Oral psoralen with UV-A therapy releases circulating growth factor(s) that stimulates cell proliferation

BACKGROUND: The mechanism by which oral psoralen with UV-A (PUVA) stimulates melanocyte proliferation in vitiligo is unknown. This study was conducted to examine the hypothesis that it does so by stimulating the release of growth factors that stimulate melanocyte proliferation. DESIGN: We examined the effect of serum samples obtained from patients with vitiligo before and following 2 and 4 months of PUVA therapy, and from non-PUVA-treated patients with vitiligo and normal individuals on the growth of melanocytes in vitro. SETTING: Outpatient clinic in referral center. PATIENTS: The study was conducted on serum samples obtained from 18 patients with vitiligo, 8 of whom were treated with PUVA, and from 10 normal individuals. INTERVENTION: Treatment with PUVA. MAIN OUTCOME MEASURE: Ability of serum samples to stimulate the growth of melanocytes in culture. RESULTS: Proliferation of melanocytes in serum collected after 4 months of PUVA therapy was on the average 3-fold greater than that in serum samples collected from the same patients prior to therapy with PUVA. This circulating growth factor was absent in serum samples of non-PUVA-treated patients with vitiligo and normal individuals. The effect was nonspecific, as it also stimulated the proliferation of fibroblasts. CONCLUSIONS: These findings suggest that PUVA treatment results in the release into the circulation of growth factor(s) that can stimulate a proliferation of melanocytes and of other cells. This could account for the repigmentation of vitiligo by PUVA treatment. As the growth factor(s) also stimulated the growth of other cells, it could also explain the thickening of the epidermis that occurs following exposure to UV light.     

Inactivation of leukocytes in platelet concentrates by photochemical treatment with psoralen plus UVA

A photochemical treatment (PCT) process using a novel psoralen and long wavelength ultraviolet light (UVA, 320-400 nm) has been developed to inactivate bacteria and viruses in platelet concentrates. This study evaluated the efficacy of PCT for inactivation of leukocytes that contaminate platelet preparations. Three psoralens, 8-methoxypsoralen (8-MOP), 4'-aminomethyl 4,5', 8-trimethylpsoralen (AMT), and the novel psoralen S-59, were compared using the following four independent but complementary biological and molecular assays. (1) T-cell viability: Treatment with 150 mumol/L S-59 and 1.0 to 3.0 Joules/cm2 UVA inactivated >5.4 +/- 0.3 log10 of T cells in full-sized single-donor plateletpheresis units. Using 1.0 Joule/cm2 UVA, the lowest dose of S-59, AMT and 8-MOP required to reduce the number of T cells to the limit of detection was 0.05 micromol/L, 1.0 micromol/L, and 10.0 micromol/L, respectively. (2) Cytokine synthesis: Treatment with 1.9 Joules/cm2 UVA and 150 micromol/L S-59 or AMT completely inhibited synthesis of the cytokine IL-8 by contaminating leukocytes during 5 days of platelet storage. After treatment with 75 micromol/L 8-MOP and 1.9 Joules/cm2 UVA, only low levels of IL-8 were detected. (3) Psoralen-DNA adduct formation: The combination of 1.9 Joules/cm2 UVA and 150 micromol/L S-59, AMT, or 8-MOP induced 12.0 +/- 3.0, 6.0 +/- 0. 9, and 0.7 psoralen adducts per 1,000 bp DNA, respectively. (4) Replication competence: Polymerase chain reaction (PCR) amplification of small genomic DNA sequences (242-439 bp) after PCT was inhibited. The degree of PCR amplification inhibition correlated with the level of adduct formation (S-59 > AMT > 8-MOP). In contrast, 2,500 cGy gamma radiation, a dose that inactivates >5 log10 of T cells in blood products, had minimal effect on cytokine synthesis and did not induce sufficient DNA strand breaks to inhibit PCR amplification of the same small DNA sequences. These results demonstrate that leukocytes are sensitive to PCT with psoralens and among the psoralens tested S-59 is the most effective. Therefore, PCT has the potential to reduce the incidence of leukocyte-mediated adverse immune reactions associated with platelet transfusion.     

