A Retrospective Study Comparing Olaparib and Bevacizumab as a Maintenance Therapy for Platinum-Sensitive Recurrent Ovarian Cancer: Impact on Recurrence-Free Survival in Japanese and Asian Populations.

The use of angiogenesis inhibitors and poly ADP-ribose polymerase inhibitors following multi-agent chemotherapy, including platinum-based agents, has become the standard treatment for platinum-sensitive recurrent ovarian cancer (PSROC). However, the optimal maintenance therapy and selection criteria for these patients remain unclear. Thus, this study aimed to optimize the treatment options and selection criteria for patients with PSROC. The clinical data of 51 patients with PSROC admitted to Nippon Medical School Chiba Hokusoh Hospital and Nippon Medical School Hospital were retrospectively collected. The log-rank test was used for the survival analysis, and Cox proportional hazard regression analysis was used for the multivariate survival analysis. Of the 51 patients, 17 received maintenance therapy with bevacizumab (Bev), and 34 received olaparib (Ola). Recurrence-free survival (RFS) was significantly prolonged in the Ola group (27 months; 95% confidence interval (CI), 19-NA months) compared with that in the Bev group (9 months; 95% CI, 5-22 months; p = 0.000103). The efficacy of Ola was independent of background factors, including response to previous chemotherapy, homologous recombination status, histological type, or laboratory data. Ola is superior to Bev as PSROC maintenance therapy, especially in Japanese and Asian populations.

Zinc deficiency is associated with gynecologic cancer recurrence.

Zinc deficiency can cause various symptoms, including hair loss, anemia, and taste disorders. Recently, the association between cancer and zinc deficiency has received much attention with respect to its antioxidant properties. However, only a few studies have investigated the association between gynecologic cancers and zinc; to date, no studies have evaluated serum zinc status at the onset of gynecologic cancer or the relationship between zinc and cancer recurrence. The objectives of the present study were to determine whether serum zinc concentrations are associated with the development of gynecologic cancer, to clarify serum zinc dynamics between the onset and recurrence of gynecologic cancer, and to identify the associated factors. Accordingly, we retrospectively determined serum zinc concentrations before treatment in gynecologic patients with benign disease or cancer at the Nippon Medical School Chiba Hokusoh Hospital. We investigated anemia and hypoalbuminemia-the most common causes of zinc deficiency-as indicators of hyponutrition to determine the causal relationship of this deficiency with chemotherapy, radiation therapy, and recurrence, which may affect zinc concentration during cancer recurrence. The results indicated that there was no difference in zinc concentration between preoperative cancer patients and noncancer patients and that serum zinc concentrations were not associated with developing gynecologic cancers. However, patients with gynecologic cancer exhibited significantly lower serum zinc concentrations following treatment, and patients with recurrent cancer were 4.8 times more likely to develop zinc deficiency than those with nonrecurrent cancer. A serum zinc concentration of <61 µg/dL was an independent predictor of recurrence. Once zinc deficiency occurred, the recurrence rate of zinc deficiency reached as high as 69%. Overall, our study indicates that zinc deficiency is associated with recurrence in gynecological cancers and physicians should monitor zinc levels during disease management.

Allergy testing for Cremophor in a patient with cervical cancer with infusion reactions to paclitaxel and docetaxel.

A woman in her 30s with cervical cancer underwent postoperative chemotherapy and showed allergic reactions to multiple taxanes. As the patient had infusion reactions to both paclitaxel and docetaxel, a prick test with Cremophor was conducted. In the absence of an allergic reaction to etoposide, we determined that the patient was allergic to pure taxane compounds. Among infusion reactions caused by taxanes, Cremophor allergy is reported in 3% of cases. Therefore, a prick test with Cremophor performed on a taxane infusion reaction will be useful in diagnosing allergy. In addition, allergy due to docetaxel may be managed by adequate premedication and continuous intravenous chlorpheniramine administration.

Maintenance therapy for long-term control of high-grade endometrial stromal sarcoma.

