However, no strong correlation was found between the levels of EGFR and COX-2 immunopositivity (R(2) = 0.05, P = 0.07). Patients in the EGFR-positive/COX-2-positive group had a higher likelihood of locoregional recurrence than those in the other three groups (P = 0.02). Of the patients in the four groups, patients positive for both oncoproteins were found to have the worst prognosis with an overall 5-year disease-free survival rate of 55% compared with 91% for the EGFR-negative/COX-2-negative patients, 88% for the EGFR-negative/COX-2-positive patients, and 69% for the EGFR-positive/COX-2-negative patients (P = 0.05, log-rank test). In addition, the synchronous coexpression of the EGFR and COX-2 oncoproteins was found to be an independent prognostic factor by univariate and multivariate analyses (relative risk = 4.0, P = 0.03). CONCLUSIONS: Given these observations, we conclude that the coexpression of EGFR and COX-2 immunoreactivity may be used as a potent molecular risk factor for predicting the poor survival of patients with the International Federation of Gynecology and Obstetrics stage IIB squamous cell carcinoma of the uterine cervix.ope

Studies on the genesis of fatty liver

의학과/석사[한글] [영문] Accumulation of lipid in the parencymal cells is rather common and most frequently observed in the liver, heart, and kidneys. The fatty liver is found in diverse conditions, which include nutritional disturbances, infectious diseases, chronic anemia or ischemia, and injuries caused by various hepatotoxic agents. Experimentally a fatty liver has been produced by carbon tetrachloride, phosphorus, ethanol, DDT, tannic acid, erotic acid, ethionine, etc. (Lombardi, 1966). Regardless of causative agents, the accumulated lipid in talc liver cell is always neutral fat. Lombardi (1966) postulated that talc accumulated fat in the liver eells is due to either; 1) disturbance in talc utilization of triglycerides, 2) increased synthesis of triglycerides, 3) decreased utilization of triglycerides, or 4) synthesis of triglycerides outside of the endoplasmic reticulum. It is customary to divide fat accumulation in the parenchymal calls into fatty infiltration and fatty degeneration. The former is due to the increased accumulation of fat without preceding on to cellular injury while in the latter the fat accumulates secondary to the prior cellular injury, The locus of fat synthesis in the liver cell is considered variously according to different investigators. Kennedy and Lebninger (1948), Green (1954) reported that talc oxidation of fatty acids takes place in the mitochondria, while Baglio and Farber (1965) reported that it takes place in the rough endoplasmie reticulum, and palace (1955) reported the smooth endoplasmic reticulum is the site of fat formation. The present investigation is aimed of studying trio mechanism, process and site of fat accumulation in the liver cells following the treatment of rats with different types of lipogenic factors. Materials and Methods Male albino rats weighing around 200 gms were used for the experiment and divided into the following group; normal control, high fat diet, carbon tetrachloride injected, ethionine injected, and talc acute anemic. The high fat diet contained 50% salad oil. The carbon tetrachloride was injected subcutaneously in a single dose of 0.2 ml. per kg of the body weight, and ethionine was injected peritoneally in a single dose of 1g. per kg of the body weight. Acute anemia was produced by withdrawing approximately 4.0ml. of whole blood by cardiac puncture. The hematocrit value was determined in anemia and normal control group with the blood drawn immediately before the animals were killed. Three animals from each group acre killed at 6, 12, 18, 24, 48, 72, 96 hours, 5, 7, and 10day intervals. Overall histologic alterations were observed by routine hematoxylin-eosin staining technic, and the degree and the pattern of fatty change were determined by the oil red-0 staining on frozen sections and thin sections taken from Epon block after osmic acid fixation counter stained with basic fuchsin. For the electronmicroscopic examinations, the tissue was fixed in 1% solution of csmic acid and dehydrated with graded alcohol. The sections were cut following Epon embeding in 400 to 500 A thickess with glass knife and stained with uranyl acetate and lead hydroxide. Observation was made with Hitachi 11-E model electronmicroscope. Results and Discussions The hamatocrit dropped markedly following the cardiac puncture and gradually returned to normal value around the 7th day. On light microscopic examinations, necrosis and ballooning of the liver cells were found in carbon tetrachloride treated group only, and mostly limited at the centrilobular zone. The animals in the remaining groups showed mild to moderate degree of vacuolization in the cytoplasm. The accumulation of the lipid started from the periportal area in the animals treated with ethionine, high fat diet and cardiac puncture, where as it was first noted at the centrilobular zone in animals treated with carbon tetrachloride. The size of the fat globules was for and rather uniform in the animals fed on a high fat diet and in the acute anemic group. The fat globules in ethionine treated animals were somewhat larger but uniform in size, while those of the carbon tetrachloride treated animals were irregular in size. The deposition of the fat apparently started from the peripheral portion of the liver cells and spread into perinuclear portion with increasing size. Thc electronmicroscopic examinations revealed no notable alteration of the cytoplasmic organelles in high fat fed animals, and mild vacuolization with destruction of microvilli of bile cansliculi in the acute anemic group, while a made dilatation of the rough endoplasmic reticulum with detachment of ribosome, decrease of free ribosome, and mild swelling of mitochondria were noted in animals treated with carbon tetrachloride or ethionine. The fat globules first appeared in the endoplasmic reticulum in all experimental groups, and their size increased from the peripheral to the perinuclear portion. In the animals treated with carbon tetrachloride or ethionine, numerous small electron dense granules appeared in the dilated rough endoplasmic reticulum preceding the appearance of fat globules, but no such granules were noted in high fat diet and acute anemic groups. Hyperplasia and aggregation of the smooth endoplasmic reticulum was noted only in carbon tetrachloride treated animals and did not seem to be related with the fatty change. Summary: The accumulation of the fat in the liver cell started within the rough endoplasmic reticulum regardless of the causal factorsm initiated at the peripheral portion of the cisternae moving toward perinuclear portion with increasing size, and associated with carbon tetrachloride or ethionine. But no such changes were noted in high fat fed and acutely anemic animals therefore a different mechanism, probably an increased synthesis of the fat in the former and a decreased utilization in the latter, must be acting.restrictio

