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1.  New perspective for nutritional support of cancer patients: Enteral/parenteral nutrition 
Cancer and its treatment result in severe biochemical and physiological alterations associated with a deterioration of quality of life (QoL). Cancer-related malnutrition may evolve into cancer cachexia due to complex interactions between pro-inflammatory cytokines and the host metabolism. Depending on the type of cancer treatment (either curative or palliative), the clinical condition of the patient and nutritional status, adequate and patient-tailored nutritional intervention should be prescribed (diet counseling, oral supplementation, enteral or total parenteral nutrition). Nutritional support has been widely advocated as adjunctive therapy for a variety of underlying illnesses, including surgery and medical oncotherapy (radiation or chemotherapy for cancer). Glutamine, n-3 fatty acids and probiotics/prebiotics are therapeutic factors that potentially modulate gastrointestinal toxicity related to cancer treatments. Enteral and parenteral nutrition may help improve patient survival, functional status and QoL, yet the benefits appear to be primarily limited to patients with good functional status and with gastrointestinal disease affecting nutritional intake. Parenteral nutrition offers the possibility of increased or maintenance of the nutrient intake in patients for whom normal food intake is inadequate and for whom enteral nutrition is not feasible, is contraindicated or is not accepted by the patient. This article reviews evidence on issues relevant to enteral and parenteral nutrition in patients with cancer.
PMCID: PMC3440777  PMID: 22977559
cancer; cachexia; enteral/parenteral nutrition; n-3 fatty acids; glutamine; prebiotic-probiotic oligosaccharides
2.  A double-blind, randomized clinical trial comparing soybean oil–based versus olive oil–based lipid emulsions in adult medical–surgical intensive care unit patients requiring parenteral nutrition 
Critical care medicine  2012;40(6):1792-1798.
Parenteral nutrition has been associated with metabolic and infectious complications in intensive care unit patients. The underlying mechanism for the high risk of complications is not known but may relate to the proinflammatory effects of soybean oil–based lipid emulsions, the only Food and Drug Administration–approved lipid formulation for clinical use.
Prospective, double-blind, randomized, controlled trial.
Medical–surgical intensive care units from a major urban teaching hospital and a tertiary referral university hospital.
Adult medical–surgical intensive care unit patients.
Parenteral nutrition containing soybean oil–based (Intralipid) or olive oil–based (ClinOleic) lipid emulsions.
Differences in hospital clinical outcomes (nosocomial infections and noninfectious complications), hospital length of stay, glycemic control, inflammatory and oxidative stress markers, and granulocyte and monocyte functions between study groups.
A total of 100 patients were randomized to either soybean oil–based parenteral nutrition or olive oil–based parenteral nutrition for up to 28 days. A total of 49 patients received soybean oil–based parenteral nutrition (age 51 ± 15 yrs, body mass index 27 ± 6 kg/m2, and Acute Physiology and Chronic Health Evaluation II score 15.5 ± 7 [±SD]), and a total of 51 patients received olive oil–based lipid emulsion in parenteral nutrition (age 46 ± 19 yrs, body mass index 27 ± 8 kg/m2, and Acute Physiology and Chronic Health Evaluation II score 15.1 ± 6 [±SD]) for a mean duration of 12.9 ± 8 days. The mean hospital blood glucose concentration during parenteral nutrition was 129 ± 14 mg/dL, without differences between groups. Patients treated with soybean oil–based and olive oil–based parenteral nutrition had a similar length of stay (47 ± 47 days and 41 ± 36 days, p = .49), mortality (16.3% and 9.8%, p = .38), nosocomial infections (43% vs. 57%, p = .16), and acute renal failure (26% vs. 18%, p = .34). In addition, there were no differences in inflammatory and oxidative stress markers or in granulocyte and monocyte functions between groups.
The administration of parenteral nutrition containing soybean oil–based and olive oil–based lipid emulsion resulted in similar rates of infectious and noninfectious complications and no differences in glycemic control, inflammatory and oxidative stress markers, and immune function in critically ill adults.
PMCID: PMC3738173  PMID: 22488002
hyperglycemia; inpatient diabetes; lipid emulsion; nutrition support; olive oil; parenteral nutrition; soybean oil
3.  Nutritional Support Process for a Patient with Short Bowel Syndrome in Conjunction with Panperitonitis: A Case Report 
Clinical Nutrition Research  2013;2(2):149-153.
Short Bowel Syndrome (SBS) is a condition that causes malabsorption and nutrient deficiency because a large section of the small intestine is missing or has been surgically removed. SBS may develop congenitally or from gastroenterectomy, which often change the motility, digestive, and/or absorptive functions of the small bowel. The surgical procedure for SBS and the condition itself have high mortality rates and often lead to a range of complications associated with long-term parenteral nutrition (PN). Therefore, careful management and appropriate nutrition intervention are needed to prevent complications and to help maintain the physiologic integrity of the remaining intestinal functions. Initial postoperative care should provide adequate hydration, electrolyte support and total parenteral nutrition (TPN) to prevent fatal dehydration. Simultaneously, enteral nutrition should be gradually introduced, with the final goal of using only enteral nutrition support and/or oral intake and eliminating TPN from the diet. A patient should be considered for discharge when macro and micronutrients can be adequately supplied through enteral nutrition support or oral diet. Currently, there is more research on pediatric patients with SBS than on adult patient population. A 35-year-old man with no notable medical history was hospitalized and underwent a surgery for acute appendicitis at a local hospital. He was re-operated on the 8th day after the initial surgery due to complications and was under observation when he suddenly complained of severe abdominal pain and high fever. He was immediately transferred to a tertiary hospital where the medical team discovered free air in the abdomen. He was subsequently diagnosed with panperitonitis and underwent an emergency reoperation to explore the abdomen. Although the patient was expected to be at a high risk of malnutrition due to short bowel syndrome resulting from multiple surgeries, through intensive care under close cooperation between the medical and nutrition support team, his nutritional status improved significantly through continuous central and peripheral parenteral nutrition, enteral nutrition, and oral intake. The purpose of this paper is to report the process of the patient's recovery.
