Nodal and systemic recurrence following observation of a positive sentinel lymph node in melanoma.

BACKGROUND: Two RCTs found no survival benefit for completion lymphadenectomy after positive sentinel lymph node biopsy compared with observation with ultrasound in patients with melanoma. Recurrence patterns and regional control are not well described for patients undergoing observation alone. METHODS: All patients with a positive sentinel node biopsy who did not have immediate completion lymphadenectomy were identified from a single-institution database (1995-2018). First recurrences were classified as node only, local and in-transit (LCIT) only, LCIT and nodal, or systemic. Regional control and factors associated with recurrence survival were analysed. RESULTS: Median follow-up was 33 months. Of 370 patients, 158 (42·7 per cent) had a recurrence. The sites of first recurrence were node only (13·2 per cent), LCIT only (11·9 per cent), LCIT and nodal (3·5 per cent), and systemic (13·8 per cent). The 3-year postrecurrence melanoma-specific survival rate was 73 (95 per cent c.i. 54 to 86) per cent for patients with node-only first recurrence, and 51 (31 to 68) per cent for those with initial systemic recurrence. In multivariable analysis, ulceration in the primary lesion (hazard ratio (HR) 2·53, 95 per cent c.i. 1·27 to 5·04), disease-free interval 12 months or less (HR 2·38, 1·28 to 4·35), and systemic (HR 2·57, 1·16 to 5·65) or LCIT and nodal (HR 2·94, 1·11 to 7·79) first recurrence were associated significantly with decreased postrecurrence survival. Maintenance of regional control required therapeutic lymphadenectomy in 13·0 per cent of patients during follow-up. CONCLUSION: Observation after a positive sentinel lymph node biopsy is associated with good regional control, permits assessment of the time to and pattern of recurrence, and spares lymphadenectomy-related morbidity in patients with melanoma.

A phase I multi-institutional study of systemic sorafenib in conjunction with regional melphalan for in-transit melanoma of the extremity.

BACKGROUND: Isolated limb infusion with melphalan (ILI-M) corrected for ideal body weight (IBW) is a well-tolerated treatment for patients with in-transit extremity melanoma with an approximate 29 % complete response (CR) rate. Sorafenib, a multi-kinase inhibitor, has been shown to augment tumor response to chemotherapy in preclinical studies. METHODS: A multi-institutional, dose-escalation, phase I study was performed to evaluate the safety and antitumor activity of sorafenib in combination with ILI-M. Patients with AJCC stage IIIB/IIIC/IV melanoma were treated with sorafenib starting at 400 mg daily for 7 days before and 7 days after ILI-M corrected for IBW. Toxicity, drug pharmacokinetics, and tumor protein expression changes were measured and correlated with clinical response at 3 months. RESULTS: A total of 20 patients were enrolled at two institutions. The maximum tolerated dose (MTD) of sorafenib in combination with ILI-M was 400 mg. Four dose-limiting toxicities occurred, including soft tissue ulcerations and compartment syndrome. There were three CRs (15 %) and four partial responses (20 %). Of patients with the Braf mutation, 83 % (n = 6) progressed compared with only 33 % without (n = 12). Short-term sorafenib treatment did alter protein expression as measured with reverse phase protein array (RPPA) analysis, but did not inhibit protein expression in the MAP kinase pathway. Sorafenib did not alter melphalan pharmacokinetics. CONCLUSION: This trial defined the MTD of systemically administered sorafenib in combination with ILI-M. Although some responses were seen, the addition of sorafenib to ILI-M did not appear to augment the effects of melphalan but did increase regional toxicity.

Phase II trial of neoadjuvant temozolomide in resectable melanoma patients.

