Surveillance for pancreatic cancer in high-risk individuals.

Background: Surveillance of individuals at high risk of pancreatic ductal adenocarcinoma (PDAC) and its precursors might lead to better outcomes. The aim of this study was to determine the prevalence and outcomes of PDAC and high-risk neoplastic precursor lesions among such patients participating in surveillance programmes. Methods: A multicentre study was conducted through the International CAncer of the Pancreas Screening (CAPS) Consortium Registry to identify high-risk individuals who had undergone pancreatic resection or progressed to advanced PDAC while under surveillance. High-risk neoplastic precursor lesions were defined as: pancreatic intraepithelial neoplasia (PanIN) 3, intraductal papillary mucinous neoplasia (IPMN) with high-grade dysplasia, and pancreatic neuroendocrine tumours at least 2 cm in diameter. Results: Of 76 high-risk individuals identified in 11 surveillance programmes, 71 had undergone surgery and five had been diagnosed with inoperable PDAC. Of the 71 patients who underwent resection, 32 (45 per cent) had PDAC or a high-risk precursor (19 PDAC, 4 main-duct IPMN, 4 branch-duct IPMN, 5 PanIN-3); the other 39 patients had lesions thought to be associated with a lower risk of neoplastic progression. Age at least 65 years, female sex, carriage of a gene mutation and location of a lesion in the head/uncinate region were associated with high-risk precursor lesions or PDAC. The survival of high-risk individuals with low-risk neoplastic lesions did not differ from that in those with high-risk precursor lesions. Survival was worse among patients with PDAC. There was no surgery-related mortality. Conclusion: A high proportion of high-risk individuals who had surgical resection for screening- or surveillance-detected pancreatic lesions had a high-risk neoplastic precursor lesion or PDAC at the time of surgery. Survival was better in high-risk individuals who had either low- or high-risk neoplastic precursor lesions compared with that in patients who developed PDAC.

Antecedentes: Se podrían obtener mejores resultados con el seguimiento de individuos de alto riesgo para adenocarcinoma ductal pancreático (pancreatic ductal adenocarcinoma, PDAC) y lesiones precursoras. El objetivo de este estudio fue determinar la prevalencia y los resultados del PDAC y de las lesiones precursoras de alto riesgo neoplásico en pacientes que participaron en programas de seguimiento. Métodos: Se llevó a cabo un estudio multicéntrico a través del registro internacional del consorcio CAPS (Common Automotive Platform Standard) para identificar a las personas de alto riesgo que se habían sometido a una resección pancreática o habían progresado a PDAC avanzado mientras estaban en seguimiento. Se definieron como lesiones neoplásicas precursoras de alto riesgo la neoplasia intraepitelial pancreática de tipo 3 (PanIN­3), la neoplasia papilar mucinosa intraductal (intraductal papillary mucinous neoplasia, IPMN) con displasia de alto grado y los tumores neuroendocrinos pancreáticos (pancreatic neuroendocrine tumours, PanNET) de ≥ 2 cm de diámetro. Resultados: De 76 individuos con lesiones de alto riesgo identificados en 11 programas de seguimiento, 71 fueron tratados quirúrgicamente y 5 fueron diagnosticados de un PDAC inoperable. De las 71 resecciones, 32 (45%) tenían PDAC o una lesión precursora de alto riesgo (19 PDAC, 4 IPMN de conducto principal, 4 IPMN de rama secundaria y 5 PanIN­3). Los otros 39 pacientes tenían lesiones que se consideraron asociadas con un menor riesgo de progresión neoplásica. La edad ≥ 65 años, el sexo femenino, el ser portador de una mutación genética y la localización de la lesión en la cabeza/proceso uncinado fueron factores asociados a las lesiones precursoras de alto riesgo o al PDAC. No hubo diferencias en la supervivencia de individuos de alto riesgo con lesiones neoplásicas de bajo riesgo frente a aquellos que presentaron lesiones precursoras de alto riesgo. La supervivencia fue peor en los pacientes con PDAC. No hubo mortalidad relacionada con la cirugía. Conclusión: Un elevado porcentaje de individuos de alto riesgo que se sometieron a resección quirúrgica tras la detección de lesiones pancreáticas en el seguimiento tenían una lesión precursora neoplásica de alto riesgo o un PDAC. La supervivencia fue mejor en individuos de alto riesgo que tenían lesiones precursoras neoplásicas de bajo o alto riesgo en comparación con aquellos pacientes que habían desarrollado un PDAC.

