James DeGaetano

Incidence of inflammatory bowel disease in Malta between 1993 and 2005: A retrospective study

Background: The primary aim of the study was to estimate the incidence of Crohns disease (CD) and ulcerative colitis (UC), collectively known as inflammatory bowel disease (IBD), in Malta in a well‐defined population during a 13‐year study period. Methods: Diagnostic criteria for CD and UC were defined. A diagnosis of IBD was obtained from the histopathology reports at St. Lukes Hospital, Malta, between January 1993 and December 2005. The date of diagnosis was defined as the date of the first histopathology report revealing signs of IBD. Results: Incidence rates were standardized using the direct method on the European Standard Population. The mean incidence of UC in males was 8.16 per 100,000 per year and for females was 7.59 per 100,000 per year, while that for CD in males was 0.96 per 100,000 per year and for females 1.622 per 100,000 per year. Using linear regression, in UC there is an almost significant (P = 0.069) increasing trend with time but no difference by gender (P = 0.591). On the other hand, in CD there is no significant trend with time (P = 0.555) but almost a significant difference by gender (P = 0.078). Conclusions: This is the first Maltese study in which the incidence of IBD has been recorded. In Malta the incidence of UC is similar to the overall incidence of other European countries while the incidence of CD is lower. In fact, the incidence rates of CD are among the lowest in Europe, similar to other southern European countries.

Expression and Clinical Significance of Wnt Players and Survivin in Pituitary Tumours

Deregulation of the Wnt pathway has been implicated in oncogenesis of numerous tissues including the pituitary gland. Immunohistochemical localization and quantification of β-catenin, Cyclin D1, c-MYC and Survivin expression in 47 pituitary adenomas (35 non-functioning, seven GH-secreting, three prolactinomas, two ACTH-secreting tumour) and six normal controls was undertaken in this study and correlation of protein expression to patient and tumour characteristics analysed. β-catenin was strictly membrane-bound with no difference observed between normal and tumour tissue. In contrast, Cyclin D1 and c-MYC localization was nuclear and significantly higher in tumour versus normal tissue (p < 0.05). c-MYC expression correlated negatively with age at diagnosis (p = 0.006, R = −0.395) while Cyclin D1 expression correlated positively with age (p = 0.036, R = 0.306) and was higher in males than in females (p = 0.036). c-MYC expression was significantly lower in patients with functional tumours requiring octreotide treatment and in patients with non-functioning tumours suffering from hypopituitarism. Survivin expression was extremely low in tumours and absent in normal controls. Involvement of the canonical Wnt pathway appears to be minimal, given the segregation of β-catenin to the membrane. Our data suggest that c-MYC may have an important role in early pituitary tumorigenesis while Cyclin D1 is likely to promote tumour growth at a later stage. We also report a novel gender difference in Cyclin D1 expression, the biological significance of which merits further analysis. The reported reduction of c-MYC in functional tumours subsequently treated with octreotide further supports a role of c-MYC in early tumorigenesis and not in recurrence. The decrease in c-MYC in patients with hypopituitarism provides the first in vivo evidence for hormonal regulation of c-MYC expression.

Clinical outcome of pediatric collagenous gastritis: Case series and review of literature

