Regulation of LOXL2 and SERPINH1 by antitumor microRNA-29a in lung cancer with idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive lung disease that is refractory to treatment and carries a high mortality rate. IPF is frequently associated with lung cancer. Identification of molecular targets involved in both diseases may elucidate novel molecular mechanisms contributing to their pathology. Recent studies of microRNA (miRNA) expression signatures showed that microRNA-29a (miR-29a) was downregulated in IPF and lung cancer. The aim of this study was to investigate the functional significance of miR-29a in lung cancer cells (A549 and EBC-1) and lung fibroblasts (MRC-5) and to identify molecular targets modulated by miR-29a in these cells. We confirmed the downregulation of miR-29a in clinical specimens of IPF and lung cancer. Restoration of miR-29a suppressed cancer cell aggressiveness and fibroblast migration. A combination of gene expression data and in silico analysis showed that a total of 24 genes were putative targets of miR-29a. Among them, lysyl oxidase-like 2 (LOXL2) and serpin peptidase inhibitor clade H, member 1 (SERPINH1) were direct targets of miR-29a by luciferase reporter assays. The functions of LOXL2 and SERPINH1 contribute significantly to collagen biosynthesis. Overexpression of LOXL2 and SERPINH1 was observed in clinical specimens of lung cancer and fibrotic lesions. Downregulation of miR-29a caused overexpression of LOXL2 and SERPINH1 in lung cancer and IPF, suggesting that these genes are involved in the pathogenesis of these two diseases.

Patients with Advanced Ovarian Cancer Administered Oral Etoposide following Taxane as Maintenance Chemotherapy.

INTRODUCTION: The concept of maintenance therapy is one of the highly relevant approaches in the management of advanced ovarian cancer. The fundamental goal of maintenance therapy is to improve survival outcomes. We attempted to reinforce maintenance chemotherapy by adding oral etoposide following taxane administration. CASES: We retrospectively evaluated 14 patients with advanced ovarian cancer who had achieved clinically defined complete response to a primary platinum/taxane chemotherapy regimen and who were administered oral etoposide (50 mg/day × 21 days per cycle monthly for 3-5 cycles) following paclitaxel or docetaxel administration as maintenance chemotherapy. With regard to oral etoposide toxicity, grade 2 oral mucositis and grade 3 anemia were observed in 1 patient each. Three to five cycles of etoposide were administered to all patients, though daily dosage was reduced to 25 mg in 2 patients due to toxicity. The median progression-free survival was 43.5 months, the median overall survival was 86 months, and 5-year overall survival was 77.1%. CONCLUSION: The results from this ovarian cancer treatment evaluation suggest that oral etoposide may be administered safely following paclitaxel or docetaxel as maintenance chemotherapy. We expect this regimen to contribute to the improvement in the survival outcomes of patients with advanced ovarian cancer.

Recurrent ovarian cancer with multiple lymph nodes metastases successfully treated with lymphadenectomy as secondary cytoreductive surgery: A case report.

INTRODUCTION: Occasionally, lymph node metastases represent the only component at the time of recurrence of ovarian cancer. Here we report the case of a 78-year-old Japanese female who underwent successful surgery for recurrent ovarian cancer with multiple lymph node metastases. PRESENTATION OF CASE: The patient was referred to our institution with recurrent disease accompanied by chemoresistant multiple retroperitoneal lymph node metastases five years after the initial therapy for stage IIIc serous adenocarcinoma of the ovary. Positron emission tomography/computed tomography (PET/CT) revealed the involvement of two para-aortic nodes and two pelvic nodes, with no other positive site. The patient underwent systematic para-aortic and pelvic lymphadenectomy, and the metastatic nodes were completely resected. Histopathological examination revealed metastatic high-grade adenocarcinoma in four of 63 dissected lymph node specimens. The patient has been in clinical remission for over four years without any further additional therapies. DISCUSSION: In our case, the metastatic nodes predicted by PET/CT completely corresponded to the actual metastatic nodes; however, PET/CT often fails to identify microscopic disease in pathological positive nodes. We cannot reliably predict whether lymph node metastasis will persist in the limited range. Therefore, systematic lymphadenectomy with therapeutic intent should be performed, although it does not always mean that we remove all cancer cells. CONCLUSION: The findings from this case suggest that, even if used as secondary cytoreductive surgery in the context of a recurrent disease, systematic aortic and pelvic node dissection might sometimes contribute to the control if not cure of ovarian cancer.

A feasibility study on maintenance of docetaxel after paclitaxel-carboplatin chemotherapy in patients with advanced ovarian cancer.