Phase II randomized trial of carboplatin, paclitaxel, bevacizumab with or without cixutumumab (IMC-A12) in patients with advanced non-squamous, non-small-cell lung cancer: a trial of the ECOG-ACRIN Cancer Research Group (E3508).

BACKGROUND: Cixutumumab is a fully human IgG1 monoclonal antibody to the insulin-like growth factor type I receptor that can potentially reverse resistance and enhance the efficacy of chemotherapy. METHODS: Bevacizumab-eligible patients with stage IV or recurrent non-squamous, non-small-cell lung cancer and good performance status were randomized to receive standard doses of paclitaxel, carboplatin, and bevacizumab to a maximum of six cycles followed by bevacizumab maintenance (CPB) until progression (arm A) or CPB plus cixutumumab 6 mg/kg i.v. weekly (arm B). RESULTS: Of 175 patients randomized, 153 were eligible and treated (78 in arm A; 75 in arm B). The median progression-free survival was 5.8 months (95% CI 5.4-7.1) in arm A versus 7 months (95% CI 5.7-7.6) in arm B (P = 0.33); hazard ratio 0.92 (95% CI 0.65-1.31). Objective response was 46.2% versus 58.7% in arm A versus arm B (P = 0.15). The median overall survival was 16.2 months in arm A versus 16.1 months in arm B (P = 0.95). Grade 3/4 neutropenia and febrile neutropenia, thrombocytopenia, fatigue, and hyperglycemia were increased with cixutumumab. CONCLUSIONS: The addition of cixutumumab to CPB increased toxicity without improving efficacy and is not recommended for further development in non-small-cell lung cancer. Both treatment groups had longer OS than historical controls which may be attributed to several factors, and emphasizes the value of a comparator arm in phase II trials. CLINICALTRIALS.GOV IDENTIFIER: NCT00955305.

Endoscopic pH monitoring for patients with suspected or refractory gastroesophageal reflux disease.

BACKGROUND: Wireless pH studies can offer prolonged pH monitoring, which may potentially facilitate the diagnosis and management of patients with gastroesophageal reflux disease (GERD). The aim of the present study was to evaluate the detection rate of abnormal esophageal acid exposure using prolonged pH monitoring in patients with suspected or refractory GERD symptoms. METHODS: Patients undergoing prolonged ambulatory pH studies for the evaluation of GERD-related symptoms were assessed. Patients with a known diagnosis of GERD were tested on medical therapy, while patients with suspected GERD were tested off therapy. The wireless pH capsules were placed during upper endoscopy 6 cm above the squamocolumnar junction. RESULTS: One hundred ninety-one patients underwent a total of 198 pH studies. Fifty ambulatory pH studies (25%) were excluded from the analysis: 27 patients (14%) had insufficient data capture (less than 18 h on at least one day of monitoring), 15 patients had premature capsule release (7%), seven were repeat studies (3.5%) and one had intolerable pain requiring capsule removal (0.5%). There were 115 patients undergoing pH studies who were off medication, and 33 patients were on therapy. For the two groups of patients, results were as follows: 32 (28%) and 22 (67%) patients with normal studies on both days; 58 (50%) and five (15%) patients with abnormal studies on both days; 18 (16%) and three (9%) patients with abnormal studies on day 1 only; and seven (6%) and three (9%) patients with abnormal studies on day 2 only, respectively. CONCLUSIONS: Prolonged 48 h pH monitoring can detect more abnormal esophageal acid exposure but is associated with a significant rate of incomplete studies.

Endoscopic retrograde cholangiopancreatography after pancreaticoduodenectomy for benign and malignant disease: indications and technical outcomes.

