Relationship between APC genotype, polyp distribution, and oral sulindac treatment in the colon and rectum of patients with familial adenomatous polyposis.

PURPOSE: Familial adenomatous polyposis is an inherited colorectal cancer syndrome characterized by the presence of multiple adenomatous colorectal polyps. Molecular studies have revealed that germline mutations in the APC gene are the underlying cause of the disease. The nonsteroidal anti-inflammatory agent sulindac has been shown to reduce the number of colorectal adenomas. Most sulindac trials in the large bowel have focused on the distal colon and relatively little is known about its effect on the proximal colon. Moreover, it is unknown whether the site of the APC mutation affects the efficacy of sulindac. METHODS: This study investigated whether there were regional differences in the effect of sulindac on the colon and whether response to sulindac was dependent on the site of mutation in the APC gene. In an open prospective study 17 patients with familial adenomatous polyposis were treated with 300 mg oral sulindac daily for four months followed by a washout phase of six months. Ten of the patients had an intact colon and seven had rectal stumps only. The number, size, and the degree of dysplasia of the adenomas were evaluated by colonoscopy at entry, end of treatment and end of the study. RESULTS: Overall, a statistically significant decrease in the number of adenomas was observed (120 +/- 112 to 28 +/- 64, P = 0.007). After cessation of sulindac treatment the number of adenomas increased to 48 +/- 44.5, but remained significantly lower than the values observed at baseline. In the ten patients with intact colons, adenomas decreased by sevenfold in the proximal colon (103 +/- 73 to 15.1 +/- 47.4, P = 0.011) and twofold in the distal colon (80 +/- 52 to 29.6 +/- 37.2, P = 0.005). The size of adenomas and the grade of dysplasia also decreased. No correlation could be seen between the APC mutation site and the response to treatment. CONCLUSION: These data indicate that sulindac reduces the number of adenomas in the entire colon and that the effect seems to be more pronounced in the proximal colon.

[Critical thoughts on current laser surgery of the cornea]. / Kritische Gedanken zur heutigen Laserchirurgie der Kornea.

OBJECTIVE: To analyze critically refractive surgery of the cornea by excimer laser and to compare laser surgery with other methods of treatment of refractive errors of the eye. MATERIAL AND METHODS: This analysis has to be restricted to a comparison of the treatment of myopia by keratotomy and photoablation with the ArF excimer laser. Correction of hypermetropia and of astigmatismus has to be left out, along with all the other methods to correct myopia, such as glasses, contact lenses, keratomileusis, epikeratoplasty, alloplastic implants, implantation of intraocular lenses with negative power, and replacement of the clear lens by an posterior chamber lens. The essential literature is screened. For intrastromal ablation with the picosecond Nd:YLF laser we relay on own experiences, also with the use of the ArF excimer laser we are not without own experiences. RESULTS AND STATEMENTS: For comparison of refractive surgery of the cornea not only the PERK study and the recommendations of the American Academy of Ophthalmology have to be considered, but also the newest developments in radial keratotomy such as two-step incision and reoperation with reopening of the keratotomy wounds. With these techniques the same precision can be reached as with the excimerlaser, and also higher myopias can be corrected. The dangers of the procedure, such as infection, perforation at surgery or laceration by contusion remain much larger. Intrastromal photoablation did not reach clinical maturity. Superficial photoablation is an almost safe procedure. A reduction of 3 D of myopia can be reached with satisfying precision, although higher myopias are still a problem. Pain following the ablation is considerable. Haze and disturbed vision at night can be present; infectious keratitis is rare, but possible. CONCLUSIONS: The critical fact of both procedures, keratotomy and photoablation with excimer laser, remains that healthy eyes are treated; therefore, even rare complications weigh much heavier than if sick eyes are treated. Because this is cosmetic surgery, the individuum asking for this type of procedure has to pay for on his own. Olson demands: "In determining when new technology is acceptable, we must consider the financial cost and the expected benefit to society. Is it an equitable tradeoff?" If we look at refractive surgery, especially laser photoablation, in the context of the needs for ophthalmic care of the whole world, then this type of surgery is out of proportion. The balance could be restored if, with every laser application, funds were given for third-world projects. Excimer-laser surgery may be justified insofar as the research with these lasers leads to useful therapeutic methods.

Novel germline APC gene mutation in a large familial adenomatous polyposis kindred displaying variable phenotypes.

