Immunotherapy for Uterine Cervical Cancer Using Checkpoint Inhibitors: Future Directions.

Immune checkpoint inhibitors (ICIs) have demonstrated marked clinical effects worldwide, and "cancer immunotherapy" has been recognized as a feasible option for cancer treatment. Significant treatment responses have already been attained for malignant melanoma and lung cancer, ahead of gynecologic cancer. In cervical cancer, however, results are only available from phase II trials, not from phase III trials. Cervical cancer is a malignant tumor and is the fourth most common cancer among women worldwide. Since the introduction of angiogenesis inhibitors, treatment for recurrent and advanced cervical cancers has improved in the past five years, but median overall survival is 16.8 months for advanced cervical cancer, and all-stage five-year overall survival rate is 68%, indicating that treatment effects remain inadequate. For this reason, the development of new therapeutic approaches is imperative. We describe herein the KEYNOTE-158 and CheckMate 358 clinical trials, which were conducted for cervical cancer, and discuss future directions, including potential combinations with concurrent chemoradiation therapy (CCRT), as noted for other types of cancer.

Prevention of lymphocele development in gynecologic cancers by the electrothermal bipolar vessel sealing device.

OBJECTIVE: A number of new techniques have been developed to prevent lymphocele formation after pelvic lymphadenectomy in gynecologic cancers. We assessed whether the electrothermal bipolar vessel sealing device (EBVSD) could decrease the incidence of postoperative lymphocele secondary to pelvic lymphadenectomy. METHODS: A total of 321 patients with gynecologic cancer underwent pelvic lymphadenectomy from 2005 to 2011. Pelvic lymphadenectomy without EBVSD was performed in 134 patients, and pelvic lymphadenectomy with EBVSD was performed in 187 patients. We retrospectively compared the incidence of lymphocele and symptoms between both groups. RESULTS: Four to 8 weeks after operation, 108 cases of lymphocele (34%) were detected by computed tomography scan examination. The incidence of lymphocele after pelvic lymphadenectomy was 56% (75/134) in the tie ligation group, and 18% (33/187) in the EBVSD group. We found a statistically significant difference in the incidence of lymphocele between both groups (p<0.01). To detect the independent risk factor for lymphocele development, we performed multivariate analysis with logistic regression for three variables (device, number of dissected lymph nodes, and operation time). Among these variables, we found a significant difference (p<0.001) for only one device. CONCLUSION: Use of the EBVSD during gynecological cancer operation is useful for preventing the development of lymphocele secondary to pelvic lymphadenectomy.

Validity of intraoperative diagnosis at laparoscopic surgery for ovarian tumors.

STUDY OBJECTIVE: To evaluate the accuracy and usefulness of intraoperative diagnosis of ovarian tumor during laparoscopic surgery. DESIGN: Retrospective cohort study (Canadian Task Force classification II-3). SETTING: Tertiary care university hospital. PATIENTS: We reviewed the cases of 262 patients who underwent laparoscopic surgery at our institution between January 2005 and December 2011 in whom a benign ovarian tumor was diagnosed intraoperatively. INTERVENTIONS: Intraoperative pathologic assessment of frozen sections. MEASUREMENTS AND MAIN RESULTS: Intraoperative diagnosis of ovarian tumors demonstrated sensitivity of 80%, specificity of 99.6%, positive predictive value of 80%, and diagnostic accuracy of 99.2%. Mucinous tumors diagnosed intraoperatively showed differing intraoperative and final pathologic diagnoses significantly more frequently than did other types of tumors. CONCLUSION: Intraoperative pathologic assessment of benign ovarian tumors during laparoscopic surgery is reliable. However, clinicians should recognize that it is possible to make an incorrect diagnosis in some situations and should exercise caution accordingly.

[Safety and efficacy of pegylated liposomal Doxorubicin and Carboplatin on platinum-sensitive recurrent epithelial ovarian cancer].