A Study on sensitivity analysis in interior-point methods

학위논문(박사)--서울대학교 대학원 :산업공학과,2000.Docto

내부점 기법에서 최적기저 회복에 관한 연구

학위논문(석사)--서울대학교 대학원 :산업공학과,1996.Maste

Clinico-pathological survey on ovarian tumors at Severance hospital

의학과/석사[한글] [영문] Ovarian tumors are one of the many neoplasms seen in the practice of Gynecology. Because of the various types no basic etiology has been established. Numerous classifications have been devised based on etiology, histology and embryology but no one has been universally accepted by gynecologists or pathologists. Only a few statistical surveys on ovarian tumors have been reported in Korea and even the small numbers of reports show great variation in their results. The author undertook this study because of the importance of a clinico-pathologic survey of ovarian tumors as observed in Korea. A clinico-pathological as well as statistical survey was made on a series of 230 ovarian tumors admitted, operated upon and confirmed with post-operative histopathological study at th Department of Obstetrics & Gynecology and Department of Surgery, Severance Hospital, Yonsei University during a period of 5 years and 7 months from January, 1961 to July, 1966. The results obtained are as follows: 1. The incidence of benign tumors was 87.4% of all ovarian tumors while that of malignant ones 12.6%. 2. Age distribution of benign tumors was between 26-46 (Average 36 years), while that of malignant ones 31-59 (Average 45 years). 3. Menstruation was regular in 57.8%, irregular in 11.7% and the rest were amenorrheic. Patients with benign tumors had regular cycle in 59.7%, irregular in 11.4% while those with malignant tumors were regular in 44.8%, irregular in 11.7%. 4. Among the subjective symptoms complained of by the patient, 51.3% noticed a lower abdominal mass, 47.4% complained of lower abdominal pain and 15.6% had backache. 5. As to the objective signs among the ovarian tumors, ascites were observed in 27 cases (11.7%), cachexia in 6 cases (2.6%). In malignant tumors ascites and cachexia were noted in 65.5%, 20.7% respectively while in benign ones none had cachexia and only 3.9% had ascites. 6. The gross size of benign and malignant ovarian tumors were average 11 cm, 10.5 cm respectively while that of non-neoplastic cyst among the benign tumors was average 9.9 cm. 7. Of all the ovarian tumors 45.9% were noted in the right ovary, 33.8% in the left. Benign tumors were observed 51.3% in right ovary, 37.8% in left while among the malignant tumors 24.1% were in right, 17.2% in left. We can see the greater occurrence of tumors in right ovary in both the benign and malignant category. 8. The order of incidence of the benign tumors was dermoid cyst 30.4%, pseudomucinous cystadenoma 15.4%, simple cyst 14.4% and serous cystadenoma 11.4% while the incidence of the malignant ones was serous papillary cystadenocarcinoma 34.5%, Krukenberg tumor 24.1% and pseudomucinous cystadenocarcinoma 20.7%. 9. Among the neoplastic ovarian cysts dermoid cysts were bilateral in 14.8%, serous cystadenoma in 8.7% and pseudomucinous systadenoma in 6.4%. 10. The incidence of malignancy in the serous neoplasms, pseudomucinous ones and dermoid cysts was 43.5%, 19.4% and 1.6% respectively while the malignancy of all the ovarian tumors was 12.6%.restrictio

