Indiana University Hospital

Nonalcoholic fatty liver disease (NAFLD) is characterized by hepatic steatosis in the absence of a history of significant alcohol use or other known liver disease. Nonalcoholic steatohepatitis (NASH) is the progressive form of NAFLD. The Pathology Committee of the NASH Clinical Research Network designed and validated a histological feature scoring system that addresses the full spectrum of lesions of NAFLD and proposed a NAFLD activity score (NAS) for use in clinical trials. The scoring system comprised 14 histological features, 4 of which were evaluated semi-quantitatively: steatosis (0-3), lobular inflammation (0-2), hepatocellular ballooning (0-2), and fibrosis (0-4). Another nine features were recorded as present or absent. An anonymized study set of 50 cases (32 from adult hepatology services, 18 from pediatric hepatology services) was assembled, coded, and circulated. For the validation study, agreement on scoring and a diagnostic categorization ("NASH," "borderline," or "not NASH") were evaluated by using weighted kappa statistics. Inter-rater agreement on adult cases was: 0.84 for fibrosis, 0.79 for steatosis, 0.56 for injury, and 0.45 for lobular inflammation. Agreement on diagnostic category was 0.61. Using multiple logistic regression, five features were independently associated with the diagnosis of NASH in adult biopsies: steatosis (P = .009), hepatocellular ballooning (P = .0001), lobular inflammation (P = .0001), fibrosis (P = .0001), and the absence of lipogranulomas (P = .001). The proposed NAS is the unweighted sum of steatosis, lobular inflammation, and hepatocellular ballooning scores. In conclusion, we present a strong scoring system and NAS for NAFLD and NASH with reasonable inter-rater reproducibility that should be useful for studies of both adults and children with any degree of NAFLD. NAS of > or =5 correlated with a diagnosis of NASH, and biopsies with scores of less than 3 were diagnosed as "not NASH."

Osteoarthritis is the most common form of arthritis, affecting millions of people in the United States. It is a complex disease whose etiology bridges biomechanics and biochemistry. Evidence is growing for the role of systemic factors (such as genetics, dietary intake, estrogen use, and bone density) and of local biomechanical factors (such as muscle weakness, obesity, and joint laxity). These risk factors are particularly important in weight-bearing joints, and modifying them may present opportunities for prevention of osteoarthritis-related pain and disability. Major advances in management to reduce pain and disability are yielding a panoply of available treatments ranging from nutriceuticals to chondrocyte transplantation, new oral anti-inflammatory medications, and health education. This article is part 1 of a two-part summary of a National Institutes of Health conference. The conference brought together experts on osteoarthritis from diverse backgrounds and provided a multidisciplinary and comprehensive summary of recent advances in the prevention of osteoarthritis onset, progression, and disability. Part 1 focuses on a new understanding of what osteoarthritis is and on risk factors that predispose to disease occurrence. It concludes with a discussion of the impact of osteoarthritis on disability.

BACKGROUND: The recurrence score based on the 21-gene breast cancer assay predicts chemotherapy benefit if it is high and a low risk of recurrence in the absence of chemotherapy if it is low; however, there is uncertainty about the benefit of chemotherapy for most patients, who have a midrange score. METHODS: We performed a prospective trial involving 10,273 women with hormone-receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative, axillary node-negative breast cancer. Of the 9719 eligible patients with follow-up information, 6711 (69%) had a midrange recurrence score of 11 to 25 and were randomly assigned to receive either chemoendocrine therapy or endocrine therapy alone. The trial was designed to show noninferiority of endocrine therapy alone for invasive disease-free survival (defined as freedom from invasive disease recurrence, second primary cancer, or death). RESULTS: Endocrine therapy was noninferior to chemoendocrine therapy in the analysis of invasive disease-free survival (hazard ratio for invasive disease recurrence, second primary cancer, or death [endocrine vs. chemoendocrine therapy], 1.08; 95% confidence interval, 0.94 to 1.24; P=0.26). At 9 years, the two treatment groups had similar rates of invasive disease-free survival (83.3% in the endocrine-therapy group and 84.3% in the chemoendocrine-therapy group), freedom from disease recurrence at a distant site (94.5% and 95.0%) or at a distant or local-regional site (92.2% and 92.9%), and overall survival (93.9% and 93.8%). The chemotherapy benefit for invasive disease-free survival varied with the combination of recurrence score and age (P=0.004), with some benefit of chemotherapy found in women 50 years of age or younger with a recurrence score of 16 to 25. CONCLUSIONS: Adjuvant endocrine therapy and chemoendocrine therapy had similar efficacy in women with hormone-receptor-positive, HER2-negative, axillary node-negative breast cancer who had a midrange 21-gene recurrence score, although some benefit of chemotherapy was found in some women 50 years of age or younger. (Funded by the National Cancer Institute and others; TAILORx ClinicalTrials.gov number, NCT00310180 .).

