A Tale of Two Lymphomas.

We present a patient with coeliac disease who developed refractory coeliac disease II, which was complicated by the development of metachronous lymphomas.

The Irish Helicobacter pylori Working Group consensus for the diagnosis and treatment of H. pylori infection in adult patients in Ireland.

BACKGROUND: Irish eradication rates for Helicobacter pylori are decreasing and there is an increase in the prevalence of antibiotic-resistant bacteria. These trends call into question current management strategies. OBJECTIVE: To establish an Irish Helicobacter pylori Working Group (IHPWG) to assess, revise and tailor current available recommendations. METHODS: Experts in the areas of gastroenterology and microbiology were invited to join the IHPWG. Questions of relevance to diagnosis, first-line and rescue therapy were developed using the PICO system. A literature search was performed. The 'Grading of Recommendations Assessment, Development and Evaluation' approach was then used to rate the quality of available evidence and grade the resulting recommendations. RESULTS: Key resultant IHPWG statements (S), the strength of recommendation and quality of evidence include S8: standard triple therapy for 7 days' duration can no longer be recommended (strong and moderate). S9: 14 days of clarithromycin-based triple therapy with a high-dose proton pump inhibitor (PPI) is recommended as first-line therapy. Bismuth quadruple therapy for 14 days is an alternative if available (strong and moderate). S12: second-line therapy depends on the first-line treatment and should not be the same treatment. The options are (a) 14 days of levofloxacin-based therapy with high-dose PPI, (b) 14 days of clarithromycin-based triple therapy with high-dose PPI or (c) bismuth quadruple therapy for 14 days (strong and moderate). S13: culture and antimicrobial susceptibility testing should be performed following two treatment failures (weak and low/very low). CONCLUSION: These recommendations are intended to provide the most relevant current best-practice guidelines for the management of H. pylori infection in adults in Ireland.

Myeloid Engraftment in Humanized Mice: Impact of Granulocyte-Colony Stimulating Factor Treatment and Transgenic Mouse Strain.

Poor myeloid engraftment remains a barrier to experimental use of humanized mice. Focusing primarily on peripheral blood cells, we compared the engraftment profile of NOD-scid-IL2Rγc(-/-) (NSG) mice with that of NSG mice transgenic for human membrane stem cell factor (hu-mSCF mice), NSG mice transgenic for human interleukin (IL)-3, granulocyte-macrophage-colony stimulating factor (GM-CSF), and stem cell factor (SGM3 mice). hu-mSCF and SGM3 mice showed enhanced engraftment of human leukocytes compared to NSG mice, and this was reflected in the number of human neutrophils and monocytes present in these strains. Importantly, discrete classical, intermediate, and nonclassical monocyte populations were identifiable in the blood of NSG and hu-mSCF mice, while the nonclassical population was absent in the blood of SGM3 mice. Granulocyte-colony stimulating factor (GCSF) treatment increased the number of blood monocytes in NSG and hu-mSCF mice, and neutrophils in NSG and SGM3 mice; however, this effect appeared to be at least partially dependent on the stem cell donor used to engraft the mice. Furthermore, GCSF treatment resulted in a preferential expansion of nonclassical monocytes in both NSG and hu-mSCF mice. Human tubulointerstitial CD11c(+) cells were present in the kidneys of hu-mSCF mice, while monocytes and neutrophils were identified in the liver of all strains. Bone marrow-derived macrophages prepared from NSG mice were most effective at phagocytosing polystyrene beads. In conclusion, hu-mSCF mice provide the best environment for the generation of human myeloid cells, with GCSF treatment further enhancing peripheral blood human monocyte cell numbers in this strain.

A combined antral and corpus rapid urease testing protocol can increase diagnostic accuracy despite a low prevalence of Helicobacter pylori infection in patients undergoing routine gastroscopy.