PMCID: PMC3728465  PMID: 23908982
Short bowel syndrome; Nutritional support; Enteral nutrition; Parenteral nutrition
4.  Assessment of Nutrition Education Among Pediatric Gastroenterologists: A Survey of NASPGHAN Members 
Pediatric gastroenterology is the only pediatric subspecialty with nutrition as part of its official curriculum and objective. However, pediatric gastroenterology fellows feel that their baseline knowledge in nutrition is suboptimal. The purpose of this study was to assess the perceived effectiveness of nutrition training among pediatric gastroenterologists, identify areas of need for additional education, and determine the perceived role of the gastroenterologist in obesity management.
A survey was sent to members and fellows of the North American Society of Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN) to assess general nutrition education as well as obesity management and educational needs.
A total of 272 responses were received, for an overall response rate of 15.2% (272/1,784). Most responders reported having average or above-average knowledge base in all nutritional topics. There was strong interest in additional resources and a continuing medical education (CME) module on several nutrition topics including: nutritional requirements in specific gastrointestinal (GI) disease, failure to thrive/growth failure, and parenteral nutrition support, with the format of CME dependent on the topic. There was also a strong interest in additional CME on the management of pediatric obesity (67%), as most responders felt that the management of obesity in children requires subspecialty care. However, the perceived role of the pediatric gastroenterologist was one of support to treat the gastrointestinal and hepatic co-morbidities of obesity rather than serve as the main provider of comprehensive obesity care.
Pediatric gastroenterologists identified gaps in their nutrition knowledge base that may be attributed to the current nutrition education training during fellowship. Multiple topics were identified for additional nutrition education, including obesity management. The nutrition management challenges of today necessitate improved baseline nutrition knowledge and this focus on nutrition should begin at the fellowship level.
PMCID: PMC3493684  PMID: 22699840
Nutrition education; pediatric gastroenterology; obesity
5.  Small Bowel Transplant 
The Medical Advisory Secretariat undertook a review of the evidence on the effectiveness and cost-effectiveness of small bowel transplant in the treatment of intestinal failure.
Small Bowel Transplantation
Intestinal failure is the loss of absorptive capacity of the small intestine that results in an inability to meet the nutrient and fluid requirements of the body via the enteral route. Patients with intestinal failure usually receive nutrients intravenously, a procedure known as parenteral nutrition. However, long-term parenteral nutrition is associated with complications including liver failure and loss of venous access due to recurrent infections.
Small bowel transplant is the transplantation of a cadaveric intestinal allograft for the purpose of restoring intestinal function in patients with irreversible intestinal failure. The transplant may involve the small intestine alone (isolated small bowel ISB), the small intestine and the liver (SB-L) when there is irreversible liver failure, or multiple organs including the small bowel (multivisceral MV or cluster). Although living related donor transplant is being investigated at a limited number of centres, cadaveric donors have been used in most small bowel transplants.
The actual transplant procedure takes approximately 12-18 hours. After intestinal transplant, the patient is generally placed on prophylactic antibiotic medication and immunosuppressive regimen that, in the majority of cases, would include tacrolimus, corticosteroids and an induction agent. Close monitoring for infection and rejection are essential for early treatment.
Medical Advisory Secretariat Review
The Medical Advisory Secretariat undertook a review of 35 reports from 9 case series and 1 international registry. Sample size of the individual studies ranged from 9 to 155.
As of May 2001, 651 patients had received small bowel transplant procedures worldwide. According to information from the Canadian Organ Replacement Register, a total of 27 small bowel transplants were performed in Canada from 1988 to 2002.
Patient Outcomes
The experience in small bowel transplant is still limited. International data showed that during the last decade, patient survival and graft survival rates from SBT have improved, mainly because of improved immunosuppression therapy and earlier detection and treatment of infection and rejection. The Intestinal Transplant Registry reported 1-year actuarial patient survival rates of 69% for isolated small bowel transplant, 66% for small bowel-liver transplant, and 63% for multivisceral transplant, and a graft survival rate of 55% for ISB and 63% for SB-L and MV. The range of 1-year patient survival rates reported ranged from 33%-87%. Reported 1-year graft survival rates ranged from 46-71%.
Regression analysis performed by the International Transplant Registry in 1997 indicated that centres that have performed at least 10 small bowel transplants had better patient and graft survival rates than centres that performed less than 10 transplants. However, analysis of the data up to May 2001 suggests that the critical mass of 10 transplants no longer holds true for transplants after 1995, and that good results can be achieved at any multiorgan transplant program with moderate patient volumes.
The largest Centre reported an overall 1-year patient and graft survival rate of 72% and 64% respectively, and 5-year patient and graft survival of 48% and 40% respectively. The overall 1-year patient survival rate reported for Ontario pediatric small bowel transplants was 61% with the highest survival rate of 83% for ISB.
The majority (70% or higher) of surviving small bowel transplant recipients was able to wean from parenteral nutrition and meet all caloric needs enterally. Some may need enteral or parenteral supplementation during periods of illness. Growth and weight gain in children after ISB were reported by two studies while two other studies reported a decrease in growth velocity with no catch-up growth.
The quality of life after SBT was reported to be comparable to that of patients on home enteral nutrition. A study found that while the parents of pediatric SBT recipients reported significant limitations in the physical and psychological well being of the children compared with normal school children, the pediatric SBT recipients themselves reported a quality of life similar to other school children.
Survival was found to be better in transplants performed since 1991. Patient survival was associated with the type of organ transplanted with better survival in isolated small bowel recipients.
