A case of intestinal tuberculosis presenting massive hematochezia controlled by endoscopic coagulation therapy]

The clinical manifestations of intestinal tuberculosis are non-specific. But, abdominal pain, low grade fever, weight loss, anorexia, and diarrhea are major symptoms of intestinal tuberculosis. Massive bleeding has been reported as a rare manifestation of intestinal tuberculosis. Massive hematochezia from intestinal tuberculosis has rarely been reported in the medical literature. Also, most of them were treated with anti-tuberculosis medication only or with surgery. We treated a case of intestinal tuberculosis presenting massive hematochezia with colonoscopic coagulation therapy and anti-tuberculosis medication. Here, we report a Korean man who presented with massive hematochezia from ileal tuberculosis and treated by endoscopic coagulation therapy.     

Posttransplant Lymphoproliferative Disorder of the Thorax: CT and FDG-PET Features in a Single Tertiary Referral Center

To investigate the chest computed tomography (CT) and F-18 fluoro-2-deoxy-d-glucose positron emission tomographic (FDG-PET) findings of posttransplant lymphoproliferative disorder (PTLD) in the thorax.From November 2004 to February 2013, the cases of 12 adult patients (3 female and 9 male, age range 34–68, and median age 46 years) with proven PTLD were retrospectively reviewed. The transplanted organs included the kidney (5/12), liver (4/12), heart (1/12), combined kidney and pancreas (1/12), and hematopoietic stem cell (1/12). We investigated the relationship of the Epstein–Barr virus (EBV) to the patients’ long-term follow-up, and evaluated the characteristics of the lesions on the chest CT and FDG-PET. The lesions were classified into 2 patterns: that of lymph node and lung involvement.The interval between the transplantation and the onset of PTLD was 2 to 128 months (median, 49). Positive EBV-encoded RNA in the pathologic specimens was found in 10 patients (83.3%). Eight patients were positive for EBV PCR in their blood, and 3 patients showed seroconversion without antiviral therapy. The responses to treatment were complete in 7 cases (58.3%), partial remission in 4 cases (33.3%), and undetermined in 1 case (8.3%). The more common chest CT patterns showed lymph node involvement (10/12) rather than lung involvement (3/12). The median maximum-standardized uptake value on the FDG-PET scans was 7.7 (range, 2.7–25.5).In patients with PTLD involving the thorax, lymphadenopathy was the more common manifestation on the chest CT rather than lung involvement. The lesions showed hypermetabolism on FDG-PET.     

From the Cover: Anoctamin 1 (TMEM16A) is essential for testosterone-induced prostate hyperplasia

Benign prostatic hyperplasia (BPH) is characterized by an enlargement of the prostate, causing lower urinary tract symptoms in elderly men worldwide. However, the molecular mechanism underlying the pathogenesis of BPH is unclear. Anoctamin1 (ANO1) encodes a Ca²⁺-activated chloride channel (CaCC) that mediates various physiological functions. Here, we demonstrate that it is essential for testosterone-induced BPH. ANO1 was highly amplified in dihydrotestosterone (DHT)-treated prostate epithelial cells, whereas the selective knockdown of ANO1 inhibited DHT-induced cell proliferation. Three androgen-response elements were found in the ANO1 promoter region, which is relevant for the DHT-dependent induction of ANO1. Administration of the ANO1 blocker or Ano1 small interfering RNA, inhibited prostate enlargement and reduced histological abnormalities in vivo. We therefore concluded that ANO1 is essential for the development of prostate hyperplasia and is a potential target for the treatment of BPH.Benign prostatic hyperplasia (BPH) is characterized by the anatomical enlargement of the prostate gland and is one of the most common diseases among elderly men (1). More than 50% of men aged more than 60 suffer from lower urinary tract symptoms, including urinary hesitancy, weak stream, and nocturia, which are commonly caused by bladder obstruction (2). The availability of testosterone or dihydrotestosterone (DHT) is known to cause the development of histologically characterized BPH (3). Clinical reports on BPH have suggested a positive association between BPH and prostate cancer, with increased risk of and mortality from prostate cancer among BPH patients (4). However, some epidemiologic studies have reported that BPH is not a cause of prostate cancer (5). Despite the controversy on the association between prostate cancer and BPH, common risk factors for the two diseases include chronic inflammation, metabolic disturbance, and genetic variation (6, 7). Regardless of its association with prostate cancer, BPH is still a social issue for the elderly, but the etiologic mechanisms of its pathology remain unknown.Anoctamin1 (ANO1, also known as TMEM16A) encodes a Ca²⁺-activated chloride channel (CaCC) (8–10), and is widely expressed in secretory epithelia, including the salivary gland, trachea (11), and intestine, smooth muscle (12), and sensory neurons (13). ANO1 is known to mediate various physiological functions, such as fluid and electrolyte secretion, gut motility, vascular smooth muscle contraction, and thermal nociception (14).ANO1 has been suggested to be a regulator of cell proliferation and tumorigenesis, even before it was discovered as a CaCC, and is highly expressed in several carcinomas, including gastrointestinal stromal tumors (15), esophageal squamous cell carcinoma (16), head and neck squamous cell carcinoma (17), oral cancer (18), breast cancer (19), and prostate cancer (20). The disruption of Ano1 or the administration of a pharmacological ANO1 inhibitor impairs the proliferation of interstitial cells of Cajal (21) and numerous cancer cells (19, 20, 22). ANO1 promotes tumorigenesis and cancer progression by inducing epidermal growth factor receptor-activated mitogen-activated protein kinase (MAPK)/AKT signaling (19) and regulates tumor cell motility and metastasis via the ezrin/radixin/moesin protein family (23). Thus, ANO1 is considered to be a potential target for anticancer therapy (24).BPH and prostate cancer share common characteristics, such as testosterone-dependent growth and response to hormone therapy, which indicates a causal link between the two diseases (25). Notably, ANO1 is highly overexpressed in prostate cancer cells (20). Knockdown of Ano1 results in reduced cell proliferation and the suppression of tumor progression in the breast cancer model (19). Thus, it is conceivable that ANO1 may be involved in BPH, which may progress to prostate cancer. Therefore, this study was performed to determine whether ANO1 plays a key role in testosterone-dependent prostate hyperplasia.     

