Intraperitoneal Carboplatin for Ovarian Cancer - A Phase 2/3 Trial.

Intraperitoneal Carboplatin for Ovarian CancerThis trial compared intravenous weekly paclitaxel administered with intraperitoneal or intravenous carboplatin. There was a statistically significant increase in progression-free survival in patients with ovarian cancer treated with intraperitoneal versus intravenous carboplatin and paclitaxel, with no difference in overall survival between groups.

Polarity switching of ovarian cancer cell clusters via SRC family kinase is involved in the peritoneal dissemination.

Peritoneal dissemination is a predominant pattern of metastasis in patients with advanced ovarian cancer. Despite recent progress in the management strategy, peritoneal dissemination remains a determinant of poor ovarian cancer prognosis. Using various histological types of patient-derived ovarian cancer organoids, the roles of the apicobasal polarity of ovarian cancer cell clusters in peritoneal dissemination were studied. First, it was found that both ovarian cancer tissues and ovarian organoids showed apicobasal polarity, where zonula occludens-1 (ZO-1) and integrin beta 4 (ITGB4) served as markers for apical and basal sides, respectively. The organoids in suspension culture, as a model of cancer cell cluster floating in ascites, showed apical-out/basal-in polarity status, while once embedded in extracellular matrix (ECM), the organoids switched their polarity to apical-in/basal-out. This polarity switch was accompanied by the SRC kinase family (SFK) phosphorylation and was inhibited by SFK inhibitors. SFK inhibitors abrogated the adherence of the organoids onto the ECM-coated plastic surface. When the organoids were seeded on a mesothelial cell layer, they cleared and invaded mesothelial cells. In vivo, dasatinib, an SFK inhibitor, suppressed peritoneal dissemination of ovarian cancer organoids in immunodeficient mice. These results suggest SFK-mediated polarity switching is involved in peritoneal metastasis. Polarity switching would be a potential therapeutic target for suppressing peritoneal dissemination in ovarian cancer.

Paclitaxel-carboplatin and bevacizumab combination with maintenance bevacizumab therapy for metastatic, recurrent, and persistent uterine cervical cancer: An open-label multicenter phase II trial (JGOG1079).

OBJECTIVE: This multicenter, open-label, phase II study aimed to evaluate the efficacy and safety of paclitaxel-carboplatin, bevacizumab, and bevacizumab-based maintenance therapy for metastatic, recurrent, and persistent uterine cervical cancer. METHODS: Patients with measurable diseases that were not adapted to regional therapies, such as surgery or radiotherapy, and were systematic chemotherapy-naïve were eligible. The participants received paclitaxel (175 mg/m2), carboplatin (AUC 5), and bevacizumab (15 mg/m2) every three weeks until disease progression or unacceptable adverse events occurred. The primary endpoint was progression-free survival (PFS). The secondary endpoints were overall response rate (ORR), overall survival (OS), safety, and time to treatment failure. RESULTS: Sixty-nine patients were analyzed using our protocol. The median paclitaxel- carboplatin therapy duration was six cycles; 40% of patients received bevacizumab maintenance therapy. The median PFS was 11.3 months. The median OS was not reached; the median time to treatment failure was 5.9 months. The ORR was 79.7% [95% confidence interval (CI) 63.8-88.4]; 16 patients (23.2%) showed complete response (CR) and 39 patients (56.5%) showed partial response (PR). The median PFS was 14.3 months (95% CI 7.3-17 months) for the 25 patients who received maintenance therapy and 7.4 months (95% CI 6.1-11 months) for nonrecipients (p = 0.0449). Gastrointestinal perforation/fistulas occurred in four patients (5.6%), all of whom had a history of radiation therapy. CONCLUSIONS: Paclitaxel-carboplatin and bevacizumab therapy is an acceptable and tolerable treatment for advanced or recurrent cervical cancer.

Two cases of giant peritoneal inclusion cysts requiring treatment after total laparoscopic hysterectomy.