BACKGROUND: We treated melanoma patients with temozolomide (TMZ) in the neoadjuvant setting and collected cryopreserved tumor samples before and after treatment. The primary objective was to determine whether the response proportion was higher than previously reported in widely metastatic patients. A secondary objective was to test the feasibility of obtaining adequate tissue before and after treatment for genetic testing. MATERIALS AND METHODS: Chemotherapy-naive melanoma patients who were candidates for surgical resection were eligible. TMZ was administered orally at 75 mg/m(2)/day for 6 weeks of every 8-week cycle. Cycles were repeated until complete response (CR), progression, or stable disease (SD) for two cycles. RESULTS: Of 19 assessable patients, 2 had CRs and 1 had partial response. Four patients had SD; 12 progressed. Tumor O-6-methylguanine-DNA methyltransferase (MGMT) promoter was unmethylated in all nine patients analyzed including from the two CR patients. Pretreatment tumor microarray results were obtained in 16 of 19 patients. CONCLUSIONS: The response proportion to TMZ in the neoadjuvant setting was 16%, not different than in the metastatic setting. Responses were seen even in tumors with a methylated MGMT promoter. Pretreatment cryopreserved tumor adequate for microarray analysis could be obtained in most, but not all, patients. Post-treatment tumor was unavailable in complete responders.

Microscopic satellitosis in patients with primary cutaneous melanoma: implications for nodal basin staging.

BACKGROUND: Microscopic satellitosis in melanoma is uncommon. The role of regional basin staging/therapy in patients with this high-risk feature has not been well defined. METHODS: Patients presenting from 1996 to 2005 with clinically localized melanoma containing microscopic satellitosis were identified from a prospective, single-institution database. Multiple factors were analyzed to determine their predictive value for recurrence. The management of the draining nodal basin was evaluated to determine its impact on recurrence and survival. RESULTS: Thirty-eight patients presented to our institution during this time period with clinically localized melanoma containing microscopic satellitosis. The 5-year overall and disease-free survivals in these patients were 34% and 18%, respectively. Sixty-eight percent had pathologically involved regional nodal metastases. With median follow-up of 21 months, 68% recurred, with a median time to recurrence of 9 months. Lymphovascular invasion (LVI) (p = 0.01), tumor regression (p = 0.04), and positive regional lymph nodes (p = 0.02) were associated with an increased risk of recurrence. Of the 31 patients who underwent sentinel lymph node (SLN) biopsy, 22 had metastasis in the SLN (71%). Fifteen of these patients underwent completion lymphadenectomy (CLND) and seven were observed. There was no difference in disease-free survival (DFS), disease-specific survival (DSS), or overall survival (OS) between these groups (p = 0.42). CONCLUSIONS: Pathological lymph node metastases were more prevalent (68%) than in any group previously defined. Regional nodal status predicted recurrence but not nodal recurrence. In SLN-positive patients, CLND did not improve DFS, DSS, or OS, although the number of patients was small. Further studies are needed to determine the utility of regional nodal staging/therapy in these high-risk patients.

Resection of metastatic renal cell carcinoma.

PURPOSE: Resection of solitary metastases from renal cell carcinoma (RCC) is associated with a 5-year survival rate of 35% to 50%. Selection criteria are not well defined. PATIENTS AND METHODS: We retrospectively analyzed our experience with 278 patients with recurrent RCC from 1980 to 1993. RESULTS: One hundred forty-one of 278 patients underwent a curative metastectomy for their first recurrence (44% 5-year overall survival [OS] rate), 70 patients underwent noncurative surgery (14% 5-year OS rate), and 67 patients were treated nonsurgically (11% 5-year OS rate). Favorable features for survival were a disease-free interval (DFI) greater than 12 months versus 12 months or less (55% v 9% 5-year OS rate; P < .0001), solitary versus multiple sites of metastases (54% v 29% 5-year OS rate; P < .001), and age younger than 60 years (49% v 35% 5-year OS rate; P < .05). Among 94 patients with a solitary metastasis, lung (n = 50; 54% 5-year OS rate) was more favorable than brain (n = 11; 18% 5-year OS rate; P < .05). Survival rates after curative resection of second and third metastases were not different compared with initial metastectomy (46% and 44%, respectively, v 43% 5-year OS rates; P = nonsignificant). Favorable predictors of survival by multivariate analysis included a single site of first recurrence, curative resection of first metastasis, a long DFI, a solitary site of first metastasis, and a metachronous presentation with recurrence. CONCLUSION: Selected patients with recurrent RCC who can undergo a curative resection of their disease have a good opportunity for long-term survival, particularly those with a single site of recurrence and/or a long DFI.