Collagenous gastritis (CG) is characterized by patchy subepithelial collagen bands. Effective treatment and the clinical and histological outcome of CG in children are poorly defined. The aim of this study is to summarize the published literature on the clinical outcome and response to therapy of pediatric CG including two new cases. We performed a search in Pubmed, OVID for related terms; articles including management and clinical and/or endo-histologic follow up information were included and abstracted. Reported findings were pooled in a dedicated database including the corresponding data extracted from chart review in our patients with CG. Twenty-four patients were included (17 females) with a mean age of 11.7 years. The clinical presentation included iron deficiency anemia and dyspepsia. The reported duration of follow up (in 18 patients) ranged between 0.2-14 years. Despite most subjects presenting with anemia including one requiring blood transfusion, oral iron therapy was only documented in 12 patients. Other treatment modalities were antisecretory measures in 13 patients; proton pump inhibitors (12), or histamine-2 blockers (3), sucralfate (5), prednisolone (6), oral budesonide in 3 patients where one received it in fish oil and triple therapy (3). Three (13%) patients showed no clinical improvement despite therapy; conversely 19 out of 22 were reported with improved symptoms including 8 with complete symptom resolution. Spontaneous clinical resolution without antisecretory, anti-inflammatory or gastroprotective agents was noted in 5 patients (4 received only supplemental iron). Follow up endo-histopathologic data (17 patients) included persistent collagen band and stable Mononuclear cell infiltrate in 12 patients with histopathologic improvement in 5 patients. Neither collagen band thickness nor mononuclear cell infiltrate correlated with clinical course. Intestinal metaplasia and endocrine cell hyperplasia were reported (1) raising the concern of long term malignant transformation. In summary, CG in children is a chronic disease, typically with a variable clinical response and an indolent course that is distinct from the adult phenotype. Long term therapy usually included iron supplementation but cannot be standardized, given the chronicity of the disease, variability of response and potential for adverse events.

Suppressive role exerted by microRNA-29b-1-5p in triple negative breast cancer through SPIN1 regulation

MiR-29 family dysregulation occurs in various cancers including breast cancers. We investigated miR-29b-1 functional role in human triple negative breast cancer (TNBC) the most aggressive breast cancer subtype. We found that miR-29b-1-5p was downregulated in human TNBC tissues and cell lines. To assess whether miR-29b-1-5p correlated with TNBC regenerative potential, we evaluated cancer stem cell enrichment in our TNBC cell lines, and found that only MDA-MB-231 and BT-20 produced primary, secondary and tertiary mammospheres, which were progressively enriched in OCT4, NANOG and SOX2 stemness genes. MiR-29b-1-5p expression inversely correlated with mammosphere stemness potential, and miR-29b-1 ectopic overexpression decreased TNBC cell growth, self-renewal, migration, invasiveness and paclitaxel resistance repressing WNT/βcatenin and AKT signaling pathways and stemness regulators. We identified SPINDLIN1 (SPIN1) among predicted miR-29b-1-5p targets. Consistently, SPIN1 was overexpressed in most TNBC tissues and cell lines and negatively correlated with miR-29b-1-5p. Target site inhibition showed that SPIN1 seems to be directly controlled by miR-29b-1-5p. Silencing SPIN1 mirrored the effects triggered by miR-29b-1 overexpression, whereas SPIN1 rescue by SPIN1miScript protector, determined the reversal of the molecular effects produced by the mimic-miR-29b-1-5p. Overall, we show that miR-29b-1 deregulation impacts on multiple oncogenic features of TNBC cells and their renewal potential, acting, at least partly, through SPIN1, and suggest that both these factors should be evaluated as new possible therapeutic targets against TNBC.

An unusual site for calciphylaxis: a case report

Background: Calciphylaxis is a rare condition characterized by calcification of the tunica media of small arteries with or without endovascular fibrosis, extravascular calcification and vascular thrombosis, leading to tissue ischemia and hence necrosis of tissues supplied by respective vessel. Case report: An 83-year-old lady presented with a 2-week history of rapidly progressing painful necrotic vulval lesion. This patient was being treated medically with bisphosphonates for mild hypercalcaemia secondary to a parathyroid adenoma. The diagnosis of calciphylaxis was made by biopsy of lesion, revealing extensive necrotic areas and multiple abscesses with numerous thrombosed and calcified blood vessels. Conclusions: This case shows an unusual presentation of calciphylaxis, in a patient with primary hyperparathyroidism, in the absence of end stage renal failure. The pathogenesis of the condition is still relatively unknown. Particularly of note in this case is the presentation of the lesion 9 months after the start of treatment with bisphosphonate after the relative decrease of serum parathyroid levels and serum calcium levels. This leads to the question of initiation of the pathology – did the bisphosphonate treatment have an input in initiation of the lesion? The case under review adds a new differential diagnosis to necrotic vulval lesions, other than malignancy.