Peritoneal inclusion cysts (PICs) often develop in post-operative patients. Since the incidence of adhesions is lower with laparoscopic surgery than with open surgery, PICs are less likely to occur in the former. Although post-operative adhesions or PICs rarely develop after laparoscopic surgery (such as total laparoscopic hysterectomy: TLH), we encountered two cases of giant PICs with abdominal pain after TLH. In Case 1, strong adhesion was already present when TLH was performed. Therefore, this case may have been predisposed to the development of adhesions in the abdominal cavity. However, no adhesions were observed during TLH in case 2, and there were no risk factors, such as pre-operative adhesions and endometriosis. Therefore, adhesions and PICs may develop even after TLH, and approaches need to be considered for their prevention.

A case of sarcomatoid malignant peritoneal mesothelioma diagnosed by laparoscopy.

•Malignant peritoneal mesothelioma, particularly the sarcomatoid type, is rare and aggressive.•Accurate diagnosis by ascites cytology is difficult.•Histological examination such as laparoscopy aids in diagnosis.•There is no clear consensus treatment for MPM and an extensive research program is needed.

Aggressive skeletal muscle metastasis from cervical cancer invading into the spinal canal: A case report.

We present the first case of the patient with skeletal metastasis of uterine cervical cancer which invaded the vertebral body and spinal canal, with consequent paralysis of the lower extremities.

Torsion of Normal Adnexa in a 31-year-old Woman: A Case Report and Literature Review.

It is known that a large ovarian cyst will likely cause torsion. However, normal adnexal torsion is rare and occurs in premenarchal girls in most cases. This is a case of a reproductive woman. A 31-year-old woman suffering from acute abdominal pain in the lower and right side consulted her gynecologist. The next day she had a computed tomography performed and was suspected of ovarian torsion. She did not have fever, nausea, or leukocytosis, but her abdominal pain persisted. Diagnostic laparoscopy was performed and showed torsion of the right fallopian tube, which was swollen and looked like a hydrosalpinx with a normal ovary. We did detorsion and excision of the right tube. However, pathological findings showed that the right tube was not a hydrosalpinx but was swollen due to blood stasis. We determined that this case was torsion of normal adnexa. In such cases, diagnostic laparoscopy is very effective.

Successful Pregnancy following Myomectomy Accompanied with Abdominal Radical Trachelectomy for an Infertile Woman with Early Cervical Cancer: A Case Report and Literature Review.

Women in the reproductive age group diagnosed with cervical cancer can receive radical trachelectomy in case they wish to preserve fertility. However, the indication for this procedure in infertile women with cervical cancer is controversial depending on the underlying cause of infertility. Here, we present a case of a successful pregnancy following myomectomy accompanied with abdominal radical trachelectomy for an infertile woman with early cervical cancer. The patient was a 38-year-old nulliparous woman with a significant past medical history of infertility of unknown origin. She had been undergoing treatment with assisted reproductive technologies including artificial insemination and in vitro fertilization for over four years. During her treatment for infertility, she was diagnosed with stage IB1 cervical squamous cell carcinoma. She received abdominal radical trachelectomy and abdominal myomectomy in the same surgical procedure. Six months after the surgery, she went for the first embryo transfer and became pregnant. At 26 weeks of pregnancy, a male baby weighing 980 g was delivered with an Apgar score of 3/5/7 by cesarean section due to chorioamnionitis. The baby has received general care in a neonatal intensive care unit for four months and weighed 4520 g when discharged.

Epithelioid Angiosarcoma Arising from a Huge Leiomyoma: A Case Report and a Literature Review.

Uterine mesenchymal tumors other than leiomyosarcoma, carcinosarcoma, and endometrial stromal sarcomas are extremely uncommon. We describe a case of epithelioid angiosarcoma of the uterus and review previous literature on such rare tumors. A 48-year-old woman presented with a 1-year history of abdominal fullness and 10kg weight loss. Pelvic magnetic resonance imaging (MRI) revealed a huge (30×18cm) uterus accompanied by degeneration and necrosis. She underwent supracervical hysterectomy and right salpingo-oophorectomy. We postoperatively diagnosed the mass as an epithelioid angiosarcoma arising from a leiomyoma. Vasodilatation was observed within the range of 2 cm × several mm in the leiomyoma, and proliferation of atypical cells was observed covering the surface of the luminal side. The tumor showed a partly fine vascular structure and was associated with obvious nuclear atypia and mitotic figures. She received 6 courses of adjuvant chemotherapy with paclitaxel, epirubicin, and carboplatin, and there have been no signs of recurrence for 10 months.

