[Significance of Mesenchymal Stem Cells in Gastrointestinal Disorders]. / Bedeutung mesenchymaler Stammzellen in der Viszeralmedizin.

In this review we summarise the recent developments regarding the experimental and clinical use of mesenchymal stem cells (MSCs), focusing mainly on the treatment of gastrointestinal disorders. Next to their relevance in the field of regenerative medicine and immunology, this population of cells has also raised great expectations for possible applications in cancer therapy. While clinical trials were able to demonstrate the efficacy of MSCs in cases of inflammatory bowel disease and degenerative conditions of the liver, controversial results have been presented regarding their antineoplastic potential in gastrointestinal tumours. MSCs can differentiate into a large variety of specialised cells. They are capable of regulating both wound healing and immune responses through paracrine and endocrine signalling. Moreover, MSCs can be transfected with a great number of different therapeutic genes - considering their ability to selectively migrate towards neoplastic tissues, this feature allows for targeted therapy of solid tumours. Transfected genes can be designed so that they are expressed exclusively in the vicinity of the tumour, eventually triggering apoptosis in cancer cells. In this review, we demonstrate the natural distribution of exogenously applied MSCs in the host. Furthermore, we mention various methods of tracking MSCs in vivo and different parameters of administration that tend to influence therapeutic outcome (e.g., origin of MSCs, mode of application, or the potency of transfected genes). Finally, this review points out the hazards of MSC therapy, emphasising the risks related to their widespread clinical use.

KRAS allel-specific activity of sunitinib in an isogenic disease model of colorectal cancer.

PURPOSE: To investigate the impact of different KRAS mutations on treatment with the tyrosine kinase inhibitor sunitinib in SW48 colorectal cancer cell line variants. MATERIALS AND METHODS: Isogenic SW48 KRAS wt, G12A, G12C, G12D, G12R, G12S, G12 V, and G13D cells were evaluated for ERK phosphorylation with and without EGF stimulation. In addition, the respective cell lines were tested for the effect of sunitinib on ERK/ELK phosphorylation, cell cycle, and cytotoxicity. RESULTS: Compared to KRAS wt cells, all KRAS mutant variants were associated with resistance to sunitinib treatment. In the MTT chemosensitivity assay, the grade of resistance was less pronounced in G13D and highest in G12A, G12C, and G12S mutant cells. The reduction in ERK phosphorylation due to treatment with sunitinib was highest in G12V (89 %) mutant cells and lowest in G12A (24 %) mutant cells. ELK phosphorylation was less decreased in all KRAS mutant variants compared to KRAS wt cells following sunitinib treatment. The grade of resistance appears to correlate with the individual KRAS-dependent intrinsic activation of ERK. CONCLUSION: Our isogenic cell culture model suggests that KRAS mutations in SW48 colorectal cancer cells are linked to resistance to the multityrosine kinase inhibitor sunitinib. KRAS G13D mutant SW48 cells represented the KRAS subspecies with the lowest grade of resistance. Future studies will have to clarify whether KRAS can be used to guide sunitinib treatment or-in general-a treatment with a multityrosine kinase inhibitor in mCRC.

Cholecystoduodenal fistula in a nonagenarian. Can laparotomy play a role in the era of laparoscopic? Case report.

Cholecystoduodenal fistula, a rare complication of biliary lithiasis, occurs in 0.5% to 3% of patients affected by cholelithiasis. Diagnosis is not easy and is usually incidental at surgery. The literature guidelines call for a laparoscopic approach to treating these patients; here, however, we report a case of a very elderly patient in which, among other reasons, open surgery was the treatment of choice to decrease morbidity and mortality.

Emergency gastric ulcer complications in elderly. Factors affecting the morbidity and mortality in relation to therapeutic approaches.

