Home parenteral nutrition (HPN) in patients with post-bariatric surgery complications.

BACKGROUND & AIMS: Obesity is a worldwide health problem. Bariatric surgery (BS) is becoming one of the most commonly used methods for fighting obesity and its associated comorbidities. However, current BS techniques can be associated with early or late complications that may require nutritional support. The aim of this retrospective observational study was to determine the indications and outcomes for patients on Home parenteral nutrition (HPN) due to post-bariatric surgery complications. METHODS: A specific questionnaire was designed by the ESPEN HAN/CIF working group and submitted to HPN centers. This questionnaire included: patient demographics, type of surgery, BMI before surgery and at start of HPN, indications for HPN including technical and nutritional complications (early within 2 months after surgery or late), outcome, PN regimen, and HPN complications. Patients were retrospectively included from January 2008 to June 2014. RESULTS: Eighteen HPN centers responded to the survey. A total of 2880 HPN patients were treated during the study period, 77 of whom had BS (65 females; mean age 51 ± 7 years); gastric bypass was performed in 69% of the patients; mean BMI was 44.4 before surgery and 23.2 at the start of HPN. Indications for HPN were early complications in 17 cases and late complications in 60 cases. Early complications were mostly anastomotic leakage/fistula; late complications were hypoalbuminemia, and vitamin and trace element deficiencies. Out of 77 patients, 16 needed a surgical re-intervention, 29 were weaned off HPN, and 6 died (no HPN-related deaths). During the HPN period, 58% of the patients were re-hospitalized and central venous complications were observed in 41%. Diabetes mellitus was described in 17/77 patients. HPN was supportive in 60 patients and exclusive in 17 patients (mean caloric intake: 23 ± 6 kcal/k BW/day and 1.2 g/kBW/day). Only 7/77 patients resumed their professional activities on HPN. CONCLUSIONS: This is the largest observational multicenter study describing the use of HPN in patients with post-BS complications. Severe hypoalbuminemia is a major late complication. Rates of re-hospitalization and CVC infection were high. HPN may be a "bridge therapy" before surgical revision after BS. The high mortality rate reflects the complexity of these cases.

Composition of personalized and standard nutritional mixtures in patients on home parenteral nutrition.

BACKGROUND/OBJECTIVES: The compounding of personalized parenteral nutrition mixtures (PPNMs) for home parenteral nutrition (HPN) gives the possibility to better satisfy nutritional requirements for patients in selected clinical conditions. The objective of this study was to compare the composition of PPNMs prescribed in selected cases, by a practitioner nutritionist, with that of industrially manufactured standard parenteral nutrition mixtures (SPNMs). SUBJECTS/METHODS: Two hundred and ninety-eight patients (151 men, 147 women, aged 17-87 years) on HPN, followed up in 2011 at our Center, were retrospectively recruited. RESULTS: Industrially manufactured SPNMs were prescribed in 230 (77.2%) patients, whereas compounded PPNMs were prescribed in 68 (22.8%). Formulation of PPNMs, adjusted for body weight, did not significantly differ from SPNMs as regards total daily calorie amount, but was significantly different as far as nutrient composition is concerned (P<0.01). Analysis on the daily amount of nutrients per kg of body weight and per patient disease showed that 16/34 (47%) benign chronic intestinal failure (CIF) patients, 47/233 (20%) cancer patients and 5/31 (16%) patients grouped as 'having other diseases' needed personalized mixtures (in PPNMs 4-9 nutrients were significantly different from those in SPNMs). Moreover, in CIF patients receiving PPNMs, frequent changes in the formulation (mean 6 times per year, range 1-28) were necessary. CONCLUSIONS: Our data suggest that, presently, PPNMs cannot be completely replaced by SPNMs owing to special needs in macro and/or micronutrients of some patients and/or the necessity of frequent changes in the nutritional mixture composition, at least until stabilization of clinical and metabolic conditions.

The prognosis of incurable cachectic cancer patients on home parenteral nutrition: a multi-centre observational study with prospective follow-up of 414 patients.

