The human health risks assessment of mercury in soils and plantains from farms in selected artisanal and small-scale gold mining communities around Obuasi, Ghana.

Food consumption remains the commonest pathway through which humans ingest higher levels of mercury (Hg). Long-term exposure to Hg through Hg-contaminated food may result in acute or chronic Hg toxicity. Incessant discharge of Hg waste from ASGM facilities into nearby farms contaminates food crops. Ingestion of such food crops by residents may lead to detrimental human health effects. The human health risks upon exposure to total mercury (THg) and methylmercury (MeHg) in farmland soils and plantains from farms sited near ASGM facilities were studied in four communities around Obuasi, Ghana. The human health risk assessment was evaluated using hazard quotient (HQ), estimated average daily intake (e AvDI), hazard index (HI) and Hg elimination and retention kinetics. Tweapease, Nyamebekyere and Ahansonyewodea had HQ, e AvDI and HI for THg of plantains for both adults and children below the recommended USEPA limit of 1, 3 × 10-4 mg/kg/day and 1, respectively. Odumase had HQ, e AvDI and HI for THg of plantains for both adults and children, higher than the guideline values. This meant that only Odumase may cause non-carcinogenic human health effects upon repeated exposure. The HQ, e AvDI and HI values of MeHg for all the study areas were far below guideline values, hence may not pose any non-carcinogenic human health risks to residents even upon repeated exposure. Retention and elimination kinetics of Hg also showed that only plantains from Odumase may pose significant non-carcinogenic human health risks to residents because the final amount of inorganic mercury exceeded the extrapolated USEPA guideline value of 0.393 µg/kg/year.

Characterization and identification of the proteins bound to two types of polyhydroxyalkanoate granules in Pseudomonas sp. 61-3.

Pseudomonas sp. 61-3 accumulates two types of polyhydroxyalkanoates (PHAs), poly(3-hydroxybutyrate) [P(3HB)], and poly(3HB-co-3-hydroxyalkanoates) [P(3HB-co-3HA)], and some proteins associated with their PHA granules have been identified. To date, PhaFPs (GA36) and PhaIPs (GA18) were identified from P(3HB-co-3HA) granules. In this study, the gene encoding GA24 associated with P(3HB) granule was identified as phbPPs. PhbPPs was composed of 192 amino acids with a calculated molecular mass of 20.4 kDa and was assumed to be a phasin. phbFPs gene and unknown ORF were also found on phb locus. PhbFPs was anticipated to be the transcriptional repressor of phbPPs gene. PhbPPs was bound to the P(3HB-co-3HA) granules with 3HB composition of more than 87 mol%, and PhaIPs and PhaFPs were bound to the P(3HB-co-3HA) granules with 3HA (C6-C12) composition of more than 13 mol% in the producing cells, suggesting that localization of these proteins is attributed to the monomer compositions of the copolymers.

HER2 and EGFR gene copy number alterations are predominant in high-grade salivary mucoepidermoid carcinoma irrespective of MAML2 fusion status.

AIMS: In this study, we aimed to investigate the molecular mechanisms underlying the development of mucoepidermoid carcinoma (MEC). METHODS AND RESULTS: In 31 cases, we examined the MAML2 fusion status using reverse transcriptase-polymerase chain reaction, and HER2 and EGFR status using immunohistochemistry and chromogenic in-situ hybridization. MAML2 fusions were detected in 15 (57.7%) of 26 MECs analysed, including 11 of 16 (68.8%) low-grade, two of four (50%) intermediate-grade and two of six (33.3%) high-grade MECs. HER2 gene amplification and an increased EGFR gene copy number (with balanced chromosome 7 high-polysomy) were each detected in four of 28 (14.3%) MECs analysed. Irrespective of MAML2 fusion status, all seven high-grade MECs had an increased gene copy number of either HER2 or EGFR, in a mutually exclusive manner, whereas such abnormalities were extremely rare in low- and intermediate-grade MEC. CONCLUSIONS: These results suggest that HER2 or EGFR gene abnormality could play an important role in the development of high-grade MEC, and also in the progression from MAML2 fusion-positive low-/intermediate-grade to high-grade in a subset of MEC. Furthermore, we suggest that high-grade MEC comprises a heterogeneous group of tumours in terms of molecular pathogenesis, in particular MAML2 fusion status.