BACKGROUND AND STUDY AIMS: Patients undergoing pancreaticoduodenectomy develop postoperative complications related to surgery and their disease. Very little data are available on the role or success of endoscopic retrograde cholangiopancreatography (ERCP) in such patients. The aim of this study was to evaluate the indications and role of diagnostic and therapeutic ERCP after pancreaticoduodenectomy for both benign and malignant disease. PATIENTS AND METHODS: This study was a 10-year (1990 - 2000) single institution retrospective review of all ERCPs performed on patients who had undergone pancreaticoduodenectomy surgery. Indications for the ERCP and technical procedural success were studied. RESULTS: 29 patients with a pancreaticoduodenectomy underwent 56 ERCPs. Reasons for surgery were neoplasia and chronic pancreatitis. Indications for ERCP included evaluation of jaundice and pain. Technical success related to the clinical indication (jaundice 69 %, pain 54 %). CONCLUSION: ERCP plays an important role in the management of postpancreatic surgery problems including biliary and anastomotic strictures, and should be the modality of choice. However, surgical technique may make the afferent limb inaccessible, and the ductal anastomosis difficult to identify in patients with some types of pancreaticoduodenectomy. Closer collaboration between surgeon and endoscopist may allow alterations in surgical technique to improve postoperative ERCP success.

Endoluminal gastroplication for treatment of patients with classic gastroesophageal reflux symptoms and borderline 24-h pH studies.

BACKGROUND: Patients with classic gastroesophageal reflux disease (GERD) symptoms and borderline 24-h pH studies are not considered to be good candidates for surgical fundoplication. Endoluminal gastroplication (ELGP) is a new endoscopic treatment for patients with GERD. The aim of this study was to evaluate the efficacy of ELGP in these patients. METHODS: Patients with heartburn, regurgitation symptoms and a DeMeester score of less than 30 were studied. ELGP involved placement of two or three plications within 2 cm of the gastroesophageal junction. Clinical outcomes measured were heartburn symptom score (HSS), regurgitation frequency score (RFS) and medication use. RESULTS: Twenty-five patients (11 M, 14 F, mean age of 51 years) had a medication use of 11.5 doses of proton-pump inhibitors per week prior to ELGP. Average lower esophageal sphincter pressure measured 15 +/- 8 mmHg, and average DeMeester score was 18 +/- 8. Nine patients had hiatal hernias and 11 had esophagitis. Twenty-four patients were available for a mean follow-up of 12 months. HSS significantly decreased from 48 to 17 (P < 0.01) and RFS was reduced from 1.8 to 0.7 (P < 0.01). Proton-pump inhibitor use was 5.3 doses per week (P < 0.01) post-ELGP; 12 patients (50%) were off medications, 3 (13%) had a 50% reduction in medication use, and in 9 (37%) there was no change. Complications were bleeding in one patient and aspiration pneumonia in another patient. CONCLUSIONS: Endoluminal gastroplication provides symptomatic relief for patients with classic GERD symptoms despite medical therapy and borderline 24-h pH studies.

Clinical outcome of the use of enteral stents for palliation of patients with malignant upper GI obstruction.

BACKGROUND: The endoscopically placed enteral stent has emerged as a reasonable alternative to palliative surgery for malignant intestinal obstruction. This is a report of our experience with the use of enteral stents for nonesophageal malignant upper GI obstruction. METHODS: Data on all patients who had undergone enteral stent placement were reviewed. Those with a diagnosis of pancreatic cancer were compared with another similar cohort of patients who underwent palliative gastrojejunostomy. RESULTS: Thirty-one procedures were performed on 29 patients (mean age 67.7 years). Thirteen (45%) were men and 16 (55%) women. The diagnoses were gastric (13.8%), duodenal (10.3%), pancreatic (41.4%), metastatic (27.6%), and other malignancies (6.9%). Malignant obstruction occurred at the pylorus (20.7%), first part of duodenum (37.9%), second part of duodenum (27.6%), third part of duodenum (3.5%), and anastomotic sites (10.3%). Twenty-nine (93.5%) procedures were successful and good clinical outcome was achieved in 25 (80.6%). Re-obstruction by tumor ingrowth occurred in 2 patients after a mean of 183 days. The median survival time for patients with pancreatic cancer who underwent enteral stent placement compared with those who underwent surgical gastrojejunostomy was 94 and 92 days, charges were $9921 and $28,173, and duration of hospitalization was 4 and 14 days, respectively (latter 2 differences with p value < 0.005). CONCLUSION: Endoscopic enteral stent placement of nonesophageal malignant upper GI obstruction is a safe, efficacious, and cost-effective procedure with good clinical outcome, lower charges, and shorter hospitalization period than the surgical alternative.

