Ophthalmic pterygium: a stem cell disorder with premalignant features.

Pterygia are common ocular surface lesions thought to originate from limbal stem cells altered by chronic UV exposure. Traditionally regarded as a degenerative condition, pterygia also display tumor-like features, such as a propensity to invade normal tissue and high recurrence rates following resection, and may coexist with secondary premalignant lesions. This study was initiated to determine the rate of concurrent ocular surface diseases in patients with pterygia recruited from the practice of a single surgeon operating in a Sydney metropolitan hospital. One hundred pterygium specimens were histopathologically reviewed and selected cases were immunohistochemically assessed to confirm diagnosis. Along with previously documented typical features including epithelial proliferation, goblet cell hyperplasia, angiogenesis, inflammation, elastosis, stromal plaques, and Bowman's membrane dissolution, we identified five cases of ocular surface squamous neoplasia, six cases of primary acquired melanosis, two compound nevi (one suspect invasive melanoma), and one dermoid-like lesion. In 18 specimens, clusters of basal epithelial cells that coexpressed cytokeratin-15/-19 and p63-α were identified at the head of the pterygium, coinciding with clinical observation of Fuchs' flecks. Our data show that significant preneoplastic lesions may be associated with pterygium and that all excised pterygia should undergo histological examination. The presence of p63-α-positive epithelial cell clusters supports the hypothesis that pterygia develop from limbal epithelial progenitors.

Appendicectomy as a therapy for ulcerative proctitis.

OBJECTIVES: Available data regarding whether appendicectomy performed after the onset of ulcerative colitis can modulate its clinical course are currently limited. This study aimed at addressing this issue. METHODS: In this study, we report a prospective case series of 30 adult patients (median age 35 years, range 17-70 years; male/female: 11/19) with ulcerative proctitis (median duration of symptoms 5 years, range 8 months to 30 years; median Simple Clinical Colitis Activity Index score 9, range 7-12), who underwent appendicectomy in the absence of any history suggestive of previous appendicitis. Patients were subsequently followed up clinically with the assessment of the Simple Clinical Colitis Activity Index for a median of 14 months (range 9-32 months). RESULTS: After appendicectomy, the clinical activity index improved significantly to a median score of 2 (range 0-12) (P<0.0005). The improvement in the clinical activity index occurred in 27 of 30 (90%) patients, whereas the index remained unchanged in the remaining 3 of 30 (10%) patients. Furthermore, 12 of 30 (40%) patients experienced a complete resolution of symptoms (clinical activity index score of 0) by 12 months, such that all pharmacological treatments could be withdrawn, and have remained in remission off all previous treatments for a median 9 months (range 6-25 months). The time required for a complete resolution of symptoms post appendicectomy ranged from 1 to 12 months (median 3 months) (Kaplan-Meier analysis). None of the clinical or histological factors analyzed were significantly associated with post-appendicectomy outcome. CONCLUSIONS: This case series, the largest reported so far, provides rationale for controlled trials to properly evaluate the possible role of appendicectomy in the treatment of ulcerative proctitis.

Deep anterior lamellar keratoplasty using the manual dissection technique of Melles: a histopathologic correlation.

PURPOSE: To report the histopathologic findings in the host tissue of 2 human keratoconic corneas undergoing maximum-depth anterior lamellar keratoplasty (MDALK) using the manual dissection technique described by Melles. METHODS: Corneal buttons were examined from 2 patients with keratoconus who underwent MDALK using the manual dissection technique of Melles and converted to penetrating keratoplasty after rupture of the lamellar bed. Manual dissection was performed in 1 patient, and combined manual and viscoelastic dissection of Descemet membrane (DM) was performed in the other. RESULTS: Light microscopy of the corneal buttons showed a deep pre-Descemet dissection plane with minimal residual stroma. DM appeared to be thinned in both eyes and measured 3 to 8 microm in thickness. CONCLUSION: By using the manual dissection technique of Melles, LK can be performed exposing the smooth DM of the recipient bed. We confirmed exposure of DM in patient corneas, using this technique by light microscopy. There may be an increased risk of rupture of DM during surgery when this membrane is thinned, particularly in patients with keratoconus. This surgical technique allows conversion to penetrating keratoplasty after rupture of DM.

