The neuronal marker protein gene product 9.5 (PGP 9.5) is phenotypically expressed in human breast epithelium, in milk, and in benign and malignant breast tumors

The aim of this study was to examine the expression of the well-established neuronal marker protein gene product 9.5 (PGP 9.5) in nonneuroendocrine tissues of the human breast. Using antibodies directed against PGP 9.5 in an immunohistological technique, a positive staining of nerves and, surprisingly, a positive cytoplasmic reaction were obtained in normal breast epithelium, in all cases of fibroadenomata (n = 7) and in carcinoma cells in 5 out of 16 cases of breast cancers. In screening several human breast cancer cell lines, a positive immunoreaction was observed in 4 out of 6 of the cell lines. To exclude the possibility that this immunoreactivity was false, positive lysates from the same cell lines and preparations from human breast milk were subjected to NaDodSO4-polyacrylamide gel electrophoresis and Western blotting. This study confirmed the presence of PGP 9.5 in both milk and breast cancer cell lines. Because any contamination with nerve fibers can be excluded having used cell culture material or milk, it can be concluded that the presence of PGP 9.5 in the normal epithelium and in breast cancer cells is genuine. PGP 9.5 expression is, therefore, a feature of normal breast epithelia and breast cancer cells and cannot be regarded as 'neuron' specific.     

Affinity and selectivity of PD156707, a novel nonpeptide endothelin antagonist, for human ET(A) and ET(B) receptors

6-Thioguanine (6TG) a cytostatic antimetabolite is currently used to treat patients with cancer, in particular leukemias. However, one drawback of such use is the development of 6TG resistance. Hypoxanthine-guanine phosphoribosyl transferase (Hprt) plays a crucial role in the bioactivation of 6TG. Loss of Hprt has been associated with the resistance of leukemias to 6TG chemotherapy, however, nothing has been known about the effect of Hprt status on tissue specific toxicity of 6TG in vivo. We determined the effect of Hprt status on the tissue-specific toxicity of 6TG in vivo in transgenic Hprt-deficient mice. The approximate lethal dose for Hprt-deficient mice was 23-fold higher than for the wild-type. Serum biochemical analyses of 6TG-treated wild-type mice showed elevated serum enzyme levels characteristic of liver damage whereas the levels in Hprt-deficient 6TG-treated mice were within normal physiological limits. Histopathological examination of tissues from wild-type and from Hprt-deficient mice showed contrasting spectrums of microscopic lesions. Wild-type mice had loss of hematopoietic cells from bone marrow starting at the lowest dose of 25 mg/kg 6TG whereas Hprt-deficient mice had normal bone marrow and spleen even at doses of 720 mg/kg 6TG. Wild-type mice also experienced severe loss of epithelial cells from the gastrointestinal tract starting at 50 mg/kg; however, the gastrointestinal tract of Hprt -/- mice remained unaffected. Wild-type livers revealed atrophy and necrosis at doses of 25 mg/kg 6TG although Hprt -/- livers displayed no effect until 507 mg/kg. In this study we show that Hprt-deficient mice had 6TG-resistant bone marrow and there are several other factors contributing to 6TG resistance in patients. Because variations among people exist in terms of their 6TG sensitivity, determining 6TG sensitivity of lymphocytes prior to 6TG chemotherapy and restricting treatment to 6TG-sensitive patients may improve the efficacy.     

Recognition of a 31,000 molecular weight protein synthesized by the mussel Mytilus galloprovincialis Lmk. during Dinophysis spp. algal bloom in the Gulf of Trieste (upper Adriatic Sea)