Gastrointestinal stromal sarcoma--a case report of palliative enteral stenting.

We report a case of metastatic gastrointestinal stromal sarcoma (GISS) in a 33-year-old man who subsequently underwent successful palliative endoscopically-placed enteral stenting for duodenal stenosis secondary to extrinsic compression. Enteral stenting for palliative relief of malignant gastrointestinal obstruction is recommended for its safety, efficacy and cost-effectiveness.

Theory of mind and executive functions in normal human aging and Parkinson's disease.

Although the majority of research in theory of mind (TOM) has focused on young children or individuals with autism, recent investigations have begun to look at TOM throughout the lifespan and in other neurological and psychiatric populations. Some have suggested that TOM may represent a dissociable, modular brain system that is related to, but separable, from other brain functions including executive functions (EF). Recently, studies have shown that TOM performance can be compromised following an acquired brain insult (e.g., damage to the right hemisphere). However, the relationship of such impaired TOM performance to other brain functions in these cases has not been explored. This study investigated the effects of both normal human aging and Parkinson's disease on TOM. The relationship of TOM performance and EF in these groups was also examined. The results suggested that although TOM performance appeared compromised in the group of individuals with Parkinson's disease, the elderly control participants were relatively unimpaired relative to younger individuals. Significant relationships between several measures of TOM and EF were also found. The implications of these findings, and also the finding that failure on one measure of TOM did not necessarily predict failure on all measures of TOM, are discussed.

Acceptance of an ABO-incompatible mismatched (AB(+) to O(+)) liver allograft with the use of daclizumab and mycophenolate mofetil.

Liver allograft survival rates of 50% to 60% are reported in blood group A, group B, group O (ABO)-incompatible mismatched grafts even when aggressive immunosuppressive protocols, including plasmapheresis, OKT(3), cyclophosphamide, cyclosporine, prostaglandin E(1), and steroids, are used. A 59-year-old woman, blood type O(+), required emergency retransplantation posttransplantation day 2 because of primary nonfunction of the liver allograft. A blood type AB(+) allograft was used. Induction immunosuppressive therapy included tacrolimus, mycophenolate mofetil, OKT(3) (muromonab-CD(3)), steroids, and prostaglandin E(1). In addition, plasmapheresis was performed daily for 9 days. OKT(3) and prostaglandin E(1) were also discontinued postoperative day 9. Biopsy-proven acute cellular rejection was diagnosed postoperative day 12 and was treated with double-dose OKT(3) (10 mg) for another 6 days. On the day OKT(3) was discontinued, daclizumab, 60 mg, was administered intravenously. This dose was repeated every 2 weeks for a total of 5 doses. At 1-year follow-up, the patient is doing very well with normal liver function. We are unaware of previous reports of the use of daclizumab and mycophenolate mofetil as part of an immunosuppressive protocol aimed to induce acceptance of ABO-incompatible mismatched liver allografts. Based on our experience with this case, it seems that mycophenolate mofetil is an adequate replacement for cyclophosphamide. We also believe daclizumab provided adequate protection at a critical time. Further experience with both these drugs is required to establish their role in ABO-incompatible mismatched liver allografts.

The cultural bounds of maternal accommodation: how Chinese and American mothers communicate with deaf and hearing children.

