Dose Contribution to the Regional Lymph-Node Metastases and Point B from Intracavity and Interstitial Hybrid Brachytherapy in Locally Advanced Cervical Cancer.

PURPOSE: Analyzing dose distributions to regional lymph-node metastases (RLNMs) in locally advanced cervical cancer (LACC) patients undergoing intracavitary and interstitial hybrid brachytherapy (IC/IS). METHODS: Dose distributions of eleven LACC patients with 38 RLNMs, and who received 38 IC/IS sessions were analyzed in EQD2, considering RLNM positions and ipsilateral interstitial needles; these RLNMs, excepting the para-aortic region, were classified into four groups. RESULTS: RLNMs had a median of two ipsilateral interstitial needles per session. Significant differences were observed in total RLNM D90, depending on whether the position was cranial or caudal of the uterine base (85.5 vs. 378.9 cGy, p < 0.0001), and whether the RLNM D90 was associated with a number of ipsilateral interstitial needles between 0-1 or 2 or more (68.4 vs. 112.2 cGy, p = 0.006) per session. At each session, Group 1 RLNMs (cranial of the uterine base, 0-1 ipsilateral interstitial needle) had a mean D90 of 21.1 cGy; Group 2 (cranial, 2 or more), 73.8; Group 3 (caudal, 0-1), 94.7; and Group 4 (caudal, 2 or more), 136.1. CONCLUSION: RLNMs located caudal of the uterine base associated with two or more ipsilateral interstitial needles in IC/IS had a higher dose contribution, which should be considered when calculating the RLNMs' dose of external beam boost irradiation.

MucoUp® as a spacer in brachytherapy for uterine cervical cancer: A first-in-human experience.

We first used MucoUp®, a hyaluronic acid used in endoscopic resection, as a spacer in brachytherapy. In five cervical cancer patients, MucoUp® insertion increased a 90% dose of the high-risk CTV to over 80 Gy while decreasing the dose of organs at risk. No related adverse events were observed.

A case of a large solitary fibrous tumor arising from the retroperitoneum resected completely using an intra-aortic balloon.

Solitary fibrous tumors (SFTs) are rare mesenchymal cell-derived tumors that can cause substantial bleeding during surgery due to hyper-vascularization. We report a case of a large retroperitoneal SFT resected completely using an intra-aortic balloon. A 71-year-old female with a history of type 2 diabetes mellitus presented with a tumor that was diagnosed as an insulin-like growth factor-II-producing benign SFT using computed tomography-guided biopsy. The tumor had grown from 6 to 20 cm in diameter within 4 years, with concurrent and severe hypoglycemia. Preoperative computed tomography findings showed substantial blood flow toward the tumor. The retroperitoneal tumor was observed to be widely attached. Substantial hemorrhaging during tumor resection was observed despite vascular embolism. We inflated the intra-aortic balloon for 45 min and resected the tumor completely. In conclusion, large SFT resection requires preoperative tumor blood flow evaluation and preparation of both a vascular embolism and an intra-aortic balloon.

Phosphorylation independent eIF4E translational reprogramming of selective mRNAs determines tamoxifen resistance in breast cancer.

Eukaryotic translation initiation factor 4E (eIF4E) selectively promotes translation of mRNAs with atypically long and structured 5'-UTRs and has been implicated in drug resistance. Through genome-wide transcriptome and translatome analysis we revealed eIF4E overexpression could promote cellular activities mediated by ERα and FOXM1 signalling pathways. Whilst eIF4E overexpression could enhance the translation of both ERα and FOXM1, it also led to enhanced transcription of FOXM1. Polysome fractionation experiments confirmed eIF4E could modulate the translation of ERα and FOXM1 mRNA. The enhancement of FOXM1 transcription was contingent upon the presence of ERα, and it was the high levels of FOXM1 that conferred Tamoxifen resistance. Furthermore, tamoxifen resistance was conferred by phosphorylation independent eIF4E overexpression. Immunohistochemistry on 134 estrogen receptor (ER+) primary breast cancer samples confirmed that high eIF4E expression was significantly associated with increased ERα and FOXM1, and significantly associated with tamoxifen resistance. Our study uncovers a novel mechanism whereby phosphorylation independent eIF4E translational reprogramming in governing the protein synthesis of ERα and FOXM1 contributes to anti-estrogen insensitivity in ER+ breast cancer. In eIF4E overexpressing breast cancer, the increased ERα protein expression in turn enhances FOXM1 transcription, which together with its increased translation regulated by eIF4E, contributes to tamoxifen resistance. Coupled with eIF4E translational regulation, our study highlights an important mechanism conferring tamoxifen resistance via both ERα dependent and independent pathways.

