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Leukocytosis and thrombocytosis at the first diagnosis predicts clinical outcome in uterine cervical cancer patients
Abstracts / Journal of Reproductive Immunology 118 (2016) 109–141
most common (31%), followed by types 16 (24%), 58 (17%), and 56 (12%). About types 52 and 16 detection rate was, 27% and 17% in chronic cervicitis, 32% and 17% in CIN2, 38% and 35% in CIN3, 42% and 0% in cervical cancer. Detection rate of type 16 has risen in comparison to the type 52 with the progress of cervical lesion. In the age of the study, high-risk HPV detection rate was 56% at 20 s, 49% at 30 s, 33% at 40 s, 32% at 50 s, 30% at 60 s, 37% at 70 s. It showed a declining trend with age. On the other hand, while type 16 was highest at 20 s (34%), type 52 was most common at the 30 s and later (39% at 30 s, 25% at 40 s, 45% at 50 s). In the high-risk HPV positive 161 patients, single infection was detected in 132 patients, and multiple infection was detected in 29 patients. In the single infection, type 52 was detected in 36 patients, and type 16 was detected in 25 patients. On the other hand, in the multiple infection, type 52 was detected in 14 patients, and type 16 was detected in 14 patients. In the multiple infection, type 16 detection rate was increased. About cervical lesion, detection rate of single infection and multiple infection was 14% and 14% in chronic cervicitis, 45% and 47% in CIN2, 28% and 38% in CIN3. Detection rate of multiple infection has risen in comparison to single infection with the progress of cervical lesion. There are differences of the distribution of HPV genotypes in the patients with CIN and cervical cancer. It seems to there are specific differences of the distribution of HPV genotypes in the progress of cervical lesion. Conflicts of interest: The authors have no conflict of interest to declare. http://dx.doi.org/10.1016/j.jri.2016.10.059 51 The expression of APOBEC3G in cervical intraepithelial neoplasia Takashi Iizuka ∗ , Mitsyhiro Nakamura, Masahiro Takakura, Hiroshi Fujiwara Department of Obstetrics and Gynecology, Kanazawa University Hospital, Ishikawa, Japan Object: The AID (activation-induced cytidine deaminase)/APOBEC (apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like) family is a group of cytidine deaminase, which convert cytosine to uracil. APOBEC3G, the prototype of this family, is expressed strongly in lymphoid tissue. APOBEC3G has antiviral activity against HIV as an innate immune system. Recently, it is reported that APOBEC3G is associated with HPV infection. In this study, we investigated the association between uterine cervical dysplasia and expression of APOBEC3G. Method: This study included patients with cervical intraepithelial neoplasia and microinvasive squamous cell carcinoma, who had undergone cervical conization from 2013/4/1 to 2015/3/31. We analyzed the expression of APOBEC3G and p16/INK4a by immunohistochemistry. This study was approved by Medical Ethical Review Board of Kanazawa University. Result: In total 35 cases, 16 cases were diagnosed as CIN1 or CIN2 (low-grade lesion) and 19 cases were diagnosed as CIN3 or microinvasive SCC (high-grade lesion). In high grade lesion, 14 cases (73.6%) expressed APOBEC3G whereas 5 cases (31.2%) expressed APOBEC3G in low grade lesion (p < 0.05). In dysplastic lesions, APOBEC3G was strongly expressed in basal lesions. We also found a significant association between APOBEC3G and p16/INK4a expression. Conclusion: In cervical dysplasia and cancer, high-grade lesions expressed APOBEC3G more than low-grade lesions. These results indicate that APOBEC3G will be associated with HPV infection to
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cervical cells, HPV integration into genome of host cells, and cervical carcinogenesis. Conflicts of interest: The authors have no conflict of interest to declare. http://dx.doi.org/10.1016/j.jri.2016.10.060 52 The effect of abdominal radical trachelectomy on ovarian reserve: Serial changes in serum anti-Müllerian hormone levels Miho Kitai ∗ , Asa Shimizu, Kazuhiro Suzuki, Ai Kogiku, Kasumi Yamamoto, Tokihiro Senda, Takaya Shiozaki, Tamotsu Sudo, Syoji Nagao, Satoshi Yamaguchi Hyogo Cancer Center Gynecology, Japan Objective: To evaluate the effect of abdominal radical trachelectomy on ovarian reserve and compare it with abdominal radical hysterectomy and a control group that did not have surgery. Method: We enrolled eighteen women who had abdominal radical trachelectomy with pelvic