BACKGROUND: Prior studies with the use of a prospective-retrospective design including archival tumor samples have shown that gene-expression assays provide clinically useful prognostic information. However, a prospectively conducted study in a uniformly treated population provides the highest level of evidence supporting the clinical validity and usefulness of a biomarker. METHODS: We performed a prospective trial involving women with hormone-receptor-positive, human epidermal growth factor receptor type 2 (HER2)-negative, axillary node-negative breast cancer with tumors of 1.1 to 5.0 cm in the greatest dimension (or 0.6 to 1.0 cm in the greatest dimension and intermediate or high tumor grade) who met established guidelines for the consideration of adjuvant chemotherapy on the basis of clinicopathologic features. A reverse-transcriptase-polymerase-chain-reaction assay of 21 genes was performed on the paraffin-embedded tumor tissue, and the results were used to calculate a score indicating the risk of breast-cancer recurrence; patients were assigned to receive endocrine therapy without chemotherapy if they had a recurrence score of 0 to 10, indicating a very low risk of recurrence (on a scale of 0 to 100, with higher scores indicating a greater risk of recurrence). RESULTS: Of the 10,253 eligible women enrolled, 1626 women (15.9%) who had a recurrence score of 0 to 10 were assigned to receive endocrine therapy alone without chemotherapy. At 5 years, in this patient population, the rate of invasive disease-free survival was 93.8% (95% confidence interval [CI], 92.4 to 94.9), the rate of freedom from recurrence of breast cancer at a distant site was 99.3% (95% CI, 98.7 to 99.6), the rate of freedom from recurrence of breast cancer at a distant or local-regional site was 98.7% (95% CI, 97.9 to 99.2), and the rate of overall survival was 98.0% (95% CI, 97.1 to 98.6). CONCLUSIONS: Among patients with hormone-receptor-positive, HER2-negative, axillary node-negative breast cancer who met established guidelines for the recommendation of adjuvant chemotherapy on the basis of clinicopathologic features, those with tumors that had a favorable gene-expression profile had very low rates of recurrence at 5 years with endocrine therapy alone. (Funded by the National Cancer Institute and others; ClinicalTrials.gov number, NCT00310180.).

This document is the first update of the American College of Gastroenterology (ACG) colorectal cancer (CRC) screening recommendations since 2000. The CRC screening tests are now grouped into cancer prevention tests and cancer detection tests. Colonoscopy every 10 years, beginning at age 50, remains the preferred CRC screening strategy. It is recognized that colonoscopy is not available in every clinical setting because of economic limitations. It is also realized that not all eligible persons are willing to undergo colonoscopy for screening purposes. In these cases, patients should be offered an alternative CRC prevention test (flexible sigmoidoscopy every 5-10 years, or a computed tomography (CT) colonography every 5 years) or a cancer detection test (fecal immunochemical test for blood, FIT).

This brief review focuses on calcium balance and homeostasis and their relationship to dietary calcium intake and calcium supplementation in healthy subjects and patients with chronic kidney disease and mineral bone disorders (CKD-MBD). Calcium balance refers to the state of the calcium body stores, primarily in bone, which are largely a function of dietary intake, intestinal absorption, renal excretion, and bone remodeling. Bone calcium balance can be positive, neutral, or negative, depending on a number of factors, including growth, aging, and acquired or inherited disorders. Calcium homeostasis refers to the hormonal regulation of serum ionized calcium by parathyroid hormone, 1,25-dihydroxyvitamin D, and serum ionized calcium itself, which together regulate calcium transport at the gut, kidney, and bone. Hypercalcemia and hypocalcemia indicate serious disruption of calcium homeostasis but do not reflect calcium balance on their own. Calcium balance studies have determined the dietary and supplemental calcium requirements needed to optimize bone mass in healthy subjects. However, similar studies are needed in CKD-MBD, which disrupts both calcium balance and homeostasis, because these data in healthy subjects may not be generalizable to this patient group. Importantly, increasing evidence suggests that calcium supplementation may enhance soft tissue calcification and cardiovascular disease in CKD-MBD. Further research is needed to elucidate the risks and mechanisms of soft tissue calcification with calcium supplementation in both healthy subjects and CKD-MBD patients.