BACKGROUND: The effects of an increased risk of sampling error and the lower prevalence of Helicobacter pylori infection on the diagnostic accuracy of standard invasive tests needs to be considered. Despite evidence of enhanced yield with additional biopsies, combined Rapid Urease Tests (RUTs) have not been widely adopted. We aimed to compare the diagnostic efficacy of a combined antral and corpus rapid urease test (RUT) to a single antral RUT in a low prevalence cohort. METHODS: Between August 2013 and April 2014 adult patients undergoing a scheduled gastroscopy were prospectively recruited. At endoscopy biopsies were taken and processed for single and combined RUTs, histology and culture using standard techniques. Infection was defined by positive culture or detection of Helicobacter like organisms on either antral or corpus samples. RESULTS: In all 123 patients were recruited. H. pylori prevalence was low at 36%, n = 44. There was a significant difference in positivity between single and combined RUTs, 20% (n = 25) versus 30% (n = 37), p = 0.0094, (95% CI 0.15-0.04). The number needed to treat (NNT) for an additional diagnosis of infection using a combined versus a single RUT is 4 (95% CI 2.2-11). The only factor associated with a reduction in RUT yield was regular proton pump inhibitor (PPI) use. Overall the sensitivity, specificity, positive and negative predictive value for any RUT test was 84%, 100%, 100% and 92% respectively. CONCLUSION: Our data suggests taking routine antral and corpus biopsies in conjunction with a combined RUT appears to optimizing H. pylori detection and overcome sampling error in a low prevalence population.

Sustained participation, colonoscopy uptake and adenoma detection rates over two rounds of the Tallaght-Trinity College colorectal cancer screening programme with the faecal immunological test.

BACKGROUND: Studies to date support the use of the faecal immunological test (FIT) in colorectal cancer screening programmes, and it has been widely adopted across Europe, Canada, Australia, and the USA. Successive screening rounds are necessary to detect and prevent colorectal cancer. The overall success of FIT screening will depend on several factors, the most important probably being the acceptability of repeated screening rounds. Being a newer form of occult blood testing, there is little data available on its overall efficacy over time. AIMS: The aim of this study was to assess key performance indices during a second round of FIT screening in an Irish cohort and to compare results between successive rounds. METHODS: A biennial, two tests, two-step design with postal invites and colonoscopy offered to anyone with a single FIT greater than 100 ngHb/ml was used. Recommended key performance measures were assessed and compared, including participation, positivity, colonoscopy uptake and adenoma and cancer detection rates. RESULTS: In round two, 9863 individuals (98.6%) of the round one cohort were contacted. The round two participation rate was 47.5% (n=4685), only slightly lower than the 51% registered in round one. Male sex and younger age were associated with lower uptake. Overall positivity decreased from 10 to 8% over time (P<0.0001). Although the number of cancers detected during round two decreased significantly, overall neoplasia detection rates remained stable; positive predictive values for cancer and adenoma were 4 versus 1% and 37 versus 35%, respectively. CONCLUSION: Repeated rounds of FIT screening in the Tallaght-Trinity College cohort achieved stable participation and neoplasia detection rates, suggesting that this mode of screening is both effective and acceptable to patients in the long term.

Isolated active ileitis: is it a mild subtype of Crohn's disease?

BACKGROUND: Ileal intubation is being increasingly performed at colonoscopy and has in turn lead to an increasingly recognized subgroup of patients-those with mild terminal ileal inflammation, an entity that we have coined isolated active ileitis (IAI). The aims of this study were to define the natural history of IAI and determine if IAI shares a similar genetic and serologic profile with Crohn's disease (CD). METHODS: Patients with IAI were identified from our institution's histopathology and endoscopy databases. Cases attended for repeat colonoscopy and blood were analyzed for the expression of antineutrophil cytoplasmic antibody, anti-OmpC, anti-Saccharomyces cerevisiae antigen (ASCA) IgA, ASCA IgG, and anti-CBir antibodies and NOD2 genotyping. Age and sex-matched healthy controls, CD, and UC cases were also recruited. RESULTS: Sixty-three patients with IAI were recruited. There was no significant difference in the prevalence of antibodies between IAI cases and healthy controls for antineutrophil cytoplasmic antibody, OmpC, ASCA IgA, or ASCA IgG. The presence of all 5 antibodies was significantly higher in the CD group than the IAI group, P < 0.05. There were 28.6% of CD cases that carried one or more NOD2 variants, compared to 26.2% of the IAI cohort and 6.1% of healthy controls. Forty-three cases underwent follow-up ileocolonoscopy. Six of 43 cases (14%) had definite CD. CONCLUSIONS: A majority of IAI cases developed persistent symptoms and terminal ileal abnormalities; however, only 14% developed classical, histological, or radiological features of CD. Although patients with IAI have a low level of seropositivity, similar to healthy controls, they do share an excess of NOD2 mutations with CD cases.

Large cell neuroendocrine carcinoma of the ampulla of Vater.