OBJECTIVES: To demonstrate gastroesophageal reflux induced by proximal gastrectomy and to report preventive measures, such as total gastrectomy followed by Roux-en-Y esophagojejunostomy. METHODS: Thirteen patients underwent proximal gastrectomy (PG), and six patients underwent total gastrectomy (TG). Two of the 13 patients who received PG later underwent completion total gastrectomy. All patients were followed with endoscopy, radionuclide scintigraphy, and 24-h pH monitoring. RESULTS: Endoscopic examination revealed evidence of esophagitis in all PG group patients; however, none of the TG group had esophagitis. Prolonged esophageal transit was observed in 11 patients (10 in the PG group, one in the TG group). Increased residual fraction was found in 10 patients (nine in the PG group, one in the TG group). An increase in the retrograde index was found in 14 cases (11 in the PG group, three in the TG group). Positive enterogastroesophageal reflux was identified in 11 patients (eight in the PG group, three in the TG group). Twenty-four hour pH monitoring resulted in 10 positives (10 in the PG group, none in the TG group). CONCLUSIONS: Frequently, proximal gastrectomy will lead to significant gastroesophageal reflux and, subsequently, to varying degrees of esophagitis. The clinical symptoms are usually characteristic. However, the severity of esophagitis and the mechanism of reflux can be determined only by integrated interpretation of a reflux study. The study should include endoscopy, radionuclide scintigraphy, and 24-h pH monitoring. Although a total gastrectomy with Roux-en-Y diversion can reduce the incidence of acid reflux, neutral enteroesophageal reflux may be observed during a radioactive isotope study. Fortunately, neutral refluxes rarely cause esophagitis. A proximal gastrectomy should be avoided in adenocarcinoma of the gastric cardia, except in early cancer. Symptomatic palliation can be relieved by medication. However, completion total gastrectomy is the only effective method for eradicating unrelenting symptoms.     

Plasma interleukin-6 is not a mediator of changes in lipoprotein lipase activity in cancer patients

BACKGROUND/AIMS: Cancer cachexia is characterized by a variety of metabolic disorders. Alterations in fat metabolism have been reported to be associated with suppression of tissue lipoprotein lipase (LPL) activity in tumor-bearing animals. Interleukin-6 (IL- 6) has been documented to reduce tissue LPL activity and may play a role in inducing cancer cachexia. This study was conducted to clarify the changes in LPL activity and the role of IL-6 in patients with either gastrointestinal cancer or breast cancer. METHODOLOGY: Twelve patients with colorectal cancer, 7 patients with gastric cancer, 7 patients with breast cancer and 5 normal volunteers were studied. Serum concentrations of triglycerides (TG), non-esterified fatty acids (NEFA) and IL-6 were measured. LPL activity was measured in plasma post-heparin administration. The relationships of LPL activity to tumor progression, body weight loss and serum IL-6 levels were examined. The effect of tumor resection on LPL activity was also studied. RESULTS: LPL activity was suppressed with tumor progression in patients with either gastrointestinal cancer or breast cancer. Suppression of LPL activity and the degree of weight loss were negatively correlated in patients with either gastric or colorectal cancer (r = -0.5826, p = 0.011) but not in patients with breast cancer. The decrease in LPL activity was not always reversed after resection of the tumor. Circulating IL-6 did not correlate with either plasma LPL activity or tumor progression. CONCLUSIONS: Reduced LPL activity in patients with advanced gastrointestinal or breast cancer may reflect changes in nutritional status. Serum IL-6 is less likely to be a mediator of these alterations.     

