David A. August

Effects of purified green and black tea polyphenols on cyclooxygenase- and lipoxygenase-dependent metabolism of arachidonic acid in human colon mucosa and colon tumor tissues

The effects of green and black tea polyphenols on cyclooxygenase (COX)- and lipoxygenase (LOX)-dependent arachidonic acid metabolism in normal human colon mucosa and colon cancers were investigated. At a concentration of 30 microg/mL, (-)-epigallocatechin-3-gallate (EGCG), (-)-epigallocatechin (EGC), and (-)-epicatechin-3-gallate (ECG) from green tea and theaflavins from black tea inhibited LOX-dependent activity by 30-75%. The formation of 5-, 12-, and 15-LOX metabolites was inhibited to a similar extent. Tea polyphenols also inhibited COX-dependent arachidonic acid metabolism in microsomes from normal colon mucosa, with ECG showing the strongest inhibition. The formation of thromboxane (TBX) and 12-hydroxyheptadecatrienoic acid (HHT) was decreased to a greater extent than other metabolites. The inhibitory effects of tea polyphenols on COX activity, however, were less pronounced in tumor microsomes than in normal colon mucosal microsomes. Theaflavins strongly inhibited the formation of TBX and HHT, but increased the production of prostaglandin E(2) (PGE(2)) in tumor microsomes. The enhancing effect of theaflavins on PGE(2) production was related to the COX-2 level in the microsomes. Although theaflavin inhibited ovine COX-2, its activity in the formation of PGE(2) was stimulated by theaflavin when ovine COX-2 was mixed with microsomes, suggesting that theaflavin affects the interaction of COX-2 with other microsomal factors (e.g. PGE synthase). The present results indicate that tea polyphenols can affect arachidonic acid metabolism in human colon mucosa and colon tumors, and this action may alter the risk for colon cancer in humans.

A.S.P.E.N. Clinical Guidelines: Nutrition Support Therapy During Adult Anticancer Treatment and in Hematopoietic Cell Transplantation

Nutrition status has an important effect on quality of life and sense of well-being in cancer patients. Malnutrition and weight loss are often contributors to the cause of death in cancer patients. 1 Cancer cachexia is a syndrome characterized by progressive, involuntary weight loss. Clinical features include host tissue wasting, anorexia, skeletal muscle atrophy, anergy, fatigue, anemia, and hypoalbuminemia. Causes of cancer cachexia include anorexia, mechanical factors affecting the gastrointestinal tract related to tumor, side effects of surgery, chemotherapy and/or radiation therapy, alterations in intermediary and energy metabolism, and changes in the host cytokine and hormonal milieu. The cancer cachexia syndrome (CCS), which is observed in approximately 50% of cancer patients, involves heterogeneous physiologic and metabolic derangements resulting in potentially life-threatening malnutrition. 2 Although often seen in patients with advanced malignancies, CCS may be present in the early stages of tumor growth. Weight loss in cancer patients is of prognostic significance. For any given tumor type, survival is shorter in patients who experience pretreatment weight loss. 3-5

Home Parenteral Nutrition for Patients with Inoperable Malignant Bowel Obstruction

The use of home parenteral nutrition (HPN) in patients with inoperable malignant bowel obstruction (IMBO) is controversial. The efficacy, safety, and indications for HPN in these patients is uncertain, and its benefit is difficult to demonstrate. The records of 17 patients (9, ovarian cancer; 4, colon cancer; 4, other) with IMBO receiving HPN managed by the Nutrition Support Team (NST) at Yale-New Haven Hospital from 1980 to 1989 were reviewed. Median survival was 53 days and was longest in the two patients with appendiceal carcinomatosis (208 and 159 days), intermediate in patients with colon cancer (median 90 days), and shortest in patients with ovarian cancer (median 39 days). Survival was unrelated to age or sex. All patients died of their underlying disease; 82% of deaths occurred at home. Only one treatment-related complication requiring readmission occurred. Fourteen patients and their families (82%) perceived their therapy as highly beneficial or beneficial. The NST agreed with this assessment in 11 patients but did not share this perception in three patients. These three patients had a short duration of HPN (less than 25 days) or minimal rehabilitation. It is concluded that HPN for patients with IMBO is associated with a low complication rate, may be most beneficial for those patients with gastrointestinal tract primary tumors, and is usually perceived by patients and care providers as beneficial. HPN has palliative benefit and facilitates compassionate home care for carefully selected patients with IMBO.

Review of American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.) Clinical Guidelines for Nutrition Support in Cancer Patients: Nutrition Screening and Assessment:

It is clear that cancer patients develop complex nutrition issues. Nutrition support may or may not be indicated in these patients depending on individual patient characteristics. This review article, the first in a series of articles to examine the A.S.P.E.N. Guidelines for the Use of Parenteral and Enteral Nutrition in Adult and Pediatric Patients Cancer Guidelines, evaluates the evidence related to the use of nutrition screening and nutrition assessment in cancer patients. This first article will provide background concerning nutrition issues in cancer patients as well as discuss the role of nutrition screening and nutrition assessment in the care of cancer patients. The goal of this review is to enrich the discussion contained in the Clinical Guidelines, cite the primary literature more completely, and suggest updates to the guideline statements in light of subsequent published studies. Future articles will explore the guidelines related to nutrition support in oncology patients receiving anticancer therapies.