BACKGROUND: The role of home parenteral nutrition (HPN) in incurable cachectic cancer patients unable to eat is extremely controversial. The aim of this study is to analyse which factors can influence the outcome. PATIENTS AND METHODS: We studied prospectively 414 incurable cachectic (sub)obstructed cancer patients receiving HPN and analysed the association between patient or clinical characteristics and surviving status. RESULTS: Median weight loss, versus pre-disease and last 6-month period, was 24% and 16%, respectively. Median body mass index was 19.5, median KPS was 60, median life expectancy was 3 months. Mean/median survival was 4.7/3.0 months; 50.0% and 22.9% of patients survived 3 and 6 months, respectively. At the multivariable analysis, the variables significantly associated with 3- and 6-month survival were Glasgow Prognostic Score (GPS) and KPS, and GPS, KPS and tumour spread, respectively. By the aggregation of the significant variables, it was possible to dissect several classes of patients with different survival probabilities. CONCLUSIONS: The outcome of cachectic incurable cancer patients on HPN is not homogeneous. It is possible to identify groups of patients with a ≥6-month survival (possibly longer than that allowed in starvation). The indications for HPN can be modulated on these clinical/biochemical indices.

Iron absorption following a single oral dose of ferrous sulfate or ferric gluconate in patients with gastrectomy.

BACKGROUND: Iron deficiency anemia frequently occurs in gastrectomized patients. METHODS: Serum iron levels following the ingestion of a single oral dose of 105 mg elemental iron, taken as ferrous sulfate (FeS) or ferric gluconate (FeG), have been evaluated in 20 gastrectomized patients (and 20 controls). All subjects participated on 2 different test days, 1 month apart: they took a single dose of 105 mg elemental iron as FeS or FeG after a night of fasting. Serum iron concentrations at baseline, 30, 60, 120 and 180 min after the oral dose administration were measured. RESULTS: In patients and controls receiving FeG, serum iron levels did not significantly change. After oral ingestion of FeS, patients' serum iron levels gradually increased. The increase in serum iron levels was 148 and 168% at 120 and 180 min in patients (p < 0.0001 for both evaluations), whilst in controls, it was 216% at 120 min and 234% at 180 min, i.e. significantly higher than in gastrectomized patients (p < 0.001 for both evaluations). CONCLUSIONS: In gastrectomized patients, a single oral dose of FeS shows a significant increase in iron serum concentration, albeit lower than in controls. Further studies on a larger sample of patients will be necessary to confirm these results.

The good, the bad and the ugly: a tale of miR-101, miR-21 and miR-155 in pancreatic intraductal papillary mucinous neoplasms.

BACKGROUND: This multicenter study evaluated three candidate microRNAs (miRNAs) (miR-21, miR-155 and miR-101) as potential biomarkers in intraductal papillary mucinous neoplasms (IPMNs) of the pancreas. PATIENTS AND METHODS: miRNA expression was quantified by quantitative RT-PCR in 86 laser-microdissected specimens, including 65 invasive IPMNs, 16 non-invasive IPMNs and 5 normal pancreatic ductal tissues. Univariate and multivariate analyses compared miRNAs and clinical parameters with overall (OS) and disease-free survival (DFS). RESULTS: miR-21 and miR-155 were up-regulated in invasive IPMNs compared with non-invasive IPMNs, as well as in non-invasive IPMNs compared with normal tissues. Conversely, miR-101 levels were significantly higher in non-invasive IPMNs and normal tissues compared with invasive IPMNs. High levels of miR-21 were associated with worse OS [hazard ratio (HR) = 2.47, 95% confidence interval (CI) = 1.37-5.65, P = 0.0047]. Patients with high-miR-21 expression also had a shorter median DFS (10.9 versus 29.9 months, P = 0.01). Multivariate analysis confirmed miR-21 as independently prognostic for mortality and disease progression (death risk: HR = 3.3, 95% CI = 1.5-7.0, P = 0.02; progression risk: HR = 2.3, 95% CI = 1.2-4.8, P = 0.02), as well as positive lymph-node status (death risk: HR = 2.6, 95% CI = 1.1-6.3, P = 0.03; progression risk: HR = 2.2, 95% CI = 1.0-4.8, P = 0.04). CONCLUSIONS: miR-21, miR-155 and miR-101 showed significant differences in invasive versus non-invasive IPMNs. miR-21 emerged as an independent prognostic biomarker in invasive IPMNs and should be validated in prospective studies.

Hypercalcemia in cancer patients: pathobiology and management.