Skin-sparing mastectomy. Oncologic and reconstructive considerations

OBJECTIVE: The authors compared skin-sparing mastectomy and traditional mastectomy both followed by immediate reconstruction in the treatment of breast cancer. SUMMARY BACKGROUND DATA: Skin-sparing mastectomy is used increasingly in the treatment of breast cancer to improve the aesthetic results of immediate reconstruction. The oncologic and reconstructive outcomes of this procedure have never been analyzed closely. METHODS: Institutional experience with 435 consecutive patients who underwent total mastectomy and immediate reconstruction from January 1989 through December 1994 was examined. Mastectomies were stratified into skin-sparing (SSM) and non-skin-sparing (non-SSM) types. RESULTS: Three hundred twenty-seven SSMs and 188 non-SSMs were performed. The mean follow-up was 41.3 months (SSM, 37.5 months, non-SSM, 48.2 months). Local recurrences from invasive cancer occurred after 4.8% of SSMs versus 9.5% of non-SSMs. Sixty-five percent of patients who underwent SSMs had nothing performed on the opposite breast versus 45% in the group of patients who underwent non-SSM (p = 0.0002). Native skin flap necrosis occurred in 10.7% of patients who underwent SSMs versus 11.2% of patients who underwent non-SSMs. CONCLUSIONS: Skin-sparing mastectomy facilitates immediate breast reconstruction by reducing remedial surgery on the opposite breast. Native skin flap necrosis is not increased over that seen with non-SSM. Skin-sparing mastectomies can be used in the treatment of invasive cancer without compromising local control.     

Radiation treatment decreases transforming growth factor alpha expression in squamous carcinoma of the tongue

Ionizing radiation (XRT) is often used to treat squamous cell carcinoma of the tongue (SCCT) but little is known of its genetic effects on surviving cancer cells. The effect of XRT on p53, epidermal growth factor receptor (EGFR), and transforming growth factor alpha (TGF alpha) tumor marker expression was evaluated using immunohistochemical analysis in 79 patients with SCCT. Sixty-six patients received no radiation, while 13 received XRT before surgery. Radiation did not influence EGFR or p53 expression. TGF alpha expression, however, was significantly decreased in radiated tumors (15% versus 43%, P = 0.04). These data suggest that XRT either decreases the expression of TGF alpha in SCCT (suggesting a genetic alteration in surviving cancer cells), or does not kill cancer cells with decreased TGF alpha expression. In the latter case, diminished TGF alpha expression may serve as a marker of radioresistance.     

The E7 protein of human papillomavirus (HPV) type 16 expressed by recombinant vaccinia virus can be used for detection of antibodies in sera from cervical cancer patients

PURPOSE: The objective of this study was to assess the complications and efficacy of gastrostomy (GT) feedings in pediatric cancer patients. PATIENTS AND METHODS: We reviewed the medical records of 33 pediatric cancer patients who received enteral nutrition via a GT. RESULTS: Median age was 9.4 years (range, 1-19.8 years), and 28 of the 33 patients had solid tumors. Seventeen patients had a significant weight loss (median, 8.5%) and therapy-related weight loss was anticipated in 16 patients. The GT device was placed an average of 5.5 months after diagnosis. Twenty-five patients were fed via a tube and eight via a button device. The tube was placed surgically in 21 cases (including all eight button types) and endoscopically in 12. Nutritional support lasted a median of 9.5 months. One or more complications occurred in 30 patients and were categorized as (a) insertion site reactions (inflammation, 23; infection/colonization, 14; exuberant granulation tissue, 6); (b) mechanical problems (leaking, 3; obstruction, 2; breakage, 1; accidental dislodgement, 2); (c) insertion site bleeding, 8; and (d) feeding intolerance, 12. Only one insertion site cellulitis progressed to a systemic infection. All eight patients with a button GT experienced insertion site complications, with local infection occurring significantly more often in patients with the button than in those with the tube GT. There were no significant associations between insertion technique and type of complication. Twenty-seven patients (82%) achieved or maintained ideal body weight with this intervention. CONCLUSIONS: GT feeding was associated with minor complications, but permitted effective nutritional support for pediatric cancer patients.     

Control of clofibrate toxicity in uremic hypertriglyceridemia

A daily dose of 1.5 to 2.0 gm of clofibrate lowers serum triglyceride (TG) levels in patients with normal renal function but causes muscle toxicity and elevated creatine phosphokinase (CPK) levels in patients with long-term renal failure. Plasma clofibrate disappearance is prolonged as much as seven times normal in severely uremic patients. A marked reduction in the standard 14 gm/wk clofibrate dose to a total dose of 1.0 to 1.5 gm/wk effectively lowered serum TG levels (--28%, p less than 0.02) in hypertriglyceridemic hemodialysis patients without toxicity. The serum clofibrate level at this dose was comparable to that in hypertriglyceridemic nonuremic patients receiving 14 gm/wk of clofibrate. The dose of clofibrate administered to hemodialysis patients can be adjusted to avoid toxicity and provide the desired therapeutic effect by monitoring serum CPK and TG levels.     

