Gene expression profiling of serrated polyps identifies annexin A10 as a marker of a sessile serrated adenoma/polyp

Sessile serrated adenomas/polyps (SSA/Ps) are precursors of colon cancer, particularly those that exhibit microsatellite instability. Distinguishing SSA/Ps from the related, but innocuous, microvesicular hyperplastic polyp (MVHP) can be challenging. In this study seven gastrointestinal pathologists reviewed 109 serrated polyps and identified 60 polyps with histological consensus. Microarray analysis was performed on six distal consensus MVHPs < 9 mm, six proximal consensus SSA/Ps > 9 mm, and six normal colon biopsies (three proximal, three distal). Comparative gene expression analysis confirmed the close relationship between SSA/Ps and MVHPs as there was overlapping expression of many genes. However, the gene expression profile in SSA/Ps had stronger and more numerous associations with cancer‐related genes compared with MVHPs. Three genes (TFF2, FABP6, and ANXA10) were identified as candidates whose expression can differentiate SSA/Ps from MVHPs, and the differences in expression were confirmed by quantitative RT‐PCR. As ANXA10 showed the most promise in differentiating these polyps, the expression of ANXA10 was evaluated by immunohistochemistry in consensus SSA/Ps (n = 26), MVHPs (n = 21), and normal colon (n = 9). Immunohistochemical expression of ANXA10 was not identified in separate samples of normal colon or in the normal colonic epithelium adjacent to the serrated polyps. Consistent with the microarray and quantitative RT‐PCR experiments, immunohistochemical expression of ANXA10 was markedly increased in SSA/Ps compared to MVHPs (p < 0.0001). An ANXA10 score ≥ 3 has a sensitivity of 73% and a specificity of 95% in the diagnosis of an SSA/P. In conclusion, we show that SSA/Ps and MVHPs have significant overlap in gene expression, but also important differences, particularly in cancer‐related pathways. Expression of ANXA10 may be a potential marker of the serrated pathway to colon cancer. Copyright © 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

Pathological features of the sessile serrated adenoma/polyp with special references of its carcinogenesis

The sessile serrated adenoma/polyp (SSA/P) has been thought as the relatively new precursor for the colorectal cancer. In the current review, the well-known pathological features including the histological definition of the SSA/P are described using the previous reports. Although the SSA/P is thought one of pre-cancerous lesions of the colorectal carcinoma, the decisive or documentary lesion like “carcinoma in adenoma” is very rare. In this review, the strict case of the carcinoma derived from the SSA/P is demonstrated using our cases. Although the genetic investigations of the SSA/P have shown the new pathway of colorectal carcinogenesis and these concepts are thought to be almost right, the verification for them should be performed using “the carcinoma in SSA/P” like the present case.     

Characterization of the pathologic and endoscopic measurements of colorectal polyp sizes with a focus on sessile serrated adenoma and high-grade dysplasia

Background: The characteristics of pathologically measured (PMS) and endoscopically measured sizes (EMS) of the colorectal polyps (CRPs) is poorly understood, particularly in polypoid unremarkable mucosa (PUM), sessile serrated adenoma (SSA), and high-grade dysplasia (HGD). Methods: To characterize the discordance and correlation between the PMS and EMS of CRPs including PUM, SSA, HGD, hyperplastic polyp (HP) and adenomas, we conducted this prospective observational study on the polyps collected between August 2012 and December 2013. Results: PMS was significantly smaller than EMS in the 497 qualified CRPs regardless of the sites (left, transverse and right colorectum) or EMS (≥1 cm and <1 cm) subgroups. The PMS and EMS discordance was associated with a diagnosis of HP and adenoma (versus PUM, SSA or HGD), single fragment (versus multiple), 3 of the 8 endoscopists and PMS<1 cm (versus ≥1 cm). Despite a good correlation between EMS and PMS in the adenomas (ĸ=0.626, 95% confidence intervals [CI], 0.505-0.746) and a moderate correlation in the serrated polyps (SPs) including HP and SSA, (ĸ=0.424, 95% CI, 0.244-0.604), 40.4% (23/57) of the adenomas and 63.6% (21/33) of the SPs with EMS≥1 cm might warrant longer follow-up intervals since their PMS were <1 cm. The PMS and EMS had linear correlations except in CRPs with HGD or EMS≥1 cm. Conclusions: The discordance between PMS and EMS is associated with the pathologic diagnosis, fragment number, endoscopists and PMS, and may lead to different follow-ups in a considerable portion of adenomas and SPs.     

Controlling infection in a district general hospital

The way in which hospital-acquired infection has been brought under control over a three-year period in a district general hospital is described.The main success has been achieved in reducing sepsis caused by Staph. aureus, especially methicillin-resistant strains, and Pseudomonas aeruginosa.These reductions were achieved in spite of inadequate ward isolation and operating theatre facilities, and before there was any marked change in patterns of prescribing antibiotics.Our experiences indicate the significant improvements that can be made in controlling nosocomial sepsis even without structural or other major alterations in a hospital, providing that the problem is fully appreciated and the infection control team are concerned enough to act vigorously in influencing their clinical colleagues.     

