Insulinoma-associated Protein 1 Expression and Its Diagnostic Significance in Female Genital Tract Neuroendocrine Carcinomas.

Neuroendocrine carcinomas (NECs) are rare, but aggressive malignant tumors of the female genital tract, especially in the uterine the cervix. Beside histologic morphology, positivity of neuroendocrine markers with immunohistochemistry plays an important role in diagnosis of NECs. Insulinoma-associated protein 1 (INSM1) is a novel marker reported to be widely expressed in a variety of neuroendocrine tumors. A previous study also suggested INSM1 has superior performance to conventional neuroendocrine markers in cervical NECs. In our present study, comparison between immunomarkers was performed in female genital tract NECs. Forty-nine patients with gynecologic NECs (4 vagina, 39 cervix, 5 endometrium, 1 ovary) were included from 1993 to 2019 at our center. Immunohistochemistry was performed with INSM1, CD56, synaptophysin (SYN), chromogranin-A (CgA), and thyroid transcription factor 1 (TTF1). The results show INSM1 has superior sensitivity and intensity compared with CD56, SYN, CgA, and TTF1 in cervical small cell NECs, but not in large cell NECs. In contrast to cervical NECs, INSM1 immunohistochemistry shows only focal and weak staining in endometrial NECs. Our result suggested INSM1 is a sensitive marker which can be used as first-line test in histologic suspicious cervical cases, especially small cell NECs. However, negative INSM1 stain does not exclude the possibility of NECs. In endometrial NECs, conventional panel with CD56, SYN, CgA has better diagnostic performance than INSM1 alone.

A new primer construction technique that effectively increases amplification of rare mutant templates in samples.

BACKGROUND: In personalized medicine, companion diagnostic tests provide additional information to help select a treatment option likely to be optimal for a patient. Although such tests include several techniques for detecting low levels of mutant genes in wild-type backgrounds with fairly high sensitivity, most tests are not specific, and may exhibit high false positive rates. In this study, we describe a new primer structure, named 'stuntmer', to selectively suppress amplification of wild-type templates, and promote amplification of mutant templates. RESULTS: A single stuntmer for a defined region of DNA can detect several kinds of mutations, including point mutations, deletions, and insertions. Stuntmer PCRs are also highly sensitive, being able to amplify mutant sequences that may make up as little as 0.1% of the DNA sample. CONCLUSION: In conclusion, our technique, stuntmer PCR, can provide a simple, low-cost, highly sensitive, highly accurate, and highly specific platform for developing companion diagnostic tests.

Correction to: A new primer construction technique that effectively increases amplification of rare mutant templates in samples.

Following publication of the original article [1], the author informed us that the legend for Fig. 2 was incorrect.

Expression of haem oxygenase-1 correlates with tumour aggressiveness and BRAF V600E expression in thyroid cancer.

AIMS: Haem oxygenase-1 (HO-1) is an inducible enzyme that participates in haem degradation. Recent studies have indicated that HO-1 activation may play a role in tumour development and progression. The aim of this study was to evaluate the expression of HO-1 in thyroid cancer and its clinicopathological significance. METHODS AND RESULTS: We observed up-regulation of HO-1 in papillary thyroid tumours in comparison with normal thyroid tissue. Immunohistochemical analysis revealed that 48% of papillary cancers and 36% of follicular cancers, but none of normal thyroid tissues, were positive for HO-1 expression. Among 129 differentiated thyroid cancers, HO-1 expression was associated with patient age (P = 0.001), TNM stage (P = 0.001), and Mayo Clinic metastasis, patient age, completeness of resection, local invasion and tumour size score (P = 0.001). BRAF V600E expression was evaluated immunohistochemically and validated by Sanger sequencing. There was a strong association between HO-1 and BRAF V600E expression in papillary cancers (P = 0.002). CONCLUSIONS: Overexpression of HO-1 in a subset of thyroid cancers is associated with tumour aggressiveness and BRAF V600E expression. HO-1 might have a potential role in prognosis and targeted treatment in patients with thyroid cancer.

Primary surgery versus primary radiation therapy for FIGO stages I-II small cell carcinoma of the uterine cervix: A retrospective Taiwanese Gynecologic Oncology Group study.