This document updates the colorectal cancer (CRC) screening recommendations of the U.S. Multi-Society Task Force of Colorectal Cancer (MSTF), which represents the American College of Gastroenterology, the American Gastroenterological Association, and The American Society for Gastrointestinal Endoscopy. CRC screening tests are ranked in 3 tiers based on performance features, costs, and practical considerations. The first-tier tests are colonoscopy every 10 years and annual fecal immunochemical test (FIT). Colonoscopy and FIT are recommended as the cornerstones of screening regardless of how screening is offered. Thus, in a sequential approach based on colonoscopy offered first, FIT should be offered to patients who decline colonoscopy. Colonoscopy and FIT are recommended as tests of choice when multiple options are presented as alternatives. A risk-stratified approach is also appropriate, with FIT screening in populations with an estimated low prevalence of advanced neoplasia and colonoscopy screening in high prevalence populations. The second-tier tests include CT colonography every 5 years, the FIT-fecal DNA test every 3 years, and flexible sigmoidoscopy every 5 to 10 years. These tests are appropriate screening tests, but each has disadvantages relative to the tier 1 tests. Because of limited evidence and current obstacles to use, capsule colonoscopy every 5 years is a third-tier test. We suggest that the Septin9 serum assay (Epigenomics, Seattle, Wash) not be used for screening. Screening should begin at age 50 years in average-risk persons, except in African Americans in whom limited evidence supports screening at 45 years. CRC incidence is rising in persons under age 50, and thorough diagnostic evaluation of young persons with suspected colorectal bleeding is recommended. Discontinuation of screening should be considered when persons up to date with screening, who have prior negative screening (particularly colonoscopy), reach age 75 or have <10 years of life expectancy. Persons without prior screening should be considered for screening up to age 85, depending on age and comorbidities. Persons with a family history of CRC or a documented advanced adenoma in a first-degree relative age <60 years or 2 first-degree relatives with these findings at any age are recommended to undergo screening by colonoscopy every 5 years, beginning 10 years before the age at diagnosis of the youngest affected relative or age 40, whichever is earlier. Persons with a single first-degree relative diagnosed at ≥60 years with CRC or an advanced adenoma can be offered average-risk screening options beginning at age 40 years.

Colorectal cancer prevention 2000: screening recommendations of the American College of Gastroenterology

BACKGROUND: The use of adjuvant chemotherapy in patients with breast cancer may be guided by clinicopathological factors and a score based on a 21-gene assay to determine the risk of recurrence. Whether the level of clinical risk of breast cancer recurrence adds prognostic information to the recurrence score is not known. METHODS: We performed a prospective trial involving 9427 women with hormone-receptor-positive, human epidermal growth factor receptor 2-negative, axillary node-negative breast cancer, in whom an assay of 21 genes had been performed, and we classified the clinical risk of recurrence of breast cancer as low or high on the basis of the tumor size and histologic grade. The effect of clinical risk was evaluated by calculating hazard ratios for distant recurrence with the use of Cox proportional-hazards models. The initial endocrine therapy was tamoxifen alone in the majority of the premenopausal women who were 50 years of age or younger. RESULTS: The level of clinical risk was prognostic of distant recurrence in women with an intermediate 21-gene recurrence score of 11 to 25 (on a scale of 0 to 100, with higher scores indicating a worse prognosis or a greater potential benefit from chemotherapy) who were randomly assigned to endocrine therapy (hazard ratio for the comparison of high vs. low clinical risk, 2.73; 95% confidence interval [CI], 1.93 to 3.87) or to chemotherapy plus endocrine (chemoendocrine) therapy (hazard ratio, 2.41; 95% CI, 1.66 to 3.48) and in women with a high recurrence score (a score of 26 to 100), all of whom were assigned to chemoendocrine therapy (hazard ratio, 3.17; 95% CI, 1.94 to 5.19). Among women who were 50 years of age or younger who had received endocrine therapy alone, the estimated (±SE) rate of distant recurrence at 9 years was less than 5% (≤1.8±0.9%) with a low recurrence score (a score of 0 to 10), irrespective of clinical risk, and 4.7±1.0% with an intermediate recurrence score and low clinical risk. In this age group, the estimated distant recurrence at 9 years exceeded 10% among women with a high clinical risk and an intermediate recurrence score who received endocrine therapy alone (12.3±2.4%) and among those with a high recurrence score who received chemoendocrine therapy (15.2±3.3%). CONCLUSIONS: Clinical-risk stratification provided prognostic information that, when added to the 21-gene recurrence score, could be used to identify premenopausal women who could benefit from more effective therapy. (Funded by the National Cancer Institute and others; ClinicalTrials.gov number, NCT00310180.).