Influence of epidermal growth factor and insulin-like growth factor 1 on nuclear maturation and fertilization of buffalo cumulus oocyte complexes in serum free media and their subsequent development in vitro.

The in vitro maturation, fertilization and development of Indian water buffalo (Bubalus sp.) cumulus oocyte complexes (COCs) to blastocysts were studied during culture, either in serum free tissue culture medium 199 (TCM 199) or Waymouth MB (WM). Based on different supplements added to these media, the experimental groups included: (a) no supplement (control); (b) hormones (FSH, LH and oestradiol) (c) Epidermal growth factor (EGF); (d) IGF-1; and (e) EGF + IGF-1. Experiments were conducted to note three end points: (1) nuclear maturation 24 h after culture (eight replicates); (2) fertilization 24 h after insemination (10 replicates); (3) development to blastocysts (nine replicates). The oocytes were cultured in groups of up to five per drop. Using a two-way (5 x 2) factorial model with interactions, the results were compared using generalized linear models with binomial errors and the logit link function. In experiment 1, the proportion of oocytes reaching metaphase II was higher for all the supplement treatments than the control treatment (t = 3.68, p < 0.0001). The proportion of oocytes reaching metaphase II was 74.7, 63.2, 64.7 and 81% with hormone (chi2 = 17.23, p < 0.0001), EGF (chi2 = 7.07, p = 0.007), IGF-1 (chi2 = 19.21, p = 0.002) and EGF + IGF-1 (chi2 = 33.04, p < 0.0001) supplementation, respectively, compared to 46.6% in the control (no supplement) group. Media did not have an effect on outcome. In experiment 2, the proportion of oocytes fertilized was significantly higher with hormones (31.0%, chi2 = 12.5, p = 0.0004), IGF-1 (35.7%, chi2 = 20.53, p < 0.0001), and the EGF + IGF-1 combination (49.7%, chi2 = 51.35, p < 0.0001) compared to control (16.2%). No significant effect of media was seen. In experiment 3, the proportion of oocytes that cleaved at 48 h after culturing was significantly higher for all supplement treatments compared to control. IGF-1 supplementation was the only treatment that did not produce a significantly higher rate of progression to blastocysts compared to the control. Once again, media had no effect on outcome. It was concluded that maturation, fertilization and development of buffalo oocytes were enhanced by all supplements tested. Enhancement was maximal with the combination of EGF+IGF-1. In contrast, no significant differences were found between the two types of media used.

Large plaque-type blue nevus with subcutaneous cellular nodules.

Unusual or atypical melanocytic nevi can be confused with malignant melanoma. The authors present two cases of an unusual variant of blue nevus that were misdiagnosed initially as malignancy. Both lesions were asymptomatic and characterized clinically by childhood onset, with slow enlargement during adolescence and subsequent nodule formation. One lesion, which measured 24 cm in greatest dimension, was located on the anterior chest wall of a 53-year-old woman. The other lesion, which measured approximately 15 cm in greatest dimension, was located on the lateral abdominal wall of a 20-year-old man. Both lesions were characterized by a multifocal dermal and subcutaneous proliferation of fusiform and dendritic pigmented melanocytes. The histologic appearance of individual foci ranged from dermal melanocytosis to common blue nevus and cellular blue nevus. The cellular foci were located in the subcutis and involved, in one patient, the stroma of the breast. The cells were immunoreactive for S-100 protein, gp100 (HMB-45), and Melan-A (A103). Ultrastructural analysis revealed melanocytes typical of blue nevus. The woman underwent complete excision of the lesion, and the man underwent only partial excision of the lesion. On clinical follow-up of 32 and 19 months, respectively, both patients are alive and well with no evidence of recurrence or progression. Because the lesions presented clinically as large plaques and were diagnosed histologically as blue nevi with subcutaneous foci of cellular blue nevus, we term this rare variant of blue nevus large plaque-type blue nevus with subcutaneous cellular nodules. Recognition of this lesion enhances our knowledge of the morphologic spectrum of melanocytic tumors and helps to avoid confusion with malignant melanoma.