lymphadenectomy and 16 patients who had abdominal radical hysterectomy for this study. Ten thousand one hundred eighty-six women were also included as a control group for comparison. The Mann–Whitney U test was used for comparison of patient characteristics and comparison of serum anti-Müllerian hormone levels between the three groups. Results: Serum anti-Müllerian hormone levels in patients with abdominal radical trachelectomy were significantly higher than those of patients with abdominal radical hysterectomy (P < 0.05). Serum anti-Müllerian hormone levels in the abdominal radical hysterectomy group were significantly lower than those in the control group (P = 0.02), with no significant difference between the abdominal radical trachelectomy and control groups. These data indicated that abdominal radical trachelectomy did not affect ovarian function with respect to ovarian reserve and the response to ovarian stimulation. Conclusions: Serum anti-Müllerian hormone levels could be useful as a marker of ovarian reserve after abdominal radical trachelectomy. It is important to avoid postoperative complications causing a reduction in ovarian function to accomplish fertilitysparing surgery. Conflicts of interest: The authors have no conflict of interest to declare. http://dx.doi.org/10.1016/j.jri.2016.10.061 53 Leukocytosis and thrombocytosis at the first diagnosis predicts clinical outcome in uterine cervical cancer patients Yoshiya Miyahara ∗ , Kaho Suzuki, Senn Wakahashi, Yasuhiko Ebina, Hideto Yamada Department of Obstetrics and Gynecology, Kobe University Graduate School of Medicine, Kobe, Japan Objective: To analyze the prognostic values of leukocytosis and thrombocytosis at the first diagnosis in patients with uterine cervical cancer in comparison with various risk factors and, to clarify whether leukocytosis and thrombocytosis can predict the prognosis of patients. Methods: We assessed retrospectively the characteristics and outcomes of 2266 patients with FIGO stage I–IV cervical cancer
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Abstracts / Journal of Reproductive Immunology 118 (2016) 109–141
between January 1990 and January 2012 in Kobe University Hospital and Hyogo cancer center. We investigated the effects of age, clinical stage, histology, and leukocytosis or thrombocytosis at the first diagnosis on Overall survival (OS), and which factor predominantly affects the OS, leukocytosis or thrombocytosis at the first diagnosis by dividing the patients into 4 groups. OS was determined using the Kaplan-Meier method and compared using log-rank test. A Cox proportional hazards regression model was used to calculate the prognostic significance. Results: Leukocytosis and thrombocytosis at the first diagnosis was observed in 318 patients (14%) and in 134 patients (5.9%), respectively. Multivariate analysis revealed that age (hazard ratio [HR];1.7, p < 0.001), advanced stage (HR;4.8, p < 0.001), histology (HR; 2.0, p < 0.001), leukocytosis (HR; 1.5, p < 0.01) and thrombocytosis (HR; 2.0, p < 0.01)were independent predictors of decreased OS. The group 1[T(+), L(+)]showed significantly shorter OS than the group 2[T(+), L(−)](p < 0.05) and the group 3[T(−),L(+)] (p < 0.001). And the group 2 [T(+), L(−)] showed significantly shorter OS than the group 3[T(−), L(+)](p < 0.001). Conclusion: Our results have demonstrated that leukocytosis and thrombocytosis at the first diagnosis are independent prognostic factors of patients with cervical cancer. In particular, attention should be payed to patients with thrombocytosis because patients with thrombocytosis had poorer OS than those with leukocytosis. Conflicts of interest: The authors have no conflict of interest to declare. http://dx.doi.org/10.1016/j.jri.2016.10.062 54 Study of teen pregnancy at our hospital in 2014–2015 Masashi Nishimoto ∗ , Kenji Teramoto, Syuji Morishima, Akira Harada Kobe City Hospital Organization Kobe City Medical Center West Hospital, Japan In these years the proportion of elderly primipara in Japan is on the increase. However, the second baby boom generation women (1971–74) are becoming peak out. This under generation, tends to increase unmarried and late marriage of 30 years old woman. On the other hand, marriage after the unplanned pregnancy is increased, in Japan it is said that there is more than 1/4. Many of the teen pregnancy is an unplanned pregnancy. And as in the Elderly pregnant women have various risks. However, she has not been able to aware of the risk of their own, or disrespect often be, it is necessary to precise perinatal management. In Japan, the percentage of teen pregnancy is 1.2%, is in our hospital was high as 5.8%. Therefore, we studied in teen pregnancy in our hospital. Conflicts of interest: The authors have no conflict of interest to declare. http://dx.doi.org/10.1016/j.jri.2016.10.063
