Pancreaticoduodenectomy for nonampullary duodenal lesions: indications and results.

BACKGROUND: Pancreaticoduodenectomy (PD) is a complex procedure, associated with a definite risk of mortality and 30-50% risk of complications. For nonampullary duodenal lesions, PD can carry a higher morbidity as they are more commonly associated with a soft pancreas and narrow-calibre main pancreatic ducts. It is therefore paramount that the risks and benefits of surgery are considered carefully in this group of patients. A preoperative histological diagnosis for duodenal lesions is normally achieved by endoscopic biopsy. In this study, we aim to assess the outcome of PD in patients with nonampullary duodenal lesions and correlate the preoperative endoscopic histology work-up with the definitive postoperative pathology. MATERIALS AND METHODS: We reviewed a prospectively collected PD database from January 2007 to December 2013. Demographic and clinical data were included. Preoperative endoscopic histology was compared with final specimen histology to assess concordance. RESULTS: Forty patients (55% women, mean age 69.4 years, range 45-83 years) underwent PD for duodenal lesions over a 7-year time period. The most common presenting symptom was epigastric pain (32.5%), followed by anaemia (20%). Overall, the complication rate was 55%, with the most frequent adverse event being pancreatic fistula in 13/40 (32.5%). The perioperative mortality was 2/40 (5%). Duodenal adenocarcinoma (65%) was the most common postoperative histological diagnosis. The mean tumour size was 36 mm (range 5-103 mm) and a median of 13 nodes were harvested. The median length of stay was 15 days (range 7-66 days). Overall, 12/40 patients (30%) had a preoperative diagnosis of high-grade dysplasia. The postoperative specimen in this subgroup of patients was reviewed carefully and only 3/12 (25%) patients had high-grade dysplasia in the resection specimen. In the remaining patients, 3/12 (25%) had adenocarcinoma in the resection specimen and 6/12 patients (50%) had low-grade dysplasia. CONCLUSION: PD carries a high mortality and morbidity, especially for duodenal lesions. We recommend a careful endoscopic review after the index case with a high-definition optical evaluation of duodenal lesions. This, in addition to an experienced histological assessment of the index biopsy material, forms an essential prerequisite in aiding the multidisciplinary team in the decision-making process with respect to triage of these lesions to conservative management, surveillance, endoscopic resection or finally surgical resection.

Physical stability vs. chemical lability in microporous metal coordination polymers: a comparison of [Cu(OH)(INA)]n and [Cu(INA)2]n: INA = 1,4-(NC5H4CO2).

Two microporous copper isonicotinate polymers [Cu(OH)(INA)] and [Cu(INA)2] have been formed hydrothermally in good yield and purity; each have 1D channels of ca. 4 x 6 A dimension, but with quite different hydrophilicities; both frameworks retain structural integrity to above 200 degrees C, however whilst [Cu(OH)(INA)] is also chemically stable, [Cu(INA)2] is highly labile and readily transforms to the molecular complex [Cu(INA)2(H2O)4] in water at room temperature.

How can transforming growth factor beta be targeted usefully to combat liver fibrosis?

Transforming growth factor beta-1 (TGF-beta 1) plays a pivotal role in tissue fibrogenesis. Understanding the factors that control resolution of fibrosis is critical to devising means to combat clinical fibrosis. Future challenges would include designing ways to block the fibrosis-specific actions of TGF-beta. Blockade of transforming growth factor beta (TGF-beta) activity in vivo in animal models has proven to be an effective means of inhibiting the fibrotic response to injury in various organs. Similarly, transgenic animals in which TGF-beta 1 expression is artificially enhanced show marked spontaneous fibrosis or increased fibrotic response to injury. TGF-beta is known to effect fibroplasias, not only by its well known action of increasing extracellular matrix synthesis but also by coordinately regulating key proteins which mediate connective tissue homeostasis. This includes down-regulation of interstitial collagenase and other matrix metalloproteinases and up-regulation of antiproteases such as tissue inhibitor of metalloproteinase I and plasminogen activator inhibitor. Whilst inhibition of TGF-beta activity appears to be well tolerated in rodents over several weeks, the ultimately lethal phenotype of TGF-beta 1 knockout mice warns us that this pluripotent cytokine is essential for normal health. Therefore, downstream pathways activated by TGF-beta, which might be specific for its fibrotic effects, might be more useful targets for human fibrotic disease therapy. For example, the TGF-beta response protein connective tissue growth factor may be a good target for antifibrotics but definitive evidence awaits development of suitable genetically modified animal models and specific inhibitors.

Development of an integrated pancreatic disease service.

