Thermotherapy for retinoblastoma.

OBJECTIVE: To evaluate the results of thermotherapy for retinoblastoma. DESIGN: Prospective, nonrandomized analysis of the treatment method. PARTICIPANTS: A total of 188 retinoblastomas in 80 eyes of 58 patients who were treated with thermotherapy. MAIN OUTCOME MEASURES: Tumor response and ocular adverse effects. RESULTS: Of 188 retinoblastomas treated with thermotherapy, mean tumor base was 3.0 mm and tumor thickness was 2.0 mm. Complete tumor regression was achieved in 161 tumors (85.6%), and 27 tumors (14.4%) developed recurrence. Using univariate analysis, the predictors of local tumor recurrence were male sex (P = .005), no color change ("no visible take") in tumor after treatment (P = .01), increasing number of treatment sessions (P = .002), and previous use of chemoreduction (P = .02). By multivariate analysis, the most important predictors of local tumor recurrence were male sex (P = .01) and previous use of chemoreduction (P = .03), the latter likely reflecting the fact that these tumors were initially larger with more ominous findings, and required chemoreduction therapy to reduce them to a size amenable to focal treatment with thermotherapy. When evaluating thermotherapy variables as a function of tumor size, it was apparent that larger tumors (> or =3.0-mm base) required greater energy and time than did smaller tumors (<3.0-mm base). Comparison of treatment variables for larger vs smaller tumors was as follows: number of treatment sessions, 3.3 vs 2.3; spot size, 1.7 vs 1.3 mm; power, 540 vs 370 mW; treatment duration, 49 vs 14 minutes; and coupling of thermotherapy with chemotherapy, 79% vs 48% of cases (P < or =.001 for each variable). Complications of thermotherapy in the 80 eyes included focal iris atrophy in 29 eyes (36%), peripheral focal lens opacity in 19 eyes (24%), retinal traction in 4 eyes (5%), retinal vascular obstruction in 2 eyes (2%), and transient localized serous retinal detachment in 2 eyes (2%). There were no cases of corneal scarring, central lens opacity, iris or retinal neovascularization, or rhegmatogenous retinal detachment. All eyes with focal lens opacity demonstrated adjacent focal iris atrophy. By multivariate analysis, the predictors of thermotherapy-induced focal iris atrophy were increasing number of treatment sessions (P = .001) and increasing tumor base (P = .02). CONCLUSIONS: Thermotherapy is used for relatively small retinoblastomas without associated vitreous or subretinal seeds. This treatment provides satisfactory control for selected retinoblastomas, with 86% of tumors demonstrating lasting regression. Tumors that measure 3.0 mm or larger in base at the time of thermotherapy require more intense treatment than smaller tumors and are at greatest risk for ocular complications such as focal iris atrophy and focal paraxial lens opacity.

Weights of parents and infants: is there a relationship?

OBJECTIVE: To assess the relationship between the measures of body weights of parents and those of their children during the first two years of life. SUBJECTS: Seventy-eight infants born to obese ('high risk') or nonobese ('low risk') mothers. METHODS: Weight, weight for length and skinfold thicknesses of the high and low risk infants were measured at 3 months, 12 months and 24 months of age. A multiple linear regression analysis assessed the contributions of nine risk factors, including paternal and maternal body mass index (BMI: kg/m2), to the weight and weight for length of infants at 12 months and 24 months of age. RESULTS: There were no differences between the high and low risk groups in weight, weight for length or skinfold thicknesses at 3 months, 12 months or 24 months of age. Neither paternal nor maternal BMI entered the multiple regression. CONCLUSIONS: These results suggest that genetic influences on the body weight of infants may be independent of those that influence BMI in adults, a circumstance that could complicate the search for genetic determinants of obesity.

Efficacy of laser-assisted uvulopalatoplasty in obstructive sleep apnea.

