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.

Clinical utility of comprehensive genomic profiling in Japan: Result of PROFILE-F study.

INTRODUCTION: Clinical sequencing has provided molecular and therapeutic insights into the field of clinical oncology. However, despite its significance, its clinical utility in Japanese patients remains unknown. Here, we examined the clinical utility of tissue-based clinical sequencing with FoundationOne® CDx and FoundationOne® Heme. Between August 2018 and August 2019, 130 Japanese pretreated patients with advanced solid tumors were tested with FoundationOne® CDx or FoundationOne® Heme. RESULTS: The median age of 130 patients was 60.5 years (range: 3 to 84 years), and among them, 64 were males and 66 were females. Major cancer types were gastrointestinal cancer (23 cases) and hepatic, biliary, and pancreatic cancer (21 cases). A molecular tumor board had been completed on all 130 cases by October 31, 2019. The median number of gene alterations detected by Foundation testing, excluding variants of unknown significance (VUS) was 4 (ranged 0 to 21) per case. Of the 130 cases, one or more alterations were found in 123 cases (94.6%), and in 114 cases (87.7%), actionable alterations with candidates for therapeutic agents were found. In 29 (22.3%) of them, treatment corresponding to the gene alteration was performed. Regarding secondary findings, 13 cases (10%) had an alteration suspected of a hereditary tumor. Of the 13 cases, only one case received a definite diagnosis of hereditary tumor. CONCLUSIONS: Our study showed that clinical sequencing might be useful for detecting gene alterations in various cancer types and exploring treatment options. However, many issues still need to be improved.

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 Report of Postoperative Chylous Ascites after Laparoscopic Sigmoidectomy].

A female in her 70s was diagnosed as sigmoid colon cancer. Laparoscopic sigmoidectomy was performed. Chylous ascites was observed after starting oral intake. As we changed the patient's diet to a low fat diet, the chylous ascites disappeared. There are certain numbers of reports of the cases improved by fasting or only fat decreased meal. It is important to prevent this complications using appropriate surgical devices.

A Pilot Study Analyzing the Clinical Utility of Comprehensive Genomic Profiling Using Plasma Cell-Free DNA for Solid Tumor Patients in Japan (PROFILE Study).

BACKGROUND: The clinical utility of plasma cell-free DNA in precision cancer medicine has not been established. A pilot study was conducted to investigate the clinical utility of comprehensive genomic profiling by liquid biopsy in a Japanese population. METHODS: In this PROFILE study, 102 patients with advanced solid tumors who showed progression with standard systemic therapy underwent liquid biopsy between August 2017 and February 2020. Liquid biopsy was performed using Guardant360. RESULTS: Of the 102 patients, 56 were women, and the median age was 65 years. Regarding the types of cancer, 31 were hepatobiliary and pancreatic cancer, 17 were gastrointestinal cancer, and 13 were breast cancer. Frequently altered genes were TP53 (53.9%, 46/102), KRAS (25.5%, 26/102), PIK3CA (19.6%, 20/102), and EGFR (17.6%, 18/102). At least one genetic aberration was detected in 92 patients (90.2%). Actionable mutation was discovered in 88 patients (86.3%), and 67 patients (65.7%) were clinical trial candidates. Of the 102 patients, 22 (21.6%) were able to receive biomarker-matched therapy. Their best responses were as follows: 1 complete response, 3 partial responses, 7 stable diseases, and 11 progressive diseases. Additionally, the treated patients were divided on the basis of matching scores (≥ 50% vs. < 50%). The patients were divided into high and low groups. The high group had a higher disease control rate (DCR) of 75% compared with 20% in the low group (P = 0.010). CONCLUSIONS: The results indicate that liquid biopsy is useful for identifying actionable mutations associated with the clinical response of selected patients.

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.

[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.

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.

[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.

[Clinical Utility of Comprehensive Genome Profiling Using FoundationOne CDx in Japanese Population(PROFILE-F Study)].

BACKGROUND: FoundationOne CDx is a cancer genome profiling test that has already been approved by the FDA, but its clinical utility in Japanese patients is unknown. In this study, we examined the clinical utility of FoundationOne CDx. METHODS: 46 samples from 43 Japanese pretreated patients with advanced solid tumors were tested with FoundationOne CDx between September 2018-January 2019. RESULTS: The median age of 43 patients was 63 years(ranged 18 to 82 years), and among them 24 were males and 19 females. Major cancer types were hepato-biliary and pancreatic(8 cases)and other digestive organs(8 cases). All 27 cases in which genome cancer board had been completed by January 17, 2019 were analyzable, and the number of detected gene mutations(except VUS)was an average of 4.3(ranged 0 to 14)per case. Of the 27 cases, one or more mutations were found in 26 cases(96%), and in all such 26 cases actionable mutations with candidates for therapeutic agents were found. In 4(15%)of them, the treatment corresponding to the gene mutation was performed. Among the cases in which target disease matched and clinical trials of the drug were being conducted in Japan, only one case participated in the trial. The most common reason for not participating in the trial was disease deterioration and PS reduction (33%). CONCLUSIONS: The FoundationOne CDx test showed that it can detect gene mutations in various cancer types in Japanese patients.

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.

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.

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.

[A Case of Appendiceal Neuroendocrine Tumor Diagnosed after Appendectomy].

A 25-year-old woman visited our hospital with a complaint of right lower abdominal pain. As a result of the examination, she was diagnosed as having acute appendicitis. After conservative treatment, we planned an elective surgery. At 3 months after discharge, laparoscopic appendectomy was performed. We found a mass of 10mm in diameter at the body of the appendix. Histopathological examination revealed the proliferation of heteromorphic cells with small round nuclei. It was positive for chromogranin A and synaptophysin in immunostaining, so we made a diagnosis of NET G1. Tumor cells infiltrated beyond the intrinsic muscle layer, but no vascular invasion was observed, and the margin was negative. In accordance with the guidelines, we followed up the patient with imaging examination and did not find any signs of recurrence.

