Mixed Goblet Cell Carcinoid-Adenocarcinoma: A Case Series

INTRODUCTION: Mixed goblet cell carcinoid-adenocarcinoma (GCC) tumors are a group of rare heterogenous neoplasms of the appendix accounting for \u3c 5% of all primary appendiceal tumors. They are characterized as an intermediate between classic carcinoid tumors and appendiceal adenocarcinomas, exhibiting both neuroendocrine and glandular/mucinous morphology that most commonly presents in Caucasian females in the fifth and sixth decades. We present three cases of mixed GCC presenting as acute appendicitis. CASE PRESENTATION: Case #1 A 65-year-old male presented with RLQ pain, nausea, emesis, and leukocytosis. CT of the abdomen revealed perforated appendicitis. The patient underwent a laparoscopic appendectomy. Pathology revealed a high-grade adenocarcinoma ex goblet cell carcinoid, signet ring type extending through the muscularis propria into the mesoappendix measuring \u3e3cm. The patient subsequently underwent a colonoscopy that revealed diverticulosis, but was otherwise normal. Patient then underwent a right hemicolectomy and partial omentectomy. Pathology revealed normal ileal, omental, and colonic tissue without evidence of carcinoma. 0/12 nodes were positive. Case #2 A 49-year-old male presented with periumbilical pain, nausea, emesis, and leukocytosis. CT of the abdomen revealed appendicitis. The patient underwent a laparoscopic appendectomy. Pathology revealed a high-grade, poorly differentiated, adenocarcinoma ex goblet cell carcinoid invading through the muscularis propria into the periappendiceal soft tissue measuring 1.5cm. The patient subsequently underwent a colonoscopy that revealed diverticulosis, but was otherwise normal. Patient then underwent a laparoscopic right hemicolectomy. Pathology revealed normal ileal and colonic mucosa without evidence of carcinoma. 0/14 nodes were positive. Case #3 A 70-year-old female presented with periumbilical pain. CT of the abdomen revealed appendicitis. The patient underwent a laparoscopic appendectomy. Pathology revealed a high-grade adenocarcinoma ex goblet cell carcinoid extending through the muscularis propria into the mesoappendix measuring 4cm. Patient then underwent an exploratory laparotomy with a right hemicolectomy. Pathology revealed normal ileal and colonic mucosa without evidence of carcinoma. 0/21 nodes were positive. CONCLUSION: Mixed GCC tumors are rare tumors that tend to present at an advanced stage and most commonly spread via direct extension. Surgical resection with a right hemi-colectomy after an appendectomy has been shown to improve the prognosis. HIPEC and adjuvant chemotherapy are other therapeutic options, but have not been shown to improve survival. In the current age of increasing rates of managing acute appendicitis non-operatively we strongly encourage surgical appendectomy in patients older than 45 years of age to avoid missing this important diagnosis and the opportunity to treat it in a timely manner

Rare Presentation of High Grade Retroperitoneal Angiosarcoma in a Patient Status Post Endovascular Aortic Repair (EVAR)

INTRODUCTION: Primary angiosarcoma of the aorta is a rare malignancy arising from the aorta’s endothelial lining. The most common presentation is claudication, however in the presence of an endograft a tumor originating in the aneurysmal sac may remain undetected and mimic common graft pathology. Diagnosis is typically delayed due to vague clinical presentation and imaging being indistinguishable from common complications of endografts such as leaks, infections or hematomas. We report a case of primary angiosarcoma of the aorta after endovascular repair of an abdominal aortic aneurysm. This case report describes the sixth case in the literature of primary angiosarcoma arising after the placement of an endovascular stent. CASE PRESENTATION: A 75 year-old male with a previous history of endovascular aortic repair for a AAA six years prior presented to the emergency room with signs and symptoms concerning for bowel obstruction. He elicited abdominal pain, nausea, emesis, obstipation and was anemic and had leukocytosis. A CT angiogram of the abdomen and pelvis displayed a large mass encasing the infra-renal aorta, without active extravasation, that was externally compressing the second portion of the duodenum and causing a gastric outlet obstruction. The mass extended into both iliac arteries with extension into a known right iliac artery aneurysm. Review of the patient’s chart revealed that this mass was not present six months prior. Patient was treated non-operatively with placement of a nasogastric tube. Concerns for a Type I or III Endoleak delayed the eventual CT-guided biopsy of the mass. Pathology revealed a malignant spindled and pleomorphic mass with extensive hemorrhage and necrosis consistent with high grade angiosarcoma. Specimen tested positive for vimentin, CD68, ERG, and CD31 on immunohistochemical staining. Patient did not wish to undergo aggressive treatment of his condition and was discharged to a hospice facility where he expired days later. CONCLUSION: Angiosarcoma is a rare malignancy representing 2% of all soft tissue sarcomas; associated with a poor prognosis with a median survival time of seven to eight months in advanced tumors. Tumors larger than 5cm and those located in the retroperitoneum, such as in the case report that we present, are associated with a poor prognosis. Doxorubicin is the mainstay of treatment for locally advanced tumors. Paclitaxel has also been shown to be effective. We present this care report to increase cognizance of this rare entity in the setting of a previously placed aortic endograft and avoid unnecessary surgical interventions