Laser-assisted uvulopalatoplasty (LAUP) enlarges the oropharyngeal airway by reshaping the uvula, soft palate, and tonsillar pillars. In contrast to a uvulopalatopharyngoplasty performed in the operating room, LAUP is staged over several office visits, is less costly, is bloodless, and is not associated with velopharyngeal insufficiency or stenosis. Previous studies have documented the efficacy of LAUP in the treatment of snoring. We explore the efficacy of LAUP in the treatment of obstructive sleep apnea. Forty-eight patients comprised the study group. Each patient snored, exhibited >50% palatal collapse on Müller's maneuver, and had nocturnal polysomnography showing a respiratory disturbance index (RDI) >10. Each patient underwent LAUP until he or she reported that snoring had ceased. Of the 29 patients who underwent post-LAUP nocturnal polysomnography, 7 had RDIs <10, oxygen saturation >86%, and no cardiac arrhythmias. LAUP reduced RDI to <10 in patients with pre-LAUP apnea indexes <3 (P = 0.05) or pre-LAUP RDIs <30 (P = 0.01). The following variables did not correlate with the success of LAUP in treating obstructive sleep apnea: age, sex, pre-LAUP weight, pre-LAUP body mass index, perioperative weight change, perioperative body mass index change, pre-LAUP snoring, and post-LAUP snoring. We conclude that LAUP is an effective means of treating patients with RDIs <30.

Effect of i.v. glucose versus combined i.v. plus oral glucose on human tumour extracellular pH for potential sensitization to thermoradiotherapy.

The purpose of this study was to determine whether intravenous or combined intravenous plus oral glucose administration was more effective inducing acute tumour acidification. Seventeen nondiabetic patients at the Henan Tumour Hospital with superficial tumour deposits of various histologies and size were administered, after fasting, either 50 g glucose intravenously (i.v., in 100 ml over 10 min) or 50 g i.v. glucose (in 100 ml over 10 min) combined with 100 g oral glucose (in 200 ml; i.v. + oral). Extracellular tumour pH (pHe) was determined with one or two indwelling needle combination pH microelectrodes. Blood glucose concentration was determined every 15-20 min by finger stick with Chem-Strips and a Glucometer. Ten patients received i.v. glucose, and seven patients received i.v. + oral glucose. Blood glucose rose to 430 +/- 15 mg/dL in both groups. However, the rate of clearance of blood glucose was greater for the i.v. glucose than for the i.v. + oral glucose group (p < 0.00002), and thus the blood glucose levels remained elevated longer after i.v. + oral than after i.v. glucose administration. Relative to the initial fasting blood glucose concentration, blood glucose was -2 +/- 7 mg/dL at 110 min after glucose administration by the i.v. route, whereas, blood glucose relative to initial values was 143 + 23 mg/dL by 110 min after glucose administration by the i.v. + oral route, p = 0.000004. The initial pHe values in the two groups of tumours were similar, 7.34 +/- 0.09 (6.78-7.71) and 7.35 +/- 0.08 (6.99-7.61), respectively. After i.v. glucose, tumour acidification occurred in nine of ten patients (-0.16 + 0.02 pH unit, range -0.24 to -0.05), and after i.v. + oral glucose tumour acidification occurred in six of seven patients (-0.19 +/- 0.07 pH unit, range -0.43 to -0.06). When the initial fasting blood glucose concentration was in excess of 82 mg/dL, all patients (12/12) exhibited tumour acidification during hyperglycaemia, whereas, only 3/5 patients exhibited tumour acidification when the initial blood glucose concentration was less than 82 mg/dL (p = 0.07). The time to maximum decrease in tumour pHe was significantly shorter after i.v. + oral glucose than after i.v. glucose (e.g., 67 +/- 11 versus 102 +/- 8 min, p = 0.02) and correlated with the rate of clearance of blood glucose (p = 0.02, r = 0.55). Larger tumours tended to exhibit a greater decrease in pHe (p = 0.08, r = 0.04). The only side effects of hyperglycaemia were transient nausea and increased urinary output. The effect of hyperglycaemia induced by administration of 200 g oral glucose was similar to i.v. administration in that 83% of tumours exhibited acidification of 0.14 +/- 0.02 pH unit by 91 +/- 7 min. We conclude that i.v. and i.v. + oral glucose administration are equally effective inducing tumour acute acidification, but no more effective than 200 g oral glucose, for investigation of hyperglycemic sensitization to thermoradiotherapy.

Ki-67 antigen staining as an adjunct to identifying cervical intraepithelial neoplasia.