Hypercalcemia is the most common life-threatening metabolic disorder associated with cancer, occurring in approximately 10-30% of all patients with neoplastic disease, although it occurs much less often in the pediatric setting. Hypercalcemia can emerge in hematologic malignancies, particularly multiple myeloma, as well as assorted solid tumors, primarily lung and breast cancers, and can even dominate the clinical picture in select patients. Early diagnosis and treatment with fluids and drugs that lower calcium levels in the blood can improve symptoms in a few days, ameliorate the quality of life of these patients, and avoid delays in the implementation of further anticancer treatments. Occasionally, the symptoms of hypercalcemia can appear gradually, and may be non-specific, resembling symptoms of many cancers and other comorbidities, especially in the elderly, thus resulting in an underestimated incidence of hypercalcemia in cancer patients. Of note, there is an increasing number of antineoplastic compounds that can interfere with calcium metabolism. Taking into consideration both the severity of hypercalcemia and the tumor status, health care providers should determine and apply appropriate treatment measures. We provide a comprehensive subjective synthesis of peer-reviewed evidence on the pathophysiology and treatment of hypercalcemia in cancer patients.

Beyond RET: potential therapeutic approaches for advanced and metastatic medullary thyroid carcinoma.

Medullary thyroid carcinoma (MTC) is a rare calcitonin-producing neuroendocrine tumour that originates from the parafollicular C-cells of the thyroid gland. The RET proto-oncogene encodes the RET receptor tyrosine kinase, which has essential roles in cell survival, differentiation and proliferation. Activating mutations of RET are associated with the pathogenesis of MTC and have been demonstrated in nearly all hereditary and in 30-50% of sporadic MTC cases, making this receptor an excellent target for small-molecule inhibitors for this tumour. Clinical trials of small organic inhibitors of tyrosine kinase receptors (TKIs) targeting the RET receptor have shown efficacy for treatment of metastatic MTC with 30-50% of patients responding to these agents. Despite the importance of the RET receptor in MTC, it is clear that other signal transduction pathways, tyrosine kinase receptors, and tumour suppressor genes are involved in MTC tumourigenesis and progression. A better understanding of molecular cross-talk between these signal pathways and the RET receptor may lead to combinatorial therapy that will improve outcomes beyond what is currently possible with RET-directed TKIs. Finally, there is evidence that immunological-based therapy using dendritic cell vaccination strategies have been effective for reducing tumour mass in a small number of patients. The identification of additional MTC-specific tumour antigens and a better understanding of specific epitopes in these tumour antigens may lead to improvement of response rates.

Malignant pheochromocytomas and paragangliomas: molecular signaling pathways and emerging therapies.

Patients having malignant pheochromocytomas and paragangliomas traditionally have been treated with systemic chemotherapy and (131)I-meta-iodobenzylguanidine. However, these therapies have limited efficacy and the potential for significant toxicity. Over the last decade, researchers have discovered new gene mutations associated with malignant pheochromocytomas and paragangliomas, facilitating a better understanding of the molecular pathways involved in the development of these tumors. This new knowledge has brought with it the potential to test new medications that specifically target the signal transduction abnormalities known to be involved in malignant transformation. We are among the groups to have recently reported the use of the tyrosine kinase inhibitor sunitinib in a limited number of patients with malignant pheochromocytomas and paragangliomas. The use of sunitinib was associated with a reduction in the size of the tumors, their biochemical markers, and symptomatic improvement. In this review, we will explore these newly understood molecular pathways and the emerging therapies that may change the management of this disease.

Non-functioning pituitary adenomas infrequently harbor G-protein gene mutations.

BACKGROUND: Mutations of the genes encoding the alpha subunit of the stimulatory G protein (Gs) and of the inhibiting Gi2 protein (GNAS1 and GNAI2 genes, respectively) have been described in various endocrine neoplasias, including pituitary tumors. AIM: To search for mutations of GNAS1 and GNAI2 in a continuous series of non-functioning pituitary adenoma (NFPA) patients neurosurgically treated. SUBJECTS AND METHODS: The surgical samples of 22 patients who have been defined and characterized on a clinical, biochemical, histological, and immunohistochemical point of view have been processed for investigating the presence of the above mutations by PCR amplification of the hot spots exons 8 and 9 of GNAS1, and exons 5 and 6 of GNAI2, followed by direct sequencing. Moreover, the promoter region of GNAI2, in order to assess the prevalence of single nucleotide polymorphisms (SNP), was investigated in the same series. RESULTS: A CGT>TGT mutation at codon 201 of GNAS1 gene in a single case of NFPA was found, but no mutation of GNAI2A was demonstrated. CONCLUSIONS: This finding suggests and confirms that G-protein mutations are rare and not crucial in NFPA development. Additionally, we found a silent SNP at codon 318 in the promoter of the Gi2alpha gene in one out of the 22 NFPA.

