Eosinophilic gastrointestinal diseases – Pathogenesis,diagnosis, and treatment

Eosinophilic gastrointestinal diseases (EGIDs) are divided into eosinophilic esophagitis (EoE) and eosinophilic gastroenteritis (EGE), depending on the involved gastrointestinal tract, though both are considered to be chronic Th2-type allergic diseases caused by food or environmental allergens. In development of EoE, refluxed gastric acid may also have an important role. For diagnosis of EGIDs, the presence of symptoms possibly originating from the involved gastrointestinal tract and dense eosinophil infiltration are important factors. Imaging studies, including endoscopy and computed tomography, along with histopathological examinations of biopsy specimens are useful for diagnosis, whereas laboratory testing of blood, urine, and stool samples has limited value. Three useful options for treating EoE patients are acid inhibitors, swallowed topical corticosteroids, and an elimination diet, while systemic administration of glucocorticoids is the standard treatment of EGE, though information is limited. Since the prevalence of EGIDs is increasing in Western countries as well as Japan, development of effective treatments based on sufficient evidence is becoming an urgent need.     

Gastric infiltration of diffuse large B-cell lymphoma： Endoscopic diagnosis and improvement of lesions after chemotherapy

Diffuse large B-cell lymphoma （DLBCL） is the most common histologic subtype of the non-Hodgkin’s lymphoma （NHL） accounting for about 40% of all NHLs. This is a case report about the endoscopic appearance of a DLBCL with infiltration to the stomach in a 39-year-old female. She had a 6-mo history of lumbar and left upper quadrant pain with intermittent episodes of melena. A computer tomograghy （CT） scan showed mural thickening of the gastric antrum. Endoscopic examination revealed multiple gastric ulcers. Definite diagnosis could be made by endoscopic biopsies and the patient had a good response to chemotherapy. This response correlated well with a further endoscopic follow-up. A follow-up endoscopic examination could be considered to evaluate a good response to chemotherapy in DLBCL patients with secondary gastric dissemination.     

Arteriovenous malformation of the pancreatic head – difficulties in diagnosis and treatment

A patient with pancreatic arteriovenous malformation who presented diagnostic and therapeutic difficulties is presented. The initial tests appeared to suggest inflammatory bowel disease, but the diagnosis was clinched by the finding of blood issuing from the ampulla of Vater. Repeated angiographic embolization did not obliterate the vascular malformation, and the symptoms eventually resolved after Whipple’s pancreaticoduodenectomy.     

Safe use of infliximab for the treatment of severe perianal Crohn’s disease after diagnosis and treatment of lymphoma

Inflammatory bowel disease is associated with an increased likelihood of developing lymphoma. However, it is still controversial if this risk may be attributed to the disease itself or rather represents an effect of immunosuppressive treatment. Although tumor necrosis factor alpha (TNFα) is a key cytokine for cancer immunosurveillance, the potential relationship between anti-TNFα agents and the pathogenesis of lymphoproliferative disorders remains unclear. Here, we describe the case of a patient with severe perianal Crohn’s disease, treated with infliximab monotherapy, whose unusual presentation with acute groin pain required surgical intervention and led to the diagnosis of diffuse large B-cell lymphoma. However, 10 months after this episode, treatment with infliximab was restarted because the patient continued with refractory and disabling perianal disease. Currently, with a follow-up of 36 months, under infliximab 10 mg/kg every 4 weeks, he maintains mild perianal Crohn’s disease and persists in sustained clinical and imaging remission of the lymphoproliferative disorder.     

Intox,detox, antidotes – Evidence based diagnosis and treatment of acute intoxications

Background and aimAim of this review is to describe the role of clinical toxicology in the context of acute medicine. A special focus is put on antidotes and important aspects of diagnosis and therapy of acute intoxications. The data of the annual report of GIZ-Nord Poisons Centre is analyzed concerning the following aspects: what intoxications are relevant in acute medicine, are there special aspects in therapy, e.g. antidotes, and what antidotes are relevant? More over intoxication-related fatalities are analyzed.Results and conclusionIn 2015 the poisons centre was consulted in 33,000 cases of acute intoxications. The most important groups are drugs (e.g. antidepressants, beta blockers and calcium channel blockers), chemical products (e.g. products containing surfactant, corrosive substances and toxic alcohols like methanol), plants and recreational drugs. Intoxications are relevant in acute medicine. Some substances can cause fatal intoxications. Important antidotes are naloxone for opiods, acetylcystein for paracetamol, fomepizole and ethanol for toxic alcohols and diazepam for intoxications caused by chloroquine.     