OBJECTIVE: We evaluated the safety and efficacy of pegylated liposomal doxorubicin(PLD)and carboplatin(CBDCA)(CD) for platinum-sensitive recurrent epithelial ovarian cancer. METHODS: From December 2010 to June 2011, 9 eligible patients with histologically confirmed, recurrent epithelial ovarian cancer, which was deemed platinum-sensitive, were enrolled onto the study. PLD(30mg/m2)and CBDCA(area under the curve[AUC]5)were administered intravenously on day 1 of the cycle. The chemotherapy regimen was repeated every 4 weeks, until disease progression or completion of 6 cycles. RESULTS: A total of 49 treatment cycles of CD were administered to 9 patients. The median platinum-free interval was 18.3 months. Patients with Grade 3/4 hematological toxicities were observed to have leucopenia(11.1%), neutropenia(44.4%), anemia (22.2%), and thrombocytopenia (22.2%). No Grade 3/4 non-hematological toxicities were observed, and no treatment related death occurred. Seven patients(77.7%)responded to CD(4 complete responses and 3 partial responses). The median progression-free survival and overall survival times were 15.1 and 23.7 months. CONCLUSION: CD treatment seems to be a safe and effective chemotherapy regimen for platinum-sensitive recurrent epithelial ovarian cancer.

[A patient with recurrent ovarian clear cell adenocarcinoma and chronic kidney disease exhibited complete response to paclitaxel plus carboplatin].

A 41-year-old woman receiving hemodialysis 3 times a week for chronic kidney disease caused by interstitial nephritis was referred to our hospital because of a pelvic mass and subsequently underwent primary surgery. The patient was diagnosed with FIGO stage Ic (b) clear cell adenocarcinoma. She did not receive postoperative chemotherapy. However, 9 months after surgery, ascites and a pelvic mass developed, on the basis of which recurrence was confirmed. She received combination chemotherapy with paclitaxel plus carboplatin (TC). Paclitaxel was administered at 175 mg/m2, and the carboplatin dosage was calculated by the Calvert formula. The glomerular filtration rate was considered to be 0, and the target area under the plasma concentration versus time curve was 5. Hemodialysis was performed 24 hours after the infusion of carboplatin. After 6 courses of combination chemotherapy, complete response was confirmed by computed tomography. The patient developed grade 3 neutropenia, grade 1 sensory neuropathy , and grade 2 alopecia, but the other adverse events were mild. In conclusion, TC combination chemotherapy was well tolerated and generated a good response in a patient with recurrent ovarian clear cell adenocarcinoma who was receiving hemodialysis for chronic kidney disease.

Fetomaternal hemorrhage with intraplacental chorioangioma.

A 37-year-old Asian woman, gravid 0 para 0, was admitted to our hospital at 34 weeks and 5 days of her pregnancy for management of preeclampsia. A few days after admission, she recognized diminished fetal movement, and a non-stress test revealed a non-reassuring fetal heart rate pattern with decreased variability. A female baby weighing 1840 g was delivered by emergency cesarean section with Apgar scores of 5 and 5 at 1 and 5 min, respectively. Significant neonatal anemia with a hemoglobin level of 4.3 g/dL was observed. The elevated level of hemoglobin F (HbF) in the maternal blood accounted for 4.6% (normal≦0.5%), and was indicative of the presence of fetomaternal hemorrhage (FMH). Microscopic examination of the placenta revealed chorioangioma. We report here a rare case of FMH with intraplacental chorioangioma, and discuss the relationship between these two pathologies.

Benign multicystic peritoneal mesothelioma mimicking recurrence of an ovarian borderline tumor: a case report.

INTRODUCTION: Benign multicystic peritoneal mesothelioma is an extremely rare tumor that occurs mainly in women in their reproductive age. Its preoperative diagnosis and adequate treatment are quite difficult to attain. CASE PRESENTATION: Our patient was a 23-year-old Japanese woman who had a history of right oophorectomy and left ovarian cystectomy for an ovarian tumor at 20 years of age. The left ovarian tumor had been diagnosed on histology as a mucinous borderline tumor. Two years and nine months after the initial operation, multiple cysts were found in our patient. A laparotomy was performed and her uterus, left ovary, omentum and pelvic lymph nodes were removed due to suspicion of recurrence of the borderline tumor. A histological examination, however, revealed that the cysts were not a recurrence of the borderline tumor but rather benign multicystic peritoneal mesothelioma. There were no residual lesions and our patient was followed up with ultrasonography. She remains free from recurrence nine months after treatment. CONCLUSION: We report a case of benign multicystic peritoneal mesothelioma mimicking recurrence of an ovarian borderline tumor. Benign multicystic peritoneal mesothelioma should be suspected when a multicystic lesion is present in the pelvis as in the case presented here, especially in patients with previous abdominal surgery.

Precise evaluation of chemotherapy-induced peripheral neuropathy using the visual analogue scale: a quantitative and comparative analysis of neuropathy occurring with paclitaxel-carboplatin and docetaxel-carboplatin therapy.