Treatment of periocular capillary hemangioma with topical clobetasol propionate

BACKGROUND: Hemangiomas pose a therapeutic challenge because they can threaten vision in infancy and early childhood. Intralesional injection of corticosteroid is widely regarded as the treatment of choice for hemangiomas which induce strabismus or significant refractive error, or occlude the visual axis. Ocular and systemic complications such as eyelid necrosis, central retinal artery occlusion, and adrenal suppression have been reported rarely after corticosteroid injection. METHODS: Three infants were treated with clobetasol propionate (Temovate) cream for vision-threatening eyelid hemangiomas. RESULTS: Treatment with this topical fluorinated corticosteroid produced a measurable reduction in the size of the hemangiomas, which permitted clearing of the visual axis. No regional side effects were noted. In addition, the patients did not demonstrate evidence of hypothalamic-pituitary-adrenal axis suppression. CONCLUSIONS: This treatment modality appears to provide an additional alternative for managing superficial periocular hemangiomas which threaten vision.     

Substitution of equally carcinogenic UV-A for UV-B irradiations lowers epidermal thymine dimer levels during skin cancer induction in hairless mice

Cyclobutane pyrimidine dimers (CPD) are the predominant DNA lesions induced by UV-B radiation, among these lesions thymine dimers are most frequent. Although UV-A radiation may also induce CPD, it has been found that equally cytotoxic or equally mutagenic UV-A and UV-B doses do not induce equal amounts of CPD, indicating that other DNA adducts contribute to the UV-A effects. Thus far it has not been established whether this finding can be extrapolated and also holds true for the more complex biological endpoint of skin cancer. Therefore, we compared thymine dimer levels during skin cancer induction by combined UV-A and UV-B daily exposures with the levels from equally carcinogenic daily UV-B exposures. From control experiments it was known that both groups would react similarly regarding the occurrences of carcinomas, with a median latency time of 170 +/- 10 days. After 50, 106 and 151 days of irradiation eight hairless mice (SKH:HR1) from both groups were euthanized and thymine dimers in epidermal cell suspensions were quantified by flow cytometry. Staining on DNA content enabled us to quantify thymine dimers in G0/G1-phase, in S-phase and in G2M-phase subpopulations. Both in total epidermal cell populations and in subpopulations of replicating epidermal cells thymine dimer levels were significantly lower in the UV-A/B combination group than in the UV-B group (0.010 < P < 0.025 and P < 0.005 respectively). This indicates that the carcinogenicity of UV-A relative to that of UV-B is not properly measured by thymine dimers and that other DNA lesions than CPD, for example, from reactive oxygen species, are likely to contribute to UV-A carcinogenicity.     

In vitro photoinhibition by psoralen and ultraviolet A radiation of human hematopoietic progenitors

The in vitro sensitivity of human hematopoietic progenitors to PUVA, 8-MOP and UVA alone was investigated. 8-MOP alone at final concentrations of 150, 200, 600 and 1,000 ng/ml did not modify colony growth of circulating and bone marrow erythroid (BFU-E), myeloid (CFU-GM) and immature (CFU-GEMM) hematopoietic progenitors obtained from normal controls. The exposure of the same progenitors to increasing doses of UVA, up to 12 J/cm2, progressively decreased hematopoietic colony growth (with estimated 50% inhibition occurring at about 5 J/cm2). In vitro PUVA treatment (8-MOP 200 ng/ml followed by UVA 5 J/cm2) caused 90% growth inhibition of circulating and bone marrow hematopoietic progenitors. In addition, the treatment completely inhibited the formation of spontaneous erythroid colonies, obtained from 5 polycythemic patients, that are considered to be a marker of this neoplastic disease. PUVA cytotoxicity was assessed by the colorimetric MTT assay. The percentage of cell death after PUVA exposure was 29 +/- 10% for both peripheral and bone marrow mononuclear cells. Our findings indicate that 8-MOP alone is not toxic to hematopoietic progenitors whereas UVA treatment determines in vitro a dose-dependent inhibition of the clonogenic capacity of normal hematopoietic cells. PUVA treatment enhances this effect, causing a quite complete inhibition of hematopoietic progenitors colony formation from normal donors and spontaneous BFU-E colony formation from polycythemic patients.     