55 Comparison of cases of spontaneous abortion early in the course of pregnancy with normal and abnormal karyotypes (16 trisomy and 22 trisomy) in which conception was achieved by assisted reproductive technology Shoji Kokeguchi ∗ , Yukiko Matsumoto, Seiji Ogata, Satoshi Yamada, Eri Okamoto, Yuri Mizusawa, Kohyu Furuhashi, Masahide Shiotani Hanabusa Women’s Clinic, Kobe, Japan Objectives: Among abortuses, normal karyotypes are detected in about 20% of cases with chromosomal analysis. This study aimed to evaluate features of spontaneous abortion early in the course of pregnancy in cases of normal karyotype and abnormal karyotype(16 trisomy and 22 trisomy). Materials and methods: In this study, 45 cases of miscarriage were investigated with samples which were obtained from dilatation and curettage. The study compared pregnancy loss patterns of 18 cases of normal karyotype (Group I), and 14 cases of 16 trisomy (Group II), and 13 cases of 22 trisomy (Group III). 16 trisomy and 22 trisomy are commonly observed in abortus analysis. Results: There were almost no differences in the grade of blastocysts among the three groups. At 4 weeks 1 day, the mean -hCG level of Groups I, II and III were 254, 436,and 480 mIU/ml respectively. The detection rates of fetal heart beat in Groups I, II and III were 76.9%(10/13), 35.7%(5/14), 76.9%(10/13) respectively. Thirty percent of Group I cases ended in intrauterine fetal death suddenly even though there were no abnormal signs in the last ultrasonography. Anti-phospholipid syndromes were not detected in Group I. Conclusions: Group I and III were similar in the early pregnancy course of the pregnancy. In our small numbers of cases, we could not find anti-phospholipid syndromes in the normal karyotype cases. We believe that miscarriage in Group I were caused by abnormal microstructure karyotype. If it is true, micro SNP array analysis may be adopted to detect the reason of abortion in normal karyotype cases. Conflicts of interest: The authors have no conflict of interest to declare. http://dx.doi.org/10.1016/j.jri.2016.10.064
most common (31%), followed by types 16 (24%), 58 (17%), and 56 (12%). About types 52 and 16 detection rate was, 27% and 17% in chronic cervicitis, 32% and 17% in CIN2, 38% and 35% in CIN3, 42% and 0% in cervical cancer. Detection rate of type 16 has risen in comparison to the type 52 with the progress of cervical lesion. In the age of the study, high-risk HPV detection rate was 56% at 20 s, 49% at 30 s, 33% at 40 s, 32% at 50 s, 30% at 60 s, 37% at 70 s. It showed a declining trend with age. On the other hand, while type 16 was highest at 20 s (34%), type 52 was most common at the 30 s and later (39% at 30 s, 25% at 40 s, 45% at 50 s). In the high-risk HPV positive 161 patients, single infection was detected in 132 patients, and multiple infection was detected in 29 patients. In the single infection, type 52 was detected in 36 patients, and type 16 was detected in 25 patients. On the other hand, in the multiple infection, type 52 was detected in 14 patients, and type 16 was detected in 14 patients. In the multiple infection, type 16 detection rate was increased. About cervical lesion, detection rate of single infection and multiple infection was 14% and 14% in chronic cervicitis, 45% and 47% in CIN2, 28% and 38% in CIN3. Detection rate of multiple infection has risen in comparison to single infection with the progress of cervical lesion. There are differences of the distribution of HPV genotypes in the patients with CIN and cervical cancer. It seems to there are specific differences of the distribution of HPV genotypes in the progress of cervical lesion. Conflicts of interest: The authors have no conflict of interest to declare. http://dx.doi.org/10.1016/j.jri.2016.10.059 51 The expression of APOBEC3G in cervical intraepithelial neoplasia Takashi Iizuka ∗ , Mitsyhiro Nakamura, Masahiro Takakura, Hiroshi Fujiwara Department of Obstetrics and Gynecology, Kanazawa University Hospital, Ishikawa, Japan Object: The AID (activation-induced cytidine deaminase)/APOBEC (apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like) family is a group of cytidine deaminase, which convert cytosine to