Metabolic disposition of antipyrine in patients with lung cancer

The metabolism of antipyrine (10 mg/kg i.v.) was studied in nine patients with cancer of the lung and in a cancer-free control group matched for age, sex, drug intake, and smoking and drinking history. The mean plasma clearance of antipyrine was 0.0475 +/- 0.009 liter/kg/hr in the tumor group and 0.0557 +/- 0.007 liter/kg/hr in the control group (p greater than 0.05). The antipyrine plasma elimination half-life was longer in the group with tumors (9.5 +/- 1.3 hr) compared to the control group (7.7 +/- 1.3 hr), but the difference was not statistically significant (p greater than 0.05). There was no difference between the groups in the excretion of two major antipyrine metabolites, 4-hydroxyantipyrine and N-demethylantipyrine, in a 48-hr urine sample. Thus, the presence of lung cancer in humans does not significantly alter antipyrine elimination.     

Relationship between insulin secretory function and endogenous hypertriglyceridemia in obese humans with insulin resistance

Eighteen obese inpatients with insulin resistance revealed by i.v. insulin test and expressed in various grades of hyperinsulinemia and hyperglycemia were examined for plasma lipid levels. A significant positive correlation was found to be present between the plasma triglyceride (TG) level and the insulin response to glucose load. A stepwise multiple regression analysis revealed that the insulin secretory response, the plasma cholesterol level and the relative body weight contributed to the level of plasma TG. No difference was found in the grades of insulin resistance between patients with and without elevated TG. The ratio of sum of plasma insulin values to that of blood glucose values during glucose tolerance test was markedly increased in patients with elevated TG. The patients with relatively blunted insulin response and impaired glucose tolerance curves showed only slight slight hypertriglyceridemia. Endogenous hypertriglyceridemia in obesity seems to be more closely correlated with plasma insulin level, and therefore, with insulin action rather than insulin resistance.     

Report of two cases presenting with myelodysplastic syndrome during treatment of recurrent breast cancer

Two women with recurrent breast cancer presenting with myelodysplastic syndrome (refractory anemia) during chemotherapy were reported. At diagnosis of myelodysplastic syndrome, white blood cell count, hemoglobin and platelet count were 3,300/mm3, 4600/mm3, 5.5 g/dl, 6.3 g/dl, 1.1 x 10(4)/mm3 and 6.8 x 10(4)/mm3, respectively, in case 1 and 2. Bone marrow taps showed hypercellular marrows with dysplastic changes of erythrocytes, granulocytes and megakaryocytes in both cases. Before the occurrence of the myelodysplastic syndrome, both patients received various cytotoxic agents (mitomycin C: 77 mg, 108 mg; cyclophosphamide: 34,400 mg, 40,000 mg; doxorubicin: 340 mg, 460 mg; methotrexate: 410 mg, 700 mg; and vincristine: 9.5 mg, 14 mg, in case 1 and 2, respectively). One patient died 2 months after the onset of the myelodysplastic syndrome, and the other died 3 months after due to progression of metastatic breast cancer. Risk-benefits analysis of chemotherapy, especially adjuvant chemotherapy, should be performed in cases of breast cancer.     