Novel Method of Cervicoplasty Using Autologous Peritoneum for Cervicovaginal Atresia.

Cervicovaginal atresia with a functional uterus is rare. There are no established surgical methods to treat this condition, and only a few reports have been published on surgical techniques. Furthermore, postoperative complications, such as restenosis, often require reoperation. A 19-year-old woman was pointed out cervical hypoplasia and referred to our hospital for further examination and treatment. A pelvic examination revealed that the vagina had a slight recession with a blind end. Transrectal ultrasound and pelvic magnetic resonance imaging revealed congenital vaginal agenesis and cervical hypoplasia. Elective surgery was performed after reshaping the vagina. A radical surgery was performed 10 months later after sufficient self-dilation by using Frank's technique in an outpatient setting. At first, we approached by laparoscopically to correct autologous peritoneum and to bladder detach, then the cervical canal was identified. Next, a skin biopsy punch was used several times to hollow out the cervical tissue to shape and expand the cervical canal. A catheter was then placed in the uterus and autologous peritoneum was wrapped around it and fixed to the cervical canal. The catheter was removed 6 weeks postoperatively, and the patient continued dilating her vagina until she was able to have sexual intercourse, and then stopped the self-dilation. Eight months postoperatively, the patient did not report any menstrual irregularities. It is important to make corrections to prevent restenosis of the vagina and cervical canal and prevent the symptoms from recurring. Make use of autologous peritoneum as graft onto the cervical canal is effective method for the treatment of cervicovaginal atresia.

CT-Guided Pelvic Lymph Nodal Brachytherapy.

PURPOSE: This is a report of our initial experience using computed tomography (CT)-guided interstitial high dose rate (HDR) brachytherapy to treat bulky pelvic nodal metastases as a part of definitive radiotherapy. MATERIAL AND METHODS: Between February 2015 and April 2019, 14 cervical/endometrial cancer patients presenting with bulky pelvic node(s) underwent nodal interstitial brachytherapy boost in our institution. In total, 17 nodes were treated. The median maximum diameters of the positive nodes at the time of diagnosis and at the first nodal implant were 25 mm (range: 10-65 mm) and 16 mm (range: 9-51 mm), respectively. Dosimetry data of the lymph nodal target volume and small bowel were collected and compared using the paired-sample t-test. Treatment-related toxicities were classified using the Common Terminology Criteria for Adverse Events version 4.0. RESULTS: The median follow-up time for all patients was 26 months. Local recurrence in pelvic nodes occurred in one patient (7%) after 16 months. One patient experienced grade 3 bladder bleeding, and one patient experienced grade 2 pubic bone fracture. No patient had grade 2 or greater gastrointestinal toxicity. In the dosimetric analysis, the mean nodal brachytherapy D90% in terms of the total equivalent dose of 2 Gy (EQD2) was 65.6 Gyαß10. The mean small bowel dose (SBD)0.1cc and SBD1cc in terms of the total EQD2 were 60.4 and 56.5 Gyαß3, respectively. Nodal D90% was significantly higher in terms of the total EQD2 than the SBD0.1cc (p = 0.003) and SBD1cc (p < 0.001). The Kaplan-Meier 2-year pelvic control estimate was 90%. CONCLUSIONS: CT-guided interstitial HDR pelvic nodal brachytherapy appears to be well tolerated with excellent local control in cervical or endometrial cancer patients with bulky pelvic nodes. This approach may offer a useful therapeutic option for unresected bulky pelvic nodes.

Usefulness of immunohistochemistry for mismatch repair protein and microsatellite instability examination in adenocarcinoma and background endometrium of sporadic endometrial cancer cases.