Treatment of Herpes simplex virus infections with topical antiviral agents

Clinical studies of topical therapy against Herpes simplex virus (HSV) infections have been reviewed. Idoxuridine (IDU) 15% in dimethyl sulfoxide (DMSO), interferons, and penciclovir result in significant clinical benefit against this virus. IDU reduced pain duration and decreased time to loss of crust in a study of 301 patients. Alpha-interferon has shown synergism with other anti-HSV drugs such as caffeine, trifluorothymidine (TFT), DMSO, and nonoxynol-9. Finally, in a study of over 2,000 patients, application of penciclovir cream, both early and late in the course of HSV infection, decreased the duration of lesions, pain, and viral shedding. Acyclovir (ACV)-resistant strains of HSV are susceptible to (S)-1-(3-hydroxy-2-phosphonylmethoxypropyl) cytosine (HPMPC), and ascorbic acid shows promising effects against HSV. Using a vehicle that enhances skin penetration of a drug or possibly further exploring combination therapy may result in efficacious treatment of HSV. The possibility of topical vaccination or topical gene therapy may also prove beneficial in the future.     

Treatment of photodamaged skin with topical tretinoin: an update

The utility of topical tretinoin in combination with sun protection has now been formally established as a useful approach to the treatment of sun-damaged skin. The early observations of our group have been confirmed in numerous well controlled clinical trials. Moreover, a great deal is known about structural and even molecular changes induced by topical tretinoin, which account for the clinical benefits achieved by this agent. A great deal has been learned in a very short period of time, and these findings represent another major use of retinoid therapy in dermatologic disease.     

Changes in serum levels of sialoglycoproteins in mice exposed to UV-B radiation

In the acute phase reaction, hepatocytes in the liver are activated and increase the plasma levels of acute phase reactants. Our previous study has shown that plasma sialic acid, an acute phase reactant, was increased following exposure of mice to UV-B radiation. Plasma sialic acid is derived from many plasma components. To clarify the type of plasma sialic acid that is increased by exposure to UV-B radiation, we performed two-dimensional electrophoresis and staining for sialic acid. Consequently, the increases in haptoglobin and hemopexin were marked and 90% or more of the increased sialic acid was derived from these two glycoproteins after exposure to UV radiation. The increase in alpha1-acid glycoprotein levels was slight and did not contribute to the total increase in plasma sialic acid after exposure to UV radiation. Plasma levels of several proteins including antichymotrypsin (ACT), were reduced following exposure to UV radiation. The discrepancy between our results and published ones regarding ACT levels are discussed in terms of the type of cytokine.     

Involvement of plasma membrane redox activity and calcium homeostasis in the UV-B and UV-A/blue light induction of gene expression in Arabidopsis

UV and blue light are important regulators of plant gene expression and development. We investigated the signal transduction processes involved in the induction of chalcone synthase (CHS) and phenylalanine ammonia-lyase (PAL) gene expression by UV-B and UV-A/blue light in an Arabidopsis cell suspension culture. Experiments with electron transport inhibitors indicated that plasma membrane redox activity is involved in both signal transduction pathways. Calcium ionophore treatment stimulated expression of the TOUCH3 gene, and this induction was strongly antagonized by UV-A/blue and UV-B light, suggesting that both light qualities may promote calcium efflux from the cytosol. Consistent with this hypothesis, experiments with specific inhibitors indicated that UV-B and UV-A/blue light regulate calcium levels in a cytosolic pool in part via the action of specific Ca2+-ATPases. On the basis of these and previous findings, we propose that plasma membrane redox activity, initiated by photoreception, is coupled to the regulation of calcium release from an intracellular store, generating a calcium signal that is required to induce CHS expression.     

Treatment of proctalgia fugax with topical nitroglycerin: report of a case

PURPOSE: We report a single case of proctalgia fugax that responded to 0.3 percent nitroglycerin ointment. METHODS: Case report. RESULTS: A single case of proctalgia fugax responded to topical application of 0.3 percent nitro glycerin ointment with no significant side effects. CONCLUSIONS: Nitroglycerin ointment is a newly described treatment for several painful anal conditions. We describe a single case of levator spasm or proctalgia fugax responding to topical application of nitroglycerin. This is only a single case report, and conclusive evidence awaits completion of a controlled clinical trial.     