[A Case of Splenic Metastasis from Serous Surface Papillary Carcinoma of the Peritoneum Treated by Laparoscopic Splenectomy].

A 50-year-old woman with abdominal fullness, lower abdominal pain, elevated serum CA125, and ascites, underwent neoadjuvant chemotherapy with 6 courses of PTX/CBDCA followed by total hysterectomy, bilateral salpingo-oophorectomy, omentectomy, and intrapelvic peritoneal stripping based on a diagnosis of serous surface papillary carcinoma(SSPC) of the peritoneum. Complete response(CR)was shown after adjuvant chemotherapy with 3 courses of the same regimen. After 6 months, serum CA125 level re-increased and abdominal CT showed small low density areas in the patient's spleen and the perisplenic fat tissue. After the additional chemotherapy with 3 courses of PTX/CBDCA were performed based on a diagnosis of metastatic lesion from SSPC, anaphylactic shock occurred as the severe adverse event. The patient was given 9 more courses of the chemotherapy changed the regimen to PTX/CDDP. The splenic metastatic lesion had grown rapidly in the followed CT and then, laparoscopic splenectomy with peritoneal resection was performed based on a diagnosis of splenic metastasis from SSPC. The pathological examinations showed the tumor to be a splenic metastasis and peritoneal dissemination from SSPC. No recurrent lesion has been detected in the 9 months since removal of the splenic metastasis without adjuvant chemotherapy and the patient has survived for 4 years and 6 months since initial treatment.

Investigation of the clinical features of lower uterine segment carcinoma: association with advanced stage disease and indication of poorer prognosis.

PURPOSE: We retrospectively analyzed the differential clinical features and prognosis of endometrial carcinomas arising from the lower uterus, which are reported to have a poorer prognosis than those arising from the upper uterus. METHODS: 246 patients with endometrial carcinoma who underwent surgery were entered as subjects. RESULTS: Twenty-three were classified as having lower uterine segment carcinomas (LUSC); the remaining 223 were upper uterine segment carcinomas (UUSC). LUSC cases were associated with a more advanced FIGO stage than UUSC (p < 0.001). Deep myometrial invasion and lymph node metastasis were more common in LUSC than in UUSC (p = 0.006 and p < 0.001, respectively). LUSC cases demonstrated significantly shorter overall survival (OS) and progression-free survival (PFS) than UUSC (p = 0.02 and p < 0.001, respectively). Multivariate cox proportional hazards analysis demonstrated that the hazard ratio for LUSC was 1.769 for OS and 3.479 for PFS. For endometrial carcinoma survival, FIGO stage and histological type were extracted as independent variables. CONCLUSIONS: LUSC is a high-risk indicator for poorer prognosis for endometrial carcinoma because it is associated with more advanced stage disease, deep myometrial invasion and lymph node metastasis, and indicates a significantly worsened PFS probability. Our analysis concludes that LUSC is FIGO stage-dependent and an important factor for OS.

Case Report: Pulmonary Tumor Thrombotic Microangiopathy in a Cervical Cancer Patient.

Pulmonary tumor thrombotic microangiopathy (PTTM) is a rapidly progressive and often fatal pulmonary disease induced by tumor emboli within the small pulmonary arteries. PTTM presents clinically as progressive hypoxia and pulmonary hypertension. Most cases of PTTM are caused by an adenocarcinoma of the stomach. We present the first case report of PTTM caused by cervical squamous cell carcinoma. An 82-year-old woman presented with vaginal bleeding and exertional dyspnea. A cervical mass biopsy showed squamous cell carcinoma. Computed tomography revealed ground glass opacity of the bilateral peripheral lung fields. Hypoxia and pulmonary hypertension gradually worsened after admission. Treatment for acute heart failure was started, but was ineffective. She died of respiratory failure 31 days after admission. She was diagnosed at autopsy as having PTTM induced by cervical squamous cell carcinoma. PTTM needs to be considered in any patient with advanced cancer and lung-related issues to rule out metastatic disease, even in the absence of imaging findings.

Serum fibrinogen levels could be an index of successful use of balloon tamponade in postpartum hemorrhage.

