Protein nutrition, faecal flora and iron metabolism: the role of milk-based formulae

This paper explores the role of milk-based formulae in achieving four aspects of nutritional health in infants and toddlers: in the suckling, to mimic the amino acid metabolism and the faecal flora of a breast-fed baby; in the weanling, to achieve adequate protein intakes in later infancy and beyond and to achieve satisfactory haemoglobin concentrations in the early toddler years. Milk-based formulae have two roles in infant nutrition: as so-called breast milk substitutes and as a safety net during the weaning period; the latter role may be the more important.     

PAROXYSMAL TACHYCARDIA IN INFANCY AND CHILDHOOD I. Paroxysmal Supraventricular Tachycardia

A 1 to 30 year follow-up study of 54 infants and children with paroxysmal supraventricular tachycardia is presented. In 28 cases the first attack occurred in infancy, and in 18 of these already in the first months of life. Nine patients had organic heart disease. The WPW syndrome was diagnosed in 30 cases. When first seen, most of the infants presented signs of incipient or manifest congestive heart failure, which was very unusual in the children, most of whom had only minor symptoms. Four children had experienced brief syncopes during attacks. Digitalis was effective against congestive heart failure and, when continued, may have prevented failure during subsequent attacks. Whether digitalis and other anti-arrhythmic agents facilitated conversion to sinus rhythm could not be established in this study. Vagal stimulation was only rarely effective. Preventive treatment with digitalis or other antiarrhythmic drugs seemed to have little if any effect on the frequency of recurrent attacks. Out of 23 infants who were followed for at least 5 years, 17 had been free from attacks during the last 3 years and 13 of these had had their last attack before the age of 6 months. Out of 23 children followed for 5 years or more, only 3 had been free from recurrences during the last 3 years. Patients with the WPW-syndrome had a somewhat higher incidence of recurrent attacks.     

Importance of radiation therapy for breast cancer patients treated with high-dose chemotherapy and stem cell transplant

PURPOSE: To determine local-regional failure rates in breast cancer patients treated with surgery and high-dose chemotherapy with stem cell transplant and to relate local-regional failure to the use and timing of radiation treatment. METHODS AND MATERIALS: We retrospectively reviewed the records of 165 breast cancer patients treated on institutional protocols with surgery and high-dose chemotherapy with stem cell transplant. All patients had either Stage III disease, 10 or more positive axillary lymph nodes, or 4 or more positive axillary lymph nodes following neoadjuvant chemotherapy. Twelve patients had inflammatory breast cancer. Thirteen patients treated with breast preservation and 5 patients who died from toxicity within 30 days of transplant were excluded from the analyses of local-regional recurrences. In the remaining 147 patients, 108 were treated with adjuvant radiation and 39 were not. The disease stage distribution for these two groups was comparable. The median follow-up for surviving patients was 35 months. RESULTS: The 3- and 5-year actuarial disease-free survival (DFS) for the entire group was 60% and 51%, respectively. The 5-year rates of freedom from isolated local-regional recurrence were 95% in the patients treated with adjuvant radiation and 86% in the patients who did not receive radiation (p = 0.014, log rank comparison). The 5-year rates of any local-regional recurrence as a first event (isolated recurrences plus those with simultaneous local-regional and distant recurrences) were 92% versus 82%, respectively for patients whose treatment did and did not include radiation (p = 0.038). We could not demonstrate a correlation of the timing of radiation with the risk of local-regional recurrence. CONCLUSIONS: These data indicate that high-dose chemotherapy does not negate the importance of radiation in optimizing local-regional control in patients with high-risk breast cancer. Given the results of recent randomized trials studying postmastectomy radiation, which show that improving local-regional control improves overall survival (OS), we believe that all breast cancer patients with high-risk primary breast cancer who are treated with high-dose chemotherapy with stem cell transplant should receive radiation as a component of their treatment.     

Local-regional control in breast cancer patients with a possible genetic predisposition