High-grade endometrial stromal sarcoma (HG-ESS) is a malignant uterine tumour with a poor prognosis. This study aimed to demonstrate the usefulness of maintenance chemotherapy with paclitaxel (PTX) and carboplatin (CBDCA) for HG-ESS recurrence, by examining a case of HG-ESS tumour progression as a result of maintenance therapy interruption because of the COVID-19 pandemic. The patient was a woman in her 60s who presented with lower abdominal pain, nausea and a pelvic tumour, which was diagnosed as HG-ESS. Chemotherapy with PTX (175 mg/m2 day 1) + CBDCA (area under the concentration-time curve 5 day 1) every 21-28 days (TC therapy) was administered for long-term maintenance of HG-ESS. After 26 cycles, chemotherapy had to be postponed because of the COVID-19 pandemic, thus leading to disease progression and eventually death. In conclusion, TC therapy can prolong survival in patients with HG-ESS, and maintenance chemotherapy should not be postponed.

Efficacy and Adverse Events of Carboplatin Desensitisation Therapy for Gynaecological Cancer: A Retrospective Study.

BACKGROUND: Carboplatin, the key drug used in treating gynaecological cancer, has an approximately 12-16% risk of hypersensitivity reactions. We aimed to investigate the efficacy and adverse effects of carboplatin desensitisation therapy for gynaecological cancer. METHODS: The desensitisation protocol was standardised as a four-step, 4-h, carboplatin administration in the hospital. A retrospective medical record review was conducted on 15 patients who underwent carboplatin desensitisation for gynaecological malignancies at our hospital. Patients' data were analysed to evaluate the treatment success rate, therapeutic effect of desensitisation, adverse events, and treatment. RESULTS: Of 91 carboplatin desensitisation cycles scheduled; the completion rate was 93.4% (85/91). Adverse events occurred in 23 of these 91 (25.3%). In four (4.4%) of the 23 cycles, hypersensitivity reactions could be treated only by discontinuing the infusion and slowing the administration, while in the remaining 19 (20.9%), medication was administered intravenously after discontinuing the infusion to manage hypersensitivity reactions. No treatment-related deaths occurred. Overall, 23 series of anti-cancer agent regimens, including carboplatin desensitisation, were administered to the 15 patients. The therapeutic response rate was 82.6% and the disease control rate was 95.7%. CONCLUSIONS: Carboplatin desensitisation was beneficial in patients with a history of carboplatin-induced hypersensitivity reactions.

Somatic gene mutations in malignant steroid cell tumours and response to multiple treatments.

Malignant ovarian steroid cell tumours are a rare subgroup of sex cord-stromal tumours. There are no systematic reviews on the associated treatments, and little is known about their genomic profile. We describe a case of a pelvic malignant ovarian steroid cell tumour in a premenopausal woman in her 40s. She received cytoreductive surgery and six cycles of paclitaxel+carboplatin+bevacizumab. After recurrence, the tumour was surgically removed again, followed by radiation and hormone blockade therapy. Complete remission was achieved after treatment with bleomycin, etoposide and cisplatin. She remained in a platinum-sensitive relapse state and subsequently received maintenance therapy with olaparib. Since the tumour was initially refractory to treatment, tissue specimens were screened for gene mutations using a next-generation sequencing oncology panel and a somatic variant detection system, which revealed somatic gene mutations in ARID1A, PIK3CA, TERT and ATM, some of which are involved in DNA repair.

Beyond BRCA Status: Clinical Biomarkers May Predict Therapeutic Effects of Olaparib in Platinum-Sensitive Ovarian Cancer Recurrence.