Treatment of warts with topical pyruvic acid: with and without added 5-fluorouracil

Numerous studies have suggested that epilepsy and asthma may be related conditions. There has, however, been little epidemiologic data published to support this association. We conducted a retrospective study to determine whether the prevalence of epilepsy is increased among children with asthma, and the prevalence of asthma is increased among children with epilepsy, in comparison with the general pediatric population. We reviewed the medical records, at a large city hospital, of two groups of pediatric outpatients: (1) 400 consecutive patients with asthma followed regularly at the asthma and allergy clinic; and (2) 201 consecutive patients with idiopathic epilepsy followed regularly at the pediatric neurology clinic. Patients with a history of birth prior to 36 weeks' gestational age were excluded. Among the 400 cases of asthma, there were three patients with idiopathic epilepsy (prevalence of 0.75%). The prevalence of epilepsy was similar in mild (0.79%) and moderate-to-severe (0.73%) asthma. Among the 201 cases of idiopathic epilepsy, there were 12 patients with asthma (prevalence of 5.97%). Similar percentages of epilepsy patients with and without asthma reported generalized tonic-clonic, complex partial, simple partial, and myoclonic seizures as their predominant type. The prevalence values in this study are consistent with the prevalence of epilepsy and asthma in the general pediatric population. Our findings therefore suggest that idiopathic epilepsy and asthma are not etiologically related or mutually predisposing conditions. Small samples, failure to exclude patients born prematurely, and the equation of electroencephalographic (EEG) abnormalities with epilepsy may account for the results of previous studies.     

Evaluation of structurally different carotenoids in Escherichia coli transformants as protectants against UV-B radiation

Escherichia coli cells transformed with several carotenogenic genes to mediate the formation of zeta-carotene, neurosporene, lycopene, beta-carotene, and zeaxanthin were exposed to UV-B radiation. Short-term kinetics revealed that endogenous levels of neurosporene and beta-carotene protected E. coli against irradiation with UV-B. Zeaxanthin protected against only the photosensitized UV-B treatment. All other carotenoids were ineffective.     

Treatment of rosacea: topical clindamycin versus oral tetracycline

BACKGROUND: A new topical antibiotic preparation, clindamycin in a lotion base, was compared with oral tetracycline in the treatment of rosacea. Forty-three patients clinically diagnosed as having rosacea were examined in an investigator-blinded study. METHODS: Patients used topical clindamycin lotion applied twice daily or the usual oral dose of tetracycline hydrochloride (250 mg four times a day for 3 weeks, then 250 mg twice a day for the remaining 9 weeks). Patients' lesions were examined clinically at 3-week intervals over a period of 12 weeks. RESULTS: Topical clindamycin treatment produced similar clinical results to oral tetracycline and was superior in the eradication of pustules. CONCLUSIONS: These results show topical clindamycin in a lotion base to be a safe and effective alternative to oral tetracycline therapy in the treatment of rosacea.     

调强放疗结合腔内放疗同步化疗治疗中晚期宫颈癌的临床观察

目的 研究调强放疗、腔内治疗并同步化疗治疗中晚期(IIB-ⅢB)宫颈癌的疗效及毒副反应.方法 选择宫颈癌患者60例,随机分为调强组(调强放疗,腔内放疗结合同步化疗,30例),常规组(常规四野箱式外照射,腔内放疗结合同步化疗,30例).治疗方法:调强组给予56～60 Gy剂量,常规组予50～54 Gy盆腔照射.腔内放疗:A点给予5 Gy/次,2次/周,共6～8次.所有病人接受多西他赛和顺铂同步化疗,每3周一次,共3个疗程.比较临床疗效和急性、晚期毒副反应.结果 两组病人资料类似.中位随访时间是47个月.调强组与常规组的1,2,3年生存率分别为90.0%,86.7%,80.0%以及86.7%,70.0%,60.0%;两组比较差异没有显著性(P>0.05).调强组中有7例(23.33%)患者复发,常规组有17例(56.67%)复发,两组比较差异有统计学意义(P＜0.05).常规组中3,4级急性和晚期消化道反应和泌尿道反应的发生率比调强组高,差异有统计学意义(P＜0.05).血液骨髓毒副反应的比较,两组结果相似.结论 调强放疗结合腔内放疗并同步多西他赛、顺铂化疗,是治疗局部晚期宫颈癌有效的方法.     