Mercury waste from artisanal and small-scale gold mining facilities: a risk to farm ecosystems-a case study of Obuasi, Ghana.

Frequent discharge of mercury waste from artisanal and small-scale gold mining (ASGM) facilities into nearby farms may contaminate foodstuffs and the entire farms. High contamination levels may result in ecological risks to the soil, plants, animals, humans, and the entire farm ecosystem. This original research is the first study within the catchment areas that describes the effects of mercury waste on the entire farm ecosystem. In this study, the contamination levels and the associated ecological risks of farmland soils, plantains, and cassavas from farms sited near ASGM facilities in four communities around Obuasi, Ghana, were evaluated using the Hakanson (1980) model. Results showed that all samples except for the edible parts of plantains from Tweapease, Nyamebekyere, and Ahansonyewodea and plantain peels from Nyamebekyere and Ahansonyewodea were contaminated and may pose moderate to very high ecological risks. All farms were also contaminated and may pose considerable to very high ecological risks. The farms at Odumase were the highest contaminated with degree of contamination (Cdeg) above 20, while those at Ahansonyewodea were the least contaminated with Cdeg = 8.1. This meant that farms at Odumase may pose the highest potential ecological risk (Per) to plants, animals, humans, and the entire farm ecosystem since Per > 600, while the farms at Ahansonyewodea may pose the least ecological risks with Per = 324. There is, therefore, the need for strict control of ASGM activities in these study areas to preserve the integrity of the ecosystem.

HER-2/neu gene amplification in carcinoma ex pleomorphic adenoma in relation to progression and prognosis: a chromogenic in-situ hybridization study.

AIMS: The aim of this study was to investigate the potential role of HER-2/neu in the stepwise progression of carcinoma ex pleomorphic adenoma (CXPA) and to evaluate its prognostic significance in CXPA. METHODS AND RESULTS: We examined HER2 overexpression and HER2 amplification by immunohistochemistry and chromogenic in-situ hybridization in 31 cases of CXPA with ductal differentiation (eight intraductal, five intracapsular, and 18 extracapsular) and seven cases of atypical pleomorphic adenoma (PA). HER2 overexpression and HER2 amplification were found in 17 (54.8%) and 12 (38.7%) of the 31 CXPA cases, respectively. HER2 amplification was more prevalent in extracapsular CXPAs (9/18 cases; 50%) than intracapsular CXPAs (1/5 cases; 20%), intraductal CXPAs (2/8 cases; 25%), or atypical PAs (0/7 case; 0%). The status of HER2 amplification was essentially retained from the intraductal to the extracapsular component in individual extracapsular CXPAs. In addition, HER2 amplification was significantly associated with a worse prognosis (shorter disease-free survival time and shorter overall survival time) among extracapsular CXPAs (each P < 0.05). CONCLUSIONS: These results suggest that HER2 may play an important role in the progression of CXPA, and that HER2 amplification may be an additional prognostic indicator of CXPA.

[Laryngeal preservation for hypopharyngeal cancer by radiotherapy with S-1 and vitamin A(TAR therapy)].

The objective of this study was to analyze the outcome of hypopharyngeal cancer patients who underwent triple combination treatment with S-1, vitamin A and radiation(TAR therapy), and to analyze the role of TAR therapy for treating locally advanced hypopharyngeal cancer patients. 146 patients(stage I: 10 cases, stage II : 22 cases, stage III : 23 cases, stage IV: 91 cases)with hypopharyngeal squamous cell carcinoma were treated with TAR therapy(S-1; orally, 65mg/m²day, twice a day; vitamin A(retinol palmitate): 50, 000 I U/day, intra-musculary on each day of radiation; radiation: 1. 5-2 Gy/day, 5 days/week). Histologic complete responders at 30-40 Gy continued TAR therapy up to 60-70 Gy. Nonresponders at 30-40 Gy underwent surgery. The overall 5-year survival and disease-specific 5-year survival rates were 50. 5%and 59%respectively. The cumulative 3-year laryngeal preservation rate for stage I was 100%, 82. 5% for stage II, 66. 6% for stage III, and 35%for stage IV. Laryngeal preservation was fair in T1/T2 patients(81%), but not satisfactory in T3/T4 patients(21. 4%). S- 1 is administered orally, and TAR therapy can be conducted in the clinic with low toxicity. However, protocols with high intensity may be necessary to improve laryngeal preservation for locally advanced(T4)hypopharyngeal cancer.