CONTEXT: Large cell neuroendocrine carcinomas of the ampulla of Vater are rare and confer a very poor prognosis despite aggressive therapy. There are few case reports of large cell neuroendocrine carcinomas of the ampulla of Vater in the literature and to date no studies have been done to establish optimal management. We describe a pooled case series from published reports of neuroendocrine carcinomas of the ampulla of Vater including a case which presented to our institution. METHODS: A narrative review was undertaken including all published English case reports of large cell neuroendocrine carcinomas of the ampulla of Vater. Our primary outcome was to determine the overall survival. RESULTS: Twenty cases of large cell neuroendocrine carcinomas of the ampulla of Vater were identified. Seventy-six percent of patients were reported to have died of disease with a mean survival of 11.8 months. Twenty percent of the tumours were associated with an adenoma. The approximate median survivals were 15 months for those with an associated adenoma and 11 months without. CONCLUSIONS: This pooled analysis demonstrates both the rarity and poor prognosis of large cell neuroendocrine carcinomas of the ampulla of Vater. Although surgical resection is the mainstay of treatment, we review common adjuvant chemotherapy regimes. Prognosis may be improved when these tumours are associated with adenomas, however, further studies are needed.

Complex rectal polyps: other treatment modalities required when offering a transanal endoscopic microsurgery service.

PURPOSE: Complex rectal polyps may present a clinical challenge. The study aim was to assess different treatment modalities required in the management of patients referred for transanal endoscopic microsurgery. METHODS: Patients referred with complex rectal polyps from 1998 to 2008 were entered prospectively to a colorectal database. These data was analyzed for referral pattern, histology, surgical procedures performed, and subsequent outcome. RESULTS: Of the 209 patients referred (101 female, 108 male, median age of 65 years, range of 24-89), 132 (63%) were deemed suitable for transanal endoscopic microsurgery. Seventeen patients required a second staged procedure; three patients required an anterior resection at time of index surgery. Seventeen patients referred for transanal endoscopic microsurgery went direct to anterior resection, 37 underwent snare polypectomy (SP), and 17 patients underwent transanal excision. Six patients had no surgery (three unfit for anesthesia and three had no residual lesions). Thus, 37% of the patients referred for transanal endoscopic microsurgery required a different treatment modality. CONCLUSIONS: Majority of patients referred to our unit with complex rectal polyps were suitable for transanal endoscopic microsurgery. However, this study highlights that in offering a transanal microsurgery service, one should be prepared for a diversity of pathology necessitating a range of management options.

Increased spontaneous apoptosis, but not survivin expression, is associated with histomorphologic response to neoadjuvant chemoradiation in rectal cancer.

PURPOSE: Survivin has been shown to be an important mediator of cellular radioresistance in vitro. This study aims to compare survivin expression and apoptosis to histomorphologic responses to neoadjuvant radiochemotherapy (RCT) in rectal cancer. MATERIALS AND METHODS: Thirty-six pre-treatment biopsies were studied. Survivin mRNA and protein expression plus TUNEL staining for apoptosis was performed. Response to treatment was assessed using a 5-point tumour regression grade. RESULTS: Survivin expression was not found to be predictive of response to RCT (p = NS). In contrast, spontaneous apoptosis was significantly (p = 0.0051) associated with subsequent response to RCT. However, no association between survivin expression and levels of apoptosis could be identified. CONCLUSIONS: This in vivo study failed to support in vitro studies showing an association between survivin and response to chemotherapy and radiation therapy. These results caution against the translation of the in vitro properties of survivin into a clinical setting.

Small cell cervical cancer: an unusual finding at cholecystectomy.

BACKGROUND: Small cell carcinoma of the cervix is a rare cancer, comprising less than 3% of all cervical neoplasms. It uniformly has a poor prognosis, and has a high mortality even with early stage disease. It can metastasise rapidly and metastatic sites include lung, liver, brain, bone, pancreas and lymph nodes. CASE: Here, we report the case of a 60-year-old woman with no symptoms of cervical pathology who developed post-renal failure following a laparoscopic cholecystectomy. The cause was bilateral ureteric obstruction from metastatic small cell cervical cancer and metastases were subsequently found on her gallbladder specimen. CONCLUSION: This is an unusual presentation of small cell cervical cancer and demonstrates the aggressive nature of this disease.

BRAF T1799A mutation occurring in a case of malignant struma ovarii.