Adverse Events
Despite improvement in patient and graft survival rates, small bowel transplant is still associated with significant mortality and morbidity.
Infection with subsequent sepsis is the leading cause of death (51.3%). Bacterial, fungal and viral infections have all been reported. The most common viral infections are cytomegalorvirus (18-40%) and Epstein-Barr virus. The latter often led to ß-cell post-transplant lymphoproliferative disease.
Graft rejection is the second leading cause of death after SBT (10.4%) and is responsible for 57% of graft removal. Acute rejection rates ranged from 51% to 83% in the major programs. Most of the acute rejection episodes were mild and responded to steroids and OKT3. Antilymphocyte therapy was needed in up to 27% of patients. Isolated small bowel allograft and positive lymphocytotoxic cross-match were found to be risk factors for acute rejection.
Post-transplant lymphoproliferative disease occurred in 21% of SBT recipients and accounted for 7% of post-transplant mortality. The frequency was higher in pediatric recipients (31%) and in adults receiving composite visceral allografts (25%). The allograft itself is often involved in post-transplant lymphoproliferative disease. The reported incidence of host versus graft disease varied widely among centers (0% - 14%).
Surgical complications were reported to occur in 85% of SB-L transplants and 25% of ISB transplants. Reoperations were required in 45% - 66% of patients in a large series and the most common reason for reoperation was intra-abdominal abscess.
The median cost of intestinal transplant in the US was reported to be approximately $275,000US (approximately CDN$429,000) per case. A US study concluded that based on the US cost of home parenteral nutrition, small bowel transplant could be cost-effective by the second year after the transplant.
There is evidence that small bowel transplant can prolong the life of some patients with irreversible intestinal failure who can no longer continue to be managed by parenteral nutrition therapy. Both patient survival and graft survival rates have improved with time. However, small bowel transplant is still associated with significant mortality and morbidity. The outcomes are inferior to those of total parenteral nutrition. Evidence suggests that this procedure should only be used when total parenteral nutrition is no longer feasible.
PMCID: PMC3387750  PMID: 23074441
6.  Review of data of the patients receiving total parenteral nutrition at the intensive care unit of a university hospital. 
Parenteral nutrition is commonly administered to patients in intensive care units who cannot be fed gastrointestinally. Several problems might be encountered during parenteral nutrition. We designed this study to evaluate two years' data of the patients who received parenteral nutrition at the intensive care unit of the university hospital. Forty-five patients who were treated at this hospital between January 1, 2004 and December 31, 2005 were included in this study. Patient data were collected via questionnaires designed based on the information in the literature. Blood, urinary, oropharyngeal and catheter entry site cultures were obtained and analyzed on the third and seventh days of the treatment. We found the following results: 31.1% of the patients received parenteral nutrition due to renal insufficiency; ready-made amino acid/lipid solutions were used in 86.7% of the patients; 77.8% of the solutions were administered through a peripheral vein; 88.6% of total parenteral nutrition solutions given thorough the peripheral vein had higher osmolarities than 800 mOsmol/L; routine Fe and Fe binding capacity, prothrombin time, cholesterol and triglyceride level assessments were not performed before the initiation of treatment; and the culture tests most commonly revealed Staphylococcus epidermidis in the blood, Candido species in urine, Streptococcus in throat, and Staphylococcus aureus at catheter entry sites. Based on these results, we suggest that organizing a nutrition support team would be useful in order to improve the quality of the nursery and to provide close and rational management and follow-up of the patients receiving total parenteral nutrition.
PMCID: PMC2569689  PMID: 17225841
7.  Nutrition support to patients undergoing gastrointestinal surgery 
Nutrition Journal  2003;2:18.
Nutritional depletion has been demonstrated to be a major determinant of the development of post-operative complications. Gastrointestinal surgery patients are at risk of nutritional depletion from inadequate nutritional intake, surgical stress and the subsequent increase in metabolic rate.
Fears of postoperative ileus and the integrity of the newly constructed anastomosis have led to treatment typically entailing starvation with administration of intravenous fluids until the passage of flatus. However, it has since been shown that prompt postoperative enteral feeding is both effective and well tolerated. Enteral feeding is also associated with specific clinical benefits such as reduced incidence of postoperative infectious complications and an improved wound healing response. Further research is required to determine whether enteral nutrition is also associated with modulation of gut function.
Studies have indicated that significant reductions in morbidity and mortality associated with perioperative Total Parenteral Nutrition (TPN) are limited to severely malnourished patients with gastrointestinal malignancy. Meta-analyses have shown that enteral nutrition is associated with fewer septic complications compared with parenteral feeding, reduced costs and a shorter hospital stay, so should be the preferred option whenever possible.
Evidence to support pre-operative nutrition support is limited, but suggests that if malnourished individuals are adequately fed for at least 7–10 days preoperatively then surgical outcome can be improved.
Ongoing research continues to explore the potential benefits of the action of glutamine on the gut and immune system for gastrointestinal surgery patients. To date it has been demonstrated that glutamine-enriched parenteral nutrition results in reduced length of stay and reduced costs in elective abdominal surgery patients. Further research is required to determine whether the routine supplementation of glutamine is warranted.
A limitation for targeted nutritional support is the lack of a standardised, validated definition of nutritional depletion. This would enable nutrition support to be more readily targeted to those surgical patients most likely to derive significant clinical benefit in terms of improved post-operative outcome.
PMCID: PMC293477  PMID: 14641921
8.  Parenteral Nutrition–Associated Liver Injury and Increased GRP94 Expression Prevented by ω-3 Fish Oil–Based Lipid Emulsion Supplementation 
Parenteral nutrition in infants with gastrointestinal disorders can be lifesaving, but it is also associated with parenteral nutrition–associated liver disease. We investigated the effects of incorporating ω-3 fish oil in a parenteral nutrition mixture on signs of parenteral nutrition–associated liver disease and explored the mechanism involved in this process.