The purpose of the work was to determine the feasibility and predictive value of Ki-67 immunostaining of cervical cytology and the detection of cervical dysplasia. Air-dried cervical smears were stained with MIB-1 antibody to identify the Ki-67 antigen. Nuclear decoration in abnormal squamous nuclei determined immunoreactivity. One hundred twenty-four nonpregnant patients underwent colposcopy and directed biopsies for abnormal cytology. Sensitivity (0.89), specificity (0.65), positive predictive value (0.60), and negative predictive value (0.91) were found for Ki-67 immunostaining in detection of high-grade cervical intraepithelial neoplasia (CIN) in 124 patients and positive Ki-67 staining was a significant predictor of high-grade CIN in both univariate (odds ratio 15.5 (95% CI 5.5-43.8) and multivariable (odds ratio 21.5 (95% CI 5.0-92.0) analysis. In 101 patients with ASCUS and LGSIL, Ki-67 immunostaining demonstrated the following in detection of high-grade CIN: sensitivity (0.96), specificity (0.67), positive predictive value (0.49), and negative predictive value (0.98). Ki-67 immunostaining of cervical cytology is a predictor of significant cervical pathology with high sensitivity and negative predictive value. Ki-67 immunostaining of cervical cytology may represent a new and cost-effective triage tool for patients with minor abnormalities on cytology.

Intra- and perioperative complications associated with tandem and colpostat application for cervix cancer.

PURPOSE: The purpose of this study was to chronicle the acute morbidity associated with the implantation of tandems and colpostats in women with carcinoma of the cervix; to determine factors that predispose to the development of such complications; and to assess whether the use of ultrasound allowed the apparatus to be safely implanted in women at relatively high risk for perforation of hollow viscous organs. METHODS: A database from two Philadelphia institutions was used to assess the aforementioned factors among 143 tandems/colpostats inserted into 100 women with cervix cancer. Twenty patients had insertion under ultrasound guidance because of stenotic cervical os, fibrosis from external-beam irradiation, indeterminate orientation of endometrial cavity axis, or previous perforation. Univariate and multivariate analyses were performed to identify predictors of intra- and perioperative complications. RESULTS: Intraoperative complications occurred in 7 of 143 placements (5%). These included uterine perforations (n = 4), vaginal lacerations (n = 2), and one instance of bladder perforation. Only older age, whether entered as a continuous or a dichotomous variable, was associated statistically with these complications. Perioperative complications (e.g., fever, bowel obstruction, exacerbation of chronic obstructive pulmonary disease, cardiac complication) occurred in 54 of 143 implanted women. In univariate analysis, older age and underlying chronic obstructive pulmonary disease (COPD) appeared to be associated with perioperative complications. A multivariate analysis showed that underlying COPD predisposed to perioperative complications during the first implant and that age over 60 years independently predicted for complications during any implant. CONCLUSIONS: Intraoperative complications are relatively rare events. Ultrasonography seems to allow safe intrauterine insertion of the tandem despite the selection of difficult cases for this adjunctive imaging tool. Patient age over 60 years independently predicts for perioperative complications. COPD predicts for perioperative complications during the first but not the second implant, implying that physicians are able to optimize the medical management of pulmonary disease to allow a second implant to be performed more safely.

Plaque radiotherapy for juxtapapillary choroidal melanoma. Visual acuity and survival outcome.

OBJECTIVES: To assess the effect of plaque radiotherapy on the visual acuity of patients with juxtapapillary choroidal melanoma and to determine the clinical predictive factors for radiation retinopathy, radiation papillopathy, local tumor recurrence, and distant metastasis. DESIGN: A retrospective review of the medical records of 93 patients with juxtapapillary choroidal melanoma who were treated initially with plaque radiotherapy. RESULTS: During a mean follow-up of 78 months, radiation retinopathy developed in 81 patients (87%) and radiation papillopathy developed in 48 patients (52%) after a mean interval of 21 and 27 months, respectively. The univariate variables that were significant predictors of radiation retinopathy were history of diabetes mellitus (P = .05) and use of a notched radioactive plaque (P = .04). The factors predictive of radiation papillopathy were age (> 45 years; P = .01), history of diabetes mellitus (P = .05), mushroom-shaped tumor configuration (P = .006), and nasal location of the tumor (P = .04). By using Kaplan-Meier survival curves, we found that the proportion of the 93 patients with radiation retinopathy was 87 (94%) at 5 years and with radiation papillopathy was 53 (57%) at 5 years. By using life-table analysis, we found that the proportion of the 93 patients who experienced a decrement of at least 3 lines of visual acuity was 67 (72%) by 50 to 60 months. Local tumor recurrence was documented in 14 patients (15%) after a mean interval of 41 months. The age of the patient (< 35 years; P = .02) and the superior (P = .004) and inferior (P = .05) locations of the tumor were predictive of local tumor recurrence. Distant metastasis developed in 11 patients (12%) after a mean interval of 44 months. The factors predictive of distant metastasis were a tumor with a basal diameter larger than 6.0 mm (P = .05), the superior location of the tumor (P = .01), and local tumor recurrence (P < .001). CONCLUSION: Based on these observations, plaque radiotherapy remains a potential option vs enucleation for the management of juxtapapillary choroidal melanoma.