uracil. APOBEC3G, the prototype of this family, is expressed strongly in lymphoid tissue. APOBEC3G has antiviral activity against HIV as an innate immune system. Recently, it is reported that APOBEC3G is associated with HPV infection. In this study, we investigated the association between uterine cervical dysplasia and expression of APOBEC3G. Method: This study included patients with cervical intraepithelial neoplasia and microinvasive squamous cell carcinoma, who had undergone cervical conization from 2013/4/1 to 2015/3/31. We analyzed the expression of APOBEC3G and p16/INK4a by immunohistochemistry. This study was approved by Medical Ethical Review Board of Kanazawa University. Result: In total 35 cases, 16 cases were diagnosed as CIN1 or CIN2 (low-grade lesion) and 19 cases were diagnosed as CIN3 or microinvasive SCC (high-grade lesion). In high grade lesion, 14 cases (73.6%) expressed APOBEC3G whereas 5 cases (31.2%) expressed APOBEC3G in low grade lesion (p < 0.05). In dysplastic lesions, APOBEC3G was strongly expressed in basal lesions. We also found a significant association between APOBEC3G and p16/INK4a expression. Conclusion: In cervical dysplasia and cancer, high-grade lesions expressed APOBEC3G more than low-grade lesions. These results indicate that APOBEC3G will be associated with HPV infection to
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cervical cells, HPV integration into genome of host cells, and cervical carcinogenesis. Conflicts of interest: The authors have no conflict of interest to declare. http://dx.doi.org/10.1016/j.jri.2016.10.060 52 The effect of abdominal radical trachelectomy on ovarian reserve: Serial changes in serum anti-Müllerian hormone levels Miho Kitai ∗ , Asa Shimizu, Kazuhiro Suzuki, Ai Kogiku, Kasumi Yamamoto, Tokihiro Senda, Takaya Shiozaki, Tamotsu Sudo, Syoji Nagao, Satoshi Yamaguchi Hyogo Cancer Center Gynecology, Japan Objective: To evaluate the effect of abdominal radical trachelectomy on ovarian reserve and compare it with abdominal radical hysterectomy and a control group that did not have surgery. Method: We enrolled eighteen women who had abdominal radical trachelectomy with pelvic lymphadenectomy and 16 patients who had abdominal radical hysterectomy for this study. Ten thousand one hundred eighty-six women were also included as a control group for comparison. The Mann–Whitney U test was used for comparison of patient characteristics and comparison of serum anti-Müllerian hormone levels between the three groups. Results: Serum anti-Müllerian hormone levels in patients with abdominal radical trachelectomy were significantly higher than those of patients with abdominal radical hysterectomy (P < 0.05). Serum anti-Müllerian hormone levels in the abdominal radical hysterectomy group were significantly lower than those in the control group (P = 0.02), with no significant difference between the abdominal radical trachelectomy and control groups. These data indicated that abdominal radical trachelectomy did not affect ovarian function with respect to ovarian reserve and the response to ovarian stimulation. Conclusions: Serum anti-Müllerian hormone levels could be useful as a marker of ovarian reserve after abdominal radical trachelectomy. It is important to avoid postoperative complications causing a reduction in ovarian function to accomplish fertilitysparing surgery. Conflicts of interest: The authors have no conflict of interest to declare. http://dx.doi.org/10.1016/j.jri.2016.10.061 53 Leukocytosis and thrombocytosis at the first diagnosis predicts clinical outcome in uterine cervical cancer patients Yoshiya Miyahara ∗ , Kaho Suzuki, Senn Wakahashi, Yasuhiko Ebina, Hideto Yamada Department of Obstetrics and Gynecology, Kobe University Graduate School of Medicine, Kobe, Japan Objective: To analyze the prognostic values of leukocytosis and thrombocytosis at the first diagnosis in patients with uterine cervical cancer in comparison with various risk factors and, to clarify whether leukocytosis and thrombocytosis can predict the prognosis of patients. Methods: We assessed retrospectively the characteristics and outcomes of 2266 patients with FIGO stage I–IV cervical cancer
130
Abstracts / Journal of Reproductive Immunology 118 (2016) 109–141