PURPOSE: Local control rates for breast cancer in genetically predisposed women are poorly defined. Because such a small percentage of breast cancer patients have proven germline mutations, surrogates, such as a family history for breast cancer, have been used to examine this issue. The purpose of this study was to evaluate local-regional control following breast conservation therapy (BCT) in patients with bilateral breast cancer and a breast cancer family history. METHODS AND MATERIALS: We retrospectively reviewed records of all 58 patients with bilateral breast cancer and a breast cancer family history treated in our institution between 1959 and 1998. The primary surgical treatment was a breast-conserving procedure in 55 of the 116 breast cancer cases and a mastectomy in 61. The median follow-up was 68 months for the BCT patients and 57 months for the mastectomy-treated patients. RESULTS: Eight local-regional recurrences occurred in the 55 cases treated with BCT, resulting in 5- and 10-year actuarial local-regional control rates of 86% and 76%, respectively. In the nine cases that did not receive radiation as a component of their BCT, four developed local-regional recurrences (5- and 10-year local-regional control rates of BCT without radiation: 49% and 49%). The 5- and 10-year actuarial local-regional control rates for the 46 cases treated with BCT and radiation were 94% and 83%, respectively. In these cases, there were two late local recurrences, developing at 8 years and 9 years, respectively. A log rank comparison of radiation versus no radiation actuarial data was significant at p = 0.009. In the cases treated with BCT, a multivariate analysis of radiation use, patient age, degree of family history, margin status, and stage revealed that only the use of radiation was associated with improved local control (Cox regression analysis p = 0.021). The 10-year actuarial rates of local-regional control following mastectomy with and without radiation were 91% and 89%, respectively. CONCLUSIONS: Patients with a possible genetic predisposition to breast cancer had low 5-year rates of local recurrence when treated with breast conserving surgery and radiation, but the local failure rate exceeded 50% when radiation was omitted. Our data are consistent with the hypothesis that patients with an underlying genetic predisposition develop cancers with radiosensitive phenotypes.     

Clinical outcome of patients with lymph node-negative breast carcinoma who have sentinel lymph node micrometastases detected by immunohistochemistry

BACKGROUND: The ideal pathologic assessment of sentinel lymph nodes (SLNs) in patients with breast carcinoma remains controversial. The authors evaluated how detailed assessment of SLNs using immunohistochemistry (IHC) and serial sectioning would affect treatment decisions and outcomes in patients with breast carcinoma who had negative SLNs on standard hematoxylin and eosin staining. METHODS: The SLNs from patients who were treated between June 1998 and June, 1999 and who had negative lymph node status determined by hematoxylin and eosin staining (n = 84 patients) were evaluated further with serial sectioning and cytokeratin IHC. Patients were offered adjuvant therapy based on primary tumor factors. RESULTS: The median patient age was 57 years, and the median tumor size was 1.2 cm. At a median follow-up of 40.2 months, 81 patients (96%) were alive with no evidence of disease, 1 patient was alive with disease, 1 patient had died of disease, and 1 patient had died of other causes. Fifteen patients (18%) had micrometastases identified on IHC. Of the total 84 patients, information regarding adjuvant therapy was not available for 5 patients. Of the remaining 79 patients, 10 patients (13%) were not offered adjuvant chemotherapy but had positive SLN status determined by IHC. SLN status based on IHC evaluation did not correlate with age (P = 0.077), tumor size (P = 0.717), grade (P = 0.148), estrogen receptor status (P = 1.000), or lymphovascular invasion (P = 0.274). Furthermore, IHC-detected positive SLN status did not correlate with distant metastasis (P = 0.372) or overall or distant metastasis-free survival (P = 0.543 and P = 0.540, respectively). CONCLUSIONS: Although the finding of SLN micrometastases by IHC may change management in > 12% of patients, preliminary results suggested that such micrometastases do not affect outcomes significantly.     

Predictors of systemic recurrence and disease-specific survival after ipsilateral breast tumor recurrence

BACKGROUND: In patients with breast carcinoma, ipsilateral breast tumor recurrence (IBTR) after breast-conserving therapy (BCT) is an independent predictor of systemic recurrence and disease-specific survival (DSS). However, only a subgroup of patients with IBTR develop systemic recurrences. Therefore, the management of isolated IBTR remains controversial. The objective of the current study was to identify determinants of systemic recurrence and DSS after IBTR. METHODS: The medical records of 120 women who underwent BCT for Stage 0-III breast carcinoma between 1971 and 1996 and who subsequently developed isolated IBTR were reviewed. Clinicopathologic factors were studied using univariate and multivariate analyses for their association with DSS and the development of systemic recurrence after IBTR. RESULTS: The median time to IBTR was 59 months. At a median follow-up of 80 months after IBTR, 45 patients (37.5%) had a systemic recurrence. Initial lymph node status was the strongest predictor of systemic recurrence according to the a univariate analysis (P = 0.001). Other significant factors included lymphovascular invasion (LVI) in the primary tumor, time to IBTR < or = 48 months, clinical and pathologic IBTR tumor size > 1 cm, LVI in the recurrent tumor, and skin involvement at IBTR. In a multivariate logistic regression analysis, initially positive lymph node status (relative risk [RR], 5.3; 95% confidence interval [95% CI], 1.4-20.1; P = 0.015) and skin involvement at IBTR (RR, 15.1; 95% CI, 1.5-153.8; P = 0.022) remained independent predictors of systemic recurrence. The 5-year and 10-year DSS rates after IBTR were 78% and 68%, respectively. In a multivariate Cox proportional hazards model analysis, only LVI in the recurrent tumor was found to be an independent predictor of DSS (RR, 4.6; 95% CI, 1.5-14.1; P = 0.008). CONCLUSIONS: Patients who initially had lymph node-positive disease or skin involvement or LVI at IBTR represented especially high-risk groups that warranted consideration for aggressive, systemic treatment and novel, targeted therapies after IBTR. Determinants of prognosis after IBTR should be taken into account when evaluating the need for further systemic therapy and designing risk-stratified clinical trials.     

