Colonic lymphomatous polyposis mantle cell lymphoma: a case report and review of literature.

INTRODUCTION: Mantle cell lymphoma is a rare lymphoma of the gastrointestinal tract that may present as multiple lymphomatous polyposis. We report a case of lymphomatous polyposis with a review of the literature. CASE REPORT: A 56-year-old man of Black ethnicity and Ivorian nationality with no relevant past medical history, consulted for a sudden onset symptoms of gastrointestinal obstruction, which evolved over 2 days. Macroscopic examination revealed the presence of multiple polyploid formations of the colonic mucosa. Histology showed diffuse lymphomatous proliferation of submucosa consisting off small lymphoid cells with a hyperchromatic crenelated nucleus, suggesting lymphomatous polyposis. Immunohistochemical examination showed expression by the tumor cells of antibodies to CD20, CD5, Bcl2, and cyclin D1. They did not express antibodies to CD10 and CD23. The Ki67 proliferation index was 25%. We have thus retained the diagnosis of mantle cell lymphomatous polyposis. CONCLUSION: Multiple lymphomatous polyposis is a rare entity characterized by the presence of numerous gastrointestinal polyploid lesions sometimes involving several segments of the gastrointestinal tract. Typical lymphoma presenting as lymphomatous polyposis is mantle cell lymphoma; although, other tumors may have this aspect.

Predictors of Intensive Care Admission Among Adult Patients with Sickle Cell Disease in Eastern Province of Saudi Arabia.

Purpose: Sickle cell disease (SCD) comprises a complex group of hematologic disorders that are collectively the most common monogenic disorder and are associated with increased risk of intensive care unit admission (ICU). The purpose of this study is to investigate factors that predict admission of adult patients with SCD to the ICU. Patients and Methods: This was a cross-sectional study that enrolled adult patients with SCD from Saudi Arabia. Results: A total of 107 patients with SCD, with a median age 31.9±12.1 years, were evaluated retrospectively. Regarding predictors of ICU admission, patients who indicated a history of blood transfusions were at 8.047-fold higher risk of ICU admission (OR=8.047; 95% CI=2.392-27.07; p=0.001). Patients who started hydroxyurea were at least 3.071 times more likely to be admitted than those who did not (OR=3.071; 95% CI=1.164-8.104; p=0.023). We also observed three or more hospitalizations per year to be associated with increased risk of ICU admission (OR=3.393; 95% CI=1.285-8.960; p=0.014), with those making 3 to 5 visits annually having at least 10.4 times higher risk (OR=10.38; 95% CI=10.098-98.19; p=0.041) and those with 6 to 10 ER admissions having 18 times higher risk (OR=18.00; 95% CI=2.149-150.8; p=0.008). Finally, patients with high WBC were predicted to have at least 3.34 times higher risk of ICU admission (OR=3.337; 95% CI=1.131-9.846; p=0.029). Conclusion: SCD is a multi-systemic disease associated with increased morbidity and mortality. Recognition of high-risk features in patients helps to eliminate subjectivity in ICU referral decision. Frequent hospitalization and emergency visits, multiple blood transfusions, and elevated white blood cell count were significantly associated with a higher rate of ICU admission despite hydroxyurea usage.

A Randomized Open-Label Study of Two Methods of Proton Pump Inhibitors Discontinuation.

Background Proton pump inhibitors (PPIs) are effective in treating gastroesophageal reflux disease (GERD). Unfortunately, they are often inappropriately prescribed and long-term use has potential adverse effects. A single best method for discontinuation of PPIs does not currently exist. The objective of this study was to determine if there is a significant difference in successfully discontinuing PPI use at 12 months between patients discontinuing abruptly or tapering first. Methodology We conducted a randomized trial with 38 patients diagnosed with GERD. We collected six weekly and then monthly surveys of symptoms based on the Dyspepsia Symptom Severity Index. Chart review at 12 months determined whether the patient was able to discontinue PPI. Results A Kaplan-Meier survival analysis at 12 months did not show a statistically significant difference between the abrupt and taper groups for discontinuation of PPI medication (p = 0.75). Cox regression analysis showed no association of alcohol use, smoking, or caffeine use with failure to discontinue PPI, but H2 blocker use was associated with a 79% reduction in risk of failure to discontinue PPI (p = 0.004). The taper group had significantly less symptoms 14, 18, 22, and 30 weeks after discontinuation. Conclusions Our study suggests that there is no difference in successful discontinuation of PPIs between abrupt and taper methods at 12 months; however, there are less symptoms in the taper method, and H2 blocker use is associated with success. Further study is needed with larger numbers of participants and randomization of H2 blocker use.