Struma ovarii is an extremely rare tumor that occasionally undergoes malignant transformation. Because struma ovarii is composed of thyroid tissue, it is conceivable that the pathogenetic events involved in thyroid follicular transformation may take place also in struma ovarii. The authors describe a case of a classical variant of papillary thyroid carcinoma arising in a struma ovarii of a 22-year-old female. The tumor was heterozygous for BRAF T1799A mutation. No ret/ PTC-1 or ret/PTC-3 rearrangements were detected. This finding would suggest that malignant struma ovarii is similar histologically and genetically to primary papillary thyroid carcinoma.

COX-2 overexpression in pretreatment biopsies predicts response of rectal cancers to neoadjuvant radiochemotherapy.

PURPOSE: To determine the utility of COX-2 expression as a response predictor for patients with rectal cancer who are undergoing neoadjuvant radiochemotherapy (RCT). METHODS AND MATERIALS: Pretreatment biopsies (PTB) from 49 patients who underwent RCT were included. COX-2 and proliferation in PTB were assessed by immunohistochemistry (IHC) and apoptosis was detected by TUNEL stain. Response to treatment was assessed by a 5-point tumor-regression grade (TRG) based on the ratio of residual tumor to fibrosis. RESULTS: Good response (TRG 1+2), moderate response (TRG 3), and poor response (TRG 4+5) were seen in 21 patients (42%), 11 patients (22%), and 17 patients (34%), respectively. Patients with COX-2 overexpression in PTB were more likely to demonstrate moderate or poor response (TRG 3+4) to treatment than were those with normal COX-2 expression (p=0.026, chi-square test). Similarly, poor response was more likely if patients had low levels of spontaneous apoptosis in PTBs (p=0.0007, chi-square test). CONCLUSIONS: COX-2 overexpression and reduced apoptosis in PTB can predict poor response of rectal cancer to RCT. As COX-2 inhibitors are commercially available, their administration to patients who overexpress COX-2 warrants assessment in clinical trials in an attempt to increase overall response rates.

Infarcted angiomatous nasal polyps.

Angiomatous nasal polyps are a rarely reported subtype of inflammatory sinonasal polyps that are characterized by extensive vascular proliferation and ectasia. Compromise of their vascular supply may occasionally lead to infarction, resulting in clinical, radiological and pathological features that simulate a neoplastic process. In the present paper, the salient characteristics of this unusual entity are described. The clinical, radiological and pathological features of two patients with infarcted angiomatous nasal polyps are presented. Grossly, the polyps had an unusual inhomogenous appearance and texture and were associated with a foul odor. CT findings included bony expansion and destruction. MRI findings included markedly inhomogenous contrast enhancement on T1-weighted images. Histopathologically, both cases showed abundant vascular ectasia, with widespread intraluminal thrombosis and necrosis. Recanalization and reparative changes were also present. Angiomatous nasal polyps are poorly documented in the literature. Although entirely benign, they may simulate neoplastic processes, thus awareness of their existence is of considerable importance.

Gastric mucosal mast cells are increased in Helicobacter pylori-negative functional dyspepsia.

BACKGROUND & AIMS: Mast cells might be involved in pathogenesis of functional dyspepsia because they can release a wide range of potent mediators, capable of altering gastric nerve and muscle function. This study aimed to determine whether mast cell numbers were increased in the gastric mucosa of patients with functional dyspepsia compared to control subjects. METHODS: Biopsy samples were taken from the antrum and corpus of 111 patients: 20 asymptomatic control subjects, 62 patients with Rome criteria functional dyspepsia (33 Helicobacter pylori positive, 29 H. pylori negative), and 29 inflammatory control subjects (H. pylori positive). Mast cells were detected immunohistochemically by using a mouse monoclonal antibody specific for tryptase. Quantification was performed with light microscopy, and results were expressed as mast cells/mm(2) +/- standard error of mean. RESULTS: Mast cells were significantly increased in H. pylori negative functional dyspepsia samples compared to normal control samples in the antrum (230.1 +/- 11.3 vs. 94.8 +/- 8.4, P < 0.001) and corpus (264.1 +/- 27.1 vs. 123.9 +/- 11.5, P = 0.001). Mast cells were also significantly increased in the antrum of patients with H. pylori positive functional dyspepsia compared to asymptomatic control subjects (166.5 +/- 17.0 vs. 94.8 +/- 8.4, P < 0.03). However, there was no significant difference between mast cell numbers in patients with H. pylori positive functional dyspepsia compared to inflammatory control subjects. CONCLUSIONS: Mast cells are increased in functional dyspepsia, independently of inflammation. This might contribute to the pathogenesis of functional dyspepsia by altering signaling in the brain-gut axis.