Changing feeding trends as a cause of electrolyte depletion in infants with cystic fibrosis.

Between June 1979 and June 1980, 16 infants with cystic fibrosis (CF) were cared for at the James Whitcomb Riley Hospital for Children. Five of these children (average age 5.8 months) had a total of eight episodes of electrolyte depletion, with six episodes unassociated with high environmental temperature, fever, or significant gastrointestinal symptoms. Their primary symptoms were poor weight gain and anorexia. According to their dietary records, these five infants, at the time of their initial presentation, had an average electrolyte intake of 8 mEq of sodium, 12 mEq of potassium, and 10 mEq of chloride per day. All infants had been fed either standard infant formula or breast milk. Infant feeding surveys indicate that the estimated average sodium intake of 6-month-old infants has decreased from 45 mEq/day in 1965 to 15 mEq/day since 1977 when manufacturers stopped adding salt to baby foods. In addition, since 1971 the percentage of infants 6 months age receiving breast milk or standard infant formula rather than cow's milk, which is higher in sodium content, has increased from 33% to 72%. This decreased salt intake places the infant with CF at greater risk for electrolyte depletion than in the past. It is expected that a larger percentage of infants with CF will have electrolyte depletion as their initial symptom especially during periods of increased sweating or when electrolyte losses are experienced during gastrointestinal illnesses. CF should be suspected in any infant with electrolyte depletion, and infants known to have CF need daily salt supplementation. Serum electrolytes should be measured if the infant is experiencing weight loss or anorexia, particularly during periods of excessive salt losses.

Effect of splenectomy on morbidity and survival following curative gastrectomy for carcinoma.

We performed a retrospective analysis of 392 patients who underwent curative resection of gastric adenocarcinoma to evaluate the impact of splenectomy on survival from gastric cancer and postoperative morbidity. Twelve factors, including splenectomy, were associated with a poor prognosis by univariate analysis. Multivariate analysis identified six of these factors, but not splenectomy, as independently predictive of death due to gastric cancer. The apparent adverse effect of splenectomy was due to its association with other significant risk factors. Postoperative complications occurred more commonly in patients who underwent splenectomy than in those who did not (45% vs 21%); patients in the splenectomy group also had a higher percentage of infectious complications than those in the nonsplenectomy group (75% vs 47%). We conclude that splenectomy has no direct influence on survival, but that it increases the morbidity of curative gastrectomy and should be avoided unless the spleen is close to or invaded by the tumor.

Radiation-associated sarcoma of bone and soft tissue.

Radiation-associated sarcomas are uncommon, constituting less than 5% of all sarcomas, and generally associated with a poor prognosis. We reviewed the medical records of 565 patients with sarcoma and a second malignancy seen at our institution between 1943 and 1989; 160 of these patients (28%) were considered to have a radiation-associated sarcoma. The most common diagnosis for which radiation had been given was breast cancer (26%), followed by lymphoma (25%) and carcinoma of the cervix (14%). The most common histologic types of radiation-associated sarcoma were osteogenic (21%), malignant fibrous histiocytoma (16%), and angiosarcoma/lymphangiosarcoma (15%). Most of the tumors were high grade (87%). Three variables had prognostic significance in multivariate analysis: the presence of metastatic disease, the completeness of operative resection in patients with localized disease, and the size of the primary tumor in patients who underwent complete resection of the sarcoma. Survival was independent of histologic subtype or site of disease.

Mutagen sensitivity as an indicator of soft tissue sarcoma risk.