Intrasubject variability of objective voice measures.

Recent advances in the diagnosis and treatment of voice disorders necessitate the need for accurate and reliable objective voice measurements. There are many instruments commonly used to analyze voice data. Many, if not most, of these instruments have not been adequately tested for reliability or consistency. This study evaluates the intrasubject variability of the objective voice measurements from two commonly used voice analysis instruments. The study also presents data correlating subjective mood states, room temperatures, sleep times of the subject, time since last meal, and hydration levels to the various acoustic measures. Several weak but significant correlations were obtained and are discussed. Guidelines for the appropriate use of these instruments are described.

National Transplantation Pregnancy Registry: analysis of pregnancy outcomes in female liver transplant recipients.

Outcomes from 48 pregnancies in 34 female liver transplant recipients were analyzed. Data were collected via interviews, questionnaires, and hospital records. All recipients were treated with cyclosporine-based immunosuppression except 2 patients treated with FK506 and 2 treated with no immunosuppression. The age at conception was 26.1 +/- 5.9 years (mean +/- SD) with a transplant interval (time from transplantation to conception) of 2.9 +/- 2.5 years. There were 49 outcomes (1 set of twins): miscarriage 9 (18%), therapeutic abortion 4 (8%), and live birth 36 (74%). No stillbirths or ectopic pregnancies were reported. Of the 36 live births, the gestational age was 36.9 +/- 3.5 weeks, the birthweight was 2,604 +/- 698 grams, 39% were premature (< 37 weeks), and 31% had low birthweight (< 2,500 grams). No birth defects or neonatal deaths (< 28 days) were reported. The newborn complication rate was 17% (n = 6), 5% in premature infants. The incidence of drug-treated hypertension was 46%; pre-eclampsia 21%; infectious complications 26%; and Caesarean section 47%. Recipients with hypertension had a higher proportion of premature infants (71%) than normotensive patients (38%) (P = .04 by Fisher's exact test). Acute rejection was diagnosed in 6 pregnancies, 2 of which were ended by therapeutic abortion. Four recipients who continued their pregnancies were treated with increased immunosuppression for rejection, and all delivered livebirths. There were two grafts lost within 6 months of pregnancy. The only maternal death occurred in a patient who required retransplantation for recurrent C hepatitis 3 months afte therapeutic abortion and died 6 months later. The other recipient with graft loss was successfully retransplanted for chronic rejection 6 months after delivery. We draw the following conclusions: (1) female liver transplant recipients can safely undergo pregnancy, although there is a high rate of premature and low birthweight infants; (2) pregnancies in this population should be considered high-risk and require close monitoring of liver function; and (3) altered graft function during pregnancy should be thoroughly investigated.

Risk factors for growth and metastasis of small choroidal melanocytic lesions.