Molecular biological methods for studying the gut microbiota : the EU human gut flora project

Seven European laboratories co-operated in a joint project (FAIR CT97-3035) to develop, refine and apply molecular methods towards facilitating elucidation of the complex composition of the human intestinal microflora and to devise robust methodologies for monitoring the gut flora in response to diet. An extensive database of 16S rRNA sequences for tracking intestinal bacteria was generated by sequencing the 16S rRNA genes of new faecal isolates and of clones obtained by amplification with polymerase chain reaction (PCR) on faecal DNA from subjects belonging to different age groups. The analyses indicated that the number of different species (diversity) present in the human gut increased with age. The sequence information generated, provided the basis for design of 16S rRNA-directed oligonucleotide probes to specifically detect bacteria at various levels of phylogenetic hierarchy. The probes were tested for their specificity and used in whole-cell and dot-blot hybridisations. The applicability of the developed methods was demonstrated in several studies and the major outcomes are described

Isoform-selective susceptibility of DISC1/phosphodiesterase-4 complexes to dissociation by elevated intracellular cAMP levels

Disrupted-in-schizophrenia 1 (DISC1) is a genetic susceptibility factor for schizophrenia and related severe psychiatric conditions. DISC1 is a multifunctional scaffold protein that is able to interact with several proteins, including the independently identified schizophrenia risk factor phosphodiesterase-4B (PDE4B). Here we report that the 100 kDa full-length DISC1 isoform (fl-DISC1) can bind members of each of the four gene, cAMP-specific PDE4 family. Elevation of intracellular cAMP levels, so as to activate protein kinase A, caused the release of PDE4D3 and PDE4C2 isoforms from fl-DISC1 while not affecting binding of PDE4B1 and PDE4A5 isoforms. Using a peptide array strategy, we show that PDE4D3 binds fl-DISC1 through two regions found in common with PDE4B isoforms, the interaction of which is supplemented because of the presence of additional PDE4B-specific binding sites. We propose that the additional binding sites found in PDE4B1 underpin its resistance to release during cAMP elevation. We identify, for the first time, a functional distinction between the 100 kDa long DISC1 isoform and the short 71 kDa isoform. Thus, changes in the expression pattern of DISC1 and PDE4 isoforms offers a means to reprogram their interaction and to determine whether the PDE4 sequestered by DISC1 is released after cAMP elevation. The PDE4B-specific binding sites encompass point mutations in mouse Disc1 that confer phenotypes related to schizophrenia and depression and that affect binding to PDE4B. Thus, genetic variation in DISC1 and PDE4 that influence either isoform expression or docking site functioning may directly affect psychopathology