Clinical outcome of long-term home parenteral nutrition in non-oncological patients: a report from two specialised centres.

OBJECTIVE AND METHODS: Forty-one (20 m, 21 f) non-oncological home parenteral nutrition (HPN) patients (52.0+/-16.6 years, BMI 20.2+/-4.0 kg/m(2)), enrolled from 1995 to 2005, underwent a clinical and biochemical follow-up at 3 months, 1 and 3 years. RESULTS: At admittance the Karnofsky Index ranged between 40 and 50 in 13 (31.7%) and 60 and 80 in 28 (68.3%) patients; the most frequent underlying disease was mesenteric infarction (11 patients, 27%). All had a central venous access. Mean catheterization days were 864+/-992, while mean HPN days were 630+/-668. At the 3-month follow-up, all patients were on HPN, at 1 year 24 (58.5%) and at 3 years 11 (27%). At 3 months, 1 and 3 years there was a significant increase in BMI (p=0.001), body weight (p=0.001) and Karnofsky Index (p=0.001), as well as an improvement of several biochemical parameters. Survival rate of HPN patients was 90.2% at 1 year, 87.8% at 3 years and 82.9% at 5 years. As to HPN-related complications, there was a central venous catheter (CVC) obstruction in 8 patients (19.5%) and 47 CVC infections in 24 (58.5%) patients. The infection rate was 1.32/(00) days of catheterization (1.8/(00) from 1995 to 1998 and 1.0/(00) from 1999 to 2005). Hospitalisation was necessary in over 50% of patients, and death occurred in 8, always as a consequence of the primary disease. CONCLUSIONS: The experience of the nutritional team and careful patient and caregiver training reduce CVC infection rate and the overall risk of complications possibly due to HPN.

TTF-2/FOXE1 gene polymorphisms in Sicilian patients with permanent primary congenital hypothyroidism.

Thyroid transcription factor-2 (TTF-2/FOXE1) is a polyalanine domain protein that regulates thyroid embryogenesis, but very few patients with permanent primary congenital hypothyroidism (pCH) harbor germline mutations of this or other transcription factors that are involved in thyroid development that might explain the etiology of pCH. Variations within the polyalanine tract are found in a variety of genes and are often reported in association with malformation syndromes; pCH is frequently associated with thyroid malformations and extra-thyroidal malformations. Therefore, in this study we investigated whether alanine (Ala) length polymorphisms and non-polymorphic mutations of the TTF-2 gene in pCH patients might be involved in the pathogenesis of pCH. The entire coding region of the TTF-2 gene was analyzed in 57 Sicilian patients and 142 healthy controls. We found that the homozygous Ala14 polymorphism (Ala14/14) was less frequent in the pCH group than in the controls. In contrast, significantly more pCH patients than controls harbored the Ala16 polymorphism (Ala16/16 and Ala14/16). However, neither the Ala14/14 nor the Ala16 polymorphism was related to extra-thyroidal malformations. Two of the 57 patients carried Ala11/14 and Ala12/14, and one Ala14/14 patient also had the silent polymorphism 387 C/T (Leu129Leu). Other than known polymorphic variants we found no mutation in the TTF-2 gene. Therefore, this study demonstrates that mutations in the TTF-2 gene are rare in pCH patients and suggests that variations in the length of the Ala-tract could at least partially explain the etiology of pCH but not that of extra-thyroidal malformations.

Adult home parenteral nutrition: a clinical evaluation after a 3-year experience in a Southern European centre.