BACKGROUND: The management of small melanocytic choroidal tumors is controversial. An important reason for this controversy is that the natural course and metastatic potential of these lesions are not defined clearly. Prior studies that have attempted to elucidate the natural course of these lesions have focused on selected small groups of patients with presumed small choroidal melanomas. There are no large studies investigating the growth potential and metastatic potential for the spectrum of small melanocytic choroidal tumors when considered as an unselected whole group. In addition, the clinical features of these tumors predictive of metastases have not yet been identified. METHODS: A retrospective review was performed on 1329 patients with small melanocytic choroidal tumors measuring 3 mm or less in thickness. Clinical parameters of the patient and tumor were obtained and analyzed for their relation to eventual tumor growth and metastasis using a Cox proportional hazards regression model. RESULTS: Tumor growth was documented in 18% of patients. The factors predictive of tumor growth (multivariate analysis) included greater tumor thickness (P = 0.0001), posterior tumor margin touching optic disc (P = 0.0001), symptoms of flashes, floaters (P = 0.002), and blurred vision (P = 0.003) relative to no symptoms, orange pigment on the tumor surface (P = 0.004), and the presence of subretinal fluid (P = 0.05). The relative risk (RR) was greatest for initial tumor thickness 2.1 to 3.0 mm (RR = 5.2) and tumor thickness 1.1 to 2.0 mm (RR = 4.3) relative to tumors 1 mm or less in thickness, as well as posterior margin touching the optic disc (RR = 2.6). After adjusting for significant tumor variables, the effect of interventional tumor treatment showed a decreasing risk for tumor growth compared with continued observation without treatment. Of 1329 patients, metastases developed in 35 (3%). The factors predictive of metastases (multivariate analysis) included posterior tumor margin touching the optic disc (P = 0.003), documented growth (P = 0.003), and greater tumor thickness (P = 0.004). The relative risk for metastases was greatest for tumor thickness 1.1 to 3.0 mm (RR = 8.8) and growth (RR = 3.2). CONCLUSION: Of small choroidal melanocytic tumors measuring 3 mm or less in thickness at the time of initial examination, 18% demonstrated growth and 3% metastasized during the period of follow-up. Based on this analysis, the clinical features of these tumors can be used to estimate the risk for tumor growth and metastases and assist the clinician with patient management.

Extracellular pH distribution in human tumours.

Extracellular pH (pHc) was determined by needle microelectrodes in 67 tumour nodules in 58 patients. The objective was to evaluate the relationship between pHe, tumour histology and tumour volume. The mean age of the patients was 62 years, mean depth of the lesions was 2.7 +/- 0.2 cm, and mean tumour volume was 187 +/- 60 cm3. Lesions were located in readily accessible areas such as on the limbs, neck or chest wall. Tumour histologies included: 48% adenocarcinoma; 34% squamous cell carcinoma; 8% soft tissue sarcoma; and 10% malignant melanoma. The mean tumour pHe for the entire group of tumours was 7.06 +/- 0.05 (range 5.66-7.78). Variation in pHe measurements between tumours was greater than the variation in measurements within tumour (F = 7.11, p < 0.01). In adenocarcinomas pHe was 6.93 +/- 0.08 (range 5.66-7.78), in soft tissue sarcomas 7.01 +/- 0.21 (6.25-7.45), in squamous cell carcinomas 7.16 +/- 0.08 (6.2-7.6), and in malignant melanomas 7.36 +/- 0.1 (6.98-7.77). Tumour pHe was significantly different between the four histological groups (p < 0.001). When adenocarcinoma and soft tissue sarcoma lesions were grouped together, pHe was 6.94 +/- 0.08 compared with 7.20 +/- 0.07 in squamous cell carcinomas and malignant melanomas lesions (p < 0.01). Tumour pHe increased as a function of the logarithm of tumour volume at 0.07 +/- 0.02 pH unit/ln cm3 (p = 0.006, r = 0.34). In conclusion, tumour histology and tumour volume were the most important factors determining the range of pHe's.(ABSTRACT TRUNCATED AT 250 WORDS)

Variables affecting birthweight and graft survival in 197 pregnancies in cyclosporine-treated female kidney transplant recipients.

Outcomes from 197 pregnancies in 141 female kidney transplant recipients were analyzed from data collected via questionnaires, hospital records, and phone interviews. All recipients were maintained on cyclosporine (CsA) before and during pregnancy. Of the livebirths, 54% were premature (< 37 wk) and 50% were low-birthweight (LBW) (< 2500 g). The incidence of recipient drug-treated hypertension (HTN) was 56%; preeclampsia, 29%; infections and complications 22%; and rejection during pregnancy and up to 3 mo. post delivery (rej.), 11%. Graft loss within 2 years of delivery occurred in 9% of recipients (GrL < 2). No recipients reported a pregnancy after a postpregnancy graft loss. Mean serum creatinine was reported before, during, and after pregnancy. Mean cyclosporine doses were similar in recipients during and after pregnancy. Data were analyzed by logistic regression using SAS. Outcomes included prematurity, LBW, rej., and GrL < 2. In a case-controlled study comparing a recipient group with graft dysfunction during pregnancy vs. a group with good graft function, there was a trend toward lower mean prepregnancy CsA doses (in mg/kg) in the graft dysfunction group. A decline in recipient graft function during pregnancy is associated with lower newborn birthweights and lower maternal graft survival in cyclosporine treated female kidney recipients. Pregnancy-related infections and complications are associated with rejection and graft loss in this population. Close monitoring of CsA dosing and serum creatinine levels during pregnancy and immediately postpartum is recommended as CsA dosage adjustment may be required.