Localized nodular pigmented villonodular synovitis of the upper ankle joint – diagnosis and treatment

This paper introduces a case of local pigmented villonodular synovits (PVNS) of the upper ankle joint in a 37-year old patient. PVNS is a neoplasia of the synovial membrane. Two different entities of PVNS are known: generalized diffuse and local nodular. They differ in their degree of destruction and growth configuration, which is crucial for prognosis and operative treatment. The most common location of the local nodular form is the knee joint, followed by the finger joints. Occurrence in the ankle joint is not common but should be considered if clinical findings are present. MRI is the method of choice for diagnosis and assessment of the bone situation. Treatment consists of radical excision of the neoplasia. Radiosynoviorthesis is recommended as a post-operative treatment to increase the probability of a total removal of persisting PVNS cells. The rate of recurrence seems to be between 8 and 46%.     

Flow cytometry in lymphoma diagnosis and prognosis: useful?

Flow cytometry has become an important tool in the diagnosis of mature lymphoid neoplasms and the determination of prognosis in selected cases. The advantages of flow cytometry are based largely on its ability to analyse, rapidly and simultaneously, multiple cell properties in a quantitative manner. Flow cytometric immunophenotyping is useful in diagnosing lymphoma under the WHO classification system, where lymphoid neoplasms are separated into distinct clinical entities based upon morphology, immunophenotype, genetic abnormalities and clinical features. Flow cytometry can quantify the expression of proteins associated with a good or poor prognosis, detect multidrug resistance, and measure cell proliferation, making it useful in measuring prognostic indicators in lymphoid neoplasia. The unique attributes of flow cytometry therefore make it a valuable technique in the diagnosis and classification of lymphomas as well as the assessment of prognostic markers in lymphoma patients.     

Molecular biology and the diagnosis and treatment of liver diseases

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Hemosuccus pancreaticus： Problems and pitfalls in diagnosis and treatment

Hemosuccus pancreaticus is a rare cause of intermittent upper gastrointestinal bleeding. We report two cases of hemosuccus pancreaticus with multiple episodes of upper gastrointestinal bleeding. The causes of hemorrhage were rupture of pseudoaneurysm of the splenic artery and bleeding from the wall of pancreatic pseudocyst. Interventional radiology is the first modality for early diagnosis and possible treatment of hemosuccus pancreaticus. When angiography shows no abnormal findings or interventional radiological therapy can not be successful, surgery should be considered without delay. Our patients herein underwent surgery without recurrence or sequelae. Intraoperative ultrasonography and pancreatoscopy were helpful modalities for confirming the source of hemorrhage and determining the cutting line of the pancreas. When we encounter intermittent upper gastrointestinal bleeding with an obscure source, hemosuccus pancreaticus should be included in differential diagnoses especially in patients with chronic pancreatitis, which would lead to a prompt and proper treatment.     

Ischemic colitis： Clinical practice in diagnosis and treatment

Ischemic colitis is the most common form of ischemic injury of the gastrointestinal tract and can present either as an occlusive or a non-occlusive form. It accounts for 1 in 1000 hospitalizations but its incidence is underestimated because it often has a mild and transient nature. The etiology of ischemic colitis is multifactorial and the clinical presentation variable. The diagnosis is based on a combination of clinical suspicion, radiographic, endoscopic and histological findings. Therapy and outcome depends on the severity of the disease. Most cases of the non-gangrenous form are transient and resolve spontaneously without complications. On the other hand, high morbidity and mortality and urgent operative intervention are the hallmarks of gangrenous ischemic colitis.     

The diagnosis and treatment of whipple’s disease

Whipple’s disease is a rare, chronic, and systemic infectious disease caused by the ubiquitously occuring bacterium Tropheryma whippelii. For two reasons, the disease represents a good example for documenting the input of modern molecular-based techniques into pathogenetic, diagnostic, and therapeutic concepts in clinical medicine. First, the unidentified and uncultivable causative organism has been characterized by novel molecular-genetic techniques. Second, in contrast to other chronic inflammatory disorders, clinical manifestations of T. whippelii infection seem to be based on reduced T-cell helper type 1 (TH1) activity. These findings have led to an improved pathophysiologic understanding of the disease and to new aspects in treatment strategies that are discussed in this paper.     