Progestins in the Fertility‐Sparing Treatment and Retreatment of Patients With Primary and Recurrent Endometrial Cancer

Endometrial cancer is the most common gynecologic cancer in developed countries. Approximately 3%–14% of endometrial cancers are diagnosed in young women under 40 who want to preserve their fertility. The incidence of endometrial cancer in this age group is increasing, for which fertility‐sparing therapy is increasingly used because it is one of the most important quality of life issues in these women. Progestin therapy is the most common type of fertility‐sparing therapy. In this review, the most up‐to‐date findings regarding fertility‐sparing progestin therapy for young women with primary and recurrent endometrial cancer is addressed in terms of diagnosis, treatment, follow‐up, and oncologic and reproductive outcomes. Fertility‐sparing progestin therapy is highly effective in selected young women with primary and recurrent endometrial cancer. The selection of appropriate patients through comprehensive pretreatment evaluation is of paramount importance to achieve the best outcomes without compromising survival. Because of the high rate of recurrence after successful fertility‐sparing therapy, close surveillance is mandatory, and prophylactic hysterectomy is the best option for patients who have completed family planning. Pregnancy outcomes are very promising with the aid of assisted reproductive technologies. Continuous daily oral medroxyprogesterone acetate and megestrol acetate are the preferred progestins for fertility‐sparing therapy, but future studies should be performed to determine the optimal dose and treatment duration of these agents.     

A Dosimetric Comparative Analysis of TomoDirect and Three-Dimensional Conformal Radiotherapy in Early Breast Cancer

Purpose

The purpose of this study is to compare dosimetric parameters of intensity-modulated mode of TomoDirect and three-dimensional conformal radiotherapy (3D-CRT) in patients with early breast cancer.

Methods

TomoDirect and 3D-CRT planning were carried out for 26 patients with early breast cancer who had received breast-conserving surgery. A total of 50.4 Gy in 28 fractions were prescribed to the planning target volume. The organs at risk (OAR) such as lung and heart were contoured. Planning target volume (PTV) dose coverage, radiation conformity index (RCI), radical dose homogeneity index (rDHI), and irradiation dose of organs at risk were compared between TomoDirect and 3D-CRT planning.

Results

The mean PTV dose (51.65±0.37 Gy) and V_47.8 (100%) in TomoDirect were significantly higher than the mean PTV dose (50.88±0.65 Gy) and V_47.8 (89.23%±0.06%) in 3D-CRT (all, p<0.001). The RCI value in TomoDirect was significantly better than that in 3D-CRT (1.00 vs. 1.13, p<0.001). However, the rDHI value in TomoDirect was not significantly better than that in 3D-CRT (0.72 vs. 0.67, p=0.056). The mean lung dose and V₁₀, V₂₀, V₃₀, and V₄₀ values of ipsilateral lung in TomoDirect were significantly lower than those in 3D-CRT (all, p<0.05). There is no significant difference in the V₁₀, V₂₀, V₃₀, and V₄₀ values of heart between TomoDirect and 3D-CRT. And the mean dose for heart in TomoDirect was marginally lower than that in 3D-CRT (1.05 Gy vs. 1.62 Gy, p=0.085). The mean dose for left anterior descending coronary artery in left breast cancer was significantly lower in TomoDirect than in 3D-CRT (7.2 Gy vs. 12.1 Gy, p<0.001).