Argatroban Treatment and Decreased Fibrinogen in a Septic Patient.

Disseminated intravascular coagulation (DIC) is a consumptive coagulopathy associated with multiple conditions. Diagnosis is based upon clinical and laboratory findings with assessment of fibrinogen, platelets, D-dimer, prothrombin time/international normalized ratio and activated partial thromboplastin time. Herein, we report a case of a 39-year-old female patient diagnosed with endocarditis complicated by pulmonary septic emboli. For anticoagulation, the patient initially was treated with a heparin drip, but the patient remained subtherapeutic despite increasing dosage. The patient was transitioned to argatroban and developed an acute drop in the fibrinogen level. With concern for possible DIC, argatroban was held with a repeat panel six hours later revealing a significantly improved fibrinogen level. It was discovered that the Clauss method, which measures the capability of fibrinogen to form a clot after a high concentration of thrombin is added to diluted plasma, was used to measure fibrinogen at our institute. Argatroban may falsely reduce measured fibrinogen levels in vitro, caused by this method.

Treating Venous Thromboembolism Post Intracranial Hemorrhage: A Case Report.

Venous thromboembolism (VTE) is a significant issue occurring due to genetic, acquired and circumstantial risk factors. Treatment is according to the clinical situation and judgment for long term anticoagulation based on individual risk. Anticoagulation after a history of a hemorrhagic stroke poses a therapeutic dilemma. We present a case of a 68-year-old male who presented with right-sided chest pain and shortness of breath. Workup included a CT that was positive for multiple right-sided pulmonary emboli (PE). The patient has a past medical history of Factor V Leiden Mutation, recurrent PE, and deep vein thrombosis (DVT). Two months prior he was diagnosed with a 1.3-cm intracranial hemorrhage (ICH) from multiple cavernous angiomas. At that time his warfarin was discontinued and an inferior vena cave (IVC) filter was placed. Facing the recent ICH and now multiple and recurrent PE, it was decided to resume anticoagulation based on ICH location. ICH from a deep source is likely a better characteristic that favors a resumption of anticoagulation. Our case will highlight that IVC filters cannot be solely relied upon in patients that are at high risk for thrombotic events with underlying genetic thrombophilia.

Pediatric Cancer Variant Pathogenicity Information Exchange (PeCanPIE): a cloud-based platform for curating and classifying germline variants.

Variant interpretation in the era of massively parallel sequencing is challenging. Although many resources and guidelines are available to assist with this task, few integrated end-to-end tools exist. Here, we present the Pediatric Cancer Variant Pathogenicity Information Exchange (PeCanPIE), a web- and cloud-based platform for annotation, identification, and classification of variations in known or putative disease genes. Starting from a set of variants in variant call format (VCF), variants are annotated, ranked by putative pathogenicity, and presented for formal classification using a decision-support interface based on published guidelines from the American College of Medical Genetics and Genomics (ACMG). The system can accept files containing millions of variants and handle single-nucleotide variants (SNVs), simple insertions/deletions (indels), multiple-nucleotide variants (MNVs), and complex substitutions. PeCanPIE has been applied to classify variant pathogenicity in cancer predisposition genes in two large-scale investigations involving >4000 pediatric cancer patients and serves as a repository for the expert-reviewed results. PeCanPIE was originally developed for pediatric cancer but can be easily extended for use for nonpediatric cancers and noncancer genetic diseases. Although PeCanPIE's web-based interface was designed to be accessible to non-bioinformaticians, its back-end pipelines may also be run independently on the cloud, facilitating direct integration and broader adoption. PeCanPIE is publicly available and free for research use.

A Challenging Case of Coexisting Type A and Type B Lactic Acidosis: A Case Report.