BACKGROUND: Some regimens of chemotherapy cause peripheral neuropathy such as pain in muscles and joints and numbness in the limbs. It is often difficult to estimate the neuropathy accurately and analyze it in detail. The aim of this study was to investigate whether chemotherapy-induced peripheral neuropathy could be appropriately estimated by using the visual analogue scale (VAS). METHODS: Ninety-three patients who received paclitaxel and carboplatin treatment (TC) or paclitaxel and docetaxel treatment (DC) participated in answering a questionnaire about peripheral neuropathy using the VAS. As a result, 134 cycles of TC and 79 cycles of DC were evaluated. The average of VAS scores at every 10 days after each cycle of chemotherapy began was calculated. The daily change in VAS scores was also analyzed, and average VAS scores compared between TC and DC. RESULTS: Daily changes in peripheral neuropathy for each treatment could be demonstrated in detail. Pain and numbness had separate patterns of appearance. For both pain and numbness, a greater VAS score was observed in patients receiving TC than in those receiving DC. As the number of cycles grew, peripheral neuropathy became more serious in TC. CONCLUSIONS: The VAS could appropriately recognize the difference in peripheral neuropathy between TC and DC. Moreover, the VAS could also catch the change in peripheral neuropathy. This result suggests that the VAS system is a useful tool for managing peripheral neuropathy.

Primary adenocarcinoma of the vagina successfully treated with neoadjuvant chemotherapy consisting of paclitaxel and carboplatin.

Primary vaginal adenocarcinoma unassociated with antenatal diethylstilbestrol (DES) exposure is extremely rare. The strategy for treating this disease has not yet been established due to its rarity and, therefore, the prognosis remains poor. A 69-year-old woman presented with vaginal bleeding but no history of antenatal DES exposure. She had a solid tumor in the recto-vaginal space, diagnosed as FIGO stage III vaginal adenocarcinoma. After neoadjuvant chemotherapy consisting of paclitaxel and carboplatin, the tumor became undetectable. Thereafter, radiotherapy was applied to the pelvis and vagina in order to reinforce the state of remission. The patient remains free from recurrence 1 year after discharge. The present case was successfully treated with chemotherapy and radiotherapy, suggesting that chemotherapy may be an option for the treatment of this type of tumor.

Cap43/NDRG1/Drg-1 is a molecular target for angiogenesis and a prognostic indicator in cervical adenocarcinoma.

Cap43 is a nickel- and calcium-inducible gene that plays important roles in the primary growth of malignant tumors, as well as in invasion and metastasis, most likely through its ability to induce cellular differentiation. This study investigated associations of Cap43 expression with angiogenesis and other clinicopathological factors in cervical adenocarcinoma. The clinical records of 100 women who underwent surgery for cervical adenocarcinoma were reviewed retrospectively. Microvessel density and the expression of Cap43 and VEGF in the surgical specimens were evaluated immunohistochemically. The Cap43 expression level was significantly associated with angiogenesis, tumor diameter, stromal invasion, lymphovascular space invasion, lymph node metastasis, and histopathological differentiation. Kaplan-Meier analysis showed a significant association between the Cap43 expression level and survival: high Cap43 expression was related to poor survival. Our results suggest that increased expression of Cap43 is associated with angiogenesis and may be a poor prognostic indicator in women with cervical adenocarcinoma.

Polypoid endocervical adenomyoma: a case report with clinicopathologic analyses.

A case of polypoid endocervical adenomyoma (PEA) in the uterine cervix was encountered in the uterine cervix of a 56-year-old woman. Grossly, a well-circumscribed polypoid tumor was observed protruding from the uterine cervix. Based on the findings of imaging studies, it was assumed to be an adenoma malignum in the uterine cervix. The tumor was composed of a mixture of proliferating glands of endocervical type and fascicles of smooth muscle. No distinct nuclear anaplasia, architectural abnormality or any evidence of destructive stromal invasion was observed. Adenoma malignum, which shows a gastric phenotype with immunoreactivity for HIK-1083, was a serious diagnostic possibility. In the present case, the tumor was a well-circumscribed polypoid lesion, with no cytologic or architectural abnormality; however, focal immunoreactivity was shown for HIK-1083, which thus suggested it to be PEA. Therefore, the results of these ancillary diagnostic modalities should be interpreted with caution and combined with the gross and light microscopy findings.