Seven-day-old New Zealand rabbits were divided into 3 groups of 8, and for 1 week they were infused via the right jugular vein with standard total parenteral nutrition with soybean oil (TPN-soy) or TPN with ω-3 fish oil–based lipid emulsion (TPN-FO), or naturally nursed with rabbit milk (control). Serum and liver tissues were analyzed for serological indicators and pathology, respectively. Reverse-transcriptase polymerase chain reaction was used to evaluate the messenger RNA levels of the endoplasmic reticulum stress chaperone protein glucose-regulated protein 94 (GRP94) in liver tissues and GRP94 protein levels were compared through immunohistochemistry and Western blot assays.
TPN-soy animals had significantly higher serum total bilirubin, direct bilirubin, and γ-glutamyl transpeptidase and lower serum albumin than the controls (P < 0.01, each) or the TPN-FO group, which were similar to the controls (P < 0.01 cf. TPN). Damage to liver tissues of the TPN-FO group was much less than that of the TPN-soy group. GRP94 messenger RNA and protein levels in liver tissues of TPN-soy animals were significantly higher than that of the controls or TPN-FO rabbits, which were similar to the controls.
Incorporating ω-3 fish oil in parenteral nutrition emulsion greatly prevented liver dysfunction and liver tissue damage in week-old rabbit kits, possibly by preventing endoplasmic reticulum stress.
PMCID: PMC4255760  PMID: 25199039
endoplasmic reticulum stress; GRP94; ω-3 fish oil emulsion; parenteral nutrition; total parenteral nutrition–associated liver disease
9.  Survey of clinical nutrition practices of Canadian gastroenterologists 
Nutrition education is a required part of gastrointestinal training programs. The involvement of gastroenterologists in clinical nutrition once their training has been completed is unknown. The aim of the present study was to determine the practice pattern of gastroenterologists in clinical nutrition and their perceived adequacy of nutrition training during their gastroenterology (GI) fellowship.
The Canadian Association of Gastroenterology mailed a survey to all of its 463 Canadian clinician members and 88 trainee members. Components of the survey included knowledge of nutritional assessment and total parenteral nutrition, involvement in a nutrition support service, physician involvement in nutritional assessment and nutrition support teams, obesity management, insertion of gastrostomy (G) tubes and management of tube-related complications, and adequacy of training in clinical nutrition.
Sixty per cent (n=279) of the Canadian Association of Gastroenterology clinicians and 38% (n=33) of the fellows responded. Of the clinicians, 80% were practicing adult gastroenterologists with the following demographics: those practicing full time in academic centres (42%), community practice (45%), completed training in the last 10 years (32%) and those that completed training in the United States (14%). Although only 6% had a primary focus of nutrition in their GI practices, 65% were involved in nutrition support (including total parenteral nutrition), 74% placed G tubes and 68% managed at least one of the major complications of G tube insertion. Respondents felt a gastroenterologist should be the physician’s consultant on nutrition support services (89%). Areas of potential inadequate training included nutritional assessment, indications for nutrition support, management of obesity and management of G tube-related complications. The majority of clinicians (67%) and trainees (73%) felt that nutrition training in their GI fellowship was underemphasized.
The majority of Canadian gastroenterologists are involved in nutrition support. However, this survey demonstrated that nutritional training is underemphasized in most training programs. It is important for GI fellowship programs to develop standardized nutrition training that prepares trainees for their practice.
PMCID: PMC2659935  PMID: 16955149
Gastroenterology; Nutrition training
10.  Mediators between Theoretical and Practical Medieval Knowledge: Medical Notebooks from the Cairo Genizah and their Significance 
Medical History  2013;57(4):487-515.
This article presents a plethora of fragments from the medical notebooks found in the Cairo Genizah that comprise a unique source of historical data for scholarly study and for a better understanding of the ways in which medieval medical knowledge in Egypt was transferred from theory to practice and vice versa. These documents provide the most direct evidence we have for preferred practical medical recipes because they record the choices of medical practitioners in medieval Cairo. Since the language most commonly used in them was Judaeo-Arabic, they were evidently written by Jews. The medical genre in the notebooks was primarily pharmacopoeic, consisting of apparently original recipes for the treatment of various diseases. There are also a few notebooks on materia medica. The subject matter of the Genizah medical notebooks shows that they were mostly of an eclectic nature, i.e. the writers had probably learnt about these treatments and recipes from their teachers, applied them at the hospitals where they worked or copied them from the books they read. Foremost among the subjects dealt with were eye diseases, followed by skin diseases, coughs and colds, dentistry and oral hygiene, and gynaecological conditions. The writers of the Genizah notebooks apparently recorded the practical medical knowledge they wished to preserve for their future use as amateur physicians, students, traditional healers or professional practitioners.
PMCID: PMC3865955  PMID: 24069914
Cairo Genizah; History of Medicine; Jewish; Medieval Middle East; Middle Ages; Notebook
11.  An open label randomized multicentre phase IIIb trial comparing parenteral substitution versus best supportive nutritional care in subjects with pancreatic adenocarcinoma receiving 5-FU plus oxaliplatin as 2nd or higher line chemotherapy regarding clinical benefit - PANUSCO 
BMC Cancer  2009;9:412.
Pancreatic cancer is an extremely aggressive malignancy. Subjects are afflicted with a variety of disconcerting symptoms, including profound cachexia. Recent data indicate that the outcome of oncological patients suffering from cancer cachexia could be improved by parenteral nutrition and that parenteral nutrition results in an improvement of quality of life and in prolonged survival.
Currently, there is no recommendation of routine use of parenteral nutrition. Furthermore, there is no clear recommendation for 2nd line therapy (or higher) for pancreatic adenocarcinoma but often asked for.
