Uterine Cervical Carcinoma: Evaluation Using Non-Gaussian Diffusion Kurtosis Imaging and Its Correlation With Histopathological Findings.

OBJECTIVE: The aim of the study was to assess non-Gaussian diffusion kurtosis imaging (DKI)'s usefulness as a noninvasive method to evaluate tumor invasion depth, histological grade, and lymph node metastasis in cervical carcinoma (CC) patients. METHODS: Twenty-two consecutive patients with histologically confirmed CC were examined by 1.5-T MRI and non-Gaussian DKI with 4 b values of 0, 500, 1000, and 2000 s/mm2. Kurtosis (K), diffusivity (D), and apparent diffusion coefficient (ADC) maps were compared with histopathological findings. RESULTS: Kurtosis maps revealed the fibrous stroma as a distinct high K zone (1.442 ± 0.373) that was significantly different from values of the cervical mucosa, outer stroma, and parametrium (0.648 ± 0.083, 0.715 ± 0.113, and 0.504 ± 0.060, respectively, P < 0.0001). Kurtosis (1.189 ± 0.228) and D (0.961 ± 0.198 × 10-3 mm2/s) values of all CCs were significantly different from those of all uterine cervical wall layers. Kurtosis and D values were significantly correlated with histological grades of CCs (r = 0.934, P < 0.0001, and r = -0.925, P < 0.0001, respectively), whereas no significant differences were found in ADC values between grades 2 and 3 CCs (P = 0.787). Metastatic and nonmetastatic lymph nodes showed significantly different K (P < 0.0001) and D (P < 0.0001) values; however, their ADC values did not show significant differences (P = 0.437). For differentiating grade 3 CCs from grade 1 or 2 CCs, the areas under the curve for K (0.991, P = 0.0375) and D (0.982, P = 0.0337) values were significantly higher than those for ADC values (0.759). For differentiating metastatic and nonmetastatic lymph nodes, the areas under the curve for K (0.974, P = 0.0028) and D (0.968, P = 0.0018) values were significantly higher than those for ADC (0.596). CONCLUSIONS: Non-Gaussian DKI may be clinically useful for noninvasive evaluation of tumor invasion depth, histological grade, and lymph node metastasis in CC patients.

Laparoscopic Abdominal Surgery after Primary Breast Reconstruction Using an Abdominal Flap.

Background and objectives: Our department has been performing primary breast reconstruction for breast cancer surgery, incorporating a transverse rectus abdominis myocutaneous flap (TRAM)/vertical rectus abdominis myocutaneous flap (VRAM) since 1998 and a deep inferior epigastric artery perforator flap (DIEP) since 2008. Currently, most gastrointestinal operations in abdominal surgery are performed laparoscopically or are robot-assisted. Cases in which abdominal surgery was performed after breast reconstruction using an abdominal flap were reviewed. Method: A total of 119 cases of primary breast reconstruction using an abdominal flap performed in our department were reviewed. Result: The reconstructive techniques were DIEP in 69 cases and TRAM/VRAM in 50 cases. After breast surgery, seven abdominal operations were performed in six cases. In DIEP cases, one robotic surgery was performed for uterine cancer, and one laparoscopic surgery was performed for ovarian tumor. In TRAM/VRAM cases, two laparoscopic cholecystectomies, one laparoscopic total gastrectomy, one laparoscopic ileus reduction, and one open total hysterectomy oophorectomy were performed. Six surgeries were completed by laparoscopy or robotic assistance. Conclusion: The survival rate after breast cancer surgery is improving, and the choice of breast reconstruction procedure should take into account the possibility of performing a prophylactic resection of the ovaries due to the genetic background and possibly postoperative abdominal surgery due to other diseases. However, in cases in which laparoscopic surgery was attempted after breast reconstruction using an abdominal flap, the laparoscopic surgery could be completed in all cases.

[A Case of Recurrent Breast Cancer with Improving Activities of Daily Living by Olaparib Treatment].