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.

Prevention of surgical site infection via antibiotic administration according to guidelines after gynecological surgery.

AIM: We modified the antimicrobial prophylaxis of surgical site infection (SSI) according to the guidelines of the Japanese Society of Chemotherapy and Japan Society of Infectious Diseases (hereinafter referred to as optimization) and measured outcomes. METHODS: From April 2016 to March 2017, we performed cesarean section and open hysterectomy with optimization, and compared the outcome to that of surgery performed without optimization between April 2014 and March 2016. We measured the rates of antibiotic discontinuation, appropriate antibiotic selection, SSI incidence, resumption of antibiotic therapy and fever incidence, as well as the length of postoperative hospital stay and medical expenses for antibiotics to evaluate the appropriateness and outcomes of antibiotic prophylaxis. RESULTS: Optimization resulted in a change in the method of selecting antibiotics for cesarean section, but there was no change in SSI incidence rate (0.74% vs 0.0%, P = 0.36). Optimization reduced the use of antibiotics and medical expenses of hysterectomy (median reduction of 50% and 78% for hysterectomy without or with lymphadenectomy, respectively). However, there was no change in outcome regarding SSI incidence (5.7% vs 0.0%, P = 0.11 and 7.8% vs 9.5%, P = 0.77, respectively). CONCLUSION: Appropriate use of antibiotics according to guidelines reduced antibiotic dose and medical expenses, but there was no change in outcome regarding SSI incidence rate. These findings suggested that implementation of dosing regimens according to the guidelines would be useful to reduce antibiotic medicine costs and prevent resistant bacteria and complications associated with antibiotics.

Exosomes of human placenta-derived mesenchymal stem cells stimulate angiogenesis.

BACKGROUND: The therapeutic potential of mesenchymal stem cells (MSCs) may be attributed partly to humoral factors such as growth factors, cytokines, and chemokines. Human term placental tissue-derived MSCs (PlaMSCs), or conditioned medium left over from cultures of these cells, have been reported to enhance angiogenesis. Recently, the exosome, which can transport a diverse suite of macromolecules, has gained attention as a novel intercellular communication tool. However, the potential role of the exosome in PlaMSC therapeutic action is not well understood. The purpose of this study was to evaluate PlaMSC-derived exosome angiogenesis promotion in vitro and in vivo. METHODS: MSCs were isolated from human term placental tissue by enzymatic digestion. Conditioned medium was collected after 48-h incubation in serum-free medium (PlaMSC-CM). Angiogenic factors present in PlaMSC-CM were screened by a growth factor array. Exosomes were prepared by ultracentrifugation of PlaMSC-CM, and confirmed by transmission electron microscopy, dynamic light scattering, and western blot analyses. The proangiogenic activity of PlaMSC-derived exosomes (PlaMSC-exo) was assessed using an endothelial tube formation assay, a cell migration assay, and reverse transcription-PCR analysis. The in-vivo angiogenic activity of PlaMSC-exo was evaluated using a murine auricle ischemic injury model. RESULTS: PlaMSC-CM contained both angiogenic and angiostatic factors, which enhanced endothelial tube formation. PlaMSC-exo were incorporated into endothelial cells; these exosomes stimulated both endothelial tube formation and migration, and enhanced angiogenesis-related gene expression. Laser Doppler blood flow analysis showed that PlaMSC-exo infusion also enhanced angiogenesis in an in-vivo murine auricle ischemic injury model. CONCLUSIONS: PlaMSC-exo enhanced angiogenesis in vitro and in vivo, suggesting that exosomes play a role in the proangiogenic activity of PlaMSCs. PlaMSC-exo may be a novel therapeutic approach for treating ischemic diseases.

[Marginal zone lymphoma of mucosa-associated lymphoid tissue of the parietal pleura; report of a case].

An 76-year-old man was referred to our hospital due to right hydrothorax. The diffuse thickening of parietal pleura with increased fluoro-2-deoxy-D-glucose (FDG) uptake was noted by computed tomography (CT) and positron emission tomography (PET). Surgical biopsy was performed and the tumor was diagnosed as mucosal associated lymphoid tissue (MALT) lymphomas of parietal pleura origin by pathology. Complete remission was achieved by postoperative chemotherapy (R-CHOP), and the patient is now alive without recurrence.

Isoprenoid geranylgeranylacetone inhibits human colon cancer cells through induction of apoptosis and cell cycle arrest.

Geranylgeranylacetone (GGA), an isoprenoid compound, is a widely used antiulcer drug developed in Japan. GGA is structurally similar to plaunotol and geranylgeraniol, another isoprenoid reported to exert strong anticancer effects. In an earlier study, GGA was shown to inhibit ovarian cancer invasion by attenuating not only Rho activation, but also Ras-MAPK activation. In this study, we aimed to test whether GGA could have a therapeutic effect on colon cancer cells. As a result, we found that GGA induced a dose-dependent decrease in the proliferative activity through induction of cell apoptosis and cell cycle arrest in the G1 phase. The induction of apoptosis was mediated by the activation of both caspase-8 and caspase-9 pathways. The induction of G1 arrest was mediated by the increase of p21 and p27, and also the decrease of phosphorylated retinoblastoma protein levels. This study showed the potential anticancer activity of GGA. As this drug is already available in Japan for clinical use as an antiulcer/antigastritis agent, clinical trials will be designed to confirm its potential usefulness for cancer patients.