OBJECTIVE: To test the concept of taxane sequencing, this feasibility trial evaluated maintenance of docetaxel after paclitaxel and carboplatin combination chemotherapy in patients with stage IC-IV ovarian cancer. METHODS: All patients received debulking surgery followed by paclitaxel and carboplatin chemotherapy. Attainment of clinically defined complete or partial response was confirmed by image scanning. Maintenance of docetaxel started at an initial dose of 70 mg/m(2) every 4 weeks for 6 cycles and was extended to 10 cycles unless disease progression and/or recurrence during the protocol therapy or unacceptable toxicities were seen. RESULTS: Stage subsets in 20 eligible patients were as follows: IIIB, 2 patients (10%); IIIC, 13 patients (65%); IV, 5 patients (25%). Neutropenia was common (40% with grade 3 or 4) and was most frequent during first or second cycle although the disabling peripheral neuropathy was not observed. Twelve patients completed protocol therapy (6≤cycles), while 8 patients failed to complete 6-cycle chemotherapy, because of progressive disease (5 patients) or grade 4 toxicities (3 patients). Median PFS was 20 months and 3-year PFS rate was 12%. Median overall survival was 39 months and 3-year OS rate was 69%. CONCLUSION: Six cycles of single-agent docetaxel maintenance chemotherapy is feasible and generally tolerable to women with advanced ovarian cancer who attained a clinically defined response to initial paclitaxel and carboplatin based chemotherapy.

Efficacy of lafutidine, a histamine H2-receptor antagonist, for taxane-induced peripheral neuropathy in patients with gynecological malignancies.

OBJECTIVE: Lafutidine, an antagonist of histamine H2-receptor, has gastroprotective activity associated with activation of capsaicin-mediated sensory nerves. The objective of this study was to investigate the efficacy of lafutidine for the treatment of taxane-induced peripheral neuropathy in patients with gynecological malignancies. METHODS: Twenty patients with taxane-induced peripheral neuropathy during the treatment of gynecological malignancy were enrolled in this study. After obtaining their informed consent, lafutidine (20mg per day) was administered orally, the efficacy of which was assessed according to the Patient Neurotoxicity Questionnaire item 1. RESULTS: Significant, moderate, slight, and no effects were observed in four, five, five, and six patients, respectively. The efficacy including significant and moderate effect was observed in nine (45%) of the 20 patients (95% confidence interval, 25.8%-65.8%). No adverse effects due to lafutidine were observed. CONCLUSION: This pilot study supports the relatively high efficacy of lafutidine for the treatment of taxane-induced peripheral neuropathy. Further prospective studies are warranted.

Evisceration occurred 1 year after vaginal vault repair for relapsed pelvic organ prolapse.

This report describes the case of an 81-year-old woman with sudden evisceration of the small intestine through the vagina. It occurred one year after repair of a vaginal vault prolapse, which was initially treated by vaginal hysterectomy and colporrhaphy three years prior to the repair. On examination, we found a 70-80-cm loop of bowel prolapsing through a 3-cm oval defect in the vaginal vault. The patient underwent emergency exploratory laparotomy under general anesthesia. After careful reduction of the eviscerated small intestine, the hernia hiatus was closed and the widened cul-de-sac was obliterated by performing a Moschcowitz culdoplasty. Rapid intervention by abdominovaginal surgery may enable smooth repositioning of the eviscerated intestine, thus preventing subsequent morbidity.

Granulosa cell tumor-like variant of endometrioid carcinoma of the ovary exhibiting nuclear clearing with biotin activity: a subtype showing close macroscopic, cytologic, and histologic similarity to adult granulosa cell tumor.

CONTEXT: The sex cord-like variant of endometrioid carcinoma of the ovary shows many similarities to Sertoli-Leydig cell tumor and granulosa cell tumor. However, few cases of the granulosa cell tumor-like variant have been reported, suggesting this tumor might often be hidden under the diagnosis of granulosa cell tumor. OBJECTIVE: To investigate the similarities and differences between the granulosa cell tumor-like variant of endometrioid carcinoma and granulosa cell tumor of the ovary and to evaluate a newly observed feature, namely, nuclear clearing (or optically clear nuclei), in this variant tumor. DESIGN: A comparative macroscopic, cytologic, histopathologic, and immunohistochemical study in specimens obtained from the following patients: 1 patient with granulosa cell tumor-like variant of endometrioid carcinoma diagnosed by frozen section examination, 3 patients with granulosa cell tumor, and 6 patients with classic endometrioid carcinoma. RESULTS: The granulosa cell tumor-like variant showed close macroscopic, cytologic, and microscopic similarities to granulosa cell tumor. However, the 2 tumors could be differentiated immunohistochemically. The former also showed intense staining for progesterone receptors and contained nonmorular nests that exhibited the so-called nuclear clearing with biotin activity. CONCLUSION: Because the granulosa cell tumor-like variant is pathologically similar to granulosa cell tumor, showing only some dissimilarities to the latter, it can easily be misdiagnosed if the possibility of this variant is not kept in mind. Identification of the typical endometrioid histologic features or related lesions or immunohistochemistry may lead to a proper diagnosis. The observation of nuclear clearing with biotin activity in nonmorular nests suggests that this tumor has endometrioid epithelial characteristics.

Uterine cervical diverticulum resembling a degenerated leiomyoma.

BACKGROUND: Uterine diverticulum is a very rare anomaly. Most previously reported cases were called "pregnancy-associated sacculations," and only 2 cases were considered true uterine diverticula. CASE: A 41-year-old woman presented with fever and lower abdominal pain. An extrauterine mass was detected, and a hysterectomy was performed. Pathological examination revealed a cystic uterine diverticulum lined with cervical glands and myometrium arising from the cervix. The final diagnosis was an infected uterine cervical diverticulum. CONCLUSION: Cervical diverticulum is a rare lesion that should be added to the differential diagnosis of a woman presenting with a pelvic mass.