AIM: To evaluate the current use of Home Parenteral Nutrition (HPN) in a Southern European region. SUBJECTS AND METHODS: A total of 159 (86 m, 73 f) HPN patients, mean age 60.1 +/- 14.2 years, BMI 18.8 +/- 3.3kg/m2, consecutively referred to the Artificial Nutrition outpatient Unit of the Federico II University Hospital in Naples (Italy), from January 2000 to December 2002 and treated for at least 4 weeks. Retrospective evaluation of baseline disease, indications and duration of HPN treatment, type of venous access, complications. RESULTS: In all, 140 (88%) were cancer and 19 (12%) noncancer patients. Main indications were carcinosis in 68 for total, and hypophagia/dysphagia in 62 patients for partial/integrative (to oral-enteral nutrition) HPN; mean duration of HPN was 81.45 +/- 110.86 days of treatment and infection rate 2.89% in the whole population and 2.66% in the 36 patients treated for more than 3 months. No other major complications have been observed. CONCLUSION: HPN is confirmed to be a safe and effective treatment when prescribed and administered by a trained team.

Three-phase sequential combined treatment with lamivudine and interferon in young patients with chronic hepatitis B.

Alpha-interferon (IFN) or lamivudine monotherapy are ineffective in treating chronic HBeAg positive patients with high viral load and low alanine aminotransferase (ALT) levels. We investigated whether priming lamivudine treatment might enhance the antiviral and immunostimulant action of lamivudine/IFN combination in young tolerant patients. Eleven chronic HBeAg positive patients received: 100 mg/day lamivudine for 3 months followed by IFN 5 MU/m2/tiw with lamivudine 100 mg/day for 6 months and then lamivudine alone 100 mg/day for 9 months. Quantitative hepatitis B virus (HBV)-DNA was evaluated during treatment and core-promoter, precore and polymerase HBV mutants were detected by direct sequencing at the end of therapy. Serum HBV-DNA levels dropped during lamivudine monotherapy and in combination with IFN. After IFN withdrawal, viraemia transiently increased to high levels in five of 11 (45%) patients who showed rt M204V/I lamivudine mutant resistant. Two patients cleared HBeAg without anti-HBe seroconversion. One patient presented core-promoter (A1762T/G1764A) and precore stop codon mutations. Hence, three-phase sequential combined lamivudine/IFN treatment reduced HBV-DNA serum level, but did not lead to HBeAg and HBV-DNA clearance in these highly viraemic, normal ALT patients. Lamivudine/IFN combination did not prevent the emergence of YMDD lamivudine resistance. New schedules of antiviral treatments must be evaluated in this population at risk of disease progression.

Predictors of survival in terminal-cancer patients with irreversible bowel obstruction receiving home parenteral nutrition.

Clinical, anthropometric, hematologic, and biochemical variables, evaluated immediately before starting nutritional treatment, were related to survival in 76 terminal-cancer patients with irreversible bowel obstruction receiving home parenteral nutrition. At baseline, abnormally low values were observed in the following percentages of patients: 40.8% for body mass index, 59.2% for serum albumin, 84.2% for hemoglobin, 48.7% for lymphocyte count, and 60% for serum cholesterol. Survival on home parenteral nutrition ranged between 6 and 301 d, with a median of 74 d. Hemoglobin, serum albumin and serum cholesterol were lower in patients with a survival of less than 3 mo. With regard to Karnofsky performance status, median survival times were 63 d for a score below or equal to 50 and 128 d for a score between 60 and 70. Albumin and a Karnofsky score above 50 (but not age, weight, body mass index, lymphocyte count, or cholesterol) emerged (with a positive sign) as predictors of survival. In conclusion, terminal-cancer patients with irreversible bowel obstruction are often malnourished, showing a high prevalence of anemia and hypoalbuminemia. Survival differs widely and can be predicted only to a limited extent from initial values of serum albumin and Karnofsky performance status.

[Congenital rubella. Present knowledge and perspectives (author's transl)]. / Rosolia congenita. Attualità e prospettive.

This paper deals with features and problems of congenital rubella and perspectives in the prevention of this infection. We discussed the factors determining whether or not the maternal infection will involve the fetus, the pathogenesis and the clinical aspects of congenital rubella, the epidemiological importance of infected infants who may be contagious for long periods of time, the problems encountered in diagnosis. The efficacy of the active immunization programs, the data available in the literature on inadvertent vaccination of pregnant women, the restriction in the prophylactic use of immunoglobulins are also reported. The great importance of the premarital serological test for women is stressed.