between January 1990 and January 2012 in Kobe University Hospital and Hyogo cancer center. We investigated the effects of age, clinical stage, histology, and leukocytosis or thrombocytosis at the first diagnosis on Overall survival (OS), and which factor predominantly affects the OS, leukocytosis or thrombocytosis at the first diagnosis by dividing the patients into 4 groups. OS was determined using the Kaplan-Meier method and compared using log-rank test. A Cox proportional hazards regression model was used to calculate the prognostic significance. Results: Leukocytosis and thrombocytosis at the first diagnosis was observed in 318 patients (14%) and in 134 patients (5.9%), respectively. Multivariate analysis revealed that age (hazard ratio [HR];1.7, p < 0.001), advanced stage (HR;4.8, p < 0.001), histology (HR; 2.0, p < 0.001), leukocytosis (HR; 1.5, p < 0.01) and thrombocytosis (HR; 2.0, p < 0.01)were independent predictors of decreased OS. The group 1[T(+), L(+)]showed significantly shorter OS than the group 2[T(+), L(−)](p < 0.05) and the group 3[T(−),L(+)] (p < 0.001). And the group 2 [T(+), L(−)] showed significantly shorter OS than the group 3[T(−), L(+)](p < 0.001). Conclusion: Our results have demonstrated that leukocytosis and thrombocytosis at the first diagnosis are independent prognostic factors of patients with cervical cancer. In particular, attention should be payed to patients with thrombocytosis because patients with thrombocytosis had poorer OS than those with leukocytosis. Conflicts of interest: The authors have no conflict of interest to declare. http://dx.doi.org/10.1016/j.jri.2016.10.062 54 Study of teen pregnancy at our hospital in 2014–2015 Masashi Nishimoto ∗ , Kenji Teramoto, Syuji Morishima, Akira Harada Kobe City Hospital Organization Kobe City Medical Center West Hospital, Japan In these years the proportion of elderly primipara in Japan is on the increase. However, the second baby boom generation women (1971–74) are becoming peak out. This under generation, tends to increase unmarried and late marriage of 30 years old woman. On the other hand, marriage after the unplanned pregnancy is increased, in Japan it is said that there is more than 1/4. Many of the teen pregnancy is an unplanned pregnancy. And as in the Elderly pregnant women have various risks. However, she has not been able to aware of the risk of their own, or disrespect often be, it is necessary to precise perinatal management. In Japan, the percentage of teen pregnancy is 1.2%, is in our hospital was high as 5.8%. Therefore, we studied in teen pregnancy in our hospital. Conflicts of interest: The authors have no conflict of interest to declare. http://dx.doi.org/10.1016/j.jri.2016.10.063
55 Comparison of cases of spontaneous abortion early in the course of pregnancy with normal and abnormal karyotypes (16 trisomy and 22 trisomy) in which conception was achieved by assisted reproductive technology Shoji Kokeguchi ∗ , Yukiko Matsumoto, Seiji Ogata, Satoshi Yamada, Eri Okamoto, Yuri Mizusawa, Kohyu Furuhashi, Masahide Shiotani Hanabusa Women’s Clinic, Kobe, Japan Objectives: Among abortuses, normal karyotypes are detected in about 20% of cases with chromosomal analysis. This study aimed to evaluate features of spontaneous abortion early in the course of pregnancy in cases of normal karyotype and abnormal karyotype(16 trisomy and 22 trisomy). Materials and methods: In this study, 45 cases of miscarriage were investigated with samples which were obtained from dilatation and curettage. The study compared pregnancy loss patterns of 18 cases of normal karyotype (Group I), and 14 cases of 16 trisomy (Group II), and 13 cases of 22 trisomy (Group III). 16 trisomy and 22 trisomy are commonly observed in abortus analysis. Results: There were almost no differences in the grade of blastocysts among the three groups. At 4 weeks 1 day, the mean -hCG level of Groups I, II and III were 254, 436,and 480 mIU/ml respectively. The detection rates of fetal heart beat in Groups I, II and III were 76.9%(10/13), 35.7%(5/14), 76.9%(10/13) respectively. Thirty percent of Group I cases ended in intrauterine fetal death suddenly even though there were no abnormal signs in the last ultrasonography. Anti-phospholipid syndromes were not detected in Group I. Conclusions: Group I and III were similar in the early pregnancy course of the pregnancy. In our small numbers of cases, we could not find anti-phospholipid syndromes in the normal karyotype cases. We believe that miscarriage in Group I were caused by abnormal microstructure karyotype. If it is true, micro SNP array analysis may be adopted to detect the reason of abortion in normal karyotype cases. Conflicts of interest: The authors have no conflict of interest to declare. http://dx.doi.org/10.1016/j.jri.2016.10.064