PANUSCO is an open label, controlled, prospective, randomized, multicentre phase IIIb trial with two parallel arms. All patients will be treated with 5-fluorouracil, folinic acid and oxaliplatin on an outpatient basis at the study sites. Additionally, all patients will receive best supportive nutritional care (BSNC). In the experimental group BSNC will be expanded with parenteral nutrition (PN). In contrast, patients in the control group obtain solely BSNC. Parenteral nutrition will be applied overnight and at home by experienced medical staff.
A total of 120 patients are planned to be enrolled. Primary endpoint is the comparison of the treatment groups with respect to event-free survival (EFS), defined as the time from randomization till time to development of an event defined as either an impairment (change from baseline of at least ten points in EORTC QLQ-C30, functional domain total score) or withdrawal due to fulfilling the special defined stopping criteria for chemotherapy as well as for nutritional intervention (NI) or death from any cause (whichever occurs first).
The aim of this clinical trial is to evaluate whether parenteral nutrition in combination with defined 2nd line or higher chemotherapy has an impact on quality of life for patients suffering from pancreatic adenocarcinoma.
Trial registration
Current Controlled Trials ISRCTN60516908.
PMCID: PMC2787534  PMID: 19943918
12.  Gut hormones, and short bowel syndrome: The enigmatic role of glucagon-like peptide-2 in the regulation of intestinal adaptation 
Short bowel syndrome (SBS) refers to the malabsorption of nutrients, water, and essential vitamins as a result of disease or surgical removal of parts of the small intestine. The most common reasons for removing part of the small intestine are due to surgical intervention for the treatment of either Crohn's disease or necrotizing enterocolitis. Intestinal adaptation following resection may take weeks to months to be achieved, thus nutritional support requires a variety of therapeutic measures, which include parenteral nutrition. Improper nutrition management can leave the SBS patient malnourished and/or dehydrated, which can be life threatening. The development of therapeutic strategies that reduce both the complications and medical costs associated with SBS/long-term parenteral nutrition while enhancing the intestinal adaptive response would be valuable.
Currently, therapeutic options available for the treatment of SBS are limited. There are many potential stimulators of intestinal adaptation including peptide hormones, growth factors, and neuronally-derived components. Glucagon-like peptide-2 (GLP-2) is one potential treatment for gastrointestinal disorders associated with insufficient mucosal function. A significant body of evidence demonstrates that GLP-2 is a trophic hormone that plays an important role in controlling intestinal adaptation. Recent data from clinical trials demonstrate that GLP-2 is safe, well-tolerated, and promotes intestinal growth in SBS patients. However, the mechanism of action and the localization of the glucagon-like peptide-2 receptor (GLP-2R) remains an enigma. This review summarizes the role of a number of mucosal-derived factors that might be involved with intestinal adaptation processes; however, this discussion primarily examines the physiology, mechanism of action, and utility of GLP-2 in the regulation of intestinal mucosal growth.
PMCID: PMC4087358  PMID: 16830359
Short bowel syndrome; Glucagon-like peptide-2; Epidermal growth factor; Insulin-like growth factor-I; Parenteral nutrition; Total parenteral nutrition; Intestinal adaptation; Intestinal mucosa; Gut hormones; Enteric nervous system
13.  Intravenous Iron Sucrose for Children with Iron Deficiency Failing to Respond to Oral Iron Therapy 
Pediatric blood & cancer  2010;56(4):615-619.
For decades parenteral iron has been used in patients with iron deficiency unresponsive to oral iron therapy and in hemodialysis-dependent patients receiving erythropoietin. Newer intravenous (IV) iron formulations such as iron sucrose have replaced high molecular weight iron dextran in dialysis patients; however, the use of parenteral iron in children without renal disease has not been well defined.
Pharmacy records were reviewed on children (≤ 18 yrs of age) who received IV iron sucrose at Children's Medical Center Dallas between January 1, 2004 and June 30, 2009. Patients who received iron sucrose for chronic renal disease were excluded from analysis.
Thirty-eight children received iron sucrose for non-renal indications, 13 with iron deficiency refractory to oral iron therapy, 13 with iron malabsorption or dependence on parenteral nutrition, 7 for chronic gastrointestinal blood loss, and 5 for miscellaneous indications. Among these 38 children, who received a total of 510 doses of IV iron sucrose, there were only 6 adverse reactions. Patients in all categories had a good response to the iron sucrose, with a median hemoglobin rise of 1.9 – 3.1 g/dl depending on the indication.
Parenteral iron is a safe and effective means to treat iron deficiency in children who cannot receive or do not respond to oral iron due to intolerance, poor adherence or iron malabsorption.
PMCID: PMC3079959  PMID: 21298748
iron sucrose; adverse effects; iron deficiency
14.  Incidence of nutritional support complications in patient hospitalized in wards. multicentric study 
Colombia Médica : CM  null;43(2):147-153.
Nutritional support generates complications that must be detected and treated on time.
To estimate the incidence of some complications of nutritional support in patients admitted to general hospital wards who received nutritional support in six high-complexity institutions.
Prospective, descriptive and multicentric study in patients with nutritional support; the variables studied were medical diagnosis, nutritional condition, nutritional support duration, approach, kind of formula, and eight complications.
A total of 277 patients were evaluated; 83% received enteral nutrition and 17% received parenteral nutrition. Some 69.3% presented risk of malnourishment or severe malnourishment at admittance. About 35.4% of those receiving enteral nutrition and 39.6% of the ones who received parenteral nutrition had complications; no significant difference per support was found (p= 0.363). For the enteral nutrition, the most significant complication was the removal of the catheter (14%), followed by diarrhea (8.3%); an association between the duration of the enteral support with diarrhea, constipation and removal of the catheter was found (p < 0.05). For parenteral nutrition, hyperglycemia was the complication of highest incidence (22.9%), followed by hypophosphatemia (12.5%); all complications were associated with the duration of the support (p < 0.05). Nutritional support was suspended in 24.2% of the patients.