Neoadjuvant androgen deprivation preceding to radical prostatectomy--its role in short-term and long-term outcomes

Neoadjuvant androgen deprivation has been demonstrated to reduce the risk of surgical margin positivity and lymphnode metastasis, and facilitate a thorough prostatectomy. On the contrary, no long-term studies have proved the beneficial effects of preoperative therapy on patients' survival. A multicenter randomized study in Japan comparing neoadjuvant therapy and immediate surgery (control) was conducted. All the patients were to receive hormonal therapy for 2 years. The results confirmed the short-term efficacy of neoadjuvent hormonal treatment, and no significant difference in clinical relapse rate (5.6% (5/90) in neoadjuvant group versus 11.6% (10/86) in control group), nor PSA relapse rate (13.3% versus 17.4%) at 2 years posttreatment; however in stage C cancer there was a tendency of a lower clinical relapse rate in neoadjuvant group (9.5%: 2/21) than the control (30.4%: 7/23). These data provide no obvious evidence for favorable long-term outcomes in neoadjuvant group, although a possibility that stage C cancer benefits from the treatment remains to be explored.     

Cisplatin and epirubicin plus oral lonidamine as first-line treatment for metastatic breast cancer: a phase II study of the Southern Italy Oncology Group (GOIM)

Lonidamine (LND) is a unique antineoplastic drug derived from indazole-3-carboxylic acid which inhibits oxygen consumption and aerobic glycolysis, interfering with energy metabolism of neoplastic cells. LND has been experimentally shown to potentiate the cytotoxic effects of epirubicin (EPI) in human breast cancer cell lines, cisplatin activity in both platinum-sensitive and -resistant human ovarian carcinoma cell lines, and EPI antineoplastic activity in some recent phase III trials carried out in advanced breast cancer. A multicenter phase II trial was carried out with the combination of cisplatin 60 mg/m2, EPI 100 mg/m2 and LND 450 mg/day p.o. in three refracted doses/day starting 2 days before cisplatin and EPI (day -2 and -1), stopping 2 days after chemotherapy (day 0, +1 and +2). Thirty patients with metastatic breast cancer were enrolled into the study. Twenty-nine patients were evaluable for objective response. The overall response rate accordingly to an intent-to-treat analysis was 73% (95% CL 54-88%). Four patients achieved complete response (13%; 95% CL 4-31%) with a median duration of 9.5 months (range 4-16) and 18 patients had partial response (60%; 95% CL 41-77%) with a median duration of 9.8 months. Stable disease was obtained in five cases (17%) and progressive disease was recorded in three patients. One patient died of progressive cancer before restaging. The overall median survival of the whole series of patients was 14+ months. The most frequent toxicities were represented by gastrointestinal and hematological side effects. The combination of cisplatin + EPI plus oral LND is active against metastatic breast carcinoma. The antineoplastic activity of the cisplatin + EPI + LND regimen is as high as that reported for more aggressive regimens such as the fluorouracil + doxorubicin + cyclophosphamide combinations without an increase in toxic effects.     

Perioperative morbidity and mortality of high-dose-rate gynecologic brachytherapy

PURPOSE: To determine the 30-day morbidity and mortality rates for patients with an intact uterus undergoing high-dose-rate (HDR) brachytherapy, and to assess risk factors which may predict for these potentially life-threatening complications. METHODS AND MATERIALS: From August 1989 to December 1994, 128 cervical and 41 medically inoperable endometrial cancer patients were treated with 5 outpatient weekly HDR brachytherapy insertions. Patients with cervical cancer also were treated with external beam radiotherapy. Acute events that resulted in either hospitalization (morbidity) or death (mortality) within 30 days of the implant were analyzed. Univariate and multivariate analyses were performed to identify risk factors. RESULTS: Overall there were 16 acute events in 169 patients (9.5%). The overall morbidity and mortality rates for the cervical and endometrial patients were 5.5%, 1.6%, 7.3%, and 9.8%, respectively. The following factors were significant by univariate analysis: age per decade, American Society of Anesthesiologists (ASA) score, Karnofsky Performance Status (KPS), significant medical history, diagnosis of cervical vs. endometrial cancer, and mean time exceeding 160 minutes for the procedure. Since age was the most significant predictive factor (p = 0.0003), bivariate analyses were performed by adjusting for age. In these analyses only ASA and KPS maintained significance, while a positive medical history was of borderline significance (p = 0.07). CONCLUSION: The morbidity and mortality rates observed in gynecologic patients selected for HDR brachytherapy were similar to low-dose-rate, but higher than other HDR reports. Reasons for this include a higher risk population, especially those with medically inoperable endometrial cancer. In the cervical cancer patients, some of the complications may have also been a result of the external beam portion of the radiation. In order to minimize the acute complications observed in the present HDR brachytherapy system, the following changes have been implemented: appropriate patient selection, anesthesiology involvement to monitor conscious sedation for high-risk patients, external beam radiotherapy alone in patients at extremely high risk, deep vein thrombosis (DVT) prophylaxis, use of intraoperative ultrasound, shorter duration in the brachytherapy suite, and preradiation treatment plans (plans executed prior to the insertion) if applicable. Finally, this analysis suggests that these procedures should be performed in a hospital-based setting where appropriate support is available.     