Risk factors for growth and metastasis of small choroidal melanocytic lesions.

PURPOSE: To investigate the clinical features that predict growth and metastasis of an unselected group of small melanocytic choroidal tumors. METHODS: A retrospective review was performed on 1329 patients with small melanocytic choroidal tumors measuring 3 mm in thickness or less. Clinical parameters of the patient and tumor were extracted and analyzed for their relationship to eventual tumor growth and metastasis using a Cox proportional hazards regression model. RESULTS: Tumor growth was documented in 18% of patients. The factors predictive of tumor growth (multivariate analysis) included greater tumor thickness, posterior tumor margin touching optic disc, symptoms of flashes, floaters, and blurred vision, orange pigment on the tumor surface, and the presence of subretinal fluid. The relative risk (rr) was greatest for initial tumor thickness > 2.0 mm (rr 5.2) and posterior margin touching the optic disc (rr 2.6). After adjusting for significant tumor variables, the effect of interventional tumor treatment showed a decreasing risk for tumor growth as compared to continued observation without treatment. Of 1329 patients, 35 (3%) developed metastases. The factors predictive of metastases (multivariate analysis) included: posterior tumor margin touching the optic disc, documented growth, and greater tumor thickness. The relative risk for metastases was greatest for tumor thickness 1.1-3.0 mm (rr 8.8) and growth (rr 3.2). CONCLUSION: Of small choroidal melanocytic tumors measuring 3 mm or less in thickness at the time of initial examination, 18% demonstrate growth and 3% metastasize during the period of followup. Based on this analysis, the clinical features of these tumors can be used to estimate the risk for tumor growth and metastases and assist the clinician with patient management.

Pulmonary function and gastroesophageal reflux in systemic sclerosis.

OBJECTIVE: To determine the relations among esophageal dysfunction, gastroesophageal reflux, and lung involvement in patients with systemic sclerosis. DESIGN: Retrospective review of esophageal motility, esophageal pH, and pulmonary function data. SETTING: University hospital outpatient clinic and community. PATIENTS: 39 consecutively referred patients who were grouped according to the presence or absence of abnormal distal (pH < 4.0 for > 5% of the 24-hour monitoring period) or proximal (pH < 4.0 for > 1% of the 24-hour period) gastroesophageal acid reflux. Patients were also grouped according to the presence or absence of distal esophageal peristalsis. MEASUREMENTS: Esophageal manometry, dual-probe (distal and proximal) esophageal 24-hour pH measurements, and pulmonary function studies (forced vital capacity, forced expiratory volume at 1 second, total lung capacity, and single-breath carbon monoxide diffusing capacity [DLco]). RESULTS: The mean total lung capacity (values as percentage predicted) was 87.1% +/- 11.2% (SD) for patients with abnormal proximal reflux and 77.8% +/- 21.6% for patients with normal proximal reflux (difference, 9.3%; 95% CI, -1.4% to 20.0%). The mean forced vital capacity for these patients was 91.1% +/- 12.4% and 85.4% +/- 25.6%, respectively (difference, 5.7%; CI, -6.9% to 18.1%). The mean total lung capacity was 83.8% +/- 15.4% for patients with abnormal distal reflux and 77.9% +/- 22.7% for patients with normal distal reflux (difference, 5.9%; CI, -7.6% to 19.4%). Among potential confounders of pulmonary measures, only smoking was related to decreased pulmonary function (smoking related to decreased DLco P < 0.01). Smoking was more common in patients with abnormal distal reflux than in those with normal distal reflux (65% compared with 25%, P = 0.03). After adjusting for smoking, the difference in mean DLco between patients with abnormal compared with normal distal reflux was 7.19% (Cl, -8.5% to 22.9%). CONCLUSION: Important measures of lung volume indicative of interstitial lung disease (total lung capacity, forced vital capacity) do not appear to be related to abnormal gastroesophageal acid reflux in patients with systemic sclerosis.

Thermoradiotherapy for superficial tumour deposits in the head and neck.