The etiology of soft tissue sarcoma is poorly understood. Exposure to environmental chemicals may play a role, but the data are not clear. We compared a group of soft tissue sarcoma patients with healthy controls to determine whether the mutagen sensitivity assay, a simple chromosome aberration assay using the radiomimetic bleomycin, might be useful to identify patients at risk for soft tissue sarcoma. Patients with a diagnosis of soft tissue sarcoma at Memorial Sloan-Kettering's outpatient clinic signed informed consent and donated 30 ml of blood. Controls were selected from the general population of Connecticut by random digit dialing. Unrepaired DNA damage was assessed for 100 metaphase spreads for each individual, with the number of breaks in chromatids being counted as breaks per cell (b/c). The 20 cases with soft tissue sarcoma had 1.03 mean b/c and the controls had 0.88 b/c (P = 0.16). Patients with soft tissue sarcoma were 5.7 times more likely to be mutagen sensitive than controls (P = 0.01), as determined after dividing subjects into sensitive or not sensitive groups based on the median b/c among controls. As mutagen sensitivity has been shown to be associated with a number of cancers and appears to reflect genetic susceptibility, this assay may be an appropriate biomarker for radiation sensitivity or it may be a marker of susceptibility to soft tissue sarcoma. Larger studies should be undertaken to assess these possibilities.

Sentinel lymph node evaluation in melanoma.

The surgical treatment of patients with cutaneous melanoma has been revolutionized by the development of lymphatic mapping and sentinel lymph node biopsy. This procedure involves injecting a radioactive tracer at the site of the primary melanoma (before wide excision); the tracer then travels via the lymphatics to the first draining or sentinel lymph node. The node is removed and evaluated for the presence of metastatic melanoma. In this way, patients who are most likely to benefit can be selected for regional lymphadenectomy. In addition, accurate and minimally invasive staging allows the surgeon to identify patients who may benefit from adjuvant and investigational immunotherapy. We review the development of lymphatic mapping, the technical details related to the procedure itself, and the published clinical studies using this new procedure. In addition, we discuss the controversial issues that have been raised with the introduction of sentinel lymph node biopsy.

Estimating the relative risk of developing melanoma in INK4A carriers.

Estimation of the relative risk of cancer due to rare germline mutations using population-based epidemiological techniques is challenging, since studies with very large numbers of subjects are required. In this pilot study using a novel study design, we evaluated the role of INK4A mutations in melanoma by comparing patients with multiple primary melanomas to those with single primaries. Patients were ascertained from the Surgery and Dermatology Clinics at Memorial Sloan-Kettering Cancer Center and at the Yale University Pigmented Lesion Clinic. Subjects completed a questionnaire covering risk factors for melanoma and were tested for INK4A mutations. Five (8%) of 65 patients with multiple primaries had a mutation, compared with none of 88 patients with single primaries (P=0.03). Examination of other factors, such as number of nevi on the arms of the patients, fair skin, hair and eye colour, and other phenotypic characteristics associated with the risk of melanoma, demonstrates that these factors exhibit higher prevalence in the multiple primary cases than in the single primaries. These results provide evidence of the utility of the new study design in evaluating the impact of rare but highly penetrant cancer risk factors.

Cytokine production by CD4+ T-cells responding to antigen presentation by melanoma cells.

Melanoma cells are unusual because, unlike most epithelial tumours, constitutive expression of HLA class II antigens is common. We have previously demonstrated that a peptide-specific CD4+ T-cell clone proliferates briskly in response to peptide and HLA class II expressing melanoma cell lines derived from metastases. Here we demonstrate that these CD4+ T-cells secrete large amounts of interferon-gamma (IFNgamma) and interleukin-10 (IL10), and insignificant quantities of IL2 or IL4, in response to peptide presentation by both melanoma and autologous B-cells. T-cells produced more IL10 when responding to peptide presentation by melanoma cells compared with B-cells, and less IFNgamma (P<0.01). Addition of IL12 did not alter the cytokines produced but increased the T-cell production of both, especially the production of IL10 in response to peptide presentation by melanoma cells. Our data suggest that differential cytokine production by CD4+ T-cells in response to peptide presentation by HLA class II expressing tumour cells may contribute to tolerance to tumour antigens.