AIM: Microsatellite instability (MSI), which reflects loss of DNA mismatch repair (MMR) activity, and immunohistochemistry (IHC) for MMR proteins are employed as screening examinations for Lynch syndrome (LS). Recent studies revealed that there is a population of MSI-high tumors in sporadic endometrial cancer (EC). However, MSI data for Japanese EC patients are scarce. Furthermore, sporadic estrogen-dependent EC (type I) is generally considered to arise from hyperplasia. Because LS is usually associated with type I EC, we hypothesized that MSI might be involved in the oncogenic process in some sporadic EC. We conducted MSI testing to reveal MSI status in sporadic Japanese EC. IHC for MMR proteins was also performed. METHODS: Ninety-eight tissue samples of sporadic ECs from Japanese patients were used for IHC and MSI examinations. We also evaluated MMR protein expressions in the background normal endometrium. RESULTS: Microsatellite instability-high was observed in 10.2% of 98 cases with sporadic EC, a lower percentage than that in Western studies. Loss of some MMR proteins was observed in 23 cases (23.5%) and there was a significant correlation with MSI-high status (P < 0.001). Concerning the background endometrium, two cases showed partial loss of MLH1 and PMS2, corresponding to adjacent EC lesions, suggesting that MMR deficiency may already be present in the background endometrium. CONCLUSION: The MSI-high rate was low in our Japanese cohort. Our data confirmed the usefulness of MMR protein assessment for MSI screening in Japanese EC patients. Furthermore, IHC of the background endometrium might reveal the mechanism of MSI-high tumorigenesis.

Case of leiomyosarcoma arising from subserosal leiomyoma.

Uterine leiomyosarcoma (LMS) is a rare tumor. It has not been established if these tumors arise de novo or from pre-existing leiomyomas (LM). We report a case herein of LMS arising from a subserosal LM. A 47-year-old nulliparous woman was diagnosed with a uterine tumor measuring 30 cm in diameter by pelvic magnetic resonance imaging. Serum CA-125 level was 369 U/mL, and the lactate dehydrogenase level was elevated (565 IU/L, respectively). Positron emission tomography-computed tomography revealed abnormal uptake (SUVmax = 25.29) of the abdominal tumor. Upon laparotomy, a large tumor with solid and cystic components was shown to arise from a subserosal LM, with invasion into the greater omentum and small intestine. Abdominal hysterectomy, bilateral salpingo-oophorectomy, omentectomy and small intestine resection were performed. Macroscopic findings showed that the LMS was adherent to a subserosal LM, without continuity between the tumor and the uterus. Our case supports the hypothesis that LMS can arise from a pre-existing LM.

Isolated Incisional Recurrence in a Patient with Early-Stage Endometrial Cancer: A Case Report and Review of the Literature.

Isolated incisional recurrence in a patient with early-stage endometrioid carcinoma is extremely rare. The mechanism of this recurrence also remains unclear. We describe a case of an isolated incisional recurrence of endometrioid carcinoma from the uterine corpus 4 years after the primary surgery. We review the previous literature and discuss the possible mechanism of isolated incisional recurrence. A 56-year-old woman diagnosed with the International Federation of Gynecology and Obstetrics Stage IA and Grade 2 endometrioid carcinoma in the uterine corpus showed an isolated cystic mass in the abdominal wall 4 years after the primary surgery. She underwent resection of the abdominal tumor, and the pathological findings showed endometrioid carcinoma, which was the same as the primary tumor. She received chemotherapy and remained disease free 8 months after chemotherapy. Long-term follow-up is required to detect recurrence, even in patients with early-stage uterine corpus carcinoma.

Safety and efficacy of neoadjuvant chemotherapy with bevacizumab in advanced-stage peritoneal/ovarian cancer patients.

OBJECTIVE: The aim of this study was to evaluate the outcomes of neoadjuvant chemotherapy (NAC) with bevacizumab (Bev) at our institute. MATERIALS AND METHODS: Eleven patients with stage IIIC or IV peritoneal/ovarian cancer who underwent interval debulking surgery (IDS) after NAC with Bev between December 2014 and December 2016 were enrolled retrospectively (TCB group). As a control group, we enrolled 13 patients evaluated between December 2012 and December 2014 who underwent IDS and received NAC without Bev (TC group). Both the TCB and TC groups received combination chemotherapy consisting of paclitaxel (175 mg/m2) or docetaxel (70 mg/m2) and carboplatin (area under the curve 6 mg/mL/min) administered intravenously every 3 weeks (cycles 3-6). RESULTS: All patients in both groups underwent IDS. There were 7 (63.6%) and 8 (61.5%) cases with stage IIIC disease and 4 (36.3%) and 5 (30.7%) with stage IV disease in the TCB and TC groups, respectively. The complete resection rate was 81.8% in the TCB group and 69.2% in the TC group. The rate of achieving either complete or optimal resection was 100% in the TCB group and 69.2% in the TC group (p = 0.043). Hematoxicity (grade 3 or higher) was observed in 9 patients (81.8%) in the TCB group and 12 (92.3%) patients in the TC group. One patient (9%) in the TCB group experienced abdominal incisional hernia due to a fascial defect. CONCLUSION: IDS after NAC with Bev is safe, with a similar efficacy as that after NAC without Bev.