OBJECTIVE: To evaluate the role of surgery, radiation therapy and chemotherapy in the management of small cell carcinoma of the uterine cervix (SCCC) through a retrospective study of Taiwanese Gynecologic Oncology Group. METHODS: We reviewed the medical records and histological files of 144 patients with FIGO stages IA-IIB SCCC treated in 11 main hospitals in Taiwan from 1987 to 2009. RESULTS: There were 110 patients receiving primary surgery and 34 primary radiation therapy. Most patients in each group also received chemotherapy as part of primary treatment. A lower loco-regional failure rate was observed in patients who received primary radiation therapy than in those who had primary surgery (6% vs. 27%; P=0.009). The 5-year overall survival (OS) was 89% for 13 surgically treated patients with cervical tumor ≤2cm and no lymphovascular space involvement (LVSI) in whom recurrence was noted in 2 of 4 patients without receiving adjuvant chemotherapy and none in the 9 patients who had chemotherapy. Excluding these 13 patients, primary radiation therapy with at least 5cycles of platinum-based chemotherapy (n=14, including 12 stages IB2-IIB) resulted in a 5-year OS of 78%, better than that of 46% by primary surgery (n=97, including 40 stages IB2-IIB) (P=0.046). CONCLUSIONS: None of the 9 patients with cervical tumor ≤2cm and no LVSI showed disease recurrence after primary surgery and adjuvant chemotherapy. For most patients with stages I-II, primary radiation therapy with aggressive chemotherapy was associated with better survival than surgery.

FTY720 mitigates torsion/detorsion-induced testicular injury in rats.

BACKGROUND: FTY720, a sphingosine-1-phosphate (S1P) receptor agonist, possesses potent anti-inflammation capacity. We evaluated the therapeutic potentials of FTY720 against testicular injury induced by testicular torsion and/or detorsion (T/D). MATERIALS AND METHODS: Young adult male Sprague-Dawley rats were allocated to receive T/D (the T/D group) and T/D plus FTY720 (4 mg/kg, the T/D-FTY group, n = 6 in each group). To investigate the possible roles of the S1P receptors, another group of rats received T/D plus FTY720 plus the potent S1P receptor antagonist VPC23019 (1 mg/kg, the T/D-FTY-VPC group, n = 6). FTY720 was administered immediately before testicular detorsion, and VPC23019 was administered 30 min before FTY720. Another set of rats that received sham operation, immediately followed by injection of normal saline, FTY720, or FTY720 plus VPC23019, served as control groups. Sham control groups were run simultaneously. After euthanization, levels of testicular injury were measured. RESULTS: Histologic findings revealed severe testicular injury changes in both the T/D and T/D-FTY-VPC groups and moderate testicular injury changes in the T/D-FTY group. In addition, malondialdehyde activity (oxidative status), concentration of interleukin-1ß (inflammation index), myeloperoxidase activity (neutrophil infiltration index), and wet-to-dry weight ratio (tissue edema index) of both the T/D and T/D-FTY-VPC groups were significantly higher than those of the T/D-FTY group. These data confirmed the protective effects of FTY720 against testicular T/D. Moreover, antagonizing the S1P receptors could reverse the protective effects of FTY720. CONCLUSIONS: FTY720 significantly mitigated testicular injury induced by testicular T/D. The mechanisms may involve activating the S1P receptors.

Epidermal Growth Factor Receptor Inconsistency by Immunohistochemistry Method Using Different Monoclonal Antibodies in Colorectal Cancer Patients.

BACKGROUND: Targeted therapy is typically used to treat colorectal cancer (CRC). The epidermal growth factor receptor (EGFR) was recognized as a potential therapeutic target. Does the EGFR protein express consistently using different monoclonal antibodies in clinics? METHODS: One hundred and sixty-four patients (mean age 61.80 ± 12.78 years) who suffered from CRC were selected at Mackay Memorial Hospital in Taiwan. Formalin-fixed and paraffin-embedded tissue sections from all patients were tested simultaneously using two commercial antibodies, Dako-EGFR (mouse monoclonal anti-EGFR clone 2-18C9, pharmDx) and NCL-EGFR (NCL-EGFR-384, Novocastra) monoclonal antibodies, to study the commutability or equality of the qualities of EGFR expression by standard immunohistochemistry (IHC) procedures. RESULTS: The EGFR expressions that were obtained by IHC staining using different monoclonal antibodies with Dako-EGFR (46.95%) and NCL-EGFR (32.32%) were fairly concordant. CONCLUSIONS: Although IHC is a convenient and feasible method for detecting the expression of EGFR, it yields controversial staining results concerning EGFR expression using various commercial antibodies in a CRC tumor section.