Contributing factors in the pathogenesis of acquired cholesteatoma: size analysis based on MDCT.

OBJECTIVE: The purpose of this article is to explore the factors that contribute to the occurrence of cholesteatoma. We studied the size of the mastoid air cells and the tympanic cavity using high-resolution CT. MATERIALS AND METHODS: Temporal bone CT scans of consecutive patients with unilateral cholesteatoma and healthy control subjects were retrospectively analyzed. We compared the total volume and the greatest cross-sectional area of the cavities of the combined mastoid air cells and tympanic cavity between the affected and unaffected sides in patients with cholesteatoma and in the control subjects. We also compared separately the measured volumes of the cavities of the mastoid air cells and tympanic cavity between the unaffected side of the patients with cholesteatoma and the control subjects. RESULTS: One hundred temporal bones of 50 patients with cholesteatoma and 50 control subjects were included. Both the volume and the cross-sectional area of the cavities of the combined mastoid air cells and tympanic cavity in the affected side of the patients with cholesteatoma were significantly smaller than those in the unaffected side (p < 0.001). Moreover, both the volume and the cross-sectional area of the cavities of the combined mastoid air cells and tympanic cavity in both affected and unaffected sides of patients with cholesteatoma were significantly smaller than those in control subjects (p < 0.001). The volume of the cavities of the mastoid air cells in the unaffected side of patients with cholesteatoma was smaller than that of the control subjects (p < 0.001). In contrast, no significant difference was found in the tympanic cavity volume between the unaffected side and the control subjects. CONCLUSION: Our results were consistent with the hypothesized contribution of mastoid air cell underdevelopment to the occurrence of cholesteatoma. A small tympanic cavity is less likely to contribute to the occurrence of cholesteatoma.

Tumor-to-tumor metastasis: lung adenocarcinoma metastasizing to a follicular variant of papillary thyroid carcinoma.

Cancer-to-cancer metastasis into a thyroid neoplasm is an uncommon phenomenon with possible diagnostic difficulties. Here, we describe a case of lung adenocarcinoma metastatic into a follicular variant of papillary thyroid carcinoma (FVPTC). A 60-year-old woman with no prior history of malignant neoplasm presented with a nodule in the right lobe of the thyroid gland, some masses in the left lung were found by radiological examination. Histopathological examination of the thyroidectomy specimen demonstrated two different components of carcinoma in a single thyroid nodule; one was FVPTC and the other was high-grade adenocarcinoma. Although both components shared the TTF-1+/CK7+/CK19+/CK20-/SP-A- immunoprofile, only the former was positive for thyroglobulin, and only the latter was positive for CEA. The epidermal growth factor receptor (EGFR) gene mutation at exon21 (L858R) was present only in the latter. The lung biopsy specimen showed cytological, immunohistochemical, and EGFR genotypic features similar to those of the high-grade adenocarcinoma component of the thyroid nodule. These findings resulted in a reliable diagnosis of lung adenocarcinoma metastasizing into an FVPCT and treatment with EGFR-targeted therapy. These results demonstrate that a panel of immunohistochemical staining and molecular analysis is helpful for both diagnosis and appropriate postoperative treatment for a patient with cancer-to-cancer metastasis.

Relative level of thymidylate synthase mRNA expression in primary tumors and normal tissues predicts survival of patients with oral tongue squamous cell carcinoma.