AIM: In elderly the incidence of the emergency gastric ulcer complications, perforation and bleeding are increasing, with a difficult management of these patients for their concomitant diseases. The aim of this work is to analyze the therapeutical approach of emergency gastric ulcer complications in elderly patients, in order to establish the factors affecting the morbidity and mortality. METHODS: Patients older than 70 years, presenting gastric ulcer, observed in a tertiary University Hospital from 1995 to 2003, have been considered for the present study. Two groups of diseases have been examined: ulcer perforation and bleeding ulcer. Age, sex, risk factors, comorbidity, methods of diagnosis, ulcer characteristics, treatment, morbidity, mortality, hospitalization time and follow-up have been considered in each group. RESULTS: Thirteen elderly patients with perforated gastric ulcer have been observed: 9 (69.2%) females and 4 (30.8%) males with a mean age of 80.5 years (range 70-90). Four patients were hospitalized in suburban hospital with an average time between the diagnosis and the surgery of 36 h, while the remnants were hospitalized directly in our Department with a medium waiting time of about 2 h. The surgical procedures were: simple closure with omentum patch in 11 cases (84.6%), and antrectomy in 2 cases (15.4%), in which the antrum was multiply perforated. Two patients presented an ulcer larger than 2 cm treated with simple suture and omental patch without morbidity and mortality. Three patients (23%) died postoperatively, due to septic shock, ventricular fibrillation and intraoperative massive haemorrhage, 2 of these patients came from other hospitals. Twenty-eight elderly patients with bleeding gastric ulcer have been observed during the same period: 13 (46.4%) females and 15 (53.6%) males with a mean age of 79.6 years (range 71-91). Except 2 patients submitted to endoscopic treatment both with adrenaline injection, all the remnant patients were managed with medical therapy (H2-receptor antagonist or proton pump inhibitors and in 7 patients [24.1%] antihaemorrhage drugs), and clinical observation, with a endoscopic control 3-4 days after from the first endoscopy. One of the 2 patients endoscopically treated developed a ulcer perforation after 11 days, and the other one rebled, without possibility of any kind of treatment due to his instable condition of health. Three patients (10.7%) died during their hospital stay not for causes strictly due to the gastric haemorrhage. CONCLUSIONS: Our results suggest that the early diagnoses and early treatment are 2 basic factor on the prognosis of elderly patients with perforated gastric ulcer. The choice between simple closure, with or without vagotomy, or gastrectomy depends from preoperative and operative health conditions of the patient. In patients with ulcer larger than 2 cm, Graham's technique can be performed safely if the preoperative and intraoperative conditions are favourable. Elderly patients with gastric ulcer bleeding show an high risk of morbidity and mortality, related to the risk factors like non steroid anti-inflammatory drugs (NSAIDs) intake or smoke. Repeated endoscopy and antiulcer drugs can manage the high stage patients of Forrest's classification with a low rate of morbidity and mortality. According to literature surgical treatment should be reserved after the second failure of endoscopic treatment.

Ocular toxocariasis: a rare presentation of a posterior pole granuloma with an associated choroidal neovascular membrane.

BACKGROUND: Ocular toxocariasis is a rare infection caused by the nematode larvae of toxocara canis, which is commonly found in dogs. Human transmission is usually via geophagia, the ingestion of food contaminated with the toxocara eggs, or contact with infected puppies, often resulting in devastating ocular and/or systemic effects. Distribution is worldwide; however, a higher incidence is demonstrated in the United States. METHODS: A 17-year-old black woman sought treatment at a neighborhood health center with a report of gradual decrease in vision from her left eye over a 3-month period. Her ocular and systemic histories were unremarkable. Anterior segment evaluation revealed no signs of anterior uveitis. The posterior pole showed a 1.5 DD, round, raised, white, subretinal lesion adjacent to the fovea with an overlying serous retinal detachment and retinal hemorrhage. RESULTS: She was referred to a retinologist who performed both fluorescein and indocyanine green (ICG) angiographies. A serum toxocara ELISA test was also ordered. Fluorescein angiography revealed hyperfluorescence consistent with the granuloma. The ICG demonstrated an occult choroidal neovascular membrane (CNV) underlying the area of hemorrhage inferotemporal to the granuloma. CONCLUSION: This paper illustrates the case presentation and includes an extensive review of the ocular and systemic manifestations of toxocariases. A description of ICG videoangiography, therapeutic approaches, and management will also be discussed.

Role of indocyanine green fluorescence videoangiography in evaluation of subretinal disease.