OBJECTIVE: The object of our study was to determine whether serum fibrinogen levels could be used to predict the success rates of balloon tamponade and decrease the use of invasive methods. METHODS: This retrospective study, conducted at Rinku General Medical Center, was aimed to identify factors associated with high success rates in balloon tamponade. Forty-six patients with postpartum hemorrhage (PPH), non-responsive to uterotonics and treated with balloon tamponade between April 2008 and March 2015, were included. RESULTS: Forty-six women were included, of which 34 underwent vaginal delivery and 12 underwent cesarean delivery. There were no complications from balloon tamponade and its success rate was 73.3%. Seven women required additional procedures: One used gauze packing, three used uterine artery embolization, and five underwent peripartum hysterectomy. The cut-off line of serum fibrinogen level was 172.5 mg/dL (P=0.002) with its 77.4% sensitivity and 66.7% specificity. CONCLUSION: We recommend measuring serum fibrinogen level for predicting whether the balloon tamponade can be used successfully or not.

Combination chemotherapy with irinotecan and gemcitabine for taxane/platinum-resistant/refractory ovarian and primary peritoneal cancer: a multicenter phase I/II trial (GOGO-Ov 6).

PURPOSE: To develop a new therapeutic strategy for taxane/platinum-resistant/refractory ovarian and primary peritoneal cancers, we evaluated the feasibility and efficacy of irinotecan and gemcitabine combination chemotherapy. METHODS: Patients with taxane/platinum-resistant/refractory cancer received escalating doses of irinotecan and gemcitabine (level 1: 80 and 800 mg/m2, respectively; level 2: 100 and 1000 mg/m2) on days 1 and 8 on a 21-day cycle. Genotyping for UGT1A1*6 and *28 polymorphisms was performed for possible adverse irinotecan sensitivity. RESULTS: A total of 35 patients were enrolled. The recommended dose was defined as 100 mg/m2 irinotecan and 1000 mg/m2 gemcitabine (level 2). The observed common grade 3/4 toxicities were neutropenia (60%), anemia (17.1%), diarrhea (8.6%), thrombocytopenia (5.7%) and nausea (5.7%). Groups homozygous for UGT1A1*6 or *28 were associated with grade 3/4 neutropenia and diarrhea. Objective responses were 20%, including one complete response and six partial responses. In 29 patients treated with the recommended dose, the median progression-free survival and overall survival were 3.8 months (95% CI 2.1-6.0 months) and 17.4 months (95% CI 9.9-21.9 months), respectively, while the 1-year survival rate was 58.6%. CONCLUSIONS: Combination chemotherapy with irinotecan and gemcitabine represents a safe and effective treatment combination for taxane/platinum-resistant/refractory ovarian and primary peritoneal cancers.

Rare hydrosalpinx in a sexually inactive adolescent successfully treated with laparoscopy.

The majority of cases of symptomatic hydrosalpinx needing treatment are caused by sexually transmitted diseases. However, here, we present a rare case of a hydrosalpinx occurring in a sexually-inactive adolescent girl successfully treated with laparoscopy. A 17-year-old girl presenting with lower abdominai symptoms had a surgical history for an inguinal hernia at infancy. Transabdominal ultrasonography revealed a multicystic lesion in the pelvis, and magnetic resonance imaging suggested hydrosalpinx. Due to the abdominal pain and a suspicion of torsion, laparoscopic surgery was performed. After aspiration and resection of a cystic tumor, we confirmed that the left ovary was normal and that the tumor involved the left fallopian tube, which was twisted at the isthmus. Although relatively rare in postmenarchal sexually inactive adolescents, clinicians and surgeons must still consider hydrosalpinx as a possible diagnosis when encountering an adolescent patient with lower abdominal pain.

Gemella morbillorum bacteremia following total laparoscopic hysterectomy for uterine corpus cancer.

Gemella morbillorum, a Gram-positive coccus facultative anaerobe, is part of the normal flora of the mucous membranes of the oropharynx, upper respiratory, gastrointestinal, and female genital tracts. However, this species can also cause serious infection. We herein report on a case of bacteremia, accompanied by peritonitis and pleuritis, in a 46-year-old immunocompetent female following a total laparoscopic hysterectomy for endometrial cancer. The case was successfully treated with antibacterial and antifungal agents.

A phase II study of postoperative concurrent carboplatin and paclitaxel combined with intensity-modulated pelvic radiotherapy followed by consolidation chemotherapy in surgically treated cervical cancer patients with positive pelvic lymph nodes.