Thymidylate synthase (TS) is a major target of 5-fluorouracil (5-FU) and dihydropyrimidine dehydrogenase (DPD) is a rate-limiting enzyme in the degradation of 5-FU. There are no studies investigating the comparison of TS and DPD mRNA expressions in oral tongue SCC (OSCC) and nontumor tissues obtained from the same patients. In addition, increased interest has been focused on the biological roles of TS and DPD as the independent prognostic factors as well as responsive determinants for cancer patients with 5-FU based therapy. We determined the expression levels of TS and DPD in tumor (T) and nontumor squamous epithelial tissues (N) of OSCC using real-time reverse transcription-polymerase chain reaction and evaluated whether the T/N ratio would correlate with clinicopathological factors. The mRNA expressions of TS and DPD were significantly higher in tumor areas than in nontumor areas. No correlation was found between the T/N ratio of each mRNA expression and gender, clinical stage, T classification, N classification or differentiation. The T/N ratio of TS in patients that died of disease was significantly higher than in patients with free of disease, whereas there were no relationships between The T/N ratio of DPD and disease status. Clinical follow-up data showed shorter overall survival periods for cases with high T/N ratio of TS than for cases with low T/N ratio of TS with the statistically significant. Our study showed that TS but not DPD seems to have prognostic value in OSCC. These findings suggest that the assessment of TS activity may be useful both in the management and in the treatment of OSCC.

[Clinical outcome of partial glossectomy or brachytherapy in early-stage tongue cancer].

Partial glossectomy and low-dose-rate (LDR) brachytherapy are both effective in early-stage tongue cancer without lymph node metastasis, although head and neck surgeons and radiation oncologists disagree on which treatment is superior. Because our subjects select the treatment modality, we compared treatment results between 39 subjects undergoing partial glossectomy and 107 undergoing brachytherapy for stage I/II tongue cancer. Local recurrence was observed in 10% and cervical lymph node recurrence in 23% following partial glossectomy, versus local recurrence in 13% and cervical lymph node recurrence in 24% following brachytherapy. Disease-free 5-year survival was 87.0% following partial glossectomy and 90.7% following brachytherapy. Because incidence of local recurrence, nodal metastasis, and prognosis were the same regardless of treatment modality, treatment should be based on the age, performance status, and quality of life among subjects.

Acute Sleep Curtailment Increases Sweet Taste Preference, Appetite and Food Intake in Healthy Young Adults: A Randomized Crossover Trial.

This study aimed to examine the effect of acute sleep curtailment on sweet taste preference, appetite and food intake, and the correlation between food intake and sweet taste preference or active ghrelin using a randomized crossover design (5 h sleep curtailment vs. 8 h control). Twenty-four participants (11 men) aged 21.4 ± 1.0 years, with BMI 19.8 ± 1.7 kg/m2, who habitually slept 5 h/night or more experienced interventions lasting three consecutive nights. Participants came into the laboratory for testing on day 4. Fasting blood tests were conducted at 8:00 a.m. to measure active ghrelin and leptin levels. Sweet taste preference was assessed by presenting five different concentration sucrose solutions at 9:00 a.m. Ad libitum intake at breakfast was assessed for 30 min from 9:30 a.m. Sweet taste preference was higher following sleep curtailment than control. Active ghrelin was likewise higher following sleep curtailment than control. Leptin did not differ between conditions. Energy intake was higher following sleep curtailment than control, being derived primarily from carbohydrates. However, sweet taste preference and active ghrelin did not correlate with energy intake. These results suggest that acute consecutive sleep curtailment increases sweet taste preference, active ghrelin, and energy intake in healthy young adults.

Close correlation between CXCR4 and VEGF expression and their prognostic implications in nasopharyngeal carcinoma.

The CXCL12/CXCR4 pathway, which is involved in biological phenomena such as inflammation, lymphoid homing and regeneration, may play an important role in tumor progression and distant metastasis, especially in organ-selective metastasis. In addition, the CXCL12/CXCR4 pathway has been reported to regulate tumor angiogenesis. In this study, we examined the immunohistochemical expression of CXCR4 and vascular endothelial growth factor (VEGF) in nasopharyngeal carcinoma. CXCR4 and VEGF mRNAs were also assessed by real-time reverse transcription-polymerase chain reaction. Overexpression of CXCR4 and VEGF was observed in 41 (53.9%) and 30 (39.5%) of 76 tumors, respectively. There was a significant positive correlation between immunohistochemical CXCR4 and VEGF expression (p=0.0339). Additionally, immunohistochemical CXCR4 expression was associated with CXCR4 mRNA expression, and immunohistochemical VEGF expression was associated with VEGF mRNA expression (p=0.0040 and p=0.0476, respectively). Furthermore, patients with VEGF-positive tumors had a significantly worse prognosis than patients with VEGF-negative primary tumors (p=0.0044). Our findings suggest that the expression of CXCR4 and VEGF is associated with metastatic progression, and that VEGF expression is a valuable prognostic marker in nasopharyngeal carcinoma.

