Hiroaki Soyama

Is there any predictor for hypersensitivity reactions in gynecologic cancer patients treated with paclitaxel-based therapy?

PurposeRecently, generic drugs of paclitaxel have been commonly used mainly by economic reasons; however, predictive factors for toxicities are not fully determined. Hypersensitivity reaction (HSR) is one of the most important adverse events in the paclitaxel-based therapy, and sometimes leads to lethal condition. The aim of the study was to identify predictors for HSR in patients treated with paclitaxel-based regimens.MethodsAll the patients treated with chemotherapy including paclitaxel at our hospital between 1998 and 2013 were retrospectively evaluated. Clinicopathological factors of the patients that developed HSR and those without HSR were compared, and predictive factors for HSR were identified.ResultsAmong 414 patients enrolled in the study, 26 patients (6.3%) developed HSR. Multivariate analyses showed that younger age (odds ratio 6.31), a history of allergy (odds ratio 3.79), and short-course premedication (odds ratio 14.1) were identified as predictive factors for HSR. There was no significant difference in the incidence of HSR between original paclitaxel and generic drug. The incidence of HSR was higher as the number of these predictors was accumulated.ConclusionsThree factors were identified as predictive factors for HSR: younger age, a history of allergy, and short-course premedication. Accumulation of these factors increased the incidence of HSR; however, the use of generic drug was not associated HSR in gynecologic cancer patients.

JAK2/STAT3 pathway as a therapeutic target in ovarian cancers

The activation of JAK2/STAT3 pathway has been reported to have critical roles in several solid tumors. The present study aimed to evaluate the correlation between JAK2/STAT3 activation and clinicopathological parameters in ovarian cancer types. Tissue microarrays made from the patients treated at the National Defense Medical College Hospital between 1984 and 2008 were evaluated using immunohistochemical (IHC) stainings. Medical charts of these patients including IHC results were retrospectively analyzed, and prognostic factors for progression-free survival and overall survival were evaluated. Among 341 enrolled patients, positive expression of p-STAT3 was observed in 95 cases (28%). Positive p-STAT3 was an independent worse prognostic factor for overall survival in all the cases. Additionally, p-STAT3 expression was related with overall survival in patients with clear-cell histology, but not in serous histology. The effect of an inhibitor of STAT3, niclosamide, was evaluated in ovarian clear-cell cancer cells, and niclosamide treatment decreased expression of p-STAT3, leading to increased apoptosis in a dose-dependent manner in vitro. The activation of JAK2/STAT3 pathway had significant impact on survival of ovarian cancers, especially for the cases with clear-cell histology. Although further analyses are needed, suppression of this pathway could be a candidate for the treatment of ovarian cancers.

Pregnancy with asymptomatic uterine complete rupture after uterine artery embolization for postpartum hemorrhage

OBJECTIVE Uterine artery embolization has become an effective treatment for postpartum hemorrhage. The safety of pregnancy after uterine artery embolization for postpartum hemorrhage has been established. CASE REPORT We present the case of a pregnant woman with asymptomatic uterine complete rupture who underwent uterine artery embolization for a previous placenta previa. She had not been diagnosed with uterine rupture until cesarean section was performed, and fortunately, we obtained the best maternal and neonatal outcomes. CONCLUSION Many studies have been reported that uterine artery embolization for postpartum hemorrhage did not affect subsequent pregnancy outcomes. However, we report that this procedure contains a potential risk for asymptomatic uterine rupture in a subsequent pregnancy. Although it is difficult to diagnose uterine rupture without symptoms, the obstetrician should be aware of the possibility of uterine rupture.

Seromucinous component in endometrioid endometrial carcinoma as a histological predictor of prognosis

Objective In 2014 World Health Organization criteria, seromucinous carcinoma was defined as a new histological subtype in ovarian carcinomas, but “seromucinous carcinoma” was not defined in endometrial carcinomas. The aim of this study was to identify seromucinous carcinoma resembling ovarian seromucinous carcinoma in endometrial carcinomas, and to evaluate the clinical significance for prognoses of the patients. Methods Central pathological review was conducted for patients with endometrioid carcinoma of the endometrium treated by primary surgery at our hospital between 1990 and 2013. Results Among 340 cases included in the study, no case had all tumor cells resembling ovarian seromucinous carcinoma in all specimens, and 31 cases (9.1%) had seromucinous component in combination with endometrioid carcinomas. Immunohistochemical analysis revealed seromucinous component had positive reactivity for cytokeratin (CK) 7, and negative reactivity for CK20 and caudal type homeobox 2 (CDX2) in all cases. Seromucinous component showed lower immunoreactivity of estrogen receptor and progesterone receptor, compared with endometrioid carcinoma component. Progression-free survival of the cases with seromucinous component was better than those without seromucinous component (p=0.049). Conclusion Seromucinous component was identified in approximately 10% of endometrioid carcinoma, and could be a histological predictor for prognosis.