Significance of allelic percentage of BRAF c.1799T > A (V600E) mutation in papillary thyroid carcinoma.

BACKGROUND: Somatic BRAF mutation is frequently observed in papillary thyroid carcinoma (PTC). Recent evidence suggests that PTCs are heterogeneous tumors containing a subclonal or oligoclonal occurrence of BRAF mutation. Conflicting results have been reported concerning the prognostic significance of the mutant allele frequency. Our present aim was to investigate the association between the percentage of BRAF c.1799T > A (p.Val600Glu) alleles and clinicopathological parameters in PTC. METHODS: Genomic DNA was extracted from fresh-frozen specimens obtained from 50 PTC patients undergoing total thyroidectomy. The BRAF mutation status was determined by Sanger sequencing. The percentage of mutant BRAF alleles was quantified by mass spectrometric genotyping, pyrosequencing, and competitive allele-specific TaqMan PCR (castPCR). RESULTS: Positive rate of BRAF mutation was 72 % by Sanger sequencing, 82 % by mass spectrometric genotying, and 84 % by pyrosequencing or castPCR. The average percentage of mutant BRAF alleles was 22.5, 31, and 30.7 %, respectively. There was a good correlation among three quantification methods (Spearman's rho = 0.87-0.97; p < 0.0001). The mutant allele frequency was significantly correlated with tumor size (rho = 0.47-0.52; p < 0.01) and extrathyroidal invasion. The frequency showed no difference in pathological lymph node metastasis. CONCLUSIONS: The percentage of mutant BRAF alleles is positively associated with tumor burden and extrathyroidal invasion in PTC. Relatively good correlations exist among mass spectrometric genotyping, pyrosequencing, and castPCR in quantification of mutant BRAF allele frequency.

Anti-inflammation effects of naloxone involve phosphoinositide 3-kinase delta and gamma.

BACKGROUND: Phosphoinositide 3-kinase (PI3K) delta and gamma (the p110δ and p110γ isoforms of PI3K) actively participate in the process of inflammation. We sought to elucidate the possible roles of PI3Kδ and PI3Kγ in mediating the anti-inflammation effects of naloxone. MATERIALS AND METHODS: Murine macrophages were treated with endotoxin, endotoxin plus naloxone, or endotoxin plus naloxone plus the PI3K inhibitors (the PI3Kδ inhibitor IC87114, the PI3Kγ inhibitor AS252424, or IC87114 plus AS252424) and denoted as the LPS, LPS + N, LPS + N + IC, LPS + N + AS, and LPS + N + IC + AS group, respectively. Differences in inflammatory molecules and levels of nuclear factor-κB (NF-κB) activation and Akt activation (indicator of PI3K activity) among these groups were compared. RESULTS: The concentrations of inflammatory molecules (macrophage inflammatory protein 2, tumor necrosis factor-α, interleukin-1ß, and cyclooxygenase-2/prostaglandin E2) and the levels of NF-κB activation (p-NF-κB p65 and p-inhibitor-κB concentrations and NF-κB-DNA binding activity) of the LPS + N group were significantly lower than those of the LPS group (all P < 0.001). These data confirmed the anti-inflammation effects of naloxone. Moreover, the anti-inflammation effects of naloxone could be counteracted by the inhibitors of PI3Kδ and PI3Kγ, as the concentrations of inflammatory molecules and the levels of NF-κB activation of the LPS + N group were significantly lower than those of the LPS + N + IC, LPS + N + AS, and LPS + N + IC + AS groups (all P < 0.05). In contrast, the concentration of phosphorylated Akt of the LPS + N group was significantly higher than those of the LPS, LPS + N + IC, LPS + N + AS, and LPS + N + IC + AS groups (all P < 0.05). CONCLUSIONS: PI3Kδ and PI3Kγ play crucial roles in mediating the anti-inflammation effects of naloxone.

Inguinal nodal metastatic squamous cell carcinoma of unknown primary (CUP) detected 7 years before the diagnosis of vulvar squamous cell carcinoma: A case report.