Modeling the dynamics of fermentation and respiratory processes in a groundwater plume of phenolic contaminants interpreted from laboratory- to field-scale.

A biodegradation model with consecutive fermentation and respiration processes, developed from microcosm experiments and simulated mathematically with microbial growth kinetics, has been implemented into a field-scale reactive transport model of a groundwater plume of phenolic contaminants. Simulation of the anaerobic plume core with H2 and acetate as intermediate products of biodegradation allows the rates and parameter values forfermentation processes and individual respiratory terminal electron accepting processes (TEAPS) to be estimated using detailed, spatially discrete, hydrochemical field data. The modeling of field-scale plume development includes consideration of microbial acclimatization, substrate toxicity toward degradation, bioavailability of mineral oxides, and adsorption of biogenic Fe(ll) species in the aquifer, identified from complementary laboratory process studies. The results suggest that plume core processes, particularly fermentation and Fe(lll)-reduction, are more important for degradation than previously thought, possibly with a greater impact than plume fringe processes (aerobic respiration, denitrification, and SO4-reduction). The accumulation of acetate as a fermentation product within the plume contributes significantly to the mass balance for carbon. These results demonstrate the value of quantifying fermentation products within organic contaminant plumes and strongly suggest that the conceptual model selected for reactive processes plays a dominant role in the quantitative assessment of risk reduction by naturally occurring biodegradation processes.

Down-regulation of KAI1/CD82 protein expression in oral cancer correlates with reduced disease free survival and overall patient survival.

Oral Squamous Cell Carcinoma (OSCC) is a common malignancy. Treatment failure is mainly due to loco-regional disease recurrence. KAI1 is a newly discovered metastasis suppressor gene. Fifty-seven patients with primary OSCC underwent surgery alone or surgery and adjuvant radiotherapy. Immunohistochemical evaluation of KAI1/CD82 and p53 proteins was carried out on specimen obtained at surgery. Within neoplastic fields, KAI1/CD82 expression was downregulated and negative in 42/57 (73.7%) cases. p53 expression was positive in 26/57 (45.6%) cases. No correlation was noted between KAI1/CD82 and p53 expression or clinicopathological parameters. Univariate and multivariate Cox proportional hazard models showed a correlation between KAI1/CD82 expression with disease free survival (P = 0.01, P = 0.009) and overall survival (P = 0.04, P = 0.053) respectively.

Progression from normal breast pathology to breast cancer is associated with increasing prevalence of mouse mammary tumor virus-like sequences in men and women.

Mouse mammary tumor virus (MMTV)-like sequences have been found in up to 40% of breast cancer samples but in <2% of normal breast tissue samples from Australian women studied by our group. Screening of a larger and more diverse cohort of female breast cancer samples has now shown a correlation of MMTV-like sequences with the severity (grade) of breast cancer. Thirty-two percent (43 of 136) of female breast cancer samples were positive for MMTV-like sequences when screened using PCR. A significant gradient of MMTV positivity was observed with increasing severity of cancer from 23% of infiltrating ductal carcinoma (IDC) grade I tumors to 34% of IDC grade II tumors (P = 0.00034) and 38% of IDC grade III tumors (P = 0.00002). We also report for the first time the detection of MMTV-like sequences in 62% (8 of 13) of male breast cancer samples and 19% (10 of 52) of male gynecomastia samples screened. MMTV-like sequences were demonstrated in various premalignant breast lesions of females, including fibroadenoma (20%) and fibrocystic disease (28%) samples, at a significantly higher prevalence than that seen in normal breast tissue (1.8%; P = 0.00001). Study of a longitudinal cohort of female breast cancer patients indicated that MMTV was co-incident with tumor but was not present when tumor was absent on histology. These results support the association of MMTV-like sequences with development of breast tumors in men and women and suggest association of MMTV with increasing severity of cancer.