Patrick Twomey

Nutrition Support in Clinical Practice: Review of Published Data and Recommendations for Future Research Directions Summary of a Conference Sponsored by the National Institutes of Health, American Society for Parenteral and Enteral Nutrition, and American Society for Clinical Nutrition

In the last 30 years, marked advances in enteral feeding techniques, venous access, and enteral and parenteral nutrient formulations have made it possible to provide nutrition support to almost all patients. Despite the abundant medical literature and widespread use of nutritional therapy, many areas of nutrition support remain controversial. Therefore, the leadership at the National Institutes of Health, The American Society for Parenteral and Enteral Nutrition, and The American Society for Clinical Nutrition convened an advisory committee to perform a critical review of the current medical literature evaluating the clinical use of nutrition support; the goal was to assess our current body of knowledge and to identify the issues that deserve further investigation. The panel was divided into five groups to evaluate the following areas: nutrition assessment, nutrition support in patients with gastrointestinal diseases, nutrition support in wasting diseases, nutrition support in critically ill patients, and perioperative nutrition support. The findings from each group are summarized in this report. This document is not meant to establish practice guidelines for nutrition support. The use of nutritional therapy requires a careful integration of data from pertinent clinical trials, clinical expertise in the illness or injury being treated, clinical expertise in nutritional therapy, and input from the patient and his/her family. (Journal of Parenteral and Enteral Nutrition 21:133-156, 1997).

Utility of Skin Testing in Nutritional Assessment: A Critical Review:

To evaluate the claim that delayed cutaneous hypersensitivity skin testing is useful in nutritional assessment of hospitalized patients, we reviewed the English language literature of the last 12 years. Although several hundred publications discussed delayed cutaneous hypersensitivity testing and nutritional status, only 15 provided new, objective data correlating these variables in hospitalized adults. Of these, only three provided age-matched control groups to control for antigen variability, lack of prior exposure, and other technical problems. The majority of reports took no account of diseases (cancer, immune disease, infection) or therapies (radiation, drugs, surgery) known to affect skin test response. In the reports specifying different degrees of malnutrition, the most important group, those with less than obvious malnutrition, were not abnormal by skin testing. Ten reports described serial skin testing during nutritional intervention. Non reported serially tested controls without nutritional intervention, important since serial testing alone can augment skin test response. Nonnutritional intercurrent therapy which might affect skin tests was seldom mentioned. In the few reports specifying that nutritional repletion was even achieved, repleted patients were not separated from unrepleted in subsequent analyses. No report examined skin testing for its predictive accuracy, cost/benefit ratio, or influence on outcome. Because of these problems in experimental design, the frequent lack of appropriate controls, and the low specificity of abnormal delayed cutaneous hypersensitivity responses, we conclude that the utility of skin testing in nutritional assessment remains unproved.

Elevated Levels of Proliferating and Recently Migrated Tumor-associated Macrophages Confer Increased Aggressiveness and Worse Outcomes in Breast Cancer

PurposeMacrophages play a major role in inflammatory processes and have been associated with poor prognosis in a variety of cancers, including breast cancer. Previously, we investigated the relationship of a subset of tumor-associated macrophages (PCNA+ TAMs) with clinicopathologic characteristics of breast cancer. We reported that high PCNA+ TAM counts were associated with hormone receptor (HR)-negative, high-grade tumors and early recurrence. To further understand the significance of elevated PCNA+ TAMs and the functionality of TAMs, we examined the expression of S100A8/S100A9 with the antibody Mac387. The heterodimeric S100A8/S100A9 complex plays a role in inflammation and is increased in several cancer types.MethodsWe performed immunohistochemistry using the Mac387 antibody on 367 invasive human breast cancer cases. Results were compared to previous PCNA+ TAM counts and were correlated with patient outcomes adjusting for HR status and histologic grade.ResultsLike PCNA+ TAMs, high Mac387 counts were associated with HR negativity, high tumor grade, younger age, and decreased recurrence-free survival. Mac387, however, appears to identify both a subset of macrophages and a subset of tumor cells. The concordance between Mac387 and PCNA+ TAM counts was low and cases that had both high Mac387 and high PCNA+ TAMs counts had a stronger association with early recurrence.ConclusionsThe presence of high numbers of PCNA+ TAMs and Mac387-positive cells in breast cancers with poor outcomes may implicate a subset of TAMs in breast cancer pathogenesis, and may ultimately serve to develop potential cellular targets for therapeutic interventions.

Gastrointestinal bleeding after operation for pancreatic cancer

Gastrointestinal bleeding after surgery for cancer of the pancreas contributes significantly to patient morbidity and to patient mortality, if the bypass was performed for palliation. Bleeding after resection of the pancreatic tumor appears to be amenable to therapy, and unaltered by the addition of vagotomy at the time of surgery. Patients undergoing palliative surgery who are expected to live beyond the postoperative period may well benefit from measures to reduce the risk of gastrointestinal bleeding.

Impaired lymphocyte responsiveness in osteosarcoma

Defects in cellular immunity have been documented in a variety of neoplasms of both lymphoid and nonlymphoid origin. Cellular immune function was studied pre-operatively in 47 patients with untreated but apparently resectable sarcomas of bone or soft tissue by measuring in vitro lymphocyte response to the mitogen PHA. This quantitative assay of lymphocyte function was used to compare patients with various subtypes of soft-tissue sarcoma (fibro, lipo, myo, and undifferentiated) to patients with osteosarcoma and to a group of over 250 age-matched normal controls. The percentage of low lymphocyte response in 32 soft-tissue sarcoma patients (19%) did not differ significantly from that in controls (16%). By contrast, 80% of 15 osteosarcoma patients had depressed lymphocyte reactivity, a highly significant difference compared both with age-matched controls (P < 0.01 by chi square) and with soft-tissue sarcoma patients (P < 0.05). This depression of lymphocyte function peculiar to osteosarcoma has important implications for understanding the pathogenesis of these tumors, for clarifying host interactions with viral agents, and for rational planning of immunotherapy.