OBJECTIVE: Metastatic squamous cell carcinoma (SCC) of inguinal lymph node region with unknown origin is a rare condition. A patient was diagnosed to have vulvar SCC 7 years after the initial diagnosis of inguinal nodal metastatic SCC of unknown primary. CASE REPORT: A 59-year-old woman with metastatic SCC of unknown origin in the right inguinal lymph node underwent tumor resection and no evidence of residual disease or possible tumor origin was detected after the surgery and a comprehensive work-up. Seven years later, she was diagnosed to have invasive right vulvar SCC with right pelvic lymph node metastasis. We performed a series of tests to evaluate the relationship between these two events. CONCLUSION: According to our investigation, the possible relationship between the two events could not be ruled out. This case emphasizes the possibility of late recurrence and the importance of long-term follow up for patients with isolated nodal CUP.

Stem cell exosome-loaded Gelfoam improves locomotor dysfunction and neuropathic pain in a rat model of spinal cord injury.

BACKGROUND: Spinal cord injury (SCI) is a debilitating illness in humans that causes permanent loss of movement or sensation. To treat SCI, exosomes, with their unique benefits, can circumvent limitations through direct stem cell transplantation. Therefore, we utilized Gelfoam encapsulated with exosomes derived from human umbilical cord mesenchymal stem cells (HucMSC-EX) in a rat SCI model. METHODS: SCI model was established through hemisection surgery in T9 spinal cord of female Sprague-Dawley rats. Exosome-loaded Gelfoam was implanted into the lesion site. An in vivo uptake assay using labeled exosomes was conducted on day 3 post-implantation. Locomotor functions and gait analyses were assessed using Basso-Beattie-Bresnahan (BBB) locomotor rating scale and DigiGait Imaging System from weeks 1 to 8. Nociceptive responses were evaluated through von Frey filament and noxious radiant heat tests. The therapeutic effects and potential mechanisms were analyzed using Western blotting and immunofluorescence staining at week 8 post-SCI. RESULTS: For the in vivo exosome uptake assay, we observed the uptake of labeled exosomes by NeuN+, Iba1+, GFAP+, and OLIG2+ cells around the injured area. Exosome treatment consistently increased the BBB score from 1 to 8 weeks compared with the Gelfoam-saline and SCI control groups. Additionally, exosome treatment significantly improved gait abnormalities including right-to-left hind paw contact area ratio, stance/stride, stride length, stride frequency, and swing duration, validating motor function recovery. Immunostaining and Western blotting revealed high expression of NF200, MBP, GAP43, synaptophysin, and PSD95 in exosome treatment group, indicating the promotion of nerve regeneration, remyelination, and synapse formation. Interestingly, exosome treatment reduced SCI-induced upregulation of GFAP and CSPG. Furthermore, levels of Bax, p75NTR, Iba1, and iNOS were reduced around the injured area, suggesting anti-inflammatory and anti-apoptotic effects. Moreover, exosome treatment alleviated SCI-induced pain behaviors and reduced pain-associated proteins (BDNF, TRPV1, and Cav3.2). Exosomal miRNA analysis revealed several promising therapeutic miRNAs. The cell culture study also confirmed the neurotrophic effect of HucMSCs-EX. CONCLUSION: Implantation of HucMSCs-EX-encapsulated Gelfoam improves SCI-induced motor dysfunction and neuropathic pain, possibly through its capabilities in nerve regeneration, remyelination, anti-inflammation, and anti-apoptosis. Overall, exosomes could serve as a promising therapeutic alternative for SCI treatment.

High-lipid enteral nutrition could partially mitigate inflammation but not lung injury in hemorrhagic shock rats.