A Comparison of Four Treatments for Generalized Convulsive Status Epilepticus

ABSTRACT Background and Methods Although generalized convulsive status epilepticus is a life-threatening emergency, the best initial drug treatment is uncertain. We conducted a five-year randomized, doubleblind, multicenter trial of four intravenous regimens: diazepam (0.15 mg per kilogram of body weight) followed by phenytoin (18 mg per kilogram), lorazepam (0.1 mg per kilogram), phenobarbital (15 mg per kilogram), and phenytoin (18 mg per kilogram). Patients were classified as having either overt generalized status epilepticus (defined as easily visible generalized convulsions) or subtle status epilepticus (indicated by coma and ictal discharges on the electroencephalogram, with or without subtle convulsive movements such as rhythmic muscle twitches or tonic eye deviation). Treatment was considered successful when all motor and electroencephalographic seizure activity ceased within 20 minutes after the beginning of the drug infusion and there was no return of seizure activity during the next 40 minutes. Analyses were performed with data on only the 518 patients with verified generalized convulsive status epilepticus as well as with data on all 570 patients who were enrolled. Results Three hundred eighty-four patients had a verified diagnosis of overt generalized convulsive status epilepticus. In this group, lorazepam was successful in 64.9 percent of those assigned to receive it, phenobarbital in 58.2 percent, diazepam and phenytoin in 55.8 percent, and phenytoin in 43.6 percent (P=0.02 for the overall comparison among the four groups). Lorazepam was significantly superior to phenytoin in a pairwise comparison (P=0.002). Among the 134 patients with a verified diagnosis of subtle generalized convulsive status epilepticus, no significant differences among the treatments were detected (range of success rates, 7.7 to 24.2 percent). In an intention-to-treat analysis, the differences among treatment groups were not significant, either among the patients with overt status epilepticus (P=0.12) or among those with subtle status epilepticus (P=0.91). There were no differences among the treatments with respect to recurrence during the 12- hour study period, the incidence of adverse reactions, or the outcome at 30 days. Conclusions As initial intravenous treatment for overt generalized convulsive status epilepticus, lorazepam is more effective than phenytoin. Although lorazepam is no more efficacious than phenobarbital or diazepam and phenytoin, it is easier to use. (N Engl J Med 1998;339:792-8.

Local dynamics and gravitational collapse of a self-gravitating magnetized Fermi gas

We use the Bianchi-I spacetime to study the local dynamics of a magnetized self-gravitating Fermi gas. The set of Einstein-Maxwell field equations for this gas becomes a dynamical system in a 4-dimensional phase space. We consider a qualitative study and examine numeric solutions for the degenerate zero temperature case. All dynamic quantities exhibit similar qualitative behavior in the 3-dimensional sections of the phase space, with all trajectories reaching a stable attractor whenever the initial expansion scalar H_{0} is negative. If H_{0} is positive, and depending on initial conditions, the trajectories end up in a curvature singularity that could be isotropic(singular "point") or anisotropic (singular "line"). In particular, for a sufficiently large initial value of the magnetic field it is always possible to obtain an anisotropic type of singularity in which the "line" points in the same direction of the field.Comment: 6 pages, 3 figures (accepted in General Relativity and Gravitation

Analyzing Powers for Deuteron-Induced Reactions Leading to Continuum Final States

This work was supported by the National Science Foundation Grant NSF PHY 78-22774 A02 & A03 and by Indiana Universit

A novel framework for the local extraction of extra-axial cerebrospinal fluid from MR brain images

The quantification of cerebrospinal fluid (CSF) in the human brain has shown to play an important role in early postnatal brain developmental. Extr a-axial fluid (EA-CSF), which is characterized by the CSF in the subarachnoid space, is promising in the early detection of children at risk for neurodevelopmental disorders. Currently, though, there is no tool to extract local EA-CSF measurements in a way that is suitable for localized analysis. In this paper, we propose a novel framework for the localized, cortical surface based analysis of EA-CSF. In our proposed processing, we combine probabilistic brain tissue segmentation, cortical surface reconstruction as well as streamline based local EA-CSF quantification. For streamline computation, we employ the vector field generated by solving a Laplacian partial differential equation (PDE) between the cortical surface and the outer CSF hull. To achieve sub-voxel accuracy while minimizing numerical errors, fourth-order Runge-Kutta (RK4) integration was used to generate the streamlines. Finally, the local EA-CSF is computed by integrating the CSF probability along the generated streamlines. The proposed local EA-CSF extraction tool was used to study the early postnatal brain development in typically developing infants. The results show that the proposed localized EA-CSF extraction pipeline can produce statistically significant regions that are not observed in previous global approach

Phenotypic and genotypic characterization of Bradyrhizobia nodulating the leguminous tree Acacia albida

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Reaction Mechanism Implications of Deuteron Rainbow Scattering

This work was supported by the National Science Foundation Grant NSF PHY 78-22774 A02 & A03 and by Indiana Universit