An integrated pancreatic disease unit needs to deliver high-quality care both to patients with malignant and non-malignant pancreatic disease. The regionalisation of pancreatic cancer services which followed the publication of policy frameworks by the Department of Health and NHS executive led to the development of disease-site-specialised high-volume multidisciplinary teams. As the majority of patients with pancreatic cancer are not suitable for surgery, partner hospitals within a region need to provide access to a wide range of non-surgical treatment. The implementation of such working may require pooling of local resources to create networks of equivalence to tertiary centres. The provision of care to non-malignant pancreatic disease can benefit from this type of working and services can be modelled on, and integrate with, cancer services. One way of achieving this is to establish working groups based upon diseases rather than traditional departments, which can deliver standardised and optimal care with a patient-centred approach. However, this poses a number of potential problems. This review examines how an integrated pancreatic unit may be developed in district general and larger hospitals, and also describes our experience in developing such a unit.

Process-induced phase transformation of berberine chloride hydrates.

Berberine is a natural quaternary ammonium alkaloid used clinically in the chloride salt form for the treatment of diarrhea in many Asian countries. Although the hydrate formation of berberine chloride (BCl) is well documented, the associated mechanism and implications in pharmaceutical formulation have not been studied in detail. In this study, pure BCl dihydrate and BCl tetrahydrate were recrystallized from water and their phase transformation behaviors under defined conditions were investigated. Additionally, pharmacopoeial grade BCl material consisting predominantly of the dihydrate form was examined for potential phase changes when being subjected to a conventional wet granulation procedure for tablet production. Results from solubility measurements, thermal analysis, variable temperature-powder X-ray diffraction (VT-PXRD), and variable temperature-Fourier transform infrared spectroscopy (VT-FTIR) confirmed the solid-state interconversions between the tetrahydrate and dihydrate at 30-49 degrees C and between the dihydrate and anhydrate at 70-87 degrees C. Consistent with the observed phase changes of the two pure hydrates, wet massing of the pharmacopoeial grade BCl sample led to a thermodynamics-driven transition to the tetrahydrate form at room temperature while subsequent tray drying at 50 degrees C caused a reversion back to the dihydrate form. The rate and extent of such hydrate conversion depended largely on the water activity of the granulated powder matrix, which in turn was governed by the particular excipients employed. The present findings have important implications in the regulation of the hydrate forms of BCl in the finished products using specific excipients.

Hollow spheres based on mesostructured lead titanate with amorphous framework.

Hollow spheres of mesostructured lead titanate, denoted as PTM-1, have been prepared via a combined oil-in-water emulsion mediated and neutral amine supermolecular templated route. The variety of reaction temperatures and KOH concentrations indicates hollow spheres can be formed under a very critical condition. The structure and composition of the as-synthesized PTM-1 have been determined by powder X-ray diffraction, high-resolution transmission electron microscopy (HRTEM), energy-dispersive X-ray spectroscopy (EDS), CHN (carbon-hydrogen-nitrogen) elemental analysis, and thermal analysis. Chemical extraction of organic templates by a cosolvent of weak acid and alcohol has resulted in the formation of a new mesoporous material of non-silica oxide with high porosity.

Expression of transforming growth factor-beta 1 by pancreatic stellate cells and its implications for matrix secretion and turnover in chronic pancreatitis.

Pancreatic stellate cells mediate fibrosis in chronic pancreatitis. Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs)-1 and -2 are crucial modulators of fibrosis. Transforming growth factor-beta (TGF-beta) is a key regulator of extracellular matrix production and myofibroblast proliferation. We have examined MMP and TIMP synthesis by transformed cultured pancreatic stellate cells and their regulation by TGF-beta 1. By Northern analysis they expressed mRNAs for procollagen 1, TIMP-1, TIMP-2, and MMP-2. Expression of membrane type-1 MMP was confirmed by Western blotting. By immunohistochemistry these enzymes localized to fibrotic areas in human chronic pancreatitis. Active TGF-beta 1 constitutes 2 to 5% of total TGF-beta 1 secreted by pancreatic stellate cells; they express TGF-beta receptors I and II. Exogenous TGF-beta 1 (10 ng/ml) significantly increased procollagen-1 mRNA by 69% and collagen protein synthesis by 34%. Similarly TGF-beta 1 at 0.1, 1, and 10 ng/ml significantly reduced cellular proliferation rate by 37%, 44%, and 44%, respectively, whereas pan-TGF-beta-neutralizing antibody increased proliferation by 40%. TGF-beta1 (10 ng/ml) down-regulated MMP-9 by 54% and MMP-3 by 34% whereas TGF-beta 1-neutralizing antibody increased MMP-9 expression by 39%. Pancreatic stellate cells express both mediators of matrix remodeling and the regulatory cytokine TGF-beta 1 that, by autocrine inhibition of MMP-3 and MMP-9, may enhance fibrogenesis by reducing collagen degradation.