The patient is a 67-year-old woman who underwent surgery for left breast cancer in 1990 and right breast cancer in 2003. In 2013, local recurrence of right breast cancer was detected. Then she underwent removal of the local recurrence, axillary lymph node dissection, and post mastectomy irradiation. In 2017 lung metastasis appeared, and she underwent endocrine therapy and chemotherapy. BRCA1/2 analysis showed BRCA1 mutation, so olaparib was started in 2020. The metastatic lesions were reduced markedly, and the skin metastases were crusted over. Although it is necessary to decide when to use olaparib in each case, there is a possibility that olaparib may be effective even in the terminal stage, and it may be considered as one of the treatment options.

Diffusion-Tensor Imaging of Uterine Cervical Carcinoma: Correlation With Histopathologic Findings.

The authors investigated the usefulness of diffusion-tensor imaging (DTI) for evaluating tumor invasion depth, histologic grade, and lymph node metastasis in patients with cervical carcinoma (CC). Fifteen consecutive patients with histologically confirmed CC underwent 1.5-T magnetic resonance imaging and DTI. The CCs were clearly depicted as hypointense areas on all DTI maps. Fractional anisotropy, mean diffusivity, and axial diffusivity showed significantly inverse correlations with CC histologic grades and were significantly different between metastatic and nonmetastatic lymph nodes.

[A Case of Lynch Syndrome with Seven Cancers in Five Organs].

The case is a woman in her 70s with a history of colon and cervical cancer in her 40s. She had gastric cancer and breast cancer in her 70s. Her eldest son died of colon cancer in his 20s, and her eldest daughter had cervical cancer in her 40s. She was suspected to have Lynch syndrome and a genetic diagnosis was performed and then confirmed. Later she developed gastric cancer and ureteral cancer. We report a case of Lynch syndrome in which she developed seven cancers in five organs, all of which were early stage cancers.

Endometrial carcinoma: Evaluation using diffusion-tensor imaging and its correlation with histopathologic findings.

BACKGROUND: Although the prognosis of endometrial carcinoma (EMC) patients strictly depends on tumor invasion depth and its histologic grade, accurate preoperative assessment of these prognostic factors is often difficult. PURPOSE: To determine the usefulness of diffusion-tensor imaging (DTI) as a noninvasive method for evaluating tumor invasion depth and its histologic grade in patients with EMC. STUDY TYPE: Prospective. POPULATION: Twenty-five consecutive patients with histologically confirmed EMC who were surgically treated at our institution. FIELD STRENGTH/SEQUENCE: DTI was performed with a 1.5T MRI system using a single-shot echo-planar imaging sequence with b values of 0 and 1000 s/mm2 and motion-probing gradients in nine noncollinear directions. ASSESSMENT: Fractional anisotropy (FA), mean diffusivity (MD), and axial diffusivity (AD) maps were analyzed by three observers and compared with histopathologic findings. STATISTICAL TESTS: Dunnett's test, Spearman's rank correlation coefficient, and receiver operating characteristic (ROC) curve analyses. RESULTS: FA maps from all patients distinctly identified the junctional zone as a high-FA zone (0.864 ± 0.037) that was significantly different from the endometrium and outer myometrium (0.251 ± 0.030 and 0.471 ± 0.091, respectively; P < 0.001). All EMCs were clearly depicted as hypointense areas on all DTI maps. AD maps provided the best tumor-to-uterus contrast, and EMCs (0.977 ± 0.120 × 10-3 mm2 /s) had significantly lower AD values than all other layers of the normal uterine wall (2.166 ± 0.408, 2.010 ± 0.289, and 2.655 ± 0.203 × 10-3 mm2 /s, respectively; P < 0.001). EMCs were clearly demarcated from the normal uterine wall, and DTI maps and histopathologic data yielded identical findings regarding tumor invasion depth. FA values showed a significant inverse correlation (r = -0.818; P < 0.001) with histologic grades 1, 2, and 3 of endometrioid adenocarcinomas. DATA CONCLUSION: In patients with EMC, DTI may be useful for evaluating tumor invasion depth and its histologic grade. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;50:250-260.

SLUG expression is an indicator of tumour recurrence in high-grade endometrial carcinomas.