Fibrinolytic response in subjects with hypertriglyceridemia and low HDL cholesterol

The combination of hypertriglyceridemia and low high-density lipoprotein cholesterol (HDL-C) appears to be an excessively high risk factor for coronary artery disease (CAD). In the Helsinki study, both coronary events and mortality were decreased by gemfibrozil, especially in subjects with low HDL-C and high triglycerides (TG). On the other hand, it is known that high levels of TG can be associated with high levels of circulating plasminogen activator inhibitor (PAI), which is also a possible risk factor for CAD. The aim of the present study was to see: 1) whether the combination of low HDL-C and high TG is associated with a more impaired fibrinolytic response than in either isolated condition, and 2) whether gemfibrozil administration can improve fibrinolysis in patients with both high TG and low HDL-C. Twelve non-obese, non-diabetic subjects (eight men, four women; mean age 55 +/- 13 yrs) with low HDL-C (< 35 mg/dL men; < 45 mg/dL women) and high TG (mean 253.6 +/- 42.6 mg/dL) entered the study (Group A). Additionally fourteen comparable subjects with normal HDL-C were also investigated (Group B), plus 12 comparable subjects with isolated low HDL-C (Group C). Ten healthy people served as the control group. The following plasma fibrinolytic parameters were measured: tissue plasminogen activator antigen, PAI antigen and activity, euglobulin fibrinolytic activity (EFA) on fibrin plates, plasminogen and alpha-2-antiplasmin activities. All except the latter two values were also measured after venous occlusion (vo). In baseline conditions, patients in Groups A and B had higher EFA values before vo and higher PAI-1 antigen and alpha-2-antiplasmin levels after vo than those of controls or the subjects in Group C. The relationship between PAI antigen and PAI activity and TG was not confirmed in our population (n = 48). We also saw no interference due to HDL-C, while there was a significant relationship between EFA before vo and both TG and cholesterol. After gemfibrozil treatment (600 mg bid for 12 weeks), the lipid profiles of subjects with high TG and low HDL-C were significantly improved. There was also a slight reduction of PAI activity after vo, while the PAI-1 antigen had decreased significantly from baseline after vo (56.3 +/- 13 ng/mL before vo; 48.4 +/- 21 ng/mL after vo; P = 0.04). The higher risk of CAD in patients with low HDL-C and high TG might be in part related to impairment of fibrinolysis, which occurs in patients with isolated high TG. The close relationship existing between both TG and cholesterol levels and fibrinolytic activity confirm the key role of this latter process in the development of CAD.     

Polymerase chain reaction-single-strand conformation polymorphism analysis for the VHL gene in chemically induced kidney tumors of rats using intron-derived primers