Treatment of non-extractable common bile duct stones with combination ursodeoxycholic acid plus endoprostheses

To assess the effect of timing of human chorionic gonadotrophin (HCG) administration in ovarian stimulation cycles, the serum oestradiol concentration and follicle profile were compared with the clinical pregnancy rate in 582 ovarian stimulation-intra-uterine insemination (OS-IUI) cycles and 3917 in-vitro fertilization-embryo transfer (IVF-ET) cycles. The pregnancy rates increased exponentially with increasing oestradiol in both OS-IUI and IVF-ET cycles (R2 = 0.720, P < 0.001) but then decreased in OS-IUI cycles when the oestradiol concentration exceeded 5000 pmol/l (R2 = 0.936, P < 0.004) at HCG administration. In OS-IUI cycles the percentages of cycles with three or more mature follicles (> or = 18 mm diameter) increased up to an oestradiol concentration of 5000 pmol/l then declined, mirroring the pregnancy rate (R2 = 0.900, P = 0.01). The exponential increase in pregnancy rate with increasing oestradiol concentration in IVF-ET cycles suggests that high oestradiol concentration does not have a deleterious effect on endometrial receptivity. The decrease in pregnancy rate in OS-IUI cycles when oestradiol concentration exceeded 5000 pmol/l reflected fewer mature follicles, resulting from premature administration of HCG to avoid severe ovarian hyperstimulation syndrome (OHSS). We recommend that HCG administration be delayed until multiple follicles have reached maturity, and reducing the risk of severe OHSS by converting high risk OS-IUI cycles to IVF-ET, or if funds or facilities are unavailable, transvaginally draining all but four or five mature follicles.     

Malignant melanoma in patients treated for psoriasis with methoxsalen (psoralen) and ultraviolet A radiation (PUVA). The PUVA Follow-Up Study

BACKGROUND: Photochemotherapy with oral methoxsalen (psoralen) and ultraviolet A radiation (PUVA) is an effective treatment for psoriasis. However, PUVA is mutagenic, increases the risk of squamous-cell skin cancer, and can cause irregular, pigmented skin lesions. We studied the occurrence of melanoma among patients treated with PUVA. METHODS: We prospectively identified cases of melanoma and documented the extent of exposure to PUVA among 1380 patients with psoriasis who were first treated with PUVA in 1975 or 1976. Using incidence data, we calculated the expected incidence of melanoma in this cohort and compared it with the observed incidence. Using regression models, we assessed the risks of melanoma associated with a long time (> or = 15 years) since the first treatment and with a large number of PUVA treatments (> or = 250). RESULTS: From 1975 through 1990, we detected four malignant melanomas, about the number expected in the overall population (relative risk, 1.1). From 1991 through 1996, we detected seven malignant melanomas (relative risk, 5.4; 95 percent confidence interval, 2.2 to 11.1). The risk of melanoma was higher in the later period than in the earlier one (incidence-rate ratio, 3.8) and higher among patients who received at least 250 PUVA treatments than among those who received fewer treatments (incidence-rate ratio, 3.1). CONCLUSIONS: About 15 years after the first treatment with PUVA, the risk of malignant melanoma increases, especially among patients who receive 250 treatments or more.     

Narrowband UV-B produces superior clinical and histopathological resolution of moderate-to-severe psoriasis in patients compared with broadband UV-B

OBJECTIVE: To compare the therapeutic effectiveness of daily exposure to narrowband (NB) UV-B vs broadband (BB) UV-B with and without tar. DESIGN: Half-body exposures to NB UV-B or BB UV-B were given daily for 4 weeks in this comparative treatment study. Narrowband UV-B was delivered from TL-01 fluorescent bulbs and BB UV-B from conventional bulbs in the same phototherapy cabinet. Narrowband UV-B was compared using a paired treatment approach to BB UV-B above the waist and to BB UV-B with tar (Goeckerman treatment) below the waist. SETTING: General clinical research center of a university hospital inpatient unit. PATIENTS: Twenty-two patients with moderate-to-severe plaque-type psoriasis completed the study. MAIN OUTCOME MEASURES: Clinical efficacy was measured weekly using psoriasis severity scoring. Therapeutic outcomes after 4 weeks were compared in paired biopsy samples from treated lesions using objective histopathological measures (quantitative reduction in epidermal acanthosis and keratin 16 expression). RESULTS: Clinical resolution of psoriasis was achieved on 86% of paired sites treated with NB UV-B vs 73% treated with BB UV-B. Histopathological resolution of epidermal hyperplasia (marked by keratin 16 expression) was achieved in 88% of lesions treated with NB UV-B vs 59% treated with BB UV-B. Epidermal acanthosis was reduced more completely by NB UV-B treatment. Clinical resolution of psoriatic lesions occurred more rapidly following NB UV-B treatment, with some patients achieving complete resolution after 2 to 3 weeks of treatment. CONCLUSIONS: Narrowband UV-B offers a significant therapeutic advantage over BB UV-B in the treatment of psoriasis, with faster clearing and more complete disease resolution. The erythema response to NB UV-B treatment was significantly more intense and persistent compared with BB UV-B. Considerably more necrotic keratinocytes were observed in histopathological sections of skin treated with NB UV-B after a single 2.0-minimum erythema dose exposure. Treatment should be coupled with obligate minimum erythema dose testing to NB UV-B and close clinical observation during dose increases.     