AIMS: To investigate how SNAIL and SLUG were involved in the nature of high-grade endometrial carcinomas (grade 3 endometrioid carcinoma, serous carcinoma and clear cell carcinoma), we analysed the correlation of their expression status with clinicopathological characteristics and evaluated their prognostic significance. METHODS AND RESULTS: We performed immunohistochemical staining in 52 high-grade endometrial carcinomas. Expression status of SNAIL and SLUG was classified into a high expression (positive in more than 50% of the tumour cells) and a low expression. Thirteen cases (25%) showed a high expression of SLUG, whereas all 52 cases showed a low expression of SNAIL. High expression of SLUG was correlated significantly with tumour recurrence (P = 0.0203) and aberrant p53 expression (P = 0.000559). Overall survival was worse in patients with high SLUG expression at all stages (P = 0.0327) and in those who underwent adjuvant therapy (P = 0.00963). Among the patients with complete tumour resection, high SLUG expression was associated with worse recurrence-free survival (RFS) in the patients at all stages (P = 0.00264), at stages III/IV (P = 0.0146), and who underwent adjuvant therapy (P = 0.000743). SLUG expression was identified as an independent factor of RFS by multivariate analysis (hazard ratio 5.938, 95% confidence interval 1.251-28.18, P = 0.025). CONCLUSIONS: SLUG expression could be correlated with TP53 mutational status and could be involved in therapeutic resistance resulting in tumour recurrence. A high expression level of SLUG can be an indicator of recurrence and a therapeutic target for long-term remission in high-grade endometrial carcinomas.

Vanishing intravenous leiomyomatosis after hysterectomy: Assessment of the need to perform complete resection.

Intravenous leiomyomatosis (IVL) is a rare smooth muscle tumor that may extend into extrauterine veins. A high IVL recurrence rate has been reported after hysterectomy. A 44-year-old woman underwent total hysterectomy as a result of uterine leiomyoma, and IVL within the left uterine vein was incidentally found during the surgery. A residual tumor within the right ovarian vein was detected on contrast-enhanced computed tomography (CT) two days postoperatively. The tumor was diagnosed as IVL because it showed contrast enhancement on preoperative magnetic resonance imaging by retrospective re-interpretation. However, the tumor completely disappeared on contrast-enhanced CT without any medical treatment five months postoperatively. This is the first report of spontaneous regression of IVL. Postsurgical imaging was important to determine the residual extrauterine extension of IVL when it was incidentally found during gynecologic surgery. A hysterectomy alone may be adequate in selected cases, but long-term follow-up imaging is strongly recommended in all cases.

Dkk-3 induces apoptosis through mitochondrial and Fas death receptor pathways in human mucinous ovarian cancer cells.

OBJECTIVE: Dkk-3 is a Wnt signaling inhibitor that is frequently inactivated in human cancers. Dkk-3 possesses an antiproliferative activity and induces apoptosis in tumor cells, suggesting that it functions as a tumor suppressor. In this study, we investigated the molecular function of Dkk-3 in human ovarian cancer cells. METHODS: We assessed the levels of Dkk-3 protein expression in human mucinous and clear cell ovarian cancer cells, and compared cell viabilities between cell lines that expressed Dkk-3 and those that did not, as well as between cells that expressed Dkk-3 and those whose expression of Dkk-3 was reduced by small interfering RNA. We also evaluated the characteristic fragmentation of DNA to detect apoptosis in Dkk-3-deficient cells. To further investigate the molecular mechanisms of apoptosis, we assessed the expression of molecules involved in apoptosis signaling pathways in Dkk-3-deficient cells. RESULTS: The expression of the Dkk-3 protein was observed in most of the ovarian cancer cell lines tested. Dkk-3-deficient cells showed faster growth than Dkk-3-replete cells. The characteristic fragmentation of DNA was not observed in Dkk-3-deficient cells, which showed decreased levels of expression in caspase-3, activated caspase-9, Bax, p53, activated caspase-8, and Fas/CD95, as well as an increase in Bcl-2 expression. CONCLUSIONS: Although Dkk-3 expression was observed in most of human ovarian cancer cell lines, Dkk-3 has a tumor-suppressive function and a proapoptotic effect, inducing apoptosis through mitochondrial and Fas death receptor pathways in human mucinous ovarian cancer MCAS cells.