Inhibition of autophagy protein LC3A as a therapeutic target in ovarian clear cell carcinomas.

Objective Ovarian clear cell carcinoma (CCC) is one of histological subtypes showing poor prognosis due to chemoresistance. The association of autophagy-related proteins and clinical implementation in CCC has not been determined. Methods The present study investigated whether expression of autophagy-related protein, light chain 3A (LC3A), was related with prognoses in the patients with CCC using immuno-histochemical stainings, and whether inhibition of autophagy modified the sensitivity to cisplatin in CCC cells in vitro. Results High expression of autophagy-related protein, LC3A, was detected in 78 cases (78%) in all CCC cases. The patients with high LC3A expression showed significantly lower response rate to primary chemotherapy (17% vs. 100%, p<0.010), and had worse progression-free survival (PFS) and overall survival (OS) compared with those with LC3A low expression. Furthermore, multivariate analyses revealed that high expression of LC3A was identified as independent worse prognostic factors for PFS and OS. Inhibition of autophagy protein LC3A using hydroxychloroquine (HCQ) increased sensitivity to cisplatin in CCC cells in vitro. Conclusion High expression of LC3A proteins was associated with lower response to platinum therapy, leading to worse prognoses in CCC. Although further studies are needed to confirm the results, inhibition of autophagy by HCQ was associated with platinum sensitivity. Autophagy protein LC3A could be a promising target for treatment for CCC.

Cervical varicosities may predict placenta accreta in posterior placenta previa: a magnetic resonance imaging study

PurposeThe aim of this study was to prenatally predict placenta accreta in posterior placenta previa using magnetic resonance imaging (MRI).MethodsThis retrospective study was approved by the Institutional Review Board of our hospital. We identified 81 patients with singleton pregnancy who had undergone cesarean section due to posterior placenta previa at our hospital between January 2012 and December 2016. We calculated the sensitivity and specificity of several well-known findings, and of cervical varicosities quantified using magnetic resonance imaging, in predicting placenta accreta in posterior placenta previa. To quantify cervical varicosities, we calculated the A/B ratio, where “A” was the minimum distance from the most dorsal cervical varicosity to the deciduous placenta, and “B” was the minimum distance from the most dorsal cervical varicosity to the amniotic placenta. The appropriate cut-off value of the A/B ratio was determined using a receiver operating characteristic (ROC) curve.ResultsThree patients (3.7%) were diagnosed as having placenta accreta. The sensitivity and specificity of the well-known findings were 0 and 97.4%, respectively. Furthermore, the A/B ratio ranged from 0.02 to 0.79. ROC curve analysis revealed that the area under the combined placenta accreta and A/B ratio curve was 0.96. When the cutoff value of the A/B ratio was set 0.18, the sensitivity and specificity were 100 and 91%, respectively.ConclusionIt was difficult to diagnose placenta accreta in the posterior placenta previa using the well-known findings. The quantification of cervical varicosities could effectively predict placenta accreta.

Zone Formation of Lymphocyte Infiltration at Invasive Front as a Biomarker of Prognosis in Endometrial Carcinomas

Objective: The clinical significance of lymphocyte infiltration (LI) at the invasive front in endometrial carcinomas (EC) has not been determined. The aim of the current study was to evaluate the association between zone formation of LI at the invasive front of the tumor margin and prognoses of the patients with EC. Methods: All available pathological slides of the enrolled cases were reviewed, and the degree of LI at the invasive front was categorized into 2 groups: strong LI and weak LI. Clinical significance of LI was evaluated retrospectively. Results: A total of 333 cases with EC were enrolled in the study: 225 cases with weak LI and 108 cases with strong LI. Weak LI was more frequently observed in the patients with grade1/2 endometrioid EC. Multivariate analyses for progression-free survival (PFS) and overall survival (OS) revealed that weak LI was identified as an independent worse prognostic factor for OS (p = 0.004) in addition to PFS (p = 0.022). Conclusion: Weak LI at the invasive front of the tumor margin was associated with worse prognoses in EC. Although further studies are needed, it is suggested that LI could be a biomarker of prognoses in EC.