OBJECTIVES: The impact of bowel preparation on the cost and efficiency of colonoscopy is uncertain. The aim of this study was to measure the impact of bowel preparation on total direct cost as well as procedure time and volume. METHODS: For 200 consecutive outpatient colonoscopies in persons with intact colons both at a private university hospital and at a public university hospital, we recorded the time spent suctioning fluid and feces from the colon and the time spent washing the colon to clean the mucosa. We prospectively asked colonoscopists to designate examinations that should be repeated at an interval sooner than would otherwise be recommended because of imperfect preparation. The data were used to perform a cost analysis of the economic effect of bowel preparation on direct costs of colonoscopy. RESULTS: Suctioning fluid and washing occupied 6% and 1.5% of total examination time (including insertion and withdrawal) at the public hospital and 9% and 1.3% at the private hospital. Patients at the public hospital were more likely to have an aborted examination (6.5% vs 1%, p = 0.004) and to be brought back earlier than suggested or required by current practice standards because of imperfect bowel preparation (20% vs 12.5%, p = 0.04). Cost analysis indicated that to complete the initial examinations and the first round of surveillance, imperfect bowel preparation resulted in a 12% increase in costs at the university hospital and a 22% increase at the public hospital. CONCLUSIONS: The increase in colonoscopy costs associated with imperfect preparation is substantial, and seems likely to vary among practices. Aborted examinations and surveillance examinations performed earlier than recommended because of imperfect preparation are appropriate targets for continuous quality improvement programs. More reliable bowel preparations, or measures to improve patient compliance with bowel preparation, could significantly reduce the costs of colonoscopy in clinical practice.

Testicular cancer has become a model for a curable neoplasm. Prior to the advent of cisplatin combination chemotherapy, standard chemotherapy consisted of dactinomycin, alone or in combination with chlorambucil and methotrexate. Disseminated germ cell tumors were chemosensitive to these older regimens, with a 50% objective response rate and a 10% to 20% complete remission rate; however, the cure rate was only 5% to 10%. In 1974, we began our initial cisplatin plus vinblastine plus bleomycin (PVB) chemotherapy. Thirty-three of 47 patients with disseminated germ cell tumors treated from 1974 to 1976 achieved a complete remission (CR), and an additional five (11%) were rendered disease-free with post-PVB resection of teratoma or carcinoma. Twenty-seven (57%) of these patients are continuously disease-free with a minimal follow-up of 13 + years. Thus, cisplatin-based chemotherapy produced a one-log increase in the cure rate compared with dactinomycin. A subsequent phase III study performed from 1976 to 1978 demonstrated that the vinblastine dosage could be reduced 25% from 0.4 mg/kg to 0.3 mg/kg with a reduction in toxicity but without any decrement in therapeutic efficacy. A third-generation PVB study from 1978 to 1981 documented that optimal cure rates were achieved with 12 weeks of induction therapy with PVB and that long-term maintenance therapy with vinblastine was unnecessary. In 1978, we initiated salvage therapy with cisplatin plus etoposide (VP-16) in patients not cured with PVB, and 25% of these patients were subsequently cured with this regimen. This represented the first time an adult solid tumor had been cured with a second-line regimen. In 1983, we began studies with third-line therapy with cisplatin plus ifosfamide combination chemotherapy, and even in this refractory setting, approximately 20% of patients are curable. From 1981 to 1984, we compared cisplatin plus VP-16 plus bleomycin (PVP16B) with PVB as first-line chemotherapy. There was a significant reduction in neuromuscular toxicity favoring the VP-16 arm, and furthermore, 78% of these patients were continuously disease-free compared with 66% with PVB. Approximately 75% of patients with disseminated germ cell tumors will be cured with PVP16B, and an additional 10% are curable with salvage chemotherapy. This represents the highest cure rate in any adult malignancy.