Complications with nutritional support in hospital-ward patients were frequent, with the removal of the catheter and hyperglycemia showing the highest incidence. Duration of the support was the variable that revealed an association with complications. Strict application of protocols could decrease the risk for complications and boost nutritional support benefits.
PMCID: PMC4001943  PMID: 24893056
Nutritional support; enteral nutrition; parenteral nutrition; complications; adults; hospitalization
15.  Intestinal pseudo-obstruction in patients with amyloidosis: clinicopathologic differences between chemical types of amyloid protein. 
Gut  1993;34(10):1412-1417.
A clinicopathologic study was made of 16 patients with amyloidosis and with clinical signs of intestinal pseudo-obstruction. amyloid deposits in the small intestine were proved in all cases by endoscopic or intra-operative biopsies, and immunohistochemical study identified the chemical types of amyloid protein: amyloid A protein (AA) in 13 cases, light chain protein (AL) in two, and beta 2-microglobulin (AH) in one. Clinically, an acute self limiting obstructive condition was evident in 13 cases with AA, and 12 of them returned to normal bowel function after receiving total parenteral nutrition. Two cases with AL and one with AH presented chronic, intermittent, obstructive symptoms, and medical treatment, including total parenteral nutrition, was ineffective with no recovery of intestinal propulsion. Pathological examination of the necropsy specimens in seven cases showed considerable differences in the preferential sites of gastrointestinal deposits between the chemical types of amyloid; extensive infiltration and replacement of the muscularis propria by amyloid deposits throughout the gastrointestinal tract, especially the small intestine, were found in the AL and the AH cases, while amyloid deposits in the myenteric plexus without appreciable muscle infiltration were shown in the AA cases. These results show that intestinal pseudo-obstruction in patients with amyloidosis is caused by either myopathy or neuropathy, and that chemical types of amyloid may determine which of the two factors has the dominant affect on the bowel function.
PMCID: PMC1374552  PMID: 8244111
16.  New therapeutic approach to corrosive burns of the upper gastrointestinal tract. 
Gut  1980;21(5):370-375.
The therapeutic approach to the management of corrosive burns of the upper gastrointestinal tract leaves a considerable morbidity and a heavy mortality rate. This work evaluates the effectiveness of a new therapeutic approach given to 94 consecutive patients. The management has been based on three major points: (1) the definition of extent of upper gastrointestinal lesions by immediate fibroendoscopy; (2) immediate protection of the upper gastrointestinal tract by total parenteral nutrition in cases with serious burns (41 cases), normal oral nutrition being allowed for minor burns (35 cases); (3) reparative surgical procedures for any of the sequelae of such burns during the fibrosing phase. The results were as follows: (a) healing, depending upon the degree of burn, occurred between eight to 90 days; (b) the frequency of subsequent local complications was small with total parenteral nutrition started a few hours after ingestion of the corrosive product; (c) after reconstructive surgery no serious complications occurred; (d) the overall morbidity stayed at a very low level (four patients). We conclude that the general prognosis of a severe burn of the upper gastrointestinal tract, without other trauma, is appreciably improved by the very early institution of total parenteral nutrition.
PMCID: PMC1419074  PMID: 6776011
17.  Total parenteral nutrition-associated cholestasis and risk factors in preterm infants 
Development of hepatic dysfunction is a well-recognized complication of total parenteral nutrition in preterm infants. Previous studies reported the incidence of total parenteral nutrition–associated cholestasis and described possible contributing factors to its pathogenesis, but little is done trying to determine its possible predictive risk factors. The aims of this study was to determine the incidence of total parenteral nutrition–associated cholestasis and to develop a possible predictive model for its occurrence.
Patients and Methods:
A review of medical records of all very low birth weight infants admitted to neonatal intensive care unit at King Khalid University Hospital, Riyadh, Saudi Arabia, between January 2001 and December 2003 was carried out. The infants were divided into two groups: Cholestasis and noncholestasis, based on direct serum bilirubin level >34 μmol/L. A multivariate logistic regression analysis was performed to calculate the statistical significance of risk factors. Receiver–operating characteristic curve was used to determine the optimal cutoff points for the significant risk factors and to calculate their sensitivity and specificity. The level of significance was set at P ≤ 0.05.
A total of 307 patients were included in the analysis. The incidence of cholestasis in the whole population was 24.1% (74 patients). Infants with cholestasis had a lower birth weight, 735.4 ± 166.4 g vs. 1185.0 ± 205.6 g for noncholestasis group (P < 0.001), whereas the mean gestational age for the two groups was 25.4 ± 2.1 week and 28.9 ± 2.1 week, respectively (P < 0.001). The significant risk factors for the development of cholestasis were birth weight (P = 0.006) with an odds ratio of 0.99 [95% confidence interval (CI), 0.98, 0.99]; sensitivity of 92%, specificity of 87%; and total parenteral nutrition duration (P < 0.001) with an odds ratio of 1.18 (95% CI, 1.10, 1.27); sensitivity of 96%, specificity of 89%.
A lower birth weight and longer duration of total parenteral nutrition were strong predictive risk factors for the development of cholestasis in preterm infants.