BACKGROUND: Loss of gut barrier function is crucial in mediating lung injury induced by hemorrhagic shock/resuscitation (HS). High-lipid enteral nutrition (HL) can preserve gut barrier function. We hypothesized that HL could also mitigate HS-induced lung injury. MATERIALS AND METHODS: Forty-eight adult male rats were randomly assigned to one of four experimental groups: HS; HS-HL; Sham; Sham-HL. HS was induced by blood drawing and mean blood pressure was maintained at 40-45 mmHg for 120 min followed by resuscitation with re-infusion of exsanguinated blood/saline mixtures. HL gavage was performed at 45 min before blood drawing and at the end of resuscitation. RESULTS: Intestinal permeability of the HS group was significantly higher than that of the Sham group (P < 0.001). Pulmonary concentrations of malondialdehyde (lipid peroxidation) and inflammatory molecules, including prostaglandin E2, tumor necrosis factor-α, interleukin-6, and macrophage inflammatory protein-2, of the HS group were significantly higher than those of the Sham group. Histologic analyses, including histopathology, wet/dry weight ratio, and neutrophil infiltration revealed moderate lung injury in the HS group. In contrast, intestinal permeability (P < 0.001) and pulmonary concentrations of tumor necrosis factor-α and macrophage inflammatory protein-2 (P = 0.021 and 0.01) of the HS-HL group were significantly lower than those of the HS group. However, pulmonary concentrations of malondialdehyde, prostaglandin E2, and interleukin-6 of the HS-HL and HS groups were comparable. Moreover, histologic analyses also revealed moderate lung injury in the HS-HL group. CONCLUSIONS: High-lipid enteral nutrition significantly mitigated gut barrier loss and partially mitigated lung inflammation but not oxidation and lung injury in hemorrhagic shock/resuscitation rats.

Hepatic carcinosarcoma: clinicopathologic features and a review of the literature.

Hepatic carcinosarcoma (HCS) is defined as a malignant tumor containing an intimate mixture of carcinomatous and sarcomatous elements. Here, we report the case of a 72-year-old man who developed HCS from an otherwise normal liver. The patient had no history of alcohol abuse or hepatitis B or C infection. An enhanced abdominal CT scan revealed a 9-cm heterogeneous tumor, with enhancement during the arterial phase and delayed wash-out in the latter phases. Also, a marked elevation in alpha-fetoprotein level (15,164 ng/mL; normal range, < 10 ng/mL) was noted. He underwent resection of liver segments V and VI under a pre-operative diagnosis of atypical hepatocellular carcinoma (HCC). The diagnosis of HCS was made based on thorough pathologic examination with a panel of immunohistochemical staining. Following surgery, the patient made an uneventful recovery, and at present, 16 months post-surgery, he remains well with no evidence of tumor recurrence. In conclusion, pre-operative diagnosis of HCS is difficult and radical resection in the early stage is encouraged to improve the prognosis of these patients.

Essential roles of surgical and pathological evaluations in the management of foreign bodies or inflammatory granulomas mimicking cervical cancer recurrence: A report of two cases.

OBJECTIVE: Positron emission tomography-computed tomography (PET/CT) is an effective modality for evaluating cervical cancer recurrence. We present two cases of suspected recurrent cervical cancer on PET/CT that were pathologically proven to be granulomas. CASE REPORT: Case 1: A 54-year-old woman with FIGO (2009) stage IB1 cervical cancer underwent radical hysterectomy and adjuvant chemoradiotherapy. Case 2: A 44-year-old woman with FIGO (2009) stage IB2 cervical cancer underwent incidental simple hysterectomy with pelvic lymphadenopathy and adjuvant concurrent cisplatin-based chemoradiotherapy. Both patients had peritoneal or pelvic masses with increased 18F-fluorodeoxyglucose (18F-FDG) uptake on PET/CT after 3 years. These masses were finally pathologically proven to be foreign bodies or inflammatory granulomas with abscess, respectively. CONCLUSION: Foreign bodies or inflammatory granuloma could be one of the differential diagnoses of increased 18F-FDG uptake on PET/CT in patients with cervical cancer after treatment. Pathological evaluation should be considered in these patients to guide further treatment.

Platonin mitigates acute lung injury induced by bilateral lower limb ischemia-reperfusion in rats.