Randomized, placebo-controlled trial of dietary supplementation of alpha-tocopherol on mutagen sensitivity levels in melanoma patients: a pilot trial.

We evaluated the effects of vitamin E (dl-alpha-tocopherol) on mutagen sensitivity levels in a randomized placebo-controlled pilot trial. In brief, a dietary supplement of 1000 mg/day vitamin E or a placebo was randomly administered for 3 months to melanoma outpatients clinically free of the disease. Plasma vitamin E and mutagen sensitivity levels were measured at baseline and at the end of the trial after 3 months. At baseline, we found no significant differences in plasma vitamin E and mutagen sensitivity levels between the two groups. We also measured dietary intake at baseline and found dietary vitamin E to be a poor predictor of plasma levels of vitamin E. After 3 months of supplementation, we found that plasma levels of alpha-tocopherol increased significantly (P = 0.0005) in the vitamin E compared to the placebo group. We also found a non-significant, but consistent decrease in plasma gamma-tocopherol concentrations in the vitamin E supplemented compared to the placebo group. We did not find any significant difference between the vitamin E and placebo groups in mutagen sensitivity levels either at baseline or after 3 months of supplementation. We conclude that short term vitamin E supplementation, although it causes increased blood levels of alpha-tocopherol, does not provide protection against bleomycin-induced chromosome damage.

Effectiveness and safety of small vs. large doses of enteric coated pancreatic enzymes in reducing steatorrhea in children with cystic fibrosis: a prospective randomized study.

Among cystic fibrosis (CF) centers, usual doses of enteric coated (EC) pancreatic enzymes vary from one to six capsules per meal based upon arbitrary criteria for stool and growth patterns. Large doses of non-EC enzymes are associated with increased serum urate (SU) and urinary uric acid (UUA) but data are unavailable for EC enzymes. This study compared the effectiveness and safety of a relatively large dose (patient's usual dose) versus a small dose (1/4 usual dose) of EC enzymes in nine nourished children with CF, regarding decreasing fecal fat and stool nitrogen losses and maintaining normal SU and UUA concentrations. A crossover study design randomly assigned large or small doses to two consecutive 7 day treatment periods within each child. Large doses of EC enzymes reduced steatorrhea and increased SU and UUA. SU was normal with both treatments and UUA was normal, i.e., 17 of 18 values were between the 10th and 95th percentiles for healthy children eating a normal diet. When fat excretion was greater than 10% with small doses of EC enzymes, large doses resulted in reduced fat excretion and normal UUA. These data suggest that large doses of EC enzymes reduce steatorrhea and are safe in patients who have malabsorbtion with small doses.

Effectiveness of enteric coated pancreatic enzymes given before meals in reducing steatorrhea in children with cystic fibrosis.

In vitro data indicate that length of enzyme incubation with food critically affects enzyme dissolution and presumably effectiveness. This study compared the effectiveness of enteric coated (EC) pancreatic enzymes given before meals with those given during meals (15 minutes after beginning of meal) in reducing steatorrhea in well-nourished children with cystic fibrosis. Eight children (6 years 11 months old to 14 years 7 months old) were studied in the General Clinical Research Center at Indiana University Hospital, Indianapolis. A crossover study design randomly assigned enzymes before or during meals during two consecutive 7-day treatment periods for each child. No difference in fat excretion was documented for the total group when the children who took enzymes before meals were compared with those who took enzymes during meals. However, a stepwise multiple regression analysis of the difference (before minus during) in fat excretion on sex, age, enzyme number, and treatment order documented a positive correlation of age with fat excretion (r = .83). Mean fat excretion in younger children (less than 10 years old) decreased significantly when enzymes were given before meals (7.14 +/- 1.95%) rather than during meals (9.92 +/- 1.61%) (P = .004). The difference in fat excretion (mean = 2.78 +/- 0.55%, range = 1.4% to 4%) translates into a half to one full year's growth potential. Younger children with cystic fibrosis may benefit clinically from taking EC enzymes before meals.