Pleomorphic Rhabdomyosarcoma of the Uterine Corpus in an Adult Who Underwent Multi-gene Panel Testing.

Background/Aim: Rhabdomyosarcoma (RMS) is the most common malignant soft tissue tumor in children. Adult primary RMS of gynecological origin is a rare condition and uterine RMS is an aggressive malignancy with a poor prognosis. The genetic variants associated with uterine RMS in adults have yet to be fully elucidated, and there is no established therapeutic strategy for rare tumors. Case Report: A 69-year-old Japanese woman was referred to our hospital with abdominal bloating. Imaging examination revealed a tumor with diameter of 85 mm located in the uterus and multiple regional lymph node metastases. Biopsy of the uterine corpus indicated possible uterine carcinosarcoma or RMS. Following debulking surgery, the patient was diagnosed with stage IVB pleomorphic RMS. The patient was treated with two courses of doxorubicin every three weeks and one course of combination chemotherapy with vincristine, actinomycin, and cyclophosphamide. Because of rapid progression of the disease, we decided to perform multi-gene panel testing to determine the most effective therapeutic strategy. However, no therapeutic plan based on genetic information was identified. The patient with chemotherapy-refractory RMS died 11 weeks after surgery. Conclusion: Our patient had advanced uterine RMS with an unresectable tumor that was resistant to chemotherapy, resulting in poor outcomes. Despite conducting multi-gene panel testing, no tailored therapeutic approach based on genetic information was found. This case highlights the challenges in managing uterine RMS in adults and underscores the urgent need for further research to identify effective treatment modalities.

Successful surgical treatment and chemotherapy for ovarian cancer in a patient with idiopathic thrombocytopenic purpura.

Ovarian clear cell adenocarcinoma (OCCA) is known to have a worse prognosis than ovarian serous adenocarcinoma due to its poor response to conventional platinum-based chemotherapy. Idiopathic thrombocytopenic purpura (ITP), which usually reveals severe thrombocytopenia, is a common autoimmune disorder. However, to date very few cases of ovarian cancer associated with ITP have been reported in the literature. We report a case of a 57-year-old woman who developed OCCA 14 years after the diagnosis of ITP. The patient presented with abdominal distention and mild tenderness. We performed the operation with high-dose immunoglobulin therapy preoperatively, and diagnosed OCCA. Postoperatively, six cycles of cytotoxic chemotherapy with irinotecan hydrochloride plus cisplatin were performed every 4-5 weeks without thrombocytopenia. We conclude that combination chemotherapy with irinotecan hydrochloride plus cisplatin is useful for a case of OCCA associated with ITP.

Texture Analysis of Apparent Diffusion Coefficient Maps in Cervical Carcinoma: Correlation with Histopathologic Findings and Prognosis.

Purpose: To determine the feasibility of texture analysis of apparent diffusion coefficient (ADC) maps and to assess the performance of texture analysis and ADC to predict histologic grade, parametrial invasion, lymph node metastasis, International Federation of Gynecology and Obstetrics (FIGO) stage, recurrence, and recurrence-free survival (RFS) in patients with cervical carcinoma. Materials and Methods: This retrospective study included 58 patients with cervical carcinoma who were examined with a 1.5-T MRI system and diffusion-weighted imaging with b values of 0 and 1000 sec/mm2. Software with volumes of interest on ADC maps was used to extract 45 texture features, including higher-order texture features. Receiver operating characteristic (ROC) analysis was performed to compare the diagnostic performance of ADC map random forest models and of ADC values. Dunnett test, Spearman rank correlation coefficient, Kaplan-Meier analyses, log-rank test, and Cox proportional hazards regression analyses were also used for statistical analyses. Results: The ADC map random forest models showed a significantly larger area under the ROC curve (AUC) than the AUC of ADC values for predicting high-grade cervical carcinoma (P = .0036), but not for parametrial invasion, lymph node metastasis, stages III-IV, and recurrence (P = .0602, .3176, .0924, and .5633, respectively). The random forest models predicted that the mean RFS rates were significantly shorter for high-grade cervical carcinomas, parametrial invasion, lymph node metastasis, stages III-IV, and recurrence (P = .0405, < .0001, .0344, .0001, and .0015, respectively); the random forest models for parametrial invasion and stages III-IV were more useful than ADC values (P = .0018) for predicting RFS. Conclusion: The ADC map random forest models were more useful for noninvasively evaluating histologic grade, parametrial invasion, lymph node metastasis, FIGO stage, and recurrence and for predicting RFS in patients with cervical carcinoma than were ADC values.Keywords: Comparative Studies, Genital/Reproductive, MR-Diffusion Weighted Imaging, MR-Imaging, Neoplasms-Primary, Pathology, Pelvis, Tissue Characterization, UterusSupplemental material is available for this article.© RSNA, 2020See also the commentary by Reinhold and Nougaret in this issue.