Evaluation of a method allowing preservation of fresh lymph nodes for flow cytometric immunophenotyping

Flow cytometric immunophenotyping (FCI) of lymph nodes (LN) requires fresh unfixed tissue, with analysis being carried out within few hours post surgery. This study evaluated a novel method for fresh LN preservation, in order to allow histomorphology‐based FCI.

Testicular mass in an elderly patient: a rare presentation of Hodgkin's lymphoma

A testicular mass in an elderly man has a high probability of being a lymphoma. However, when the pathologist is faced with a neoplastic lymphoid infiltrate in the testes, one rarely considers Hodgkins lymphoma as a possibility, as a vast majority turn out to be diffuse large B cell lymphomas. The authors discuss the second case of Hodgkins lymphoma, nodular sclerosis subtype, presenting as a painless enlarged testicle and associated symptoms similar to irreducible hernia in a 73-year-old gentleman. The patient was later found to have subdiaphragmatic lymph node disease. Hodgkins lymphoma should therefore be given due consideration in the differential diagnosis of a testicular tumour with a predominantly lymphoid infiltrate.

Crohn's disease manifesting as an isolated cecal polyp and secondary appendiceal obstruction with histologically normal bowel.

Dear Editor:Inflammatory colonic polyps usually arise on a backgroundhistory of an inflamed colon such as Crohn’s disease orulcerative colitis [1]. Similar inflammatory bowel disease(IBD)-related inflammatory polyps, occurring in the absenceof background IBD, have manifested themselves as eitherfiliform polyposis [2] or localized giant inflammatory polyps[3]. We hereby report a case of an isolated sessile cecal poleinflammatory polyp, with histological features of Crohn’sdisease, without a history or current evidence of backgroundIBD. To our knowledge, our case is the first case of such amanifestation of a common condition. Moreover, this polypalso caused secondary appendiceal obstruction, another find-ing previously unreported.A 33-year-old male, nonsmoker, presented with a 6-monthhistory of intermittent colicky right iliac fossa (RIF) pain,which spontaneously resolves after 2 days of rest. He did notreport any change in bowel habit, rectal bleeding, fever, orweight loss. His past medical history, surgical history, familyhistory, and social history were unremarkable. Examinationrevealed normal findings. No tenderness or masses were elic-ited on palpation of the abdomen. Laboratory investigationsrevealeda normal fullblood count and inflammatory markersduring pain-free periods but an elevated C-reactive protein(95mg/l)andhyperferritinemia(681ng/ml)wheninpain.Hehad normal renal, liver, iron, folate, and vitamin B

Giant gastric folds in a patient with hypoalbuminaemia.

A 70-year-old man presented with a 3-month history of persistent epigastric pain, 8 kg weight loss and lower limb swelling. Examination revealed a normal abdomen and bilateral lower limb oedema. Blood results were unremarkable except for hypoalbuminaemia (23 g/l) and peripheral eosinophilia (1.06×109/l). Urinalysis and CT of the abdomen were negative. An oesophagogastroduodenoscopy (OGD) revealed large gastric folds involving the fundus and the body of the …

A difficult case of Crohn's disease?

A young lady with a long history of recurrent infections was referred to the gastroenterology department by an infectious disease consultant because of a long history of profuse diarrhoea. A nitroblue tetrazolium (NBT) test performed in her mid-teens had shown zero reduction of the dye. The clinical, biochemical, radiological and endoscopic findings were suggestive of possible underlying Crohns disease. However, the NBT test was more suggestive of a granulomatous colitis which frequently mimics Crohns disease in patients with Chronic granulomatous disease. Management with immunosuppressants is proving to be very difficult in this patient in view of recurrent sepsis on introducing these drugs.