Children with special needs typically require family accommodation to those needs. We explore here the extent to which cultural forces shape the accommodations mothers make when communicating with young deaf children. Sixteen mother-child dyads (8 Chinese, 8 American) were videotaped at home. In each culture, 4 mothers interacted with their deaf children, and 4 interacted with their hearing children. None of the deaf children knew sign language, nor spoke at age level. We found that mothers adjusted their communicative behaviors to their deaf children, but in every case, those adjustments were calibrated to cultural norms. American mothers, for example, increased their use of gesture with deaf children but stopped far short of the Chinese range--despite the obvious potential benefits of gesturing to children who cannot hear. These findings provide the first cross-cultural demonstration that children are, first and foremost, inculcated into their cultures and, only within that framework, then treated as special cases.

Neuropsychological function in mild hyperphenylalaninemia.

Whether specific cognitive deficits related to frontal-lobe dysfunction that have been reported in individuals with phenylketonuria (PKU) are also characteristic of mild hyperphenylalaninemia (MHP) was investigated. Tests of executive function and control tasks not assessing executive function were administered to a group of individuals with MHP and a group without MHP, similar in age, gender, and IQ. Tests of academic skills and behavior-rating questionnaires were also administered to the group with MHP. No group differences were found for any measure, suggesting that the mild elevations of phenylalanine in individuals with MHP are not sufficient to produce behavioral and cognitive impairments characteristic of PKU.

The value of intravenous heme-albumin and plasmapheresis in reducing postoperative complications of orthotopic liver transplantation for erythropoietic protoporphyria.

Erythropoietic protoporphyria (EPP) is marked by a deficiency of ferrochelatase, which occurs in all cells and tissues, preventing effective conversion of proto porphyrin IX to heme and thereby blocking effective feedback inhibition of heme synthesis. The major source of the excess protoporphyrin is the bone marrow. Protoporphyrin IX may accumulate, with resultant toxicity chiefly of the marrow, skin, nervous system, and liver. Orthotopic liver transplantation (OLT) is, at present, the only adequate intervention for severe liver compromise secondary to protoporphyrin deposition, but it has been complicated by severe photosensitivity and polyneuropathy. Intravenous heme and plasmapheresis have been proposed but not previously reported as means to reduce the protoporphyrin burden before liver transplantation. We report a man with EPP who underwent preoperative heme-albumin administration and plasmaphereses that led to marked reductions in plasma and erythrocyte protoporphyrin levels. His OLT was uneventful, and he developed neither polyneuropathy nor exacerbation of photosensitivity.

A randomized trial of Lactobacillus acidophilus BG2FO4 to treat lactose intolerance.

BACKGROUND: Lactose intolerance is the most common disorder of intestinal carbohydrate digestion. Lactobacillus acidophilus BG2FO4 is a strain of lactobacilli with properties of marked intestinal adherence and high beta-galactosidase activity. OBJECTIVE: This study was designed to determine whether oral feeding of Lactobacillus acidophilus BG2FO4 leads to a lactose-tolerant state. DESIGN: We studied 42 subjects with self-reported lactose intolerance and performed breath-hydrogen tests to determine whether they were lactose maldigesters. Subjects with established lactose maldigestion (n = 24) were invited to be randomly assigned to an omeprazole-treated (hypochlorhydric) group or a non-omeprazole-treated group, but 6 subjects chose not to participate. All randomly assigned subjects (n = 18) ingested Lactobacillus acidophilus BG2FO4 twice per day for 7 d and stool samples were collected. Breath-hydrogen tests were performed and symptom scores were recorded at baseline and after lactobacilli ingestion. RESULTS: Lactose maldigestion was established in 24 of 42 subjects (57%) with self-reported lactose intolerance. In 18 lactose-maldigesting subjects, overall hydrogen production and symptom scores after ingestion of Lactobacillus acidophilus BG2FO4 were not significantly different from baseline values. Live Lactobacillus acidophilus BG2FO4 was recovered in stool samples from 7 subjects. CONCLUSIONS: Lactose intolerance is overreported in subjects with gastrointestinal symptoms after lactose ingestion. Treatment of lactose-maldigesting subjects with and without hypochlorhydria with Lactobacillus acidophilus BG2FO4 for 7 d failed to change breath-hydrogen excretion significantly after lactose ingestion.

Lactose intolerance and irritable bowel syndrome.