HYPOTHESIS: Pancreaticoduodenectomy (PD) is a safe procedure for a variety of periampullary conditions. DESIGN: Retrospective review of a prospectively collected database. SETTING: Academic tertiary care hospital. PATIENTS: A total of 516 consecutive patients who underwent PD. MAIN OUTCOME MEASURES: Patient outcomes and survival factors. RESULTS: Pathological examination demonstrated 57% periampullary cancers, 22% chronic pancreatitis, 12% cystic neoplasms, 4% islet cell neoplasms, and 5% other. Fifty-one percent of patients underwent pylorus preservation. Median operating time was 5 hours; blood loss, 1300 mL; and transfusion requirement, 1.5 U. Postoperative complications occurred in 43% of patients, including cardiopulmonary events (15%), fistula (9%), delayed gastric emptying (7%), and sepsis (6%). Additional surgery was required in 3% of patients, most commonly because of bleeding. Perioperative mortality was 3.9% overall but only 1.8% in patients with chronic pancreatitis; 25% of patients who died had preoperative complications associated with their periampullary condition. Three-year survival was 15% after resection for pancreatic cancer, 42% for duodenal cancer, 53% for ampullary cancer, and 62% for bile duct cancer. Univariate predictors of long-term survival in patients with periampullary adenocarcinoma included elevated glucose levels, liver function test results, abnormal tumor markers, blood loss, transfusion requirement, type of operation, and pathologic findings (periampullary adenocarcinoma type, differentiation, and margin and node status). Multivariate predictors were serum total bilirubin level, blood loss, operation type, diagnosis, and lymph node status. CONCLUSIONS: Pancreaticoduodenectomy continues to be associated with considerable morbidity. With careful patient selection, PD can be performed safely. Long-term survival in patients with periampullary adenocarcinoma can be predicted by preoperative laboratory values, intraoperative factors, and pathologic findings.

BACKGROUND: Allogeneic hematopoietic stem-cell transplant recipients often receive fluconazole or an amphotericin B preparation for antifungal prophylaxis. Because of concerns about fungal resistance with fluconazole and toxicity with amphotericin B, alternative prophylactic regimens have become necessary. OBJECTIVE: To compare the efficacy and safety of intravenous and oral itraconazole with the efficacy and safety of intravenous and oral fluconazole for long-term prophylaxis of fungal infections. DESIGN: Open-label, multicenter, randomized trial. SETTING: Five transplantation centers in the United States. PATIENTS: 140 patients undergoing allogeneic hematopoietic stem-cell transplantation. INTERVENTION: Itraconazole (200 mg intravenously every 12 hours for 2 days followed by 200 mg intravenously every 24 hours or a 200-mg oral solution every 12 hours) or fluconazole (400 mg intravenously or orally every 24 hours) from day 1 until day 100 after transplantation. MEASUREMENTS: Proven invasive or superficial fungal infection, drug-related side effects, mortality from fungal infection, and overall mortality. RESULTS: Proven invasive fungal infections occurred in 6 of 71 itraconazole recipients (9%) and in 17 of 67 fluconazole recipients (25%) during the first 180 days after transplantation (difference, -16 percentage points [95% CI, -29.2 to -4.7 percentage points]; P = 0.01). Superficial fungal infections occurred in 3 of 71 itraconazole recipients (4%) and in 2 of 67 fluconazole recipients (3%). In a multivariable analysis using factors known to affect the risk for invasive fungal infection after hematopoietic stem-cell transplantation, prophylaxis with itraconazole was still associated with fewer invasive fungal infections (odds ratio, 0.300 [CI, 0.111 to 0.814]; P = 0.02) caused by either yeasts or molds. More fungal pathogens were found to be resistant to fluconazole than to itraconazole. Except for more frequent gastrointestinal side effects (nausea, vomiting, diarrhea, or abdominal pain) in patients given itraconazole (24% vs. 9%; difference, 15 percentage points [CI, 2.9 to 27.0 percentage points]; P = 0.02), both itraconazole and fluconazole were well tolerated. The overall mortality rate was similar in each group (32 of 71 patients in the itraconazole group [45%] vs. 28 of 67 patients in the fluconazole group [42%]; difference, 3 percentage points [CI, -13.2 to 19.8 percentage points]; P > 0.2), but fewer deaths were related to fungal infection in patients given itraconazole (6 of 71 [9%]) than in patients given fluconazole (12 of 67 [18%]) (difference, 9 percentage points [CI, -20.6 to 1.8 percentage points]; P = 0.13). CONCLUSION: Itraconazole is more effective than fluconazole for long-term prophylaxis of invasive fungal infections after allogeneic hematopoietic stem-cell transplantation. Except for gastrointestinal side effects, itraconazole is well tolerated.