Biosynthesis of novel lactate-based polymers containing medium-chain-length 3-hydroxyalkanoates by recombinant Escherichia coli strains from glucose.

Novel lactate (LA)-based polymers containing medium-chain-length 3-hydroxyalkanoates (MCL-3HA) were produced in fadR-deficient Escherichia coli strains from glucose as the sole carbon source. The genes encoding LA and 3-hydroxybutyrate (3HB) monomers supplying enzymes [propionyl-CoA transferase (PCT), d-lactate dehydrogenase (D-LDH), ß-ketothiolase (PhaA), and NADPH-dependent acetoacetyl-CoA reductase (PhaB)], MCL-3HA monomers supplying enzymes [(R)-3-hydroxyacyl-ACP thioesterase (PhaG) and (R)-3-hydroxyacyl (3HA)-CoA ligase] via fatty acid biosynthesis pathway, and modified polyhydroxyalkanoate (PHA) synthase [PhaC1(STQK)] of Pseudomonas sp. 61-3 were introduced into E. coli LS5218. This resulted in the synthesis of a novel LA-based copolymer, P(LA-co-3HB-co-3HA). 1H-nuclear magnetic resonance (NMR) analysis revealed the composition of P(LA-co-3HB-co-3HA) to be 19.7 mol% LA (C3), 74.9 mol% 3HB (C4), and 5.4 mol% MCL-3HA units of C8 and C10. Furthermore, the recombinant E. coli CAG18497 strain carrying these genes, excluding the phaAB genes, accumulated P(92.0% LA-co-3HA) with a novel monomer composition containing C3, C8, C10, and C12. 13C-NMR analysis showed the existence of LA-3HA sequence in the polymer. The solvent cast film of P(92.0% LA-co-3HA) exhibited transparency similar to poly(lactic acid).

Primary combined small cell carcinoma and squamous cell carcinoma of the oropharynx with special reference to EGFR status of small cell carcinoma component: Case report and review of the literature.

Combined small cell carcinoma (SCC) and squamous cell carcinoma (SqCC) of the oropharynx is extremely rare and shows an aggressive clinical course. There are only 5 reported cases of combined SCC and SqCC in the English language literature. Here, we report a 59-year-old male presenting with a right tonsillar mass. The mass was biopsied, and the histological findings showed a proliferation of small-sized tumor cells with scant cytoplasm. Immunohistochemically, the tumor cells were positive for neuroendocrine markers (synaptophysin, chromogranin A, and CD56). Our first diagnosis was tonsillar small cell carcinoma. We treated the patient with concurrent chemoradiotherapy together with cisplatin followed by surgery. The resected tonsillar specimen showed a residual tumor composed of SCC and SqCC, and lymph nodes showed metastatic tumor cells of the SCC component. Immunohistochemically, the SCC component was positive for all neuroendocrine markers and p16; on the other hand, the SqCC component was positive for p40, p63, p16, and EGFR. Fluorescence in situ hybridization revealed that neither component showed any EGFR gene copy number gain. The patient was treated with adjuvant chemotherapy consisting of irinotecan and cisplatin. Liver and bone metastases developed, resulting in the death of the patient. We discuss the present case and review similar cases. Most cases of combined SCC and SqCC occur regardless of p16 status, and a therapeutic strategy has yet to be determined. Further examination of this kind of combined tumor is necessary.

Syndrome of inappropriate antidiuretic hormone secretion in a case of olfactory neuroblastoma without anti-diuretic hormone immunoreactivity: A case report and review of the literature.