The etiology of lactic acidosis can potentially be misleading, especially in a critically ill patient with malignancy. Type B lactic acidosis represents a rare and often lethal complication of malignancy. When differentiating the types of lactic acidosis, Type A is due to marked tissue hypoperfusion and Type B is due to causes in the setting of a normal perfused state. We report the case of a 56-year-old male with newly diagnosed poorly differentiated neuroendocrine metastatic carcinoma and renal cell carcinoma who presented with a decreased level of consciousness and appetite. The patient was started on a sepsis protocol from an initial intensive care unit (ICU) admission. Broad spectrum antibiotics were initiated, and despite management, his mentation and respiratory status worsened, leading to intubation and mechanical ventilation. The patient continued to have elevated lactic acid and white count levels throughout the hospital course. After extensive workup and an ICU stay of 16 days, a decision was made to pursue comfort care measures and the patient passed away shortly thereafter. The patient's persistently elevated lactic acidosis may have resulted from the inherent malignancy. The literature mentions glycolysis with enhanced metabolism as a proposed mechanism. One theory states that these changes enable cancer cells to acquire and metabolize nutrients in a way that favors proliferation over efficient adenosine triphosphate (ATP) production, resulting in elevations of lactate production. Patients presenting to the ICU with elevated lactic acid levels need to be thoroughly worked up for all potential causes. In our case, the underlying malignancies likely caused the persistently elevated lactic acidosis, despite subtherapeutic treatment and resuscitative measures.

Loeys-Dietz Syndrome Complicated by Right Coronary Artery Pseudoaneurysm.

Loeys-Dietz syndrome is a rare autosomal dominant connective tissue disorder notable for rapidly progressive vascular aneurysmal disease and craniofacial defects. Patients are at an increased risk for aneurysm rupture and dissection at younger ages compared to other aneurysmal syndromes. Early surgical intervention is important for prevention of ruptures and/or dissection. The coronary arterial tree is mostly involved as a result of postoperative complications of an aortic root repair. This fact has been sparsely reported. We report a unique case of LDS2 presenting with chest pain that was later diagnosed as a pseudoaneurysm as a result of a right coronary artery graft dehiscence.

Tumefactive Multiple Sclerosis, A Rare Variant Presenting as Multiple Ring-enhancing Lesions in an Immunocompetent Patient: A Case Report.

Tumefactive multiple sclerosis (TMS) is a rare entity which can be difficult to diagnose unless definitive diagnostic measures are taken. TMS is characterized by solitary or multiple lesions that are sized > 2 cm, with/without mass effect, edema, and ring enhancement on magnetic resonance imaging (MRI). The demyelinating lesion can mimic infections, vascular lesions, and inflammatory lesions. The clinical presentation is highly dependent on the area of the brain which is affected, and this can lead to a variety of signs and symptoms. Herein, we present the case of a 40-year-old immunocompetent female with a history of right-sided numbness of her face, arm, and leg associated with muscle weakness for about a week. Workup included an MRI showing ring-enhancing lesions in the white matter of the brain, zero oligoclonal bands in the CSF, a normal immunoglobulin G (IgG) index, and an elevated myelin basic protein (MBP) in the CSF. A biopsy was obtained that showed predominant macrophage infiltrate with loss of myelin but the preservation of axons. Suspecting a demyelinating pathology, the patient was informed that she would be started on intravenous dexamethasone for an eight-day course. With subsequent completion of this course in the hospital, the patient was discharged on oral prednisone daily for a month and a referral leading to a definitive diagnosis of TMS. The patient was started on interferon beta-1a and subsequently relapsed due to noncompliance. However, further workup showed a reduction in the mass-like lesions and a response to therapy. If suspicion for TMS is high despite workup, steroids can be used with immunomodulators in the interim to combat symptoms and potentially reduce lesions and potentially subvert the need for biopsy.

Differential responses of the vasotocin 1a receptor (V1aR) and osmoreceptors to immobilization and osmotic stress in sensory circumventricular organs of the chicken (Gallus gallus) brain.