Port site recurrence and unusual diffuse subcutaneous metastases of unexpected early stage ovarian cancer after laparoscopic surgery: a case report.

Port site recurrence is a rare but well-documented adverse event peculiar to laparoscopic surgery. We report an unusual outcome of unexpected early stage ovarian cancer in which port site recurrence occurred after laparoscopic surgery and was followed by diffuse subcutaneous metastases. A 31-year-old Japanese woman with a large tumor in her abdomen visited our hospital. Because no intratumoral solid component was detected on diagnostic imaging, the tumor was diagnosed as a benign ovarian tumor and the patient underwent left ovarian laparoscopic cystectomy. Contrary to our expectations, however, the ovarian tumor was a mucinous carcinoma. We performed additional surgery, but the tumor recurred in the umbilical area, and multiple subcutaneous metastases later appeared. The curative effect of chemotherapy and radiation was limited. This atypical metastatic distribution of an extremely small amount of cancer might have been caused by the laparoscopic procedure. Protection against tumor cell dissemination is necessary during all forms of laparoscopic surgery.

Endometrial Carcinoma: Texture Analysis of Apparent Diffusion Coefficient Maps and Its Correlation with Histopathologic Findings and Prognosis.

Purpose: To determine the feasibility of texture analysis (TA) of apparent diffusion coefficient (ADC) maps for predicting histologic grade (HG) and recurrence-free survival (RFS) in patients with endometrial carcinoma (EMC). Materials and Methods: One hundred twenty-one patients with EMC were examined by using a 1.5-T MRI system and diffusion-weighted imaging (DWI) with b values of 0 and 1000 sec/mm2. Software with volumes of interest on ADC maps was used to extract 45 texture features including higher-order texture features. Receiver operating characteristic analysis was performed to compare the diagnostic performance of the random forest (RF) model and ADC values for HG and recurrence. Results: Area under the curve (AUC) for predicting high-grade EMCs was significantly larger for RF model than for ADC values (0.967 vs 0.898; P = .0336). AUC for predicting recurrence was larger for the RF model than for ADC values (0.890 vs 0.875; P = .7248), although the difference was not significant. Mean RFS was significantly shorter for high-grade EMCs than for low-grade EMCs (P = .0002; hazard ratio, 4.9) and for ADC values less than or equal to 0.802 × 10-3 mm2/sec than for ADC values greater than 0.802 × 10-3 mm2/sec (P < .0001; hazard ratio, 32.9). RF model showed that the mean RFS was significantly shorter for the presence of recurrence than for its absence (P < .0001; hazard ratio, 94.7). Conclusion: TA of ADC maps had significantly higher diagnostic performance than did ADC values for predicting HG and was a more useful indicator than HG and ADC values for predicting RFS in patients with EMC.Keywords: Comparative Studies, Genital/Reproductive, MR-Diffusion Weighted Imaging, MR-Imaging, Neoplasms-Primary, Pathology, Pelvis, Tissue Characterization, Uterus© RSNA, 2019.

Diffusion kurtosis imaging of endometrial carcinoma: Correlation with histopathological findings.