The Meaningful Auditory Integration Scale (MAIS) was developed to evaluate meaningful use of sound in everyday situations by profoundly hearing-impaired children. Information about the use of sound in everyday situations is obtained with a parent interview technique. Initial findings obtained with this scale are reported in Experiment 1 for children who use a hearing aid, single-channel cochlear implant, multichannel cochlear implant, or two-channel tactile aid. The hearing aid users were perceived by their parents to use sound in everyday situations to a greater extent than were the users of either implant or the tactile aid. There was a trend toward slightly higher performance by the multi- than by the single-channel cochlear implant users. The tactile aid users were perceived by their parents to use sound in a meaningful way to the most limited extent. Scores on the MAIS, which were obtained on a longitudinal basis, are reported in Experiment 2. The findings suggest that meaningful auditory integration continued to develop over time in children who used each type of sensory aid.

Although most lesions that occur in the chest have a nonspecific soft-tissue appearance, fat-containing lesions are occasionally encountered at cross-sectional computed tomography (CT) or magnetic resonance imaging. The various fat-containing lesions of the chest include parenchymal and endobronchial lesions such as hamartoma, lipoid pneumonia, and lipoma. Endobronchial hamartoma usually appears at CT as a lesion with a smooth edge, focal collections of fat, or fat collections that alternate with foci of calcification. Mediastinal fat-containing lesions include germ cell neoplasms, thymolipomas, lipomas, and liposarcomas. The most frequent CT manifestation of the germ cell neoplasm teratoma is a heterogeneous mass with soft-tissue, fluid, fat, and calcium attenuation. Cardiac lesions with fat content include lipomatous hypertrophy of the interatrial septum and arrhythmogenic right ventricular dysplasia. Diagnosis of the former is made with CT when a smooth, nonenhancing, well-marginated fat-containing lesion is identified in the interatrial septum. Finally, fat may herniate into the chest at several characteristic locations. When such a lesion is identified, the time required for differential diagnosis is significantly reduced, often allowing a definitive radiologic diagnosis. Sagittal and coronal reformatted images can add valuable information by showing diaphragmatic defects and hernia contents.

Between September 1983 and December 1988, we observed 16 cases of hematologic neoplasia associated with mediastinal germ-cell tumors. Twenty-eight similar cases have been reported in the literature. A review of the clinical and cytogenetic details in these patients suggests that the hematologic neoplasia is not the result of cisplatin-based chemotherapy of the mediastinal germ-cell cancer. This syndrome was found only in patients with nonseminomatous mediastinal germ-cell tumors, particularly those with serologic or histologic evidence of yolk-sac elements. The two most common hematologic neoplasms seen in this syndrome were acute megakaryoblastic leukemia and malignant histiocytosis. Consistent cytogenetic abnormalities have not yet been identified, but the finding of the marker chromosome isochromosome (12p) in the mediastinal germ-cell tumor and associated leukemic blasts in one patient suggests that these tumors may arise from a common progenitor cell.