Response to Correspondence “Asymptomatic uterine rupture detected at cesarean section: Some different viewpoints”

We appreciate the opportunity to address the comments and concerns raised by Dr. Matsubara about our previous report [1]. We agree with his comments and would like to reply to his questions. To answer his first question, she did not complain of uterine contractions and was not at risk of preterm birth. Thus, Matsubaras hypothesis that the presence/absence of uterine contractions may affect rupture extension might be reasonable. In addition, the smooth muscle tissue around the rupture had become hardened granulation tissue. This might be one of the reasons preventing the progression of the rupture. The second question was whether the rupture was covered by the intestine/mesentery/omentum. The rupture was actually covered only partially by the right fallopian tube, mesosalpinx, and partial omentum. Matsubaras concept of “masked uterine rupture” is that the rupture is tightly covered by other abdominal tissues [2]; therefore, our case did not completely match his concept. However, our cases partial adhesion might have prevented the enlargement of the rupture to some extent. To answer his final question, we always tend to check the fundus and the back of the uterus by extracting the uterus from the abdominal cavity. However, as Dr. Matsubara mentioned, it is sometimes difficult to check the fundus due to severe adhesion around the uterus. If these conditions were exhibited in the present case, we could not have detected the rupture, and perhaps, the cesarean section would have been finished without repairing the rupture. If the repair is not performed, some patients with the condition may remain asymptomatic and the rupture may spontaneously close. However, other patients suffer from several complications. Generally, because of the reflux of menstrual blood from the rupture hole into the abdominal cavity, symptoms including dysmenorrhea, chronic pelvic pain, postmenstrual spotting, and prolonged menstrual bleeding may develop. Furthermore, this blood accumulation may cause deterioration of uterine mucus quality, block the passage of spermatozoa, or

Small Foci of Serous Component as a Predictor of Recurrence and Prognosis for Stage IA Endometrial Carcinomas

Objective: Most of the endometrial carcinomas are detected in early stages and have a better prognosis; however, predictive factors for recurrence have not been determined. Methods: Patients with grade 1 endometrioid carcinoma (EG1) according to the 2014 WHO criteria at FIGO 2009 stage IA that were identified through scanning medical charts were included, and we assessed whether the presence of uterine serous carcinoma (SC) component which comprised less than 5% of the total volume using the ovarian two-tiered grading system could be a recurrent risk factor in these patients. Results: Among 126 cases which met inclusion criteria, 12 cases had SC. SC tumors were divided into 2 groups: SC resembling high-grade serous carcinoma (HGSC) and SC resembling low-grade serous carcinoma (LGSC). Five (3.9%) cases had HGSC and 7 (5.6%) cases had LGSC. Recurrence was observed in 3 of all cases (2.3%): 2 cases with HGSC, and 1 case with LGSC. Regarding several clinicopathological factors, only the presence of SC was associated with recurrence. The sensitivity and specificity to predict recurrence using this system were 100 and 93%, respectively. Conclusion: The identification of SC using the ovarian two-tiered grading system could be an accurate predictor of recurrence in stage IA EG1.

A case of refeeding syndrome in pregnancy with anorexia nervosa

Refeeding syndrome very rarely develops during pregnancy. A 35-year-old primiparous woman pregnant with twins complained of severe fatigue at 19 weeks’ gestation. She was admitted to our hospital in a malnourished condition because of repeated self-induced vomiting due to anorexia nervosa. Just after hospitalization, she voluntarily increased her caloric intake significantly above the recommended prescribed diet, without medical permission. Nine days later, she developed refeeding syndrome. Electrolyte replacement and calorie restriction were started and her condition gradually improved. The healthy twin babies were born by cesarean section at 36 weeks’ gestation. Acute increases in caloric intake by previously malnourished pregnant women with anorexia nervosa may induce refeeding syndrome. Women with the binge eating/purging subtype of anorexia nervosa may be at additional risk due to alternating phases of starvation and overeating.