BACKGROUND: Indocyanine green (ICG) is a sterile, water-soluble, tricarbocyanine dye that can be used in fundus angiography as an adjunct to sodium fluorescein. It has a peak spectral absorption of 805 nm in blood plasma or blood, as compared with fluorescein, which has a peak spectral absorption of 465 nm. Because the absorption and emission of ICG lies around 835 nm, transmission of energy by the retinal pigment epithelium (RPE) and serosanguinated material is more efficient in this region than in the region of visible light energy. ICG has the property of being approximately 98% bound to blood protein, disallowing extravasation of excessive dye in the highly fenestrated choroidal vasculature. METHODS: The characteristics of ICG are discussed, including administration and dosage, adverse reactions and use of infrared filters for fundus photography. In addition, two cases are presented to illustrate the clinical application of ICG for diagnosis and treatment of choroidal neovascular membranes. RESULTS: ICG videoangiography can be used to reveal subfoveal choroidal neovascular membranes not previously identified with fluorescein; angiograms can also be used to dramatically highlight retinal and choroidal changes. CONCLUSIONS: The use of ICG for fundus videoangiography provides a more accurate and complete evaluation in certain cases of subretinal and choroidal disease.

Contemporary management of aniseikonia.

The diagnosis and management of aniseikonia has become a lost art. Refractive surgery and intraocular lens implantation has created a new patient population of anisometropia. Measurement of aniseikonia through instrumentation such as the space eikonometer is not readily available. Therefore, estimating the degree of aniseikonia based on the dioptral differences between the two eyes may be the most practical approach. The optical principles of spectacle magnification can be translated by the prescribing eye doctor to reduce ocular image disparity. Contemporary lens designs, such as hi-index and aspherics, allow the practitioner to modify shape and power factors to achieve higher levels of aniseikonic correction in a cosmetically fashionable pair of spectacles.

The illuminated high contrast macular grid: a pilot study.

BACKGROUND: Analysis of visual disturbances in the central 10 degrees provides valuable data for the low vision clinician. Amsler grid testing in the visually impaired can be poorly visible and it can be difficult to transcribe results. Automated perimeters will accurately map retinal defects, but the equipment is expensive and this technique is time consuming. An Amsler grid was modified using principles of luminance and contrast to improve its accuracy, and its efficacy was compared to an automated perimeter. METHODS: Eighteen visually impaired patients (28 eyes) were prospectively evaluated at the Emory Low Vision Laboratory. Each patient had three central threshold visual field tests: automated perimetry (Humphrey model 690), conventional Amsler Grid, and Illuminated High Contrast Macular Grid (IHCMG). The Humphrey central 10-2 threshold automated visual field examination was performed to map the patient's retinal function. RESULTS: The Humphrey analysis identified (mean +/- one standard deviation) 2.4 +/- 1.4 defects per patient with an average percent defect area of 33.4 +/- 14.8 degrees. The IHCMG technique was not significantly different from the Humphrey technique for identifying the number of defects (2.25 +/- 1.5) (p > 0.05) or the percent defect area (26 degrees +/- 20 degrees) (p > 0.05). The conventional Amsler grid technique significantly under-evaluated the retinal defects compared to the Humphrey analysis of the number of defects (p < 0.01) and percent area of defects (p > 0.001). CONCLUSIONS: The IHCMG technique can be used as a simple, rapid and accurate analysis of the central 10 degrees visual field in the low vision patient.

Sarcoid optic neuropathy: a case report.

BACKGROUND: Sarcoidosis is frequently overlooked as a cause of optic neuropathy. A cascade of immune interactions has been cited in the pathogenesis. Optic nerve involvement can be the initial manifestation of systemic disease, making the diagnosis even more elusive. Compatible clinicoradiographic and abnormal laboratory findings along with histologic evidence of noncaseating granuloma are necessary to secure the diagnosis of sarcoidosis. METHODS: A case report is presented of a 41-year-old patient with severe papillitis and a junctional scotoma as the first declaration heralding neurosarcoidosis (NS). Co-management with a neuroophthalmologist at an academic teaching hospital prompted the necessary diagnostic studies to preserve vision. RESULTS: Sarcoidosis was diagnosed on the basis of the patient's clinical presentation of rapid vision loss, enlarging mass in the anterior visual pathway revealed by CT and MRI, as well as increased uptake of gallium in the lungs and lacrimal glands. Also considered in the differential diagnosis were glioblastoma, lymphoma, and demyelinating disease. CONCLUSIONS: This case represents an example of triage referral involving optometry and academic ophthalmology. Rapid intervention with intravenous corticosteroids should be considered in the face of atypical optic neuritis with a suspected inflammatory etiology.

