As only a handful of lymphoma cases have been reported in conjunction with primary intestinal lymphangiectasia, it is not yet clear if this association is merely fortuitous or related to primary intestinal lymphangiectasia induced immune deficiency. We report on two female patients, 50 and 58 years old, who developed small intestinal high grade B cell lymphoma a long time (45 and 40 years, respectively) after the initial clinical manifestations of primary intestinal lymphangiectasia. They presented with a longstanding history of fluctuating protein losing enteropathy, multiple cutaneous plane warts, and markedly dilated mucosal and submucosal lymphatic channels in duodenal biopsies. One had a large ulcerated tumour of the proximal ileum and the other diffuse ileal infiltration. In both, histological examination showed centroblastic high grade B cell lymphoma associated with duodenojejuno-ileal mucosal and submucosal lymphangiectasia. They were subsequently successfully treated with surgery and postoperative chemotherapy (AVmCP: adriamycin, cyclophosphamide, Vm26, and prednisolone), and chemotherapy alone (PACOB: adriamycin, cyclophosphamide, vincristine, bleomycine, and prednisolone), respectively. A three year follow up in both cases showed persistent diffuse lymphangiectasia without evidence of lymphoma. The present findings support the hypothesis that primary intestinal lymphangiectasia is associated with lymphoma development.

The established dogma regarding the different isoforms of nitric oxide has been that constitutively expressed nitric oxide synthase is an extremely important homeostatic regulator of numerous important physiological processes whereas the inducible form of nitric oxide synthase underlies injury associated with intestinal inflammation. In this brief overview, I review some of the literature that clearly supports this contention, particularly the dramatically beneficial effects of oral L-NAME administration to animals with colitis induced by trinitrobenzene sulphonic acid (TNBS). However, I also highlight some of the gastrointestinal data that does not fit this simple tidy paradigm, particularly with respect to the inducible form of nitric oxide synthase (iNOS). For example, iNOS induced healing of skin and the intestinal mucosa, killing of certain bacteria, regulation of T cell proliferation and differentiation (Th1 v Th2), and control of leucocyte recruitment may mask or counter the toxic metabolites that are produced by iNOS. Perhaps it is not surprising that one does not always obtain benefit from inhibiting all iNOS either by gene deletion or by systemic NOS inhibition. I raise some potential flaws in our approaches to studying iNOS. For example, to date no attempts have been made to selectively inhibit iNOS in single cell types. Global inhibition of all iNOS assumes that the large variety of cell types that can produce iNOS have identical functions. Finally, I attempt to highlight areas that require additional investigation and issues that have not been explored.

Lateral sphincterotomy diminishes internal anal sphincter hypertonia and thereby reduces anal canal pressure. This improves anal mucosal blood flow and promotes the healing of anal fissures. However, sphincterotomy can be associated with long term disturbances of sphincter function. The optimal treatment for an anal fissure is to induce a temporary reduction of anal canal resting pressure to allow healing of the fissure without permanently disrupting normal sphincter function. Broader understanding of the intrinsic mechanisms controlling smooth muscle contraction has allowed pharmacological manipulation of anal sphincter tone. We performed an initial Medline literature search to identify all articles concerning "internal anal sphincter" and "anal fissures". This review is based on these articles and on additional publications obtained by manual cross referencing. Internal anal smooth muscle relaxation can be inhibited by stimulation of non-adrenergic non-cholinergic enteric neurones, parasympathetic muscarinic receptors, or sympathetic beta adrenoceptors, and by inhibition of calcium entry into the cell. Sphincter contraction depends on an increase in cytoplasmic calcium and is enhanced by sympathetic adrenergic stimulation. Currently, the most commonly used pharmacological agent in the treatment of anal fissures is topical glyceryl trinitrate, a nitric oxide donor. Alternative agents that exhibit a similar effect via membrane Ca2+ channels, muscarinic receptors, and alpha or beta adrenoceptors are also likely to have a therapeutic potential in treating anal fissures.