Specialized formulas and feedings for infants with malabsorption or formula intolerance.

The composition of specialized formulas for infants who experience malabsorption or formula intolerance is described in detail. The limited studies of efficacy, as well as a rationale for selecting an appropriate formula for infants with malabsorption or formula intolerance, are discussed. Infants with symptoms of diarrhea or emesis may have intolerance to milk lactose or milk protein. Soy formulas contain no lactose or cow's milk and should be the first choice of an alternative feeding because of cost and convenience. Some infants may be intolerant of soy as well as cow's milk protein. They benefit from formula containing neither cow's milk nor soy protein or from a specially processed milk-based formula containing hydrolyzed casein. A carbohydrate-free formula to which the desired type of carbohydrate is added may be helpful in the diagnosis and treatment of disaccharidase deficiencies and monosaccharide intolerances. Infants with extensive intestinal resections or intractable diarrhea may require specialized infant formulas with qualitative/quantitative modifications of fat, carbohydrate, and protein. Formulas with medium-chain triglycerides may be useful for infants with steatorrhea. "Preterm" formulas or milk from the infant's mother are preferred for preterm infants, since such feedings promote improved fat and carbohydrate absorption and better meet the infant's nutrient requirements.

Formulas and human milk for premature infants: a review and update.

New methods of feeding low-birth-weight infants have been developed as a result of improved knowledge concerning the nutritional requirements of the premature infant. Breast milk may offer certain nutritional and non-nutritional advantages for immature babies. Preterm milk is theoretically more appropriate than term or pooled mature breast milk. However, some nutrients may be inadequate to support intrauterine rates of growth in small premature infants. New formulas specifically designed for preterm babies appear to be safe and to promote improved weight gain, fat absorption, bone mineralization, and nitrogen retention. Nutritional needs of growing preterm infants are better met by preamture formulas than by formulas designed for term babies.

Effectiveness of two feeding methods in improving energy intake and growth of infants with cleft palate: a randomized study.

OBJECTIVE: To compare two feeding methods advocated for infants with cleft palate: (a) a squeezable plastic container with a narrow, long crosscut nipple (squeezable cleft palate nurser); and (b) a standard nipple with a crosscut (crosscut nipple). The effectiveness of a nutrition intervention protocol for these infants was also documented. DESIGN: Thirty-one infants (median age = 15 days) were randomized to one of two feeding methods (18 infants, squeezable cleft lip/palate nurser; 13 infants, crosscut nipple) within sex (21 boys, 10 girls) and palatal defect (22 cleft lip and palate, 9 isolated cleft palate) categories. The intervention included feeding technique instructions, nutrition counseling at each clinic visit, use of the same 20 kcal/oz standard formula for 12 months, and introduction of infant and soft table foods at 6 months. Four-day food records and growth data were obtained. MAIN OUTCOME MEASURES: Mean energy and protein intakes at 3 and 6 months of age and growth measurements during the first 18 months of life were obtained. STATISTICAL ANALYSES: A repeated measures analysis of variance for intakes was performed with time as the repeated measure and feeding method as the covariable. Similar analyses were completed for growth measures with sex and feeding method as covariates. RESULTS: Mean energy intake at 3 and 6 months of age (P = .24) and growth measurements during the first 18 months of life (P values: weight gain [grams per day], .73; weight, .21; length, .07; head circumference, .18; triceps and subscapular skinfolds and mid-arm circumference, .47, .48, and .69, respectively) were not significantly different. Both feeding methods were effective in supporting normal growth. APPLICATIONS: With adequate instruction related to the use of either feeding technique and close nutrition follow-up early in infancy, a dietitian or other health care practitioner may advise the use of either feeding method. These data support the need for feeding and nutrition education and early nutrition intervention.