Patterns of treatment failure following radiotherapy with combination chemotherapy for patients with high-risk stage IIB cervical carcinoma

BACKGROUND: To evaluate the patterns of treatment failure in patients with stage IIB cervical carcinoma with high-risk factors following radiotherapy given concurrently with combination chemotherapy. METHODS: A retrospective analysis of 349 patients with stage IIB cervical carcinoma with high-risk factors (lesion size >/= 4 cm, lymph node metastasis, high-risk cell type) treated by radiotherapy and cisplatin-based chemotherapy was performed. Sites of treatment failure were categorized as pelvic, pelvic plus distant metastases, and distant metastases alone. Pelvic failure included local and pelvic nodal failures. RESULTS: Of the 349 patients, treatment failure occurred in 79 patients (22.6%). Forty-six (13.2%) had persistent disease and 33 (9.5%) had recurrent disease. Among these 79 patients, overall pelvic failure was observed in 67%, of whom 72% had local failure; 19%, pelvic nodal failure; and 9%, local with pelvic nodal failure. Incidences of distant metastases alone and pelvic with distant metastases were 24% and 9%. In the 26 patients with distant metastases either alone or combined with pelvic failure, the most frequent metastatic region was the paraaortic lymph node (50%). The distant metastasis rate was 6.5% (19/289) in the pelvic tumor control group and 11.6% (7/60) in the pelvic failure group. Pelvic failure was the most frequent failure in the group with tumor size of 4 cm or more, whereas, for the positive-lymph-node group, distant metastasis was most frequent and metastases to paraaortic lymph nodes were common. The incidences of pelvic failure alone and distant metastases were similar in the high-risk cell-type group, and the distant metastasis regions were mostly paraaortic lymph nodes. CONCLUSION: Although systemic chemotherapy was administered concurrently with radiotherapy, the incidence of pelvic failure was highest, followed by paraaortic lymph node metastases, in patients with stage IIB cervical carcinoma with high-risk factors, following radiotherapy with combination chemotherapy. To evaluate the patterns of treatment failure in patients with stage IIB cervical carcinoma with high-risk factors following radiotherapy given concurrently with combination chemotherapy.ope

Genotyping of 22 human papillomavirus types by DNA chip in Korean women: Comparison with cytologic diagnosis

OBJECTIVE: More sensitive and reliable methods than individual testing (such as polymerase chain reaction, restriction fragment length polymorphism, and Southern blot) should be developed as screening tools for the detection of latent human papillomavirus. Today, the new Bethesda system recommends human papillomavirus testing as an adjuvant to the conventional Papanicolaou smear for more comprehensive identification of women at certain risk of cervical neoplasia. We performed human papillomavirus genotyping with the newly designed human papillomavirus DNA chip, which is based on polymerase chain reaction for high-throughput screening power, and compared the results with the results of a Papanicolaou smear according to the new Bethesda system. STUDY DESIGN: Polymerase chain reaction amplifications of the human papillomavirus L1 region from biologic samples were hybridized to silanized glass slides by a microarrayer, which comprised 22 specific oligonucleotide probes to their genotypes, consisting of 15 high-risk and 7 low-risk types. Two cervical cancer cell lines and 20 plasmids that contained each type of the human papillomavirus whole genome were used for the evaluation of this method; in all cases, the cancer cell lines and plasmids showed clear positive signals on their corresponding positions. A comparative study that used 685 cervicovaginal swabs was performed by human papillomavirus DNA chip microarray together with Papanicolaou diagnosis. RESULTS: Human papillomavirus was identified as positive in 31.9% of the 414 control samples and in 78.6% of the 271 neoplastic lesions. The major prevailing human papillomavirus genotypes were human papillomavirus types 16, 58, and 18, in descending order of incidence (average overall, 78.8%). Almost all of the remaining cases were comprised of human papillomavirus types 39, 52, 56, and 51. The frequency of multiple infection of human papillomavirus was highest in low-grade squamous intraepithelial lesion but was lowest in squamous cell carcinoma. All cases that exhibited infection of single human papillomavirus type 58 were squamous cell carcinoma. CONCLUSION: Human papillomavirus types 16, 18, and 58 were confirmed to be major causative factors for cervical carcinogenesis. Low-grade squamous intraepithelial lesion is a heterogeneous entity that is composed of different human papillomavirus subtypes and prevails in younger women (<40 years old). The human papillomavirus chip has potential use as a high-throughput screening test.ope