PMCID: PMC4196344  PMID: 25253364
Cholestasis; preterm; total parenteral nutrition
18.  Surgery and transplantation – Guidelines on Parenteral Nutrition, Chapter 18 
In surgery, indications for artificial nutrition comprise prevention and treatment of catabolism and malnutrition. Thus in general, food intake should not be interrupted postoperatively and the re-establishing of oral (e.g. after anastomosis of the colon and rectum, kidney transplantation) or enteral food intake (e.g. after an anastomosis in the upper gastrointestinal tract, liver transplantation) is recommended within 24 h post surgery. To avoid increased mortality an indication for an immediate postoperatively artificial nutrition (enteral or parenteral nutrition (PN)) also exists in patients with no signs of malnutrition, but who will not receive oral food intake for more than 7 days perioperatively or whose oral food intake does not meet their needs (e.g. less than 60–80%) for more than 14 days. In cases of absolute contraindication for enteral nutrition, there is an indication for total PN (TPN) such as in chronic intestinal obstruction with a relevant passage obstruction e.g. a peritoneal carcinoma. If energy and nutrient requirements cannot be met by oral and enteral intake alone, a combination of enteral and parenteral nutrition is indicated. Delaying surgery for a systematic nutrition therapy (enteral and parenteral) is only indicated if severe malnutrition is present. Preoperative nutrition therapy should preferably be conducted prior to hospital admission to lower the risk of nosocomial infections. The recommendations of early postoperative re-establishing oral feeding, generally apply also to paediatric patients. Standardised operative procedures should be established in order to guarantee an effective nutrition therapy.
PMCID: PMC2795372  PMID: 20049072
surgery; transplantation; fast track surgery; postoperative nutrition
19.  Concentration of selenium in plasma and erythrocytes during total parenteral nutrition in Crohn's disease. 
Gut  1985;26(1):50-54.
Plasma- and erythrocyte-selenium concentrations were determined in five consecutive patients with Crohn's disease given preoperative total parenteral nutrition - nil per os - for a mean period of 34 days per patient. No blood components were administered during the total parenteral nutrition. Before the total parenteral nutrition the plasma-selenium level and, to a less extent, the erythrocyte-selenium levels were below the reference values. After three weeks of total parenteral nutrition both concentrations had fallen. There were, however, clinical and biochemical signs of improvement during the total parenteral nutrition, as indicated by an increase in body weight, P-albumin and P-transferrin. In one female patient given 39 days of preoperative total parenteral nutrition containing 0.06 mumol (5 micrograms) selenium per 24 h the decreasing levels of plasma-selenium and erythrocyte-selenium were both correlated to the duration of the total parenteral nutrition (r = 0.87 and 0.96, respectively). The results suggest that total parenteral nutrition patients may be at risk for selenium deficiency, and that a supplementary administration of selenium via total parenteral nutrition may be required.
PMCID: PMC1432394  PMID: 3917420
20.  Controlled trial of bowel rest and nutritional support in the management of Crohn's disease. 
Gut  1988;29(10):1309-1315.
To define the role of bowel rest as an independent variable from nutritional support a prospective, randomised controlled trial was undertaken in 51 patients with active Crohn's disease unresponsive to other medical management. Nutritional support for 21 days was randomised to total parenteral nutrition and nil by mouth (n = 17), defined formula diet administered through a nasogastric tube (n = 19), or partial parenteral nutrition and oral food (n = 15). Nutrient input in the first two groups provided 40 non-protein kcal/kg ideal body weight /d and 1g/ kg/d protein respectively, while the third group received 15 non-protein kcal/kg/d and 0.3 g/kg/d protein intravenously and ate unrestricted food. Clinical remissions occurred in 71% of patients on parenteral nutrition, in 58% on the defined formula diet and in 60% on partial parenteral nutrition; the probability for each group of being in remission at one year, after successful therapy was 42%, 55%, and 56% respectively. These differences were not significant. In patients with active Crohn's disease bowel rest was not a major factor in achieving a remission during nutritional support and did not influence outcome during one year's follow-up.
PMCID: PMC1434018  PMID: 3143625
21.  Leakage of jejunal end of roux limb after total gastrectomy: management with a placement of a covered metallic stent: case report. 
Journal of Korean Medical Science  2003;18(3):437-440.
Postoperative leakage is a serious complication in patients after gastric surgery. It can lead to a rapid deterioration in the patient's condition and quality of life. Treatment is guided by the type of anastomosis and the patient's clinical status. The role of interventional radiology in gastrointestinal tract is evolving. Metallic stent placement has shown encouraging results for the palliation of gastrointestinal tract obstruction and fistula in malignant patients. We encountered a case of the leakage of jejunal end of Roux limb after total gastrectomy. This patient required a drainage procedure with long-term parenteral nutrition. We performed peroral placement of a covered metallic stent to avoid surgery and long-term parenteral nutrition, and he resumed adequate oral intake immediately after stent placement. This minimally invasive procedure is very promising for the treatment of a gastrointestinal fistula to avoid surgery and long-term parenteral nutritional support in selected cases.
PMCID: PMC3055055  PMID: 12808336
22.  Severe Gastrooesophageal Reflux Disease Associated with Foetal Alcohol Syndrome 
Case Reports in Pediatrics  2012;2012:509253.
Prenatal alcohol exposure may have adverse effects on the developing foetus resulting in significant growth restriction, characteristic craniofacial features, and central nervous system dysfunction. The toxic effects of alcohol on the developing brain are well recognised. However, little is known about the effects of alcohol on the developing gastrointestinal tract or their mechanism. There are few case reports showing an association between foetal alcohol syndrome and gastrointestinal neuropathy. We report a rare association between foetal alcohol syndrome and severe gastrooesophageal reflux disease in an infant who ultimately required fundoplication to optimise her growth and nutrition. The child had failed to respond to maximal medical treatment (domperidone and omeprazole), high calorie feeds, PEG feeding, or total parenteral nutrition. The effect of alcohol on the developing foetus is not limited to the central nervous system but also can have varied and devastating effects on the gastrointestinal tract.