A recent study on lactose intolerance and irritable bowel syndrome has shown that subjective lactose intolerance is increased in patients with irritable bowel syndrome, despite no increase in the prevalence of lactose maldigestion.

The aging gut. Nutritional issues.

With improvements in health care, living standards, and socioeconomic status, more adults are living to old age. As the population ages, it is increasingly important to understand the factors that affect the nutritional status and thus the health status of older adults. Many factors contribute to inadequate nutrition, including health status, financial capacities, mobility, exercise, and physiologic needs. This article considered only the potential changes in nutritional needs because of alterations in the gastrointestinal tract owing to aging. One of the most remarkable changes with aging is the frequent development of atrophic gastritis and the inability to secrete gastric acid. This process affects approximately a third of older adults in the United States and only recently was recognized to be due to infection by H. pylori in the majority of cases. The lack of gastric acid in atrophic gastritis may lead to small intestinal bacterial overgrowth and influences the absorption of a variety of micronutrients, including iron, folate, calcium, vitamin K, and vitamin B12. Lactose maldigestion is a frequent condition in older adults and is extremely common worldwide. The intolerance of dairy products leads to avoidance of these foods and likely contributes to the development of osteopenia. Overall, the small intestine and pancreas undergo astonishingly few clinically significant changes with aging. The relative preservation of overall gastrointestinal function with aging is likely due to the large reserve capacity of this multiorgan system. Further research is needed to define the precise nutritional needs for older adults because simple extrapolation of values from younger adults is now recognized to be insufficient. In addition, it is no longer acceptable to define adequate nutriture in terms of amounts of vitamins needed to maintain serum levels of a nutrient. Further RDAs must consider the functional implications of adequate nutrition. Nutrients in the elderly will be measured as to whether they result in improvements in markers of chronic disease such as homocysteine or, most importantly, in the prevention of chronic disease such as osteoporosis and cardiovascular disease.

Validity of the Wonderlic Personnel Test as a brief measure of intelligence in individuals referred for evaluation of head injury.

Some have argued that the Wonderlic Personnel Test (WPT) may represent a brief and efficient measure of intellectual functioning (e.g., Dodrill, 1980). The present study investigated the validity of the WPT as such a measure, in individuals with head injury. The findings suggested that, although the WPT showed relatively high agreement with the Wechsler Adult Intelligence Scale-Revised (WAIS-R) in the whole group, it did not have good agreement with WAIS-R scores on an individual case basis. Since clinical practice typically seeks to evaluate individual performance, it is suggested that the WPT is not a suitable tool for psychological assessment of individuals with known or suspected head injury.

Utility of hepatic iron index in American patients with hereditary hemochromatosis: a multicenter study.

BACKGROUND & AIMS: A hepatic iron index (hepatic iron concentration divided by age) of more than 1.9 has been proposed as useful to identify patients with homozygous hereditary hemochromatosis (HHC). There are limited data on the diagnostic use of the hepatic iron index in patients with HHC in the United States. This study evaluated the hepatic iron index in the diagnosis of HHC in a multicenter U.S. study. METHODS: Hepatic iron concentration was measured in 509 patients undergoing liver biopsy. The diagnosis of HHC was made using clinical, biochemical, and histopathologic criteria. RESULTS: Fifty-five patients met criteria for HHC; hepatic iron index was > 1.9 in 51 of 55 (93%) patients with HHC but in none of 454 patients with other liver diseases; hepatic iron concentration was > 71 mumol/g dry weight in 54 of 55 patients with HHC but only 1 of the other 454 patients. CONCLUSIONS: A hepatic iron index of > or = 1.9 can identify most U.S. patients with HHC but is < or = 1.9 in 7%. A "threshold" hepatic iron concentration of 71 mumol/g can almost always distinguish patients with HHC from patients with other liver diseases and may be a useful adjunct to the hepatic iron index in the diagnosis of HHC in the diverse U.S. population.

Enteral nutrition in acute pancreatitis.

A recent prospective and randomized study comparing enteral nutrition with total parenteral nutrition has shown that enteral nutrition may be a cost-effective alternative to total parenteral nutrition in patients with acute pancreatitis.