BACKGROUND: Oxidative stress and inflammatory response are crucial in mediating the development of acute lung injury induced by bilateral lower limb ischemia-reperfusion (I/R). Platonin, a potent antioxidant, possesses anti-inflammation capacity. We sought to elucidate whether platonin could mitigate acute lung injury induced by lower limb I/R. MATERIALS AND METHODS: Forty-eight adult male rats were allocated to receive I/R, I/R plus platonin (100 µg/kg intravenous injection immediately after reperfusion), sham instrumentation, or sham instrumentation plus platonin (denoted as the I/R, I/R-platonin, Sham, or Sham-platonin group, respectively; n = 12 in each group). Bilateral hind limb I/R was induced by applying rubber band tourniquets high around each thigh for 3 h followed by reperfusion for 3 h. After sacrifice, the degree of lung injury was determined. RESULTS: Histologic findings revealed moderate inflammation in lung tissues of the I/R group and mild inflammation in those of the I/R-platonin group. Total cell number and protein concentration in bronchoalveolar lavage fluid as well as the leukocyte infiltration and myeloperoxidase activity in lung tissues of the I/R group were significantly higher than those of the I/R-platonin group. The pulmonary concentrations of macrophage inflammatory protein-2, interleukin-6, and prostaglandin E(2) of the I/R group were significantly higher than those of the I/R-platonin group. Moreover, the plasma nitric oxide concentration as well as the nitric oxide and malondialdehyde concentrations in lung tissues of the I/R group were significantly higher than those of the I/R-platonin group. CONCLUSIONS: Platonin mitigates acute lung injury induced by bilateral lower limb I/R in rats.

Protective effects of dexmedetomidine-ketamine combination against ventilator-induced lung injury in endotoxemia rats.

BACKGROUND: Pulmonary inflammatory response is crucial in mediating the development of ventilator-induced lung injury (VILI) in animals experiencing endotoxemia. Dexmedetomidine and ketamine are two sedative agents with potent anti-inflammatory capacity. We sought to elucidate the anti-inflammatory effects of dexmedetomidine-ketamine combination against VILI in endotoxemia rats. MATERIALS AND METHODS: Eighty-four adult male rats were allocated to receive normal saline, VILI, VILI plus dexmedetomidine-ketamine combination (D+K), lipopolysaccharide (LPS), LPS plus D+K, LPS plus VILI, or LPS plus VILI plus D+K (designated as the NS, V, V-D+K, LPS, LPS-D+K, LPS/V, and LPS/V-D+K group, respectively; n = 12 in each group). VILI was induced by high-tidal volume ventilation (tidal volume 20 mL/kg; respiratory rate 50 breath/min; FiO(2) 21%). After being mechanically ventilated for 4 h, rats were sacrificed and the levels of pulmonary inflammatory response were evaluated. RESULTS: Histologic findings revealed severe, moderate, and mild inflammation in lung tissues of the LPS/V, LPS, and V groups, respectively, whereas those of the LPS/V-D+K, LPS-D+K, and V-D+K groups revealed moderate, mild, and normal to minimal inflammation, respectively. Moreover, the total cell number and the concentrations of macrophage inflammatory protein-2 and interleukin-1ß in bronchoalveolar lavage fluid as well as the lung water content, leukocyte infiltration, myeloperoxidase activity, and the concentrations of inducible nitric oxide synthase/nitric oxide, and cyclooxygenase 2/prostaglandin E(2) in lung tissues of the LPS/V, LPS, and V groups were significantly higher than those of the LPS/V-D+K, LPS-D+K, and V-D+K groups, respectively. CONCLUSIONS: Dexmedetomidine-ketamine combination could mitigate pulmonary inflammatory response induced by VILI in endotoxemia rats.

Magnesium sulfate mitigates lung injury induced by bilateral lower limb ischemia-reperfusion in rats.

BACKGROUND: Lower limb ischemia-reperfusion (I/R) elicits oxidative stress and causes inflammation in lung tissues that may lead to lung injury. Magnesium sulfate (MgSO(4)) possesses potent anti-oxidation and anti-inflammation capacity. We sought to elucidate whether MgSO(4) could mitigate I/R-induced lung injury. As MgSO(4) is an L-type calcium channel inhibitor, the role of the L-type calcium channels was elucidated. MATERIALS AND METHODS: Adult male rats were allocated to receive I/R, I/R plus MgSO(4) (10, 50, or 100 mg/kg), or I/R plus MgSO(4) (100 mg/kg) plus the L-type calcium channels activator BAY-K8644 (20 µg/kg) (n = 12 in each group). Control groups were run simultaneously. I/R was induced by applying rubber band tourniquets high around each thigh for 3 h followed by reperfusion for 3 h. After euthanization, degrees of lung injury, oxidative stress, and inflammation were determined. RESULTS: Arterial blood gas and histologic assays, including histopathology, leukocyte infiltration (polymorphonuclear leukocytes/alveoli ratio and myeloperoxidase activity), and lung water content, confirmed that I/R caused significant lung injury. Significant increases in inflammatory molecules (chemokine, cytokine, and prostaglandin E(2) concentrations) and lipid peroxidation (malondialdehyde concentration) confirmed that I/R caused significant inflammation and oxidative stress in rat lungs. MgSO(4), at the dosages of 50 and 100 mg/kg but not 10 mg/kg, attenuated the oxidative stress, inflammation, and lung injury induced by I/R. Moreover, BAY-K8644 reversed the protective effects of MgSO(4). CONCLUSIONS: MgSO(4) mitigates lung injury induced by bilateral lower limb I/R in rats. The mechanisms may involve inhibiting the L-type calcium channels.