Infectious and inflammatory diseases.

The systemic conditions described in this paper are (1) sarcoidosis, (2) tuberculosis, (3) toxoplasmosis, and (4) histoplasmosis. The lung is the primary target organ of granulomatous involvement for each of these disorders. This and other similarities may confuse the diagnostic picture; however, appropriate understanding of clinical, epidemiologic, pathophysiologic, immunologic, radiologic, and serologic features assists in clearly establishing a diagnosis. The goals of this paper are to help the clinician develop a working knowledge of these four conditions, as well as an understanding of which tests are appropriate to order, how to interpret their results, and which treatment and management strategies to consider.

Central retinal vein occlusion in a young patient with seropositive syphilis.

Central retinal vein occlusion (CRVO) is a common retinal vasculopathy typically affecting adults in the fifth to seventh decade of life. Systemic disease, particularly hypertension, is often a contributing factor in this sight-threatening condition. CRVO in young adults, however, is an uncommon occurrence with relatively few reported cases in the ophthalmic literature. Two studies performed on young adults (less than 40 years of age) presenting with CRVO revealed that, in most cases, there was not a strong correlation with hypertension or other systemic diseases. In more severe cases, namely those with poor visual outcome from the ischemic type of CRVO, there was a strong correlation with cardiovascular disease and diabetes mellitus. Systemic inflammatory conditions represent a small contributing factor in patients presenting with CRVO. This paper reports on a 21-year-old female with non-ischemic CRVO who was serologically positive for syphilis.

Progressive retinal changes observed in juvenile X-linked retinoschisis.

Juvenile X-linked retinoschisis (JXR) is a vitreoretinal dystrophy affecting males only. The macular and peripheral retinal alterations associated with this disorder are very specific. Initially, a stellate-shaped foveal schisis forms; as the patient becomes older, chronic retinal pigment epithelial disturbance leads to macular degeneration. Peripheral retinoschisis may also occur, but is only identified in about half of all patients with JXR. These changes, which represent degenerating vitreous, may be complicated by retinal breaks due to the thin layer of the schisis. This paper presents five cases of JXR in patients ranging from ages 4-70 years and discusses and photodocuments the progression of related retinal changes. A table of differential diagnoses is also included.

Macular coloboma.

Macular coloboma is a congenital retinochoroidal defect of the macular region. It is a bilateral, nonprogressive condition that is associated with decreased visual acuity and nystagmus. A case of a 14-year-old boy with an unusual presentation of extensive macular colobomata is described. Location of the lesions differentiated this case from true or typical retinochoroidal colobomata. Differential diagnosis also includes postinflammatory scarring.

Duane's retraction syndrome.

Duane's retraction syndrome (DRS) is a congenital abnormality of ocular motility that occurs in about 1% of strabismic patients. Three types have been described and the clinical features include incomitant horizontal strabismus, restricted motility and globe retraction. Head turn, upshoot or downshoot of the adducted eye, and bilaterality may occasionally be present. Since strabismus is invariably present in DRS, careful assessment of extraocular motility should be performed on all children with a suspected or confirmed eye turn. Early diagnosis may save practitioners and parents hours of time and financial investment with orthoptic and surgical management attempts. A case of DRS is presented.

Alcohol amblyopia.

Alcohol amblyopia is a disorder that affects a small percentage of alcoholic patients, most of whom are nutritionally deficient. A battery of tests is required to make the diagnosis including color vision and field testing. Once the diagnosis is made, physical, emotional, and visual rehabilitation should be undertaken. A case of alcohol amblyopia is presented along with optometric management techniques.