PURPOSE: In this study, we aimed to determine the usefulness of diffusion kurtosis imaging (DKI) as a noninvasive method for the evaluation of tumor invasion depth, histological grade, and lymph node metastasis in patients with endometrial carcinoma (EMC). MATERIALS AND METHODS: Our institutional review board approved this retrospective study and waived informed consent. In total, 24 patients suspected of having EMC were examined by a 1.5-T magnetic resonance imaging. DKI data were obtained using a single-shot echo-planar imaging sequence with four b values (0, 500, 1000, and 2000 s/mm2). Kurtosis (K), diffusivity (D), and apparent diffusion coefficient (ADC) maps were generated and compared with histopathological findings. RESULTS: K maps from all patients identified the junctional zone as a distinct high-K zone (1.443 ±â€¯0.362). This zone was significantly different from the zone of endometrium and outer myometrium (0.678 ±â€¯0.179 and 0.694 ±â€¯0.113, respectively; P < 0.001). K and D values of all EMCs were significantly different from those of all normal uterine wall layers. K and D values were significantly correlated with histological grades of endometrioid adenocarcinomas (r = 0.799, P < 0.001 and r = -0.799, P < 0.001, respectively), while ADC values were not (r = -0.243, P = 0.382). Metastatic and nonmetastatic lymph nodes showed significantly different K (P = 0.001) and D (P = 0.001) values, but not ADC values (P = 0.827). CONCLUSIONS: DKI may be clinically useful for the noninvasive evaluation of depth of tumor invasion, histological grade, and lymph node metastasis in patients with EMC.

Involvement of GATA-4/-5 transcription factors in ovarian carcinogenesis.

To clarify the role of GATA transcription factors in ovarian carcinogenesis, we analyzed the expression and methylation states of GATA-4/-5/-6 in eight human ovarian cancer cell lines. GATA-4/-5 were methylated in three and two cell lines without their expression, respectively. Methylation of GATA-4/-5 was also detected in nine and five of 15 primary ovarian cancers, respectively. GATA-6 was not methylated in any cases. We transiently over-expressed GATA-5 in the JHOC-5 cell line using an adenovirus system, resulting in that apoptosis was induced and apoptosis-related genes, such as Apaf-1, were up-regulated. These data suggest that GATA-4/-5 may be involved in ovarian carcinogenesis.

[Neoadjuvant intraarterial chemotherapy with nedaplatin, peplomycin and mitomycin C for advanced cervical cancer].

The aim of the present study was to examine the usefulness of neoadjuvant intraarterial chemotherapy (NAC) using nedaplatin as key drug to improve the prognosis in case of advanced cervical cancer. Twenty-five cases of advanced cervical cancer (15 cases of stage II with high risks, 10 of stage III, referred to as the 254-S group) treated by NAC using nedaplatin, mitomycin C and peplomycin were compared with 30 cases (22 cases of stage II with high risks, 8 of stage III, referred to as the CDDP group) treated using cisplatin and mitomycin C which is the conventional regimen, in terms of measurable response, pathological response, rate of lymph node metastasis, cumulative survival rate, side effects and relapse style. According to the evaluation by measurable responses, the response rate was 90% (CR 52%) in the 254-S group and 75% (CR 15%) in the CDDP group. For pathological response of the specimen, the CR rate was 16% in the 254-S group and 23% in the CDDP group. The rate of lymph node metastasis extracted surgically was 33% and 41%, respectively. The cumulative survival rate in the 254-S group was about 10% better than in the CDDP group, but no significant difference was found. Leucopenia of both groups was of the same grade. In the 254-S group, although thrombocytopenia was more critical than in the CDDP group, there was a slight tendency to kidney toxicity. The locoregional recurrence rate was 12% in the 254-S group and 30% in the CDDP group. The distant metastasis rate was 16% and 27%, respectively. Although neoadjuvant intraarterial chemotherapy using nedaplatin as a key drug was useful to improve the prognosis of advanced cervical cancer, measures against recurrence outside the pelvis and individualization of medical treatment were considered to lead to a further improvement of the prognosis.