More differences between HNPCC-related and sporadic carcinomas from the endometrium as compared to the colon

PURPOSE: Recognition of hereditary nonpolyposis colorectal cancer (HNPCC)-related endometrial carcinoma from sporadic carcinoma by histologic features as compared with colonic cases. STUDY DESIGN: Case-control study. METHODS AND MATERIALS: From the files of the Nijmegen Hereditary Cancer Clinic, HNPCC-related (n = 6) endometrial and colorectal (n = 18) carcinomas were selected. For every HNPCC-related tumor, 2 sporadic control cases were included. The tumors were evaluated for the following 7 pathologic features: tumor differentiation, T-stage, growth pattern, presence of Crohn-like lymphoid reaction, mucinous differentiation, presence of lymphangioinvasive growth, and the amount of tumor-infiltrating lymphocytes. RESULTS: HNPCC-related endometrial carcinomas were significantly more often poorly differentiated (83% versus 27%), more often showed the presence of a Crohn-like lymphoid reaction (100% versus 13%) and lymphangioinvasive growth (67% versus 0%), and high number of tumor-infiltrating lymphocytes were more often present (100% versus 36%) compared with sporadic endometrial carcinomas. The differences between HNPCC and sporadic colorectal cancer specimens were less discriminating. CONCLUSIONS: HNPCC-related endometrial carcinomas are characterized by poor differentiation, more frequent Crohn-like lymphoid reaction, lymphangioinvasive growth and more tumor-infiltrating lymphocytes. These features therefore might form the basis for selecting patients for counseling in a hereditary cancer clinic or testing for microsatellite instability or mutation analysis of mismatch repair genes, especially when they are of relatively young age.     

Clinical usefulness of botulinum toxin in the lower extremity

As the literature that pertains to botulinum toxin expands, the scope of treatment options broadens. Although initial uses of botulinum toxin focused around the head and neck, there are many uses for the toxin in the area of the foot and ankle; more possibilities are under investigation every day. We review the uses and techniques for botulinum toxin in the foot and ankle and present results of botulinum toxin treatment in 10 idiopathic toe walkers.     

Bartonella henselae infection associated with neuroretinitis, central retinal artery and vein occlusion, neovascular glaucoma, and severe vision loss

PURPOSE: To report a case of Bartonella henselae infection. DESIGN: Observational case report. METHODS: Review of the clinical, laboratory, photographic, and angiographic records of a patient with cat scratch disease associated with central retinal artery and vein occlusion, neovascular glaucoma, and severe vision loss. RESULTS: A 21-year-old man had no light perception in the left eye secondary to concurrent central retinal artery and vein occlusion believed to have resulted from infection with Bartonella henselae. Forty days later, he developed neovascular glaucoma in the left eye. CONCLUSION: Ocular complications associated with Bartonella henselae infection may include central retinal artery and vein occlusion, neovascular glaucoma, and severe vision loss.     

Effects of verteporfin therapy on central visual field function

PURPOSE: To evaluate the effect of photodynamic therapy with verteporfin on the maintenance of central visual field function. DESIGN: Randomized controlled clinical trial. PARTICIPANTS: Forty-six consecutive patients with subfoveal choroidal neovascularization (CNV) caused by age-related macular degeneration including a classic component were randomly assigned. Thirty-three participants received standard verteporfin therapy, and 13 received placebo and laser treatment. METHODS: The trial was performed as a single-center, double-masked study. Patients were examined before therapy and continuously in 3-month intervals during 2 years of follow-up. A scanning laser ophthalmoscope (SLO) was used to perform macular microperimetry. Absolute and relative scotomas were documented at each visit, and size was measured in square millimeters. MAIN OUTCOME MEASURES: The change in size of central scotoma in the verteporfin group compared with the placebo group. RESULTS: An absolute scotoma was seen in 88%, and a relative scotoma was seen in 100% of eyes before therapy. Absolute defects were associated with the classic CNV component localized angiographically. In the verteporfin group, the absolute scotoma grew from 2.5 mm(2) at baseline to a final size of 7.3 mm(2) at month 24. In the placebo group, the mean lesion size of the absolute scotoma enlarged from an initial size of 2.7 mm(2) to 31.5 mm(2) after 24 months. The relative scotoma increased from 7.9 mm(2) at baseline to 20.8 mm(2) at month 24 in the verteporfin group, whereas a progression from 8.5 mm(2) initially to 48.3 mm(2) at the final presentation was measured in the placebo group. Statistical analysis showed that both the mean absolute and relative scotoma sizes were significantly smaller in the verteporfin group than the placebo group for all intervals from 6 to 24 months (P<0.001). CONCLUSIONS: Documentation of macular function with SLO perimetry demonstrated a significant benefit of verteporfin therapy for the preservation of the central visual field. Absolute and relative scotoma sizes remained smaller after therapy. This may influence reading ability and visual rehabilitation.     

Metastatic breast carcinoma to the vitreous

PURPOSE: To evaluate the clinical and pathologic findings in two patients with prior breast carcinoma who underwent diagnostic vitrectomy for vitreous opacities and preretinal membrane. METHODS: The clinical histories and ophthalmic findings in two patients were reviewed. Vitrectomy specimens from the patients were processed by cytospin and standard tissue techniques, stained with hematoxylin and eosin, and examined immunohistochemically for cytokeratins. The original breast carcinoma specimens were reviewed. RESULTS: The vitreous in both patients contained malignant cells with cytologic features consistent with metastatic carcinoma. Immunohistochemical stains were positive for cytokeratins in the cells. The cytologic findings in the vitreous cells resembled the primary breast carcinoma. CONCLUSIONS: Breast carcinoma may metastasize to the vitreous, most likely via the retina. The clinical manifestations include vitreous cell and preretinal membrane.     