Past studies have shown that the avian vasotocin 1a receptor (V1aR) is involved in immobilization stress. It is not known whether the receptor functions in osmotic stress, and if sensory circumventricular organs may be involved. An experiment was designed with four treatment groups including a 1h immobilization acute stress (AS) group, an unstressed acute control (AC), a third given an intraperitoneal (ip) hypertonic saline injection (HS) and isotonic saline controls (IC) administered ip. One set of chick brains was perfused for immunohistochemistry while a second was sampled for quantitative RT-PCR. Plasma corticosterone (CORT) and arginine vasotocin (AVT) concentrations were significantly increased in the immobilized and hypertonic saline groups (p<0.01) compared to controls. Intense staining of the V1aR occurred throughout the organum vasculosum of the lamina terminalis (OVLT) and subseptal organ (SSO)/subfornical organ (SFO). The immunostaining allowed the boundaries of the two circumventricular organs (CVOs) to be described for the first time in avian species. Both treatment groups showed marked morphological changes in glia within the OVLT and SSO/SFO. The avian V1aR, angiotensin II type 1 receptor (AT1R), and transient receptor potential vanilloid receptor 1 (TRPV1) mRNA levels were increased in the SSO/SFO in hypertonic saline treated birds compared to isotonic controls. In contrast, the latter two genes (AT1R and TRPV1) were significantly decreased in the OVLT of birds subjected to hyperosmotic stress, while all three genes were significantly up-regulated after immobilization. Taken together, results show a possible differential function for the same receptors in two anatomically adjacent CVOs.

Breast Cancer Molecular Subtypes Defined by ER/PR and HER2 Status: Association with Clinicopathologic Parameters in Ivorian Patients.

BACKGROUND: Breast cancer is a heterogeneous disease that represents a major public health problem. The immunohistochemical determination of breast cancer subtypes with regard to estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor (HER2) status can contribute to improved selection of therapy and patientcare. The purpose of this study was to determine the prevalence of the molecular breast cancer subtypes and to assess their associations with classical clinicopathologic parameters for better therapeutic decisions in women with breast cancer in the Ivory Coast. MATERIALS AND METHODS: Formalin- fixed and paraffin-embedded blocks of patients diagnosed with primary breast carcinoma were subjected to immunohistochemical assay for the assessment of ER/RP and HER2 expression. The one-way analysis of variance evaluated the difference between breast cancer subtypes and mean age of patients. The Chi-square Test was used to compare standard clinicopathologic prognostic parameters with tumor subtypes. RESULTS: Among 302 patients, 57% were premenopausal and 43% were postmenopausal. The invasive ductal carcinoma not otherwise specified (IDC NOS) (82.8%) was the most frequent histological type, and the tumor grade 2 (56%) was predominant followed by grade 3 (20.9%). The proportion of positivity of ER, PR, and HER2 was 56%, 49%, and 15.6%, respectively. Half of patients of this study (51.6%) had luminal A breast tumor type followed by TN (32.1%). Other subtypes were luminal B (10.1% ) and non-luminal HER2+ (6.3%). CONCLUSIONS: The findings of the present study are in line with the literature and should assist in management of breast cancer in our country.

Central effect of vasotocin 4 receptor (VT4R/V1aR) antagonists on the stress response and food intake in chicks given neuropeptide Y (NPY).

Previous studies identified SR-49059 as a most effective antagonist of the avian vasotocin 4 receptor (VT4R) compared to other candidate blockers including the Manning compound using in silico 3 dimensional (3D) modeling/docking analysis of the chicken VT4R and an in vitro anterior pituitary cell culture study. The present experiments were designed to validate whether SR-49059 and the Manning compound would likewise be effective in vivo in blocking the VT4R when applied intracerebroventricularly (ICV) to chicks. Two treatments were tested, a stressor (immobilization) and administration of neuropeptide Y (NPY), a potent orexigenic compound. In the first experiment, birds were given the Manning compound, SR-49059 or physiological saline ICV followed by immobilization stress. Blood samples were taken and corticosterone (CORT) was determined by radioimmunoassay. It was hypothesized that both antagonists would reduce the stress response. A second experiment examined the role of the VT4R in food intake regulation. The Manning compound, SR-49059 or physiological saline was administered prior to NPY and food intake was monitored for 1h. It was hypothesized that each of the two antagonists coupled with NPY would augment food intake above the intake resulting from saline plus NPY administration. Related to the second experiment was a third that examined the difference between the effect of central administration of NPY versus SR-49059 in releasing CORT. Results of the first study showed that the Manning compound or SR-49059 prior to stress decreased CORT levels compared to controls while the second experiment showed that SR-49059 or the Manning compound plus NPY, enhanced food intake above that of the experimental group given saline and NPY. The last study showed that NPY increased plasma CORT above birds given SR-49059 centrally or saline administered controls. Taken together, results suggest that the avian VT4R is involved in the central neuroendocrine stress response as well as functions in appetite regulation by mediating an anorexigenic effect similar to what has been reported in mammals for the V1aR. In conclusion, similar to the past in silico and in vitro tests, the current in vivo experiments showed SR-49059 to be a most efficacious avian vasotocin receptor antagonist. Therefore based upon results of functional tests utilizing a highly specific mammalian antagonist, SR-49059, to the mammalian V1aR that likewise was most effective in blocking the avian VT4R and past reported high sequence homology between the mammalian V1aR and the VT4R, it is recommended that the chicken VT4R be renamed the avian V1aR to facilitate better communication among scientists involved in comparative studies.