Olfactory neuroblastoma (ONB) is a relatively rare nasal or paranasal malignant tumor. This tumor is rarely accompanied by paraneoplastic syndromes such as syndrome of inappropriate antidiuretic hormone secretion (SIADH). Here, we report a 31-year-old female with histologically confirmed ONB who had been diagnosed with SIADH three years prior. She was treated with surgery followed by concurrent chemoradiotherapy. SIADH resolved immediately after surgical tumor resection. Immunohistochemically, both biopsy and resected specimens from the nasal cavity had been negative for ADH. Although extremely rare, ONB may be associated with SIADH, and the possibility of this cancer should be taken into account during the follow-up of idiopathic SIADH.

Squamous cell carcinoma of the external auditory canal and middle ear: an operation combined with preoperative chemoradiotherapy and a free surgical margin.

OBJECTIVE: Treatment outcomes for squamous cell carcinoma of the temporal bone were evaluated regarding stage, therapeutic strategy, and prognostic factors. STUDY DESIGN: Retrospective case review. SETTING: University hospital and outpatient clinic. PATIENTS: Twenty-five patients with primary squamous cell carcinoma of the external auditory canal and middle ear. INTERVENTION: Preoperative chemoradiotherapy and radiotherapy were used in 7 of 12 patients. Lateral temporal bone resection was performed for the lesions not beyond the tympanic membrane. Subtotal temporal bone resection was chosen for lesions extending to the middle ear cavity when there was no invasion to the pyramidal apex, carotid canal, or dura or metastasis. Others were conservatively treated by chemoradiotherapy. When the performance status was poor or an agreement regarding the operation could not be reached, the treatment was modified. MAIN OUTCOME MEASURE: Estimated survival rates. RESULTS: The 3-year estimated survival for T1 and T2 lesions was 100%. The 5-year estimated survival for T3 and T4 lesions was 80% and 35%, respectively. The 5-year estimated survival improved up to 75% for T4 tumors with operation and 16% for those without operation after 47 months. The tumor-free surgical margin is significantly related to patient survival in T3 and T4 lesions. Multivariate analysis predicted that concomitant chronic otitis media and positive lymph nodes were significantly associated with poorer survival. CONCLUSION: The tumor-free surgical margin was important to survival. When T4 lesions did not involve the pyramidal apex, carotid canal, dura, or any lymph nodes, the surgical intervention improved the estimated survival rate to a level as good as T3 lesions.

Molecular subclassification determined by human papillomavirus and epidermal growth factor receptor status is associated with the prognosis of oropharyngeal squamous cell carcinoma.

Human papillomavirus (HPV) infection is an indicator of good response to chemoradiotherapy in oropharyngeal squamous cell carcinoma (OPSCC), and epidermal growth factor receptor (EGFR) is a molecular-therapeutic target in head and neck squamous cell carcinoma. Here we investigated the prevalence and prognostic significance of HPV infection and EGFR alteration in OPSCC. We analyzed the presence of high-risk HPV using in situ hybridization, protein expressions of p16 and EGFR using immunohistochemistry, and the EGFR gene copy number gain using chromogenic in situ hybridization (CISH) in 105 cases of OPSCC. The biopsy specimens before chemoradiotherapy were used for these analyses. HPV infection and p16 protein overexpression were detected in 53.3% and 52.4% of the OPSCCs, and each factor was associated with better overall survival (P = .0026 and P = .0026) and nonkeratinizing histology (P = .0002 and P = .0004), respectively. EGFR gene copy number gain (high polysomy or amplification) was detected in 12.4% of the OPSCCs and was correlated with EGFR protein overexpression (P = .0667) and worse overall survival (P < .0001). HPV infection and EGFR gene copy number gain (EGFR CISH positive) were mutually exclusive. The HPV-negative/EGFR CISH-positive OPSCCs had significantly worse overall survival than did the HPV-positive/EGFR CISH-negative OPSCCs and HPV-negative/EGFR CISH-negative OPSCCs (P < .0001 and P < .0001, respectively). The EGFR CISH-negative OPSCCs had favorable prognosis irrespective of HPV infection. Our results suggest that EGFR gene copy number gain-positive tumors represent an HPV-negative, aggressive subgroup of OPSCCs. The molecular subclassification of OPSCCs based on HPV infection and EGFR status may serve as important information for appropriate therapeutic strategy.

Patterns of lymphatic spread and the management of eyelid carcinomas.