The purpose of this study was to investigate the predictors of the effect of olaparib on platinum-sensitive recurrent ovarian cancer with unknown germline BRCA mutations. We retrospectively examined 20 patients with platinum-sensitive ovarian cancer who were treated at the Nippon Medical School Chiba Hokusoh Hospital, Japan, from 2018 to 2020. We found that the median progression-free survival was 11.4 months (95% Confidence interval (CI): 3.8-Not Available (NA)) in the group with NLPN score [recurrent neutrophil-lymphocyte ratio (rNLR) × number of previous regimens] >7.51, and median progression-free survival was not reached in the group with NLPN score <7.51 (95% CI: 21.8-NA) (p = 0.0185). There was a clear correlation between the degree of dose reduction of olaparib and recurrence (p = 0.00249). Our results show that NLPN scores lower than 7.51 are associated with a favorable outcome of olaparib treatment for platinum-sensitive recurrent ovarian cancer. In cases with a high rNLR, it may be necessary to start olaparib treatment as early as possible to obtain low NLPN scores. Our results imply that the effectiveness of olaparib can be determined after recurrence and before platinum treatment begins. As newer drugs for ovarian cancer are developed, the measurement of biomarker levels at the start of treatment for recurrent ovarian cancer, as shown in our study, may provide strong support for cancer treatment protocols.

Laparoscopic Repair of Vaginal Evisceration after Abdominal Hysterectomy for Uterine Corpus Cancer: A Case Report and Literature Review.

Vaginal cuff dehiscence is a rare but serious complication that can develop after hysterectomy. Emergent surgical intervention is required for vaginal cuff dehiscence due to the potential subsequent vaginal evisceration, which may lead to necrosis of the small bowel. A 62-year-old nulliparous woman with a 30-year history of smoking, diabetes mellitus, and rheumatoid arthritis (treated with oral steroids) presented with a vaginal cuff dehiscence. Thirty-eight days before the admission, she had undergone a radical operation including total abdominal hysterectomy for uterine corpus cancer at another hospital. We performed emergent laparoscopic surgery to reduce the prolapsed small bowel into the abdominal cavity and repaired the vaginal cuff with a two-layer continuous closure using absorbable barbed sutures. The patient experienced no postoperative complications, and no recurrence of the vaginal cuff dehiscence occurred. Vaginal cuff dehiscence and evisceration can be surgically managed using an abdominal, vaginal, or laparoscopic approach, and the choice of method should be based on patient characteristics and the surgeon's skills. Laparoscopic vaginal cuff repair with a two-layer continuous closure using absorbable barbed sutures is a minimally invasive technique that is safe and effective for medically stable patients with no small bowel injury or vascular compromise and no pelvic abscess.

A preoperative risk-scoring system to predict lymph node metastasis in endometrial cancer and stratify patients for lymphadenectomy.

OBJECTIVE: This study aimed to validate the preoperative scoring system adopted in the Kanagawa Cancer Center (KCC) to stratify endometrial cancer patients for lymphadenectomy according to the risk of developing lymph node metastasis (LNM). METHODS: The records of 432 and 221 uterine cancer patients treated in the KCC and Yokohama City University (YCU), respectively, were retrospectively analyzed. The KCC classified patients for LNM risk based on tumor volume, myometrial invasion, histological grade, and serum CA125 levels, while YCU used only myometrial invasion. Lymphadenectomy was omitted for 156 patients with 0 LNM risk, while pelvic lymphadenectomy (PLX) or PLX with para-aortic lymphadenectomy (PLAX) were performed for those with low and high LNM risk, respectively. The predicted and actual LNM rates were compared between the KCC and YCU patients, and cancer recurrence and overall survival were analyzed. RESULTS: There was no difference in survival between patients with LNM score 0 who were or were not treated with lymphadenectomy. None (0%) developed LNM and only 1 (0.6%) had recurrence. Patients who underwent PLX but not PLAX (low LNM score) had a low tumor recurrence rate in the para-aortic nodes (1.3%). The KCC scoring system was significantly more accurate than the YCU system in predicting LNM in the high-risk group (P<0.05) and demonstrated that PLAX was unnecessary in almost 50% of the YCU cases. CONCLUSION: The KCC preoperative scoring system is useful to predict LNM risk, and thereby prevent unnecessary lymphadenectomy or to determine its extent in endometrial cancer patients.

Clinical characteristics of pregnancies with a history of recurrent miscarriage at a Japanese perinatal center.