Neuro-fibrosarcome géant intra-thoracique de la maladie de Von Recklinghausen

Nous rapportons une fibromatose de localisation multiple chez un patient de 30 ans. L'intérêt de ce cas clinique réside en la transformation maligne de la géante fibromatose intra-thoracique en une tumeur maligne des gaines des nerfs périphériques type neuro-fibrosarcome. Sa découverte fournit une base pour quelques remarques critiques d'intérêt clinique sur la maladie de Von Recklinghausen

[Descriptive epidemiology of cancers in Cote d'Ivoire]. / Épidémiologie descriptive des cancers en Côte d'Ivoire.

The cancerous disease is a real pain in developed countries due to the ageing of the population. According to the World Report Cancer in 2000, cancer tends to be a major problem of public health in the developing nations. This study research aimed at describing the epidemiological features of cancers in Cote d'Ivoire. It is a 26-year retrospective and descriptive study focusing on all cancers confirmed histologically by using the data from the registers of Anatomic Pathology laboratory of Abidjan teaching hospitals. The parameters of the study were frequency, age, sex, site and histological type. We obtained 12,841 cancers within patients aged from 2 months to 107 years old along with 51.26-year median age and 0.9 as sex-ratio. The most important cancer locations are cervix (17.41%) followed by skin (15.81%), prostate (7.73%), breast (6.88%), and stomach (6.09%). With women, the median age was 49.23 years, and the most common cancers were cervical cancer (33.25%) followed by breast cancer (12.44%) and skin cancer (10.50%). With men, the median age was 53.95 years, and the most frequent cancers were skin cancer (21.29%) followed by prostate cancer (15.69%) and stomach cancer (8.71%). Burkitt lymphoma (33.95%), retinoblastoma (10.92%) and nephroblastoma (5.88%) are the most important cancers in children. Cancers are frequent in Cote d'Ivoire. Cervical cancer, skin cancer, and prostate are updated problems with a worse prognosis. Therefore, the screening and the early diagnosis remain the best conditions to improve the prognosis of cancer.

POND4Kids: a global web-based database for pediatric hematology and oncology outcome evaluation and collaboration.

The Pediatric Oncology Network Database, (www.pond4kids.org, POND), is a secure, web-based, multilingual pediatric hematology/oncology database created for use in countries with limited resources to meet various clinical data management needs including cancer registration, delivery of protocol-based care, outcome evaluation, and assessment of psychosocial support programs. Established as a part of the International Outreach Program at St. Jude Children's Research Hospital in Memphis, Tennessee, POND serves as a tool for oncology units to store patient data for easy retrieval and analysis and to achieve uniform data collection to facilitate meaningful comparison of information among centers. Launched in 2003, POND now has 233 sites registered with over 1,000 users in 66 countries. However, adoption and usage of POND varies widely among sites. This paper reviews some of the challenges to developing a global collaborative clinical platform based on the experiences of developing POND. The paper also presents a case study of POND use in Guatemala, where the Guatemalan National Oncology Unit (UNOP) has developed extensive internal and external global collaborations using POND.

Dilated SMV in colon cancer--is there any significance.