Improving local control with breast-conserving therapy: a 27-year single-institution experience

BACKGROUND: The risk of ipsilateral breast tumor recurrence (IBTR) after breast-conserving therapy (BCT) is associated with treatment and tumor-related variables, such as surgical margin status and the use of systemic therapy, and these variables have changed over time. Correspondingly, the authors of the current study hypothesized that the contemporary multidisciplinary management of breast carcinoma would lead to an improvement in IBTR rates after BCT. METHODS: Between 1970 and 1996, 1355 patients with pathologic Stage I-II invasive breast carcinoma underwent BCT (breast-conserving surgery and adjuvant radiation therapy) at The University of Texas M. D. Anderson Cancer Center. Contemporary methods of analyzing surgical margins were in routine use by 1994. To analyze the effect of this variable and others, patient and tumor characteristics and IBTR rates in patients treated during 1994-1996 were compared with those in patients treated from 1970 to 1993. RESULTS: Characteristics were similar in patients treated during 1994-1996 (n = 381) and those treated before 1994 (n = 974) except for patients aged >50 years (63.3% vs. 51.7%, P < 0.001), and patients who had a family history of breast carcinoma (37.9% vs. 30.8%, P = 0.017). Patients treated after 1994 were less likely to have positive or unknown margins (2.9 % vs. 24.1 %, P = 0.0001), more likely to receive chemotherapy (40.5% vs. 26%, P < 0.001), and more likely to receive hormonal therapy (33.3% vs. 19.4%, P < 0.001), but less likely to receive radiation boosts to the primary tumor bed (59.8% vs. 89%, P < 0.001). The 5-year cumulative IBTR rate was significantly lower among patients treated in 1994-1996 than among patients treated before 1994 (1.3% vs. 5.7%, P = 0.001) largely because of the drop in IBTR rates among patients aged < or = 50 years (1.4 % vs. 9.1 %, P = 0.0001). On multivariate analysis, age > 50 (hazards ratio [HR] = 0.401; P = 0.0001), presence of negative surgical margins (HR = 0.574; P = 0.017), and use of adjuvant hormonal therapy (HR = 0.402; P = 0.05) were independent predictors of improved 5-year IBTR-free survival. On subgroup analysis, use of chemotherapy was associated with increased IBTR-free survival among women aged < or = 50 years (HR = 0.383; P = 0.001). Although 5-year cumulative IBTR rates were lower among women aged > 50 years than among younger women before 1994 (2.6 % vs. 9.1%, P < 0.0001), no such difference was found in the group treated in 1994-1996 (1.2 % for age > 50 yrs vs. 1.4 % for < or = 50 yrs, P = 0.999). CONCLUSIONS: The IBTR rate after BCT appears to be declining, especially among patients < 50 years of age. However, long-term follow-up is necessary to confirm this finding. This finding may reflect changes in surgical approaches and pathologic evaluation as well as an increased use of systemic therapy. The current low incidence of IBTR with multidisciplinary management of breast carcinoma may result in more patients choosing BCT over mastectomy.     

Inpatient admissions for interventional radiology: philosophy of patient management

As an alternative to performing interventional radiology on inpatients under the care of internists and surgeons, the authors have established a cardiovascular radiology admitting service for well-screened, elective patients. The patients are admitted under the care of a cardiovascular radiology fellow and a staff physician. From April 1982 to December 1983, 133 patients were admitted to the service. Patients are cared for in a surgical ward or in an intermediate unit, as determined by the clinical situation. Advantages of this approach include a broader patient referral base, improved rapport with clinical colleagues and patients, improved follow-up data, and rapid evaluation and treatment, resulting in short hospital stays. The major disadvantages involve the commitment of time and staff necessary to provide quality care. The concept of the interventional radiologist in the role of admitting physician has important implications in terms of negotiations for additional financial compensation, commensurate with the skill and time required for performing these procedures and caring for the patient.