Laparoscopic staging compared with imaging techniques in the staging of advanced cervical cancer

OBJECTIVE: We evaluated the evidence of laparoscopy for decision regarding treatment options in advanced cervical cancer patients. METHODS: One hundred nine consecutive patients with cervical cancer FIGO stage Ib2 and higher underwent laparoscopic staging of the extent of disease. Laparoscopic and histopathologic evaluation of tumor involvement of the paraaortic and pelvic lymph nodes, wall of the bladder, and rectal pillar was compared with preoperative findings of MRI and/or CT. RESULTS: Paraaortic lymphadenectomy was performed in 101 (92.7%) patients and 21 (19.3%) patients had positive paraaortic lymph nodes. Pelvic lymphadenectomy was performed in 75 (68.8%) patients and 20 (26.7%) patients had positive pelvic lymph nodes. In 11 patients (11.5%) infiltration of the bladder and in 6 patients (6.25%) infiltration of the rectal pillar or cul-de-sac was found. Intraoperative complications associated with laparoscopic staging occurred in 3.7% of patients. The negative predictive value for the evaluation of paraaortic or pelvic lymph nodes, the bladder wall, rectal pillar, and cul-de-sac ranged from 73% (CT for pelvic lymph nodes) to 96% (MRI for bladder wall). Lack of information about the extent of disease was adjusted on the basis of laparoscopic findings in 24 (22%) patients and improved treatment plans. CONCLUSION: Laparoscopic staging of patients with advanced cervical cancer is accurate, associated with low morbidity, and helps to adjust treatment according to extent of disease.     

Changes in confocal indocyanine green angiography through two years after photodynamic therapy with verteporfin

PURPOSE: To evaluate vascular changes documented by confocal indocyanine green angiography (ICGA) through 2 years after photodynamic therapy (PDT) with verteporfin of neovascular age-related macular degeneration (AMD). DESIGN: Single-center, 2-year, randomized, double-masked, interventional, placebo-controlled trial (subset from Treatment of AMD with PDT Study [TAP]). PARTICIPANTS: Sixty patients with subfoveal choroidal neovascularization (CNV) resulting from AMD. INTERVENTION: Patients were randomized in a ratio of 2:1 to a standard regimen using verteporfin therapy at a drug dose of 6 mg/m(2) body surface area and a light dose of 50 J/cm(2) or a sham treatment with placebo infusion and light exposure. Retreatments, if persistent fluorescein leakage from CNV was documented, were scheduled at 3-month intervals for up to 2 years. Confocal ICGA with tomographic sections was performed at baseline and continuously at the month 3, 6, 12, and 24 examinations using a standardized protocol. MAIN OUTCOME MEASURES: Analysis included the size of the neovascular net, the area of late hyperfluorescence, and choroidal hypofluorescence during early- and late-phase imaging. RESULTS: In the verteporfin-treated group, the mean size of the CNV and the mean area of late leakage consistent with active leakage or staining showed no further enlargement at month 12 and were reduced at month 24. In the placebo-treated group, new vessels grew threefold compared with baseline and exhibited persistent late hyperfluorescence resulting from leakage at 24 months. Associated choroidal hypofluorescence within the treated area was significantly increased in eyes treated with verteporfin PDT compared with the control group during the first year, persisted during all ICGA phases, and was irreversible during follow-up. Image analysis revealed choroidal hypoperfusion with choriocapillary dropout, which correlated with chorioretinal atrophy clinically. Progressive destruction of choroidal integrity by fibrosis in control eyes led to a similar extent of collateral hypofluorescence in both groups through the 24-month examination. CONCLUSIONS: Indocyanine green angiography is an important adjunct in the identification of vascular effects associated with verteporfin PDT. Repeated treatments effectively arrested CNV growth and reduced leakage activity. The collateral impairment of choroidal perfusion appears to influence the visual outcome of the treatment.     

Photodynamic therapy: extended indication

OBJECTIVE: Evaluation of efficacy of photodynamic therapy (PDT) for classic choroidal neovascularization (CNV) beyond the common indication. METHODS: A group of 256 patients was treated with photodynamic therapy from January to December 2000. Ten of these patients had a predominantly classic CNV due to angioid streaks (5), parafoveal telangiectasia (2), or chorioretinitis (3). In two patients an idiopathic origin of the CNV was presumed. Another 21 patients showed a juxtafoveal classic membrane (12) or a recurrence after laser photocoagulation (9). Visual acuity was evaluated, also in correlation to age and CNV size. Continuous follow-up of CNV and leakage size was performed with fluorescein angiography. RESULTS: Overall 85% of the patients showed visual stabilization or improvement during an average observation period of 10.5 months. A correlation was found between age and visual improvement favoring younger patients; however, no correlation was found between visual improvement and CNV size. CNV and leakage size decreased moderately over the 9-month follow-up from 1.81/3.45 mm(2) to 1.61/2.60 mm(2). CONCLUSION: PDT shows efficacy for classic choroidal neovascularization beyond the common indication.     

Invertebrate models of neurologic disease: Insights into pathogenesis and therapy

The search for cures of human diseases can be very slow, expensive, and serendipitous. Roughly five decades of basic research in a handful of model systems has revealed that most animals are quite similar to one another especially at the cellular and molecular levels. The commonalities allow one to use animal models to investigate human disease mechanisms. Here, we review contributions demonstrating the use of invertebrate models to investigate human neurodegenerative diseases. We conclude that the integration of fly and worm models into programs seeking to identify therapeutic strategies for neurodegenerative disease can significantly speed progress toward finding cures for these devastating diseases.