OBJECTIVE: We examined obstetric and fetal/neonatal outcomes in women with a history of recurrent miscarriage. METHODS: We reviewed the obstetric records of all 5,829 nulliparous pregnant women who delivered at #8805;14 weeks' gestation from 2008 through 2013 at our perinatal center. Of these women, 74 had a history of recurrent miscarriage (1.3%). The control population consisted of 4,176 nulliparous women without a history of miscarriage. Demographic information and characteristics of labor were extracted from patient charts. RESULTS: The rate of maternal age #8805;40 years (p<0.01) and the rate of in vitro fertilization use (p<0.01) were higher in women with recurrent miscarriage than in women without miscarriage. Eleven women with recurrent miscarriage (14.9%) were treated with low-dose aspirin with and without subcutaneous heparin. In addition, the rate of cesarean delivery was higher in women with recurrent miscarriage than in women without miscarriage (p=0.02). However, fetal/neonatal outcomes did not differ significantly between the populations. CONCLUSION: The pregnancy of women with a history of recurrent miscarriage is not associated with adverse outcomes at our perinatal center.

A case of maternal vitamin K deficiency associated with hyperemesis gravidarum: its potential impact on fetal blood coagulability.

Vitamin K deficiency is associated with malnutrition in some complications, such as hyperemesis gravidarum, active gastrointestinal diseases, and psychological disorders. Maternal vitamin K deficiency can cause fetal bleeding, in particular, fetal intracranial hemorrhage. Although fetal hemorrhage is uncommon, severe damage to the fetus may be inevitable. We describe a pregnant woman with vitamin K deficiency possibly due to hyperemesis gravidarum. The patient was treated for the deficiency, and no fetal or neonatal hemorrhagic diseases were manifested.

Association between fibrinogen levels and severity of postpartum hemorrhage in singleton vaginal deliveries at a Japanese perinatal center.

OBJECTIVE AND METHODS: We examined the relationship between low fibrinogen levels (<200 mg/dL) and the severity of postpartum hemorrhage in singleton vaginal deliveries after 22 weeks' gestation complicated by postpartum hemorrhage requiring transfusion at our hospital. RESULTS: During a 10-year period, 61 women (0.38%) received transfusions owing to postpartum hemorrhage within the first 24 hours after delivery. Of these women, 13 (21%) had low fibrinogen levels (mean, 123 ± 68 mg/dL) when postpartum hemorrhage was diagnosed, and the other 48 (79%) had normal fibrinogen levels (mean, 305 ± 50 mg/dL). Neither total blood loss nor the incidence of additional therapies, such as hysterectomy, differed between the 2 groups of women. Women with low fibrinogen levels started to receive transfusions significantly earlier (98 ± 58 minutes after delivery) than did women with normal fibrinogen levels (142 ± 75 minutes after delivery, p=0.03) and received more units of fresh-frozen plasma (p=0.03). CONCLUSION: The early transfusion of fresh-frozen plasma in women with postpartum hemorrhage and low fibrinogen levels might help prevent adverse outcomes.

The Effect of the Gelatinous Lactulose for Postoperative Bowel Movement in the Patients Undergoing Cesarean Section.

Lactulose is a non-digestible disaccharide formed from fructose and galactose. The objective of this study was to assess the effect of lactulose on gastrointestinal function after cesarean section. One hundred patients who underwent cesarean section at the Japanese Red Cross Katsushika Maternity Hospital were enrolled in this study. They were divided into 2 groups by randomization: (1) an L group that was treated with gelatinous lactulose (N = 48) and (2) a control group (C group) that did not receive gelatinous lactulose (N = 52). The interval between cesarean section and first postoperative flatus, defecation, and walking; appearance of symptoms of ileus; use of other medicines for stimulating bowel movement; properties and state of feces; and duration of postoperative hospital stay were compared between the two groups. The two groups did not show a significant difference in postoperative outcomes, except for the incidence of loose or watery stools (50% in the L group and 26.9% in the C group, P = 0.03). This study could not demonstrate the apparent effectiveness of lactulose in improving bowel function after cesarean section. Therefore, a routine use of gelatinous lactulose after surgery may negatively impact the patients undergoing cesarean section.