Histochemistry and morphometry on bone marrow biopsies in chronic myeloproliferative disorders – aids to diagnosis and classification

 The aim of this review is to evaluate morphological characteristics of the different subtypes of chronic myeloproliferative disorders (MPDs) derived by applying immunohistochemical and morphometric techniques to bone marrow biopsies and to combine these results with relevant clinical parameters. In comparison to control specimens, a significant decrease in erythroid precursors is determinable in chronic myeloid leukemia (CML), while this cell lineage is most prominent in polycythemia vera (PV) and moderately to markedly reduced in idiopathic myelofibrosis (IMF). On the other hand, neutrophilic granulopoiesis shows a predominance in CML and a relevant increase in PV, but no conspicuous changes are detectable in essential thrombocythemia (ET). CML is characterized by a prevalent growth of dwarflike micromegakaryocytes, occurring in particular in the so-called megakaryocyte-rich subtypes (about 30%). This finding differs significantly from the pleomorphous aspect, i.e., clusters of small to giant-sized megakaryocytes in PV and the grossly abnormal (dysplastic) appearance of this cell lineage in patients with IMF. Similar cytological abnormalities of megakaryopoiesis consistent with maturation defects are never encountered in ET. The incidence of mature (resident) macrophages (phagocytic reticular cells) is significantly enhanced in IMF in comparison to the other MPDs and controls. Moreover, there is a striking difference in the density of reticulin-collagen fibers, ranging from normal (ET) to extreme values (IMF). In IMF more than 80% of the patients present with some degree of myelofibrosis-osteosclerosis at diagnosis, while the rest show an initial prefibrotic, hypercellular stage. This feature deserves special attention since, when accompanied by thrombocythemia, it may simulate ET. Sequential bone marrow biopsies in patients with IMF disclose that evolution of myelofibrosis is progressive, but occurs at a variable and unpredictable speed. A synoptical approach regarding clinical diagnosis and histological subtyping of MPDs is explicitly recommended and demonstrated by sets of diagnostic criteria. This rationale requires equal consideration of laboratory data and morphology by clinicians to include well-defined subtypes of MPDs into prospective management studies. Furthermore, it may even warrant follow-up studies and repeated bone marrow examinations in initially unclassifiable cases. Received: October 19, 1998 / Accepted: July 19, 1999     

Update on Crohn’s disease and ulcerative colitis

The 6th European Crohn’s and Colitis Organisation Congress took place in Dublin, Ireland, on the occasion of the 10th European Crohn’s and Colitis Organisation anniversary. This key annual event attracted a record number of participants and presented updated information in the field of inflammatory bowel disease in children and adults. The extensive program combined the original basic scientific program that dealt with pathogenesis and new therapeutic targets, while the clinical program focused on the possibility of optimizing current therapies, the importance of mucosal healing and features of inflammatory bowel disease-related cancer.     

Successful treatment with rituximab in a patient with primary thymic MALT lymphoma complicated with acquired von Willebrand syndrome and Sjögren syndrome

A 53-year-old female developed epigastric discomfort and back pain in 2007. Diagnostic imaging studies demonstrated a soft tissue tumor with heterogeneous enhancement in the anterior mediastinum and multiple nodules in the right lung. She underwent expanded thymectomy with subtotal resection of the right lung. The pathological diagnosis was primary thymic mucosa-associated lymphoid tissue (MALT) lymphoma. The patient complained of ocular discomfort, oral dryness and continuous nasal bleeding in 2007. Detailed examination led to a diagnosis of Sj?gren syndrome and acquired von Willebrand syndrome. Rituximab treatment for residual disease achieved not only a reduction of the lung MALT lymphoma but also clinical and hematological remission of both syndromes. This is, to our knowledge, the first reported case of primary thymic MALT lymphoma accompanied by Sj?gren and acquired von Willebrand syndromes.     

Nodular lymphocyte predominant Hodgkin lymphoma in children and adolescents – a comprehensive review of biology,clinical course and treatment options

Nodular lymphocyte predominant Hodgkin lymphoma (nLPHL) is a unique variant of Hodgkin lymphoma with an overall good prognosis. It is conspicuously different from classical Hodgkin lymphoma (cHL) and is now recognized as distinctive form of B cell lymphoma. Although it has an indolent clinical course, it has a propensity for multiple and often late relapses. Although the majority of children present with early stage disease and without B symptoms, treatment strategy has, until recently, been identical to that used for cHL. This approach is excessively toxic as it predisposes these children and adolescents to serious late effects including end organ damage to heart, gonads, lungs, thyroid and second malignant neoplasms. The aim of this article is to review the published literature on the treatment outcomes of nLPHL in affected children and adolescents, and discuss the options for treatment including surgery, chemotherapy, radiotherapy and targeted anti-CD 20 antibody therapy.     

Update on the molecular diagnosis of endocrine tumors: toward -omics-based personalized healthcare?

Genetic advances in endocrine neoplasia provided the paradigm for the practice of clinical cancer genetics: germline RET mutations in multiple endocrine neoplasia type 2. In the last 14 yr, both genetics and -omics advances have occurred, almost exponentially in the last 5 yr. The time has come to reevaluate recent advances in genomic medicine's promise to revolutionize personalized healthcare in the context of endocrine neoplasias. This update focuses on two examples of endocrine neoplasias, those of the thyroid and of the adrenal, and discusses recent advances in germline and somatic genetics and genomics, as they relate to clinical application.