The synthesis of extracellular glucan is an integral component of the sucrose-dependent colonization of tooth surfaces by species of the mutans streptococci. In investigators' attempts to understand the mechanisms of plaque biofilm development, several glucan-binding proteins (GBPs) have been discovered. Some of these, the glucosyltransferases, catalyze the synthesis of glucan, whereas others, designated only as glucan-binding proteins, have affinities for different forms of glucan and contribute to aspects of the biology of their host organisms. The functions of these latter glucan-binding proteins include dextran-dependent aggregation, dextranase inhibition, plaque cohesion, and perhaps cell wall synthesis. In some instances, their glucan-binding domains share common features, whereas in others the mechanism for glucan binding remains unknown. Recent studies indicate that at least some of the glucan-binding proteins modulate virulence and some can act as protective immunogens within animal models. Overall, the multiplicity of GBPs and their aforementioned properties are testimonies to their importance. Future studies will greatly advance the understanding of the distribution, function, and regulation of the GBPs and place into perspective the facets of their contributions to the biology of the oral streptococci.

PillCam colon capsule endoscopy (CCE) is an innovative noninvasive, and painless ingestible capsule technique that allows exploration of the colon without the need for sedation and gas insufflation. Although it is already available in European and other countries, the clinical indications for CCE as well as the reporting and work-up of detected findings have not yet been standardized. The aim of this evidence-based and consensus-based guideline, commissioned by the European Society of Gastrointestinal Endoscopy (ESGE) is to furnish healthcare providers with a comprehensive framework for potential implementation of this technique in a clinical setting.

BACKGROUND: The association of Langerhans cell histiocytosis (LCH) with a malignant neoplasm is rare and generally has been the subject of isolated case reports. METHODS: A recent case of LCH seen at the University of Minnesota in combination with acute lymphoblastic leukemia led the authors to review their own charts from 1960 onward, in addition to the literature for other reported associations of LCH and malignant neoplasms. RESULTS: In addition to the presented case and 3 cases from the files of the authors, the literature contained 87 reported cases. Of the 91 patients, 39 had LCH with malignant lymphoma (ML); 25 of these cases were Hodgkin disease. In 11 of these 39 patients, the LCH was diagnosed from 12 months to 33 years after the ML was diagnosed. In 62% of the patients with LCH-ML (24 patients), the diagnosis was made concurrently and the Langerhans cells were found in the same lymph nodes. In the remaining four patients, the diagnosis of LCH preceded that of ML by 6-24 months. In 22 patients, including 2 patients in the files of the authors, LCH was reported in association with leukemia; 16 (73%) of these cases were associated with acute nonlymphoblastic leukemia. In two cases the leukemia preceded the LCH. In 6 patients both diagnoses were made concurrently, and in 14 patients (64%) the diagnosis of LCH preceded the diagnosis of leukemia by 8 months to 17 years. In the remaining 30 patients, LCH was associated with a variety of solid tumors, including a lung carcinoma in 12 patients. In all of these 12 cases the LCH was confined to the lung, and in 75% (9 of 12) of patients the diagnoses were made concurrently. In the 16 patients in whom the LCH preceded the solid tumor, the malignant diseases in 69% (11 of 16) developed within the radiation field used for the treatment of the LCH. CONCLUSIONS: The intimate and simultaneous association of LCH with ML and lung carcinomas suggests strongly that the process that leads to the association is a reactive one. However, in the patients with leukemia and the other solid tumors, the latency of the malignant neoplasm after the diagnosis of LCH is suggestive of a therapy-related process.

Acute pancreatitis may occur after the performance of endoscopic retrograde cholangiopancreatography (ERCP) and endoscopic sphincterotomy. During ERCP and endoscopic sphincterotomy, the pancreas is subjected to many types of potential injury--mechanical, chemical, hydrostatic, enzymatic, microbiological, allergic, and thermal. These factors may act independently or in concert to induce postprocedure pancreatitis. The potential role of each etiologic factor in the development of ERCP- and endoscopic sphincterotomy-induced pancreatitis is detailed. The management of this complication is reviewed. Patient factors that increase the risk for pancreatitis and techniques to prevent or limit this complication are described. A variety of agents have been shown to prevent or treat pancreatitis in animal models, but extrapolation to humans has been almost uniformly unsuccessful. Although postprocedure pancreatitis is unlikely to be completely eliminated, careful patient selection and attention to detail may reduce the incidence of this untoward event.