In patients with insulin-dependent diabetes mellitus (IDDM), albuminuria reflects widespread vascular dysfunction. Albuminuria has been associated to defects of heparan sulfate proteoglycan (HSPG) within the extracellular matrix. Our hypothesis is that loss of HSPG in vascular walls reduces the HSPG-bound lipoprotein-lipase activity (LPLA), thereby causing elevated levels of plasma triglyceride (TG) seen in IDDM patients with albuminuria. The aim of the present study was to evaluate whether LPLA in muscle capillaries could be related to TG in IDDM patients with and without albuminuria. This is a cross-sectional study including ten healthy control subjects (group C), nine patients with IDDM and urinary albumin excretion rate (AER) of 30 mg/24 h or less (group D0) and 20 patients with IDDM and AER greater than 30 mg/24 h (group DA). Muscle LPLA, plasma TG, total cholesterol, high-density lipoprotein cholesterol (HDL), low-density lipoprotein cholesterol (LDL), and very-low-density lipoprotein cholesterol (VLDL) were measured. Between groups no difference in total cholesterol, TG, VLDL, and LDL was found. In patients with albuminuria, LPLA was reduced compared to controls, however, the difference between the groups was not statistically significant [median (range)] 35.9 mU/g (20.4-103) versus 44.6 mU/g (28.2-57.2) and 40.9 mU/g (21.7-53.5) in group DA, C, and D0, respectively, p = 0.76. AER was not correlated to LPLA. An overall negative correlation between TG and LPLA was found; r = -0.33, p = 0.04, supported by an overall significant positive correlation between LPLA and HDL; r = 0.32, p = 0.045. We conclude that, in insulin-dependent diabetes mellitus, skeletal muscle lipoprotein-lipase activity is associated with plasma triglyceride, while an association between lipoprotein-lipase activity and urinary albumin excretion is questionable.     

Artificial intelligence in medicine: the challenges ahead

Forty chemotherapy naive patients with metastatic or locally advanced breast cancer were treated in a randomized trial comparing mitozantrone 14 mg/m2 with epirubicin 75 mg/m2 given intravenously at 3-weekly intervals. There was a 40% (95% confidence interval (CI) 8-72; P = 0.013) higher partial response rate with epirubicin (11/18) than with mitozantrone (4/19). Epirubicin caused significantly more alopecia (difference 76%; 95% CI 57-96; P < 0.0001) and nausea/vomiting (difference = 38%; 95% CI 10-67; P = 0.01). Three patients who received long courses of epirubicin experienced cardiac failure; two were proved to have cardiomyopathy. The median survival for the epirubicin and mitozantrone groups were 9.5 and 8 months respectively. Thus, although epirubicin gave a higher response rate it also caused more toxicity.     

External beam radiation in patients suffering from exudative age-related macular degeneration. A matched-pairs study and 1-year clinical follow-up

BACKGROUND: The aim of this prospective study was to ascertain whether external beam irradiation is effective in patients with subretinal neovascularization (SRN) due to age-related macular degeneration (AMD). METHODS: All patients had subfoveal SRN due to AMD as verified by fluoresceinangiography. Two hundred and eighty-seven patient-eyes were treated by external beam irradiation (total dose of 16 Gy in 2-Gy fractions, 5 times a week) from January 1996. The analysis was restricted to those 73 patients with a minimum follow-up of 11 months. Eighteen patients with subfoveal SRN who refused treatment served as control group (CG). 18 patients of the treatment group (TG) were matched for visual acuity, refraction and extent of SRN. The statistical analysis was performed with the unpaired t-test. RESULTS: The mean age of the CG was 73.9 years (range 66.9-81.3 years) and of the TG 75.6 years (range: 65.7-80.6 years). The median follow-up was 13.5 months (range 11.9-18.4 months) in the CG and 12.9 months (range 11-13.9 months) in the TG. The initial visual acuity (VA) was 20/80 in both groups. After 7 months the follow-up revealed median VA of 20/400 in the CG and 20/160 in the TG (P=0.0335). The final median VA was 20/400 in both groups, with a range from 20/40 to 20/1000 in the CG and from 20/63 to 20/500 in the TG (P=0.2433). The SRN doubled in size during this time in both groups. CONCLUSION: These results suggest that external beam irradiation applied in 2-Gy fractions 5 times a week slows down the visual loss in exudative AMD for a short time. Nevertheless, the patients' reading vision could not be saved in the long term.