Circulating skin-homing T cells in atopic dermatitis. Selective up-regulation of HLA-DR, interleukin-2R, and CD30 and decrease after combined UV-A and UV-B phototherapy

BACKGROUND: As the cutaneous lymphocyte-associated antigen appears to detect circulating T cells that migrate to the skin in atopic dermatitis but not T cells that migrate to mucosal sites in allergic asthma and rhinitis, we investigated T-cell activation markers and CD30 on the cutaneous lymphocyte-associated antigen-positive circulating T-cell subset in atopic dermatitis to see whether these markers are different from those in normal controls and related to disease activity. DESIGN: Open study. SETTING: University referral center. PATIENTS: Twelve patients with atopic dermatitis and 12 healthy controls. INTERVENTION: Combined UV-A and UV-B treatment for 2 months. MAIN OUTCOMES MEASURES: Percentage of circulating cutaneous lymphocyte-associated antigen-positive T cells that express HLA-DR, interleukin-2 receptor, CD69, CD71, and CD30 (triple-color flow cytometric analysis). Clinical score, Dermatology Life Quality Index, pruritus score, and consumption of topical corticosteroids were determined. RESULTS: Increased relative numbers of cutaneous lymphocyte-associated antigen-positive T cells expressing HLA-DR, interleukin-2 receptor, and CD30 were found in patients with atopic dermatitis before treatment. Treatment with UV-A and UV-B was associated with clinical improvement and a decrease of levels of HLA-DR, interleukin-2 receptor, and CD30 in cutaneous lymphocyte-associated antigen-positive T cells. HLA-DR on cutaneous lymphocyte-associated antigen-positive T cells correlated significantly with the clinical score. CONCLUSION: Expression of HLA-DR and interleukin-2 receptor is a sensitive marker of disease activity in atopic dermatitis. Apart from giving information on disease activity in atopic dermatitis, the availability of skin-seeking T cells in the blood offers the opportunity to obtain further information on T cells that may have effector function in the skin.     

Treatment of mucosa-associated lymphoid tissue lymphoma of the stomach with radiation alone

PURPOSE: Mucosa-associated lymphoid tissue (MALT) lymphoma of the stomach (MLS) has recently been defined as a distinct clinicopathologic entity, often associated with Helicobacter pylori infection. Many regard antibiotic therapy as the primary treatment of MLS, but in the absence of H pylori infection, or when salvage of antibiotic failures is required, gastrectomy and/or chemotherapy have frequently been used. This study evaluates the efficacy of low-dose radiotherapy alone as an alternative to surgery. PATIENTS AND METHODS: Seventeen patients with stage I to II(2) low-grade MLS without evidence of H pylori infection or with persistent lymphoma after antibiotic therapy of associated H pylori infection were included in this series. Median age was 69 years (range, 39 to 84). Median total radiation dose was 30 Gy (range, 28.5 to 43.5 Gy) delivered in 1.5-Gy fractions within 4 weeks to the stomach and adjacent lymph nodes. Following treatment, all patients underwent endoscopic evaluation and biopsy at a median of 4 months, at 6-month intervals to 2 years, and annually thereafter. RESULTS: All obtained a biopsy-confirmed complete response. At a median follow-up time of 27 months (range, 11 to 68) from completion of radiotherapy, event-free survival was 100%. Treatment was well tolerated, with no significant acute side effects. All remained asymptomatic at last follow-up. CONCLUSION: These results suggest that effective treatment of MLS with low-dose radiation therapy alone is feasible and safe, and allows stomach preservation. Longer follow-up evaluation is required to determine the long-term efficacy of this treatment approach and its side effects. Further studies should clarify the indications for radiotherapy in H pylori-negative or antibiotic-resistant cases of MLS.