Rare paratesticular aggressive angiomyxoma mimicking an epididymal tumor in an 82-year-old man: Case report.

Aggressive angiomyxoma (AAM) is a rare mesenchymal myxoid tumor, and most cases occur in the pelvic region or perineum of adult females. AAM is very rare in males. Most of these cases have been diagnosed in patients aged 30-60 years, and the tumors involved the pelvic cavity, scrotum, or spermatic cord. AAM can mimic inguinal hernia, hydrocele, or paratesticular neoplasm. Four male cases have been reported with paratesticular AAM mimicking a testicular/epididymal tumor, and to the best of our knowledge, this is the oldest patient in the literature. Because of its rarity, making an exact diagnosis before surgery is difficult. Herein, we present a case of AAM in an 82-year-old man and review the literature.

Massive metastasis of breast cancer to female genital organs.

OBJECTIVE: Breast cancer metastasis to the female genital tract is rare, and the ovaries are the most frequent site of extragenital cancer metastasis. The uterus and cervix have been rarely reported as the site of metastasis. CASE REPORT: A 57-year-old woman diagnosed with invasive lobular carcinoma of the left breast 2 years prior was undergoing tamoxifen treatment. She presented with a right breast mass and postmenopausal bleeding. Synchronous right breast invasive lobular carcinoma with endometrium metastasis was diagnosed. The metastasis tumor involved the endometrium, myometrium, cervix, ovaries, and fallopian tubes. CONCLUSION: We noted the rarity of massive metastasis of the female genital tract from breast cancer. Gynecological surveillance and prompt evaluation of the endometrium led to timely diagnosis and treatment.

Simvastatin attenuates testicular injury induced by torsion-detorsion.

PURPOSE: The lipid lowering agent simvastatin has potent anti-oxidation capacity. We elucidated the potential of simvastatin to attenuate testicular injury induced by testicular torsion-detorsion. We also investigated simvastatin effects on nuclear factor-kappaB expression. MATERIALS AND METHODS: We allocated 60 adult male Sprague-Dawley(R) rats to testicular torsion-detorsion, torsion-detorsion plus simvastatin (1 or 5 mg/kg), sham operation or sham operation plus simvastatin (5 mg/kg). There were 12 rats per group. Simvastatin was administered immediately after detorsion or immediately after sham operation. Testes were harvested 30 minutes and 24 hours after detorsion to facilitate the evaluation of nuclear factor-kappaB and testicular injury, respectively. RESULTS: Histological findings revealed severe injury in testes of the torsion-detorsion and torsion-detorsion-simvastatin (1 mg/kg) groups while testes in the torsion-detorsion-simvastatin (5 mg/kg) group showed moderate injury. Myeloperoxidase activity, and cytokines, nitric oxide and malondialdehyde in testes in the torsion-detorsion-simvastatin (5 mg/kg) group were significantly lower than in the torsion-detorsion group. Values were comparable in the torsion-detorsion-simvastatin (1 mg/kg) and torsion-detorsion groups. Testicular concentrations of nuclear factor-kappaB in nuclear extracts and phosphorylated inhibitor-kappaB in cytosolic extracts in the torsion-detorsion-simvastatin (5 mg/kg) group were significantly lower than in the torsion-detorsion group. Values were comparable in the torsion-detorsion-simvastatin (1 mg/kg) and torsion-detorsion groups. CONCLUSIONS: Simvastatin protected testes from torsion-detorsion injury in a dose dependent manner. Mechanisms may involve attenuating nuclear factor-kappaB activation and decreasing oxidative stress induced by torsion-detorsion.