Carotenoids, vitamin A, and estrogen receptor status in breast cancer

Among patients with breast cancer, tumors that contain estrogen receptors (ER) are associated with improved survival and better response to hormone therapy than those not expressing these receptors. The purpose of these case comparison studies was to examine the relationship between carotenoids, vitamin A, and the tumor ER status in women at diagnosis of primary breast cancer. The focus of the first study was the relationship between dietary intake and ER status, and the focus of the second study was the relationship between ER status and the plasma carotenoid, retinol, and tocopherol concentrations. We evaluated tumor ER status and self-reported dietary intake in 142 women and plasma concentrations of carotenoids, retinol, and tocopherols in 149 women, at diagnosis of breast cancer, before any medical or surgical treatment. In the first study the overall odds of ER-positive status were increased in relation to number of mammograms in the past five years, number of breast-fed babies, dietary carotenoid intake, and more frequent intake of yellow and green vegetables. Overall odds of ER-positive status were decreased in relation to years of oral contraceptive use and preformed vitamin A intake. In the second study older women, women with higher plasma lutein concentration, and women not using beta-carotene supplements were more likely to be ER positive, when data were adjusted for body mass index and factors that may influence breast cancer risk or hormonal status. Significant independent relationships between plasma retinol or tocopherol concentrations and ER status were not observed. The strong and independent relationships between carotenoid intake, plasma lutein concentration, and ER status may relate to observations linking a carotenoid-rich diet with improved prognosis after diagnosis of breast cancer.

Nutrition Support in Surgical Oncology

This review article, the second in a series of articles to examine the American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.) Guidelines for the Use of Parenteral and Enteral Nutrition in Adult and Pediatric Patients, evaluates the evidence related to the use of nutrition support in surgical oncology patients. Cancer patients develop complex nutrition issues. Nutrition support may be indicated in malnourished cancer patients undergoing surgery, depending on individual patient characteristics. As with the first article in this series, this article provides background concerning nutrition issues in cancer patients, as well as discusses the role of nutrition support in the care of surgical cancer patients. The goal of this review is to enrich the discussion contained in the clinical guidelines as they relate to recommendations made for surgical patients, cite the primary literature more completely, and suggest updates to the guideline statements in light of subsequently published studies.

Intraoperative Fluid Administration Is Associated With Perioperative Outcomes in Pancreaticoduodenectomy: A Single Center Retrospective Analysis

Recent studies on perioperative fluid administration in patients undergoing major abdominal surgery have suggested that increased fluid loads are associated with worse perioperative outcomes. However, results of retrospective analyses of the relationship between intraoperative fluid (IOF) administration and perioperative outcomes in patients undergoing pancreaticoduodenectomy (PD) are conflicted. We sought to investigate this relationship in patients undergoing PD at our academic center.

Outcomes of microwave ablation for colorectal cancer liver metastases: A single center experience

Surgical management of colorectal cancer liver metastases continues to evolve to optimize oncologic outcomes while maximizing parenchymal preservation. Long‐term data after intraoperative microwave ablation are limited. This study investigates outcomes and patterns of recurrence in patients who underwent intraoperative microwave ablation.

Hepatic enzyme induction with phenobarbital and doxorubicin metabolism and myelotoxicity in the rabbit.

Abstract Doxorubicin (DOX) undergoes extensive liver metabolism. This study was designed to compare the pharmacokinetic and myelotoxicity profiles of DOX and metabolites with and without phenobarbital-associated hepatic enzyme induction. DOX was administered i.v. to eight rabbits with and without 7 prior days of oral phenobarbital, with venous blood samples collected between 0 and 72 hr for determination of plasma DOX and metabolite concentrations by high-performance liquid chromatography and complete blood counts obtained on days 1, 5, 7, 8, and 9. DOX AUC∞ t1/2β and CLT values were significantly reduced by phenobarbital induction (FBI), while only the formation clearance of DOX metabolites was significantly changed. PBI had no effect on nadir neutrophil counts but was associated with significantly accelerated neutrophil recovery. Hepatic enzyme induction with phenobarbital significantly reduces plasma DOX exposure while increasing the rate of metabolite formation. These effects result in significant acceleration of neutrophil recovery.

Treatment of Diaphragmatic Hernia Occurring After Transhiatal Esophagectomy

BackgroundPostesophagectomy diaphragmatic hernia (DH) is an uncommon problem but an important one to recognize and treat because of the risk of significant complications such as incarceration and strangulation. Diaphragmatic hernia appears to occur more frequently following transhiatal esophagectomy (THE) than after transthoracic procedures, likely because of the enlargement of the diaphragmatic hiatus required to perform THE.MethodsAfter 199 consecutive esophagectomies were performed at Rutgers Robert Wood Johnson University Hospital between January 2000 and June 2013, ten patients were identified with DH; all underwent diaphragmatic hernia repair (DHR). All patients who underwent esophagectomy during this time period were cataloged in a prospectively maintained database that was then retrospectively reviewed. All DH were repaired using a novel biologic plug mesh technique.ResultsTen esophagectomy patients developed DH; nine post-THE and one post-McKeown esophagectomy. One patient was excluded from analysis because of atypical presentation. Demographic data were similar between esophagectomy patients who developed DH and those who did not. Administration of neoadjuvant chemoradiation correlated with development of DH, but did not reach statistical significance. Complications directly related to DHR were few and mostly infectious, including empyema and pneumonia, and were more likely to occur in those who presented with acute obstruction. One patient presented with dysphagia post repair.ConclusionsDiaphragmatic hernia development post esophagectomy is an uncommon complication, but can have devastating results when there is bowel compromise. Repair by plugging the diaphragmatic hiatus with a biologic mesh is a safe and effective method for closing the defect and results in few complications.