Conclusion

Compared to 3D-CRT, TomoDirect could result in favorable target coverage while reducing the irradiation dose of the ipsilateral lung for patients with early breast cancer.     

Overexpression of microRNA-95-3p suppresses brain metastasis of lung adenocarcinoma through downregulation of cyclin D1

Despite great efforts to improve survival rates, the prognosis of lung cancer patients is still very poor, mainly due to high invasiveness. We developed brain metastatic PC14PE6/LvBr4 cells through intracardiac injection of lung adenocarcinoma PC14PE6 cells. Western blot and RT-qPCR analyses revealed that PC14PE6/LvBr4 cells had mesenchymal characteristics and higher invasiveness than PC14PE6 cells. We found that cyclin D1 was upregulated, miR-95-3p was inversely downregulated, and pri-miR-95 and its host gene, ABLIM2, were consistently decreased in PC14PE6/LvBr4 cells. MiR-95-3p suppressed cyclin D1 expression through direct binding to the 3′ UTR of cyclin D1 mRNA and suppressed invasiveness, proliferation, and clonogenicity of PC14PE6/LvBr4 cells. Ectopic cyclin D1 reversed miR-95-3p-mediated inhibition of invasiveness and clonogenicity, demonstrating cyclin D1 downregulation is involved in function of miR-95-3p. Using bioluminescence imaging, we found that miR-95-3p suppressed orthotopic tumorigenicity and brain metastasis in vivo and increased overall survival and brain metastasis-free survival. Consistent with in vitro metastatic cells, the levels of miR-95-3p, pri-miR-95, and ABLIM2 mRNA were decreased in brain metastatic tissues compared with lung cancer tissues and higher cyclin D1 expression was involved in poor prognosis. Taken together, our results demonstrate that miR-95- 3p is a potential therapeutic target for brain metastasis of lung adenocarcinoma cells.     

In vivo RNAi screen identifies NLK as a negative regulator of mesenchymal activity in glioblastoma

Glioblastoma (GBM) is the most lethal brain cancer with profound genomic alterations. While the bona fide tumor suppressor genes such as PTEN, NF1, and TP53 have high frequency of inactivating mutations, there may be the genes with GBM-suppressive roles for which genomic mutation is not a primary cause for inactivation. To identify such genes, we employed in vivo RNAi screening approach using the patient-derived GBM xenograft models. We found that Nemo-Like Kinase (NLK) negatively regulates mesenchymal activities, a characteristic of aggressive GBM, in part via inhibition of WNT/β-catenin signaling. Consistent with this, we found that NLK expression is especially low in a subset of GBMs that harbors high WNT/mesenchymal activities. Restoration of NLK inhibited WNT and mesenchymal activities, decreased clonogenic growth and survival, and impeded tumor growth in vivo. These data unravel a tumor suppressive role of NLK and support the feasibility of combining oncogenomics with in vivo RNAi screen.     

Quality of life and sexuality comparison between sexually active ovarian cancer survivors and healthy women

Objective

compare quality of life (QoL) and sexual functioning between sexually active ovarian cancer survivors and healthy women.

Methods

A cross-sectional study was performed in 103 successfully treated ovarian cancer survivors and 220 healthy women. All women had engaged in sexual activity within the previous 3 months, and ovarian cancer survivors were under surveillance after primary treatment without evidence of disease. QoL and sexual functioning were assessed using three questionnaires; the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30), Ovarian Cancer Module (EORTC QLQ-OV28), and the Female Sexual Function Index (FSFI). Propensity score matching was used to adjust covariates between the ovarian cancer survivor and healthy women groups. In total, 73 ovarian cancer survivors and 73 healthy women were compared.

Results

Poorer social functioning (mean, 82.4 vs. 90.9; p=0.010) and more financial difficulties (mean, 16.4 vs. 7.8; p=0.019) were observed among ovarian cancer survivors than among healthy women. Sexuality, both in terms of desire, arousal, lubrication, orgasm, satisfaction, and pain and in terms of interest in sex, sexual activity, and enjoyment of sex (EORTC QLQ-OV28) were similar between the groups. However, vaginal dryness was more problematic in ovarian cancer survivors, with borderline statistical significance (p=0.081).

Conclusion

Sexuality was not impaired in ovarian cancer survivors who were without evidence of disease after primary treatment and having sexual activities, compared with healthy women, whereas social functioning and financial status did deteriorate. Prospective cohort studies are needed.