Tumour deposits in the head and neck region were treated with hyperthermia using 915 MHz external microwave applicators and radiation therapy between 1986 and 1990. The mean (+/- SE) radiation dose was 47 +/- 2 Gy (range 21-77 Gy). All but four patients had failed previous therapy. Mean tumour volume was 40 +/- 10 cm3 (range 0.3-276 cm3). Hyperthermia was administered biweekly in 80% of the patients in 6.0 +/- 0.4 sessions (range 1-10); thermometry involved 3.6 +/- 0.4 catheters (range 1-9) and 5.7 +/- 0.4 sensors (range 1-12) per tumour. Of the 50 lesions evaluable for response, 29 had a complete response (58%), and 20 had a partial response (40%). Lesions were stratified by depth. In tumours considered potentially heatable (i.e. depth < or = 3 cm and lateral dimensions at least 2 cm less than boundary of applicator), the complete response rate was 81% (26/32, 47 +/- 2 Gy, 15 +/- 3 cm3); whereas for patients with tumours deeper than 3 cm, the complete response rate was 17% (3/18, 48 +/- 3 Gy, 110 +/- 21 cm3), p = 0.0001. Among lesions < or = 3 cm depth that exhibited a complete response, six recurred (24%, 5.8 +/- 1.8 months) while 20 lesions were recurrence free at last follow-up of 11.9 +/- 1.2 months). The overall survival of patients with lesions < or = 3 cm depth was 11.5 +/- 1.3 months (range 2.4-32.3 months) while for patients with lesions > 3 cm depth survival was 6.7 +/- 0.9 months (range 2.1-18.6 months), p = 0.01. In superficial lesions with depth < or = 3 cm, multivariate logistic regression analysis indicated that the model best correlating with complete response included radiation dose (p = 0.08) and tumour volume (p = 0.08, model p = 0.004). Multivariate proportional hazard analysis indicated that the model best correlating with duration of local control included tumour depth (p = 0.03) and previous radiation therapy (p = 0.08, model p = 0.006). Twenty-two fields were treated without any skin reactions (39%), 23 evidenced erythema (40%) and eight thermal blistering (14%). Ulceration occurred in 11 treatment fields but in all but one of these cases the ulceration may have been due to tumour breakdown as there was direct invasion of the skin by tumour prior to the initiation of treatment. The maximal skin temperature was the best predictor of morbidity although the correlation was not statistically significant (p = 0.19).

Impact of enucleation versus plaque radiotherapy in the management of juxtapapillary choroidal melanoma on patient survival.

The records of 265 consecutive patients with juxtapapillary choroidal melanoma were reviewed and a statistical non-randomised retrospective study was performed to evaluate the risk for metastasis and compare the survival rate of patients treated with plaque radiotherapy or enucleation. To obtain sufficient overlap between the enucleation and plaque radiotherapy, the statistical analysis was limited to an adjusted subgroup of 127 patients who met eligibility criteria for plaque radiotherapy and who had a minimum of 3 years of follow up after treatment. In the adjusted subgroup of 127 patients, 92 patients (72%) were initially treated with enucleation and 35 (28%) with plaque radiotherapy. In both univariate and multivariate logistic analysis models, the age of the patient (> 50 years), tumour thickness (> 3 mm), and treatment by age interaction were found to be significant factors for development of distant metastasis. In patients younger than 50 years, the method of treatment (enucleation versus plaque radiotherapy) did not significantly affect the risk of metastasis. For those older than 50 years, there was a non-significant trend for patients in the enucleation group to be at a higher risk for metastasis than those in the plaque group. In the enucleation group, patients older than 50 years had a significantly higher incidence of distant metastasis than those younger than 50 years. In the plaque radiotherapy group, there was no significant higher incidence of metastasis in patients younger than 50 years than in those older than 50 years. When a Cox proportional hazards model was used to evaluate the survival rate, there was the same statistically significant effect of treatment by age interaction as was found in the multivariate logistic model on survival time. Moreover, there was a significant effect of treatment by tumour thickness interaction on survival time. Patients in the enucleation group had a better survival rate when the thickness of the tumour was less than 3 mm compared with a tumour of more than 3 mm. There were no apparent effects of tumour thickness on survival for patients treated with plaque radiotherapy. From these results, the authors currently recommend plaque radiotherapy as a viable option to enucleation in patients with juxtapapillary choroidal melanoma.

Optic nerve invasion of retinoblastoma. Metastatic potential and clinical risk factors.