OBJECTIVE: Eyelid carcinomas are rare, and the management strategy of regional lymph node metastasis linked to eyelid carcinomas has not been standardized to date. The aim of the present study was to analyze the patterns of regional metastasis and to assess the optimal extent of surgical treatment for lymph node metastasis of eyelid carcinoma. METHODS: This study was a retrospective review of patient data from a single institution. From a series of 268 eyelid carcinomas, we selected the 21 patients with lymph node metastasis, and we analyzed the patterns of lymphatic spread, approach to treatment and outcomes. RESULTS: The most common histological type of eyelid carcinoma with regional metastasis was sebaceous carcinoma (17/21, 81.0%). Submandibular area metastases were seen only in the patients with the primary tumor originating in the medial half of the eyelid, but parotid area metastases were seen in both the patients whose tumors had a medial-half origin and those with a lateral-half origin. Although 11 of the 16 patients with parotid-area metastases underwent a tumorectomy or superficial parotidectomy (which resulted in four cases of recurrence in the parotid area), none of the five patients who underwent a total parotidectomy developed parotid-area recurrence. The incidence of regional recurrence of the patients who received adjuvant radiotherapy (14.3%) was lower than that of the patients without adjuvant radiotherapy (57.1%). CONCLUSION: Continued surveillance and optimal management of regional lymph node metastases are important for the control and survival of eyelid carcinomas.

Microsatellite instability and proliferating activity in sinonasal carcinoma: molecular genetic and immunohistochemical comparison with oral squamous cell carcinoma.

Sinonasal carcinomas arise from the respiratory epithelium that lines the nasal and paranasal cavities, and are histologically composed of either squamous or cylindrical cell carcinoma. However, molecular analysis with the purpose of distinguishing sinonasal carcinomas from other head and neck squamous cell carcinomas (HNSCCs), which arise from squamous epithelium, has been limited. Moreover, a wide range of frequency of microsatellite instability (MSI) in HNSCC has been reported. Using high-resolution fluorescent microsatellite analysis (HFRMA), we studied microsatellite alterations in 34 patients with sinonasal carcinoma. As a control, 24 oral squamous cell carcinomas were used. MSI was detected in 14 patients with sinonasal carcinoma (41%), but not in any with oral squamous cell carcinoma (p=0.002). Furthermore, in sinonasal carcinoma, 11 out of 17 (65%) T1-T3 sinonasal carcinomas demonstrated MSI, whereas only 3 out of 15 (20%) T4 tumors demonstrated MSI. Immunohistochemically, sinonasal carcinoma showed a higher MIB-1-labeling index and more frequently showed cytokeratin 18 expression when compared with oral squamous cell carcinoma. These findings suggest that sinonasal carcinoma and HNSCC have quite different molecular backgrounds regarding carcinogenesis, and the role of MSI is relatively minor in cases of advanced sinonasal carcinoma.

Toxicity to early life stages and an estrogenic effect of a bisphenol A metabolite, 4-methyl-2,4-bis(4-hydroxyphenyl)pent-1-ene on the medaka (Oryzias latipes).

In a recent study, it was reported that 4-methyl-2,4-bis(4-hydroxyphenyl)pent-1-ene (MBP), a metabolite of bisphenol A (BPA; 2,2-bis(4-hydroxyphenyl)propane), showed estrogenic activity in several in vitro assays, and the estrogenic activity of MBP was higher than that of BPA. In this study, we have investigated the early life stage toxicity and estrogenic effect of MBP on medaka (Oryzias latipes). The 96-h median lethal concentration value of MBP and BPA with 24-h-old larvae was estimated to be 1,640 and 13,900 microg/l, respectively. The hatchability of fertilized eggs exposed to MBP and BPA over 14 days was significantly decreased at doses of 2,500 microg/l and 12,500 microg/l, respectively. Moreover, to compare the potency of estrogenic activity in vivo, male medaka were exposed to various concentrations of MBP and BPA for 21 days. The lowest-observed-effect concentrations of MBP and BPA for hepatic vitellogenin induction in male medaka were estimated to be 4.1 and 1,000 microg/l, respectively. These results suggest that MBP has high toxicity for early life stages of the medaka, and that the estrogenic activity of MBP was about 250-fold higher than that of BPA to male medaka.