PMCID: PMC3432341  PMID: 22957290
23.  An Evaluation of Nutrition Support for Terminal Cancer Patients at Teaching Hospitals in Korea 
We wanted to analyze the use of nutrition support for terminal cancer patients, the effect of discussing withdrawal of nutrition support and do-not-resuscitate (DNR) consent on the use of intravenous nutrition during the patient's last week of life and at the time of death.
Materials and Methods
The study involved 362 patients with terminal cancer from four teaching hospitals, and they all died between January 1 2003 and December 31 2005. The basic demographic data, the use of intravenous nutrition during the patient's last week of life and at death, discussion of terminal nutrition withdrawal and DNR consent were evaluated.
In the week before death, the patients received artificial nutrition such as total parenteral nutrition (31%), intravenous albumin infusion (25%), and feeding tube placements (9%). A discussion concerning withdrawal of nutrition support was limited to 25 (7%) patients. DNR consent was obtained from 294 (81%) patients. None of the patients were directly involved in any of these decisions. The discussion about withdrawal of terminal nutrition and DNR consent with the patient's surrogates did not have any effect on reducing the use of parenteral nutrition.
The majority of patients dying of terminal cancer were still given potentially futile nutritional support. Modern clinical guidelines and ethical education about nutritional support at the end of life care is urgently needed in Korean medical practice to provide proper administration of terminal nutrition for end of life care.
PMCID: PMC2741647  PMID: 19771245
Nutritional support; Terminal cancer patients
24.  A risk factor analysis of healthcare-associated fungal infections in an intensive care unit: a retrospective cohort study 
The incidence of fungal healthcare-associated infection (HAI) has increased in a major teaching hospital in the northern part of Taiwan over the past decade, especially in the intensive care units (ICUs). The purpose of this study was to determine the factors that were responsible for the outbreak and trend in the ICU.
Surveillance fungal cultures were obtained from “sterile” objects, antiseptic solutions, environment of infected patients and hands of medical personnel. Risk factors for comparison included age, gender, admission service, and total length of stay in the ICU, Acute Physiology and Chronic Health Evaluation (APACHE) II scores at admission to the ICU, main diagnosis on ICU admission, use of invasive devices, receipt of hemodialysis, total parenteral nutrition (TPN) use, history of antibiotic therapy before HAI or during ICU stay in no HAI group, and ICU discharge status (ie, dead or alive). Univariable analysis followed by multiple logistic regression analysis was performed to identify the independent risk factors for ICU fungal HAIs and ICU mortality.
There was a significant trend in ICU fungal HAIs from 1998 to 2009 (P < 0.001). A total of 516 episodes of ICU fungal HAIs were identified; the rates of various infections were urinary tract infection (UTI) (54.8%), blood stream infection (BSI) (30.6%), surgical site infection (SSI) (6.6%), pneumonia (4.5%), other sites (3.5%). The fungi identified were: yeasts (54.8%), Candida albicans (27.3%), Candida tropicalis (6.6%), Candida glabrata (6.6%), Candida parapsilosis (1.9%), Candida species (0.8%), and other fungi (1.9%). Candida albicans accounted for 63% of all Candida species. Yeasts were found in the environment of more heavily infected patients. The independent risk factors (P < 0.05) of developing ICU fungal HAIs from all sites were TPN use, sepsis, surgical patients, mechanical ventilation and an indwelling urinary catheter. The independent risk factors for ICU fungal UTI included TPN use, mechanical ventilation and an indwelling urinary catheter. The independent risk factors for ICU fungal BSI included TPN use, sepsis, and higher APACHE II score. The independent risk factors for ICU fungal pneumonia included TPN use, surgical patients. The independent risk factors for ICU fungal SSI included surgical patients, and TPN use. The odds ratios of TPN use in various infection types ranged from 3.51 to 8.82. The risk of mortality in patients with ICU fungal HAIs was over 2 times that of patients without ICU HAIs in the multiple logistic regression analysis (P < 0.001).
There was a secular trend of an increasing number of fungal HAIs in our ICU over the past decade. Patients with ICU fungal HAIs had a significantly higher mortality rate than did patients without ICU HAIs. Total parenteral nutrition was a significant risk factor for all types of ICU fungal HAIs, and its use should be monitored closely.
PMCID: PMC3548709  PMID: 23298156
Intensive care unit; Fungal infection; Outbreak surveillance; Candida; Total parenteral nutrition
25.  Nutritional therapy for the management of diabetic gastroparesis: clinical review 
Diabetic gastroparesis (DGP), or slow emptying of the stomach, is a well-established complication of diabetes mellitus and is typically considered to occur in individuals with long-standing type 1 and type 2 diabetes mellitus. Clinical consequences of DGP include induction of gastrointestinal (GI) symptoms (early satiety, abdominal distension, reflux, stomach spasm, postprandial nausea, vomiting), alteration in drug absorption, and destabilization of glycemic control (due to mismatched postprandial glycemic and insulin peaks). Effective nutritional management not only helps in alleviating the symptoms, but also in facilitating better glycemic control. Although there have been no evidence-based guidelines pertaining to the nutrition care process of the DGP, the current dietary recommendations are based on expert opinions or observational studies. The dietary management of gastroparesis needs to be tailored according to the severity of malnutrition and kind of upper GI symptom by changing the volume, consistency, frequency, fiber, fat, and carbohydrates in the meal. Small frequent meals, using more liquid calories, reducing high fat or high fiber, consuming bezoar forming foods, and adjusting meal carbohydrates based on medications or insulin helps in improving the upper GI symptoms and glycemic control. Enteral nutrition can be an option for patients who fail to stabilize their weight loss, or for those who cannot gain weight with oral feedings, while total parenteral nutrition is rarely necessary for the patient with gastroparesis.
PMCID: PMC3460636  PMID: 23055757
diabetic gastroparesis; delayed gastric emptying; diabetes mellitus; bezoar; GI symptoms; glycemic control

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