OBJECTIVES: A phase II study was conducted to evaluate the efficacy and toxicity of carboplatin plus paclitaxel (TC)-based postoperative concurrent chemoradiotherapy (CCRT) followed by TC-based consolidation chemotherapy in surgically-treated early-stage cervical cancer patients. METHODS: Women with surgically-treated early-stage cervical cancer with positive pelvic lymph nodes were eligible for this study. The patients were postoperatively treated with pelvic intensity modulated radiotherapy (50.4Gy) and concurrent weekly carboplatin (AUC: 2) and paclitaxel (35mg/m(2)) (TC-based CCRT). Three cycles of consolidation chemotherapy involving carboplatin (AUC: 5) and paclitaxel (175mg/m(2)) were administered after TC-based CCRT. RESULTS: Thirty-one patients were enrolled and treated. Overall, the treatment was well tolerated, and 26 patients (83.9%) completed the planned TC-based CCRT. The most frequently observed acute grade 3/4 hematological toxicities were leukopenia and neutropenia, and diarrhea was the most common acute grade 3/4 non-hematological toxicity. After a median follow-up period of 36.5months, 2 patients (6.5%) had developed recurrent disease. The patients' estimated 3-year progression-free survival (PFS) and overall survival (OS) rates were 88.5% and 93.8%, respectively. In comparisons with historical control groups, TC-based CCRT followed by TC-based consolidation chemotherapy was found to be significantly superior to CCRT involving a single platinum agent in terms of PFS (p=0.026) and significantly superior to extended-field radiotherapy in terms of both PFS (p=0.0004) and OS (p=0.034). CONCLUSIONS: In women with surgically treated early-stage cervical cancer, pelvic TC-based CCRT followed by TC-based consolidation chemotherapy is feasible and highly effective. Future randomized trials are needed to verify the efficacy of this regimen.

Rare Primary Adenocarcinoma of the Broad Ligament: Report of Two Cases and a Literature Review.

Malignant primary tumors arising in the uterine broad ligament are extremely rare, and only 26 cases have been reported to date. We describe 2 new cases of primary adenocarcinoma of the broad ligament, and we review the previous literature on such rare tumors. In Case 1, a 71-year-old woman presented with a 2-month history of increased yellow vaginal discharge and lower abdominal pain during bowel movement. Transvaginal sonography revealed a 6.5 cm mass located on the dorsum of the uterus and a 7.0 cm mass (with cystic and solid parts) near the right adnexa. We postoperatively diagnosed the mass as a high-grade serous carcinoma of the broad ligament (pT3cNXM0). The patient is currently receiving adjuvant chemotherapy with paclitaxel and carboplatin. In Case 2, during a complete medical checkup a 43-year-old woman was found to have a pelvic mass indicative of leiomyoma. Transvaginal sonography revealed a 3.8 cm mass located on the dorsum of the uterus. Following surgery, we diagnosed the mass as a clear cell adenocarcinoma of the broad ligament (pT2bN1M0). This patient is also now receiving adjuvant chemotherapy with paclitaxel and carboplatin.

Etiology of Ascites and Pleural Effusion Associated with Ovarian Tumors: Literature Review and Case Reports of Three Ovarian Tumors Presenting with Massive Ascites, but without Peritoneal Dissemination.

Borderline ovarian tumors are benign but relatively large tumors that are often initially mistaken as ovarian cancers. We report three cases of stage I borderline ovarian tumors having massive ascites that we (preoperatively) suspected of being advanced ovarian cancer. The three patients (35, 47, and 73 years old) reported feeling fullness of the abdomen before consulting their gynecologist. By CT scan, they were diagnosed with a pelvic tumor accompanied by massive ascites, the diameters of which were 11, 20, and 11 cm, respectively. Postsurgical pathology showed all were stage I borderline ovarian tumors without dissemination; two were mucinous and one was serous. The amount of ascites was 6,300, 2,600, and 3,600 mL, respectively, and was serous in all. Cytodiagnosis of the ascites found that one was positive for tumor cells and two were negative. After resection of the mass, the ascites disappeared in all three cases. No pleural effusion was present at any time. The literature is reviewed concerning ascites and pleural effusions linked to ovarian tumors, and a supposition is forwarded of why pleural effusion presents sporadically in these cases.