The APC gene is mutated in the germline of people from families where there is a predisposition to develop polyposis coli. Many mutations have been described but the relation between their site and the phenotypic expression of the disease remains unclear. The most commonly seen mutation occurs at codon 1309. Many other mutations have been described towards the 5' end of exon 15 of the APC gene but comparatively few have been seen towards the 3' end. Recent reports have indicated the possibility of a functional boundary with respect to severity and age of onset of disease, which lies towards the 5' end of the gene. This report describes a large family whose affected members present with a very variable phenotype ranging from an early onset and severe form to a comparatively mild later onset one. The mutation that predisposes to disease in this family is at a previously undescribed site that lies towards the 3' end of exon 15 of the APC gene, which results in a stop codon. Interestingly, the stop codon is 63 codons downstream of the mutation and therefore may affect the expression of the disease. The addition of this mutation to the growing list of mutations described in the APC gene may provide some insight into the genotype/phenotype relation of the disease thus contributing to the understanding and significance of mutations at specific sites in the APC gene.

[Turcot syndrome--a rare extra-intestinal manifestation of familial adenomatous polyposis?]. / Turcot-Syndrome--eine rare extraintestinale Manifestation der familiären adenomatösen Polypose (FAP)?

The case of a 15-year-old male with Turcot syndrome is presented. When the patient was aged 10 years a medulloblastoma was diagnosed. Five years later he developed multiple adenomatous polyps of the colon and multiple "congenital hypertrophy of the retina" (CHRPE), the most common extraintestinal manifestation of FAP, were described. Family history revealed familial adenomatous polyposis with 12 family members exhibiting a FAP. The mode of inheritance of Turcot syndrome is controverted. Our case strengthens the hypothesis that the syndrome is a further extraintestinal (rare) manifestation of the FAP gene.

[The fate of corneal transplants from the Zurich eye bank]. / Das Schicksal der Hornhauttransplantate aus der Augenbank Zürich.

In a retrospective study, we investigated the survival of transplanted corneal material, which had been sent between 1988 and 1989 from the Zurich Eye Bank to both domestic and foreign physicians and clinics. A questionnaire was used to determine diagnosis, transplant survival, cause of any opacification, the occurrence of problems of epithelialisation, loosening of sutures, as well as vascularization of the host cornea. Of a total of 416 corneas, 327 or 79% could be evaluated. The mean follow-up periods of the various diagnostic groups ranged from 11 to 20 months, with a range of 1 to 35 months. After 18 months, the rate of clear transplants was 96% in the keratokonus group. This rate was significantly better than that of the bullous keratopathy group (77%, p less than 0.013) or that of all other diagnosis groups (72%, p less than 0.001). The difference to the 81% survival rate of the group with Fuchs' endothelial dystrophy was not significant. The most frequent cause of transplant opacification was primary transplant failure. Analysis of possible risk factors further confirmed that transplant opacification occurs more frequent in the presence of vascularization of the host cornea.

[Correction of astigmatism after penetrating keratoplasty]. / Astigmatismuskorrektur nach perforierender Keratoplastik.

Nine patients had a surgical correction of high astigmatism following perforating keratoplasty. In seven of them the reason for the perforating keratoplasty was keratoconus, in two of them Fuchs' endothelial dystrophy. The correction was performed in the seven 31-69 yrs old keratoconus patients 4-19 years (median 10 yrs) after the transplant, in the patients with Fuchs' dystrophy 13 month and 1 year following corneal transplant. In eight cases two circular shaped relaxing incisions of 60 degrees were performed in the steeper meridian, seven times combined with sutures in the opposite meridian. Once a wedge resection was performed. The astigmatism before correcting surgery was 8-19 dpt (median 13 dpt), 3-24 month (median 11 month) 1.75-13 dpt (median 8 dpt). The reduction of astigmatism was 3-10 dpt (median 8 dpt). In 5 of 9 patients the astigmatism could be corrected by spectacles, in two more patients no spectacles were prescribed because of cataract. After this series of astigmatic correction we think that incisions without sutures are superior. This method could replace rekeratoplsty in the future.

Morphology and time-course of defined photochemical lesions in the rabbit retina.

The present study demonstrates an experimental set-up to study light injury with defined parameters including retinal irradiance levels and spectral composition of the damaging light. The time-course of acute morphological changes at constant light intensity and increasing exposure durations (from 5-30 minutes) was evaluated, the wavelength of the damaging light being 400-550 nm. Pigment epithelial lesions appeared already after 5 minutes, and rod outer segment membrane disruptions after 15-20 minutes of light exposure. Striking was the observation of disruption and vesiculation of disk membranes at the base of rod outer segments. This "clear zone" was consistently observed beginning after twenty minutes of light exposure. The comparison of morphological changes in pigmented and albinotic eyes revealed no essential differences. This result confirms the observations of other laboratories that pigment epithelial melanin neither protects against nor promotes light damage to a significant extent. Long-term changes after light exposure revealed pigment epithelial lesions and rod outer segment disruptions, followed by macrophage invasion and pigment epithelial proliferation with subsequent loss of photoreceptor cells.