BACKGROUND: Optic nerve invasion is one of the predictors for retinoblastoma metastases. This study was designed to investigate the risk of optic nerve invasion and clinical features that may identify those children with optic nerve invasion. METHODS: We reviewed the charts of 289 children with retinoblastoma treated initially with enucleation. Logistic regression analysis was performed to assess the risk for metastases from varying degrees of optic nerve invasion and to assess the clinical and histopathologic predictors of optic nerve invasion. RESULTS: There were 84 eyes (29%) with optic nerve invasion. The invasion was prelamina cribrosa in 44 cases (15%), up to but not posterior to the lamina cribrosa in 21 cases (7%), posterior to the lamina cribrosa but not to the cut end of the optic nerve in 17 cases (6%), and to the site of optic nerve transection in 2 cases (1%). Patients with optic nerve invasion were more likely to develop metastasis (P = 0.0016), particularly those with invasion to the postlaminar and cut section of the optic nerve (P = 0.0001). Development of metastasis was not statistically associated with laminar or prelaminar involvement. If those patients with choroidal invasion simultaneous with optic nerve invasion were excluded from evaluation, the presence of optic nerve invasion alone was not significant for development of metastasis. The clinical factors found to be predictive for optic nerve invasion from a univariate analysis included exophytic growth pattern (P = 0.011), elevated intraocular pressure (> 22 mm Hg) (P = 0.02), and tumor thickness greater than or equal to 15 mm (P = 0.03). The histopathologic factor significantly associated with optic nerve invasion (univariate analysis) was simultaneous choroidal invasion (P = 0.001). A trend toward an association with optic nerve invasion was found with vitreous hemorrhage (P = 0.06), iris neovascularization (P = 0.10), and poorly differentiated retinoblastoma (P = 0.07). A multivariate analysis showed the most significant clinical factors to be exophytic growth pattern (P = 0.002), tumor thickness greater than or equal to 15 mm (P = 0.01), and vitreous hemorrhage (P = 0.05). CONCLUSIONS: Optic nerve invasion of retinoblastoma beyond the lamina cribrosa is associated with a greater metastatic risk. Large exophytic retinoblastoma with secondary glaucoma is at highest risk for optic nerve invasion.

Plaque radiotherapy in the management of retinoblastoma. Use as a primary and secondary treatment.

BACKGROUND: Radioactive episcleral plaque brachytherapy is a treatment method for selected retinoblastomas. The authors have used this technique since 1976 as both a primary and a secondary treatment method after other methods failed to achieve tumor control. METHODS: A review of the records of 400 consecutive children with retinoblastoma showed that solitary plaque radiotherapy was used as a method of management in 103 cases. The authors' overall experience was evaluated, and the results between primary and secondary plaque therapies were compared in these 103 cases. RESULTS: Of the 103 tumors, the mean basal diameter was 7 mm, and the mean thickness was 4 mm. Overlying vitreous seeds were clinically apparent in 50 cases (48%). The mean proximity of the tumor margin to the optic disc margin was 6 mm and to the foveola was 6 mm. The mean follow-up period was 40 months. In 89 cases (86%), the tumor was controlled by one plaque application, whereas in 13 cases (13%), tumor recurrence after initial tumor shrinkage necessitated subsequent treatment. Final visual outcome was good in 63 cases (62%), poor in 30 (29%), enucleation in 9 (9%), and unknown in 1 case. The poor vision was due to foveal retinoblastoma (with or without amblyopia) in 25 cases (83%). Eight of the nine enucleated eyes were treated initially with external beam radiotherapy then later with plaque radiotherapy. In 31 cases (30%), plaque radiotherapy was used as a primary treatment to the tumor, while in 72 cases (70%), it was a secondary form of management after failure of other methods to control the tumor. Statistical analysis showed that tumors treated with plaque radiotherapy as a primary measure were more likely to be larger in in base (P = 0.01) and thickness (P = 0.01) than secondary treated tumors. The secondary treated retinoblastomas were more likely to have vitreous seeds (P = 0.02) than the primary treated tumors. The rate of tumor control and patient survival was similar between the two groups. CONCLUSION: Plaque radiotherapy is very effective in treating selected retinoblastomas with a high rate of tumor control and patient survival. It can be used successfully as a primary or a secondary treatment for tumors that have not been adequately controlled by other therapeutic methods.