Drug-induced aortitis in a patient with ovarian cancer treated with bevacizumab combination therapy.

OBJECTIVE: To review and evaluate drug-induced vasculitis, which is an extremely rare complication of chemotherapy. CASE REPORT: A 47-year-old woman with ovarian cancer developed aortitis during bevacizumab combination chemotherapy. Contract-enhanced CT showed concentric thickening of the descending aorta. Antibiotics were administered, but a repeat CE-CT scan showed no resolution of the aortitis. To treat the aortitis, she was started on oral prednisolone. A subsequent CE-CT scan showed no signs of aortitis. She was thus re-started on a modified chemotherapy regimen. CONCLUSION: Aortitis should be considered in patients receiving bevacizumab combination therapy who develop persistent fever and upper-abdominal pain. Contrast-enhanced CT is useful for detecting drug-induced aortitis.

The utility and effectiveness of an internal iliac artery balloon occlusion catheter in surgery for large cervical uterine fibroids.

OBJECTIVE: Surgery for uterine cervical fibroids is difficult because of restricted surgical access and risks such as intraoperative bleeding or injury to other organs. The internal iliac artery balloon occlusion catheter (IIABOC) provides effective hemostasis for placenta previa and atonic hemorrhage, and is increasingly used in surgery for uterine fibroids for controlling intraoperative hemorrhage. We investigated the efficacy and safety of the IIABOC for controlling intraoperative bleeding in total abdominal hysterectomies (TAH) and abdominal myomectomies (AM) for large cervical fibroids. MATERIAL AND METHODS: From 2007 to 2014, the IIABOC was used in 22 cases (12 for TAH and 10 for AM) in which cervical fibroids fully occupied the pelvic cavity. Intraoperative blood loss, operating time, sample weight, use of blood transfusion, and injury to other organs were assessed. RESULT: Mean blood loss, operative time, and sample weight in the IIABOC cases were 510 mL, 178 min, and 2550 g for TAH; and 727.5 mL, 157.5 min, and 1850 g for AM. Blood loss divided by sample weight in IIABOC cases was significantly lower than that in non-IIABOC cases during the same time period, for both TAH and AM. Allogeneic blood transfusion was not necessary, and complications of injury to other organs did not occur in any of the 22 cases. CONCLUSIONS: For large cervical fibroids with limited operating space, surgery was performed under bleeding control by occlusion of the internal iliac artery with an IIABOC. This technique enables control of hemorrhage and safe operative management in gynecological surgery.

Efficacy of PET/CT to exclude leiomyoma in patients with lesions suspicious for uterine sarcoma on MRI.

OBJECTIVE: To analyze the efficacy of positron emission tomography/computed tomography (PET/CT) for the diagnosis of uterine sarcoma. MATERIALS AND METHODS: Thirty-four patients evaluated between January 2010 and March 2015 were retrospectively enrolled. All patients in whom uterine sarcoma was suspected based on contrast-enhanced magnetic resonance imaging (MRI) findings (heterogeneous, high signal intensity on T2-weighted images and/or high intensity on T1-weighted images) underwent PET/CT for further assessment. Patients were divided into 2 groups based on postoperative pathological findings: uterine sarcoma (n = 15) and leiomyoma (n = 19). The maximum standardized uptake value (SUVmax) of all lesions was measured using PET/CT; we calculated the optimal cutoff value for diagnosing sarcoma. RESULTS: The median SUVmax for uterine sarcoma and leiomyoma was 12 and 4.1, respectively; these values were significantly different. An SUVmax of greater than 7.5 was able to exclude leiomyoma with 80.8% sensitivity and 100% specificity (area under the curve, 95.3%). A cutoff SUVmax of 7.5 yields 100% specificity, and a cutoff SUVmax of 4.4 yields a 100% negative predictive value (NPV). The combination of PET/CT and lactate dehydrogenase (LDH) levels had a sensitivity of 86.6%, specificity of 100%, positive predictive value of 100%, and an NPV of 90.4%. No relation between histopathology or International Federation of Gynecology and Obstetrics (FIGO) stage and 18-fluoro-2-deoxy-d-glucose uptake value on PET/CT was seen. The surgical outcome trended toward a correlation with the SUVmax, although this was not statistically significant. CONCLUSIONS: In patients with MRI findings consistent with either uterine sarcoma or leiomyoma, PET/CT can decrease the false-positive rate by setting an optimal cutoff SUVmax of 7.5. Using this cutoff can avoid unnecessary surgery.