OBJECTIVE: Changes in splanchnic circulation have been seen in patients with colorectal cancer. We have previously reported that the inferior mesenteric vein is dilated in rectal cancer. We wanted to assess whether the superior mesenteric vein (SMV) is dilated in right-sided colon cancer. MATERIALS AND METHODS: From a colorectal database, three cohorts were formed: right colon cancer, rectal cancer, and normal. The SMV (2 cm proximal to the confluence of the SMV and portal vein) and the gastrocolic trunk (GCT) were saved and anonymized. The short-axis diameter of the vein was measured independently by three radiologists. RESULTS: The diameter of the SMV and GCT was higher in the right colon group than the other two groups. There was no correlation with the stage of tumor (locoregional or metastatic). CONCLUSION: Patients with right colon cancer showed a significantly increased mean SMV diameter at presentation, which may be due to increased venous return secondary to neovascularization. Further studies are required to evaluate this further.

POND4Kids: a web-based pediatric cancer database for hospital-based cancer registration and clinical collaboration.

The Pediatric Oncology Network Database, POND4Kids (www.pond4kids.org, POND), is an online, multilingual clinical database created for use by pediatric oncology units in countries with limited resources to meet various clinical data management needs including cancer registration, data collection and changes in treatment outcome. Established as a part of the International Outreach Program at St. Jude Children's Research Hospital in Memphis, Tennessee, POND aims to provide oncology units a tool to store patient data for easy retrieval and analysis and to achieve uniform data collection to facilitate meaningful comparison of information among centers. Currently, POND is being used to store clinical data on thousands of patients and measure their treatment improvement over a period of time. In 2009 POND included more than 100 pediatric oncology units; each has its own virtual private area. A case study of the UNOP Guatemala Clinic's use of POND is presented. On-going challenges at partner sites include inconsistent data collection methods, missing records, training for data managers, and slow or unreliable internet connections.

Aspects of antibody-catalyzed primary amide hydrolysis.

Because there are many known C-terminally amidated peptides of biological importance, there is great potential in medicine and organic synthesis for antibodies that catalyze primary amide bond hydrolysis or formation. We characterized a catalytic antibody, 13D11, raised to a phosphinate hapten, that hydrolyzed the primary amide of a dansyl-alkylated derivative of (R)-phenylalaninamide (DNS-(R)F-NH2). At pH 9.0, 13D11 hydrolyzed DNS-(R)F-NH2 with a kcat of 1.65 x 10(-7) s-1 (kcat/kuncat = 132) and a Km of 432 microM, and was stereospecifically hapten-inhibited (Ki = 14.0 microM). Control experiments indicated that the catalytic activity was not the result of a contaminating protease. In accordance with the hapten being a transition-state analog of base hydrolysis, the rate of DNS-(R)F-NH2 hydrolysis increased with hydroxide concentration to an optimum pH of 9.5. Above pH 9.5, activity declined rapidly suggesting the antibody was inactivated during the long incubation period. This work demonstrates the feasibility of generating catalytic antibodies to hydrolyze unactivated amide bonds without cofactor assistance.

Conjugates of COL-1 monoclonal antibody and beta-D-galactosidase can specifically kill tumor cells by generation of 5-fluorouridine from the prodrug beta-D-galactosyl-5-fluorouridine.

5'-O-beta-D-galactosyl-5-fluorouridine is a prodrug that can be converted by the enzyme beta-D-galactosidase to the potent antineoplastic drug 5-fluorouridine. The prodrug is more than 100x less toxic than the drug to bone marrow cells in Balb/c mice. The ratio of the IC50 of the prodrug to that of the drug determined on a variety of tumor cell lines in vitro ranged from 500:1-1000:1. An antibody-enzyme conjugate (AEC) was synthesized and purified. Maleimide-substituted COL-1 anti-CEA monoclonal antibody was linked to free thiol groups of beta-D-galactosidase. The conjugate was purified by size exclusion and ion exchange chromatography. It retained full immunoreactivity and enzyme activity. After binding to antigen-positive tumor cells, the conjugate was able to activate the prodrug and specifically kill the cells. We are continuing to investigate this model for its potential use in antibody-directed enzyme prodrug therapy (ADEPT).