Selective expression of gastric mucin MUC6 in colonic sessile serrated adenoma but not in hyperplastic polyp aids in morphological diagnosis of serrated polyps

Colonic sessile serrated adenoma, in contrast to hyperplastic polyp, is thought to be related to sporadic colorectal cancers with high microsatellite instability. However, the morphological distinction between these entities is difficult and subject to observer and sampling variation. Therefore, we elected to investigate the expression of gastric mucin MUC6 as a potential marker to separate the two in the hope of finding an objective and reproducible adjunct to morphological diagnosis. Endoscopic biopsies of colonic polyps with serrated architecture, but without cytological dysplasia were studied and categorized as sessile serrated adenoma or hyperplastic polyp, using previously published morphological criteria. Smaller groups of serrated polyps with cytological dysplasia (traditional serrated adenomas, filiform serrated adenomas and sessile serrated adenomas with cytological dysplasia) were also included. In total, 94 polyps were immunohistochemically stained with antibodies to MUC6 and to MLH-1. MUC6 was found to have 100% specificity in distinguishing sessile serrated adenoma (N=26; positive staining) from hyperplastic polyp (N=48; negative staining). Traditional serrated adenomas and filiform serrated adenomas were also negative for MUC6. Sessile serrated adenomas with cytological dysplasia were found to lose expression of MLH-1 in dysplastic areas, while retaining MUC6 expression. Neither anatomic location in the right or left colon nor polyp size appears to account for the differences in MUC6 expression.     

A general-practitioner ward in a new district general hospital

So far there are relatively few general-practitioner wards in district general hospitals in the National Health Service. The work of one such general-practitioner ward at Queen Mary's Hospital, Sidcup, is described and the advantages of this system of care for patients and doctors discussed.     

Audit of necropsies in a British district general hospital.

A comprehensive study was made of the value of necropsies carried out over a six month period in Peterborough Health Authority, using a modification of the format proposed by Schned et al in Vermont, United States of America. Cause of death, clinical correlation, clinical factors contributing to death and clinical evaluation of the necropsy were recorded. The principal diseases were cardiac (33%), and neoplastic (29%). The pathologist disagreed with the clinical cause of death in 13% of cases and major unsuspected diagnoses were found in 30%. Seventy nine per cent of necropsies provided additional information, including feedback on clinical investigations. Clinicians' questions were answered fully in 87%. Necropsies were rated as "very valuable" in 44% of cases, "valuable" in 54%, and "of no value" in only 2%. In 14% of cases the clinical consultant stated that the results of the necropsy would affect future clinical practice. These findings underline the essential place of necropsies in both audit and postgraduate education. The format described could conveniently be used by other pathology departments as part of an audit program.     

Suicide among psychiatric patients of a district general hospital

Twenty-two psychiatric patients who committed suicide while receiving hospital treatment or within 3 months of discharge from psychiatric care were studied using general population statistics, a random sample of 100 psychiatric patients and a control group matched individually with the hospital suicides. The rate of suicide among psychiatric in-patients was over 50 times that in the general population. A higher vulnerability to suicide was detected among in-patients (v. other patient groups), men (v. women) and middle-aged patients (v. older and younger patients). Suicides were differentiated from controls in having suffered more losses (P less than 0.05), being psychiatrically ill for the first time (P less than 0.05), having a past history of deliberate self-harm (P less than 0.05), and not receiving a schizophrenic diagnosis (P less than 0.02). People with mid-life crises, patients who swing rapidly into depression while receiving treatment, and individuals who are judged to be depressed because of personal problems may carry a particularly high suicide risk during psychiatric treatment.     

Carcinomas and carcinoid tumours of the appendix in a district general hospital.

In a retrospective series of 40 appendiceal tumours occurring over a 10-year period, 30 were carcinoid tumours of classical histological pattern, five were adenocarcinomas, and two were tumours intermediate in pattern between carcinoid and carcinoma. The remaining three tumours were secondaries from primary colonic tumours. The implications of the findings are discussed.     

Severe hyponatraemia: investigation and management in a district general hospital

AIMS: To study the incidence, investigation, and management of severe hyponatraemia (serum sodium < 120 mmol/litre) over a period of six months in a district general hospital. METHODS: The laboratory computer was used to identify all inpatients who had a serum sodium concentration of less than 120 mmol/litre over a six month period. The records of these patients were reviewed for the relevant demographic, clinical, and laboratory data, in addition to diagnosis, treatment, and outcome of hospitalisation. RESULTS: Forty two patients were studied, with a female to male ratio of 2 : 1. Nine patients had central nervous system symptoms, and four of these patients died in hospital. Only 14 patients had their urinary electrolytes and/or osmolality checked. A diagnosis of syndrome of inappropriate secretion of antidiuretic hormone (SIADH) was mentioned in eight patients, sometimes without checking their urinary electrolytes or osmolality. Twenty one patients died in hospital. The patients who died did not have lower serum sodium values or a higher rate of correction of hyponatraemia, but they all suffered from advanced medical conditions. CONCLUSIONS: The possible cause of hyponatraemia should always be sought and that will require an accurate drug history, clinical examination, and assessment of fluid volume, plus the measurement of urinary electrolytes and osmolality in a spot urine sample. The diagnosis of SIADH should not be confirmed without the essential criteria being satisfied. The current or recent use of diuretics is a possible pitfall in the diagnosis of SIADH. The rate of serum sodium correction of less than 10 mmol/day is probably the safest option in most cases.     

Adenocarcinoma arising in small sessile serrated adenoma/polyp (SSA/P) of the colon: Clinicopathological study of eight lesions

We reviewed the clinicopathological findings of eight cases of sessile serrated adenoma/polyps (SSA/Ps) with carcinoma, the largest diameter of which was 10 mm or less. All lesions were polyps located in the right side of the colon. Four lesions showed submucosal invasion and one lesion invaded the proper muscle layer. The depth of invasion, however, did not seem to be related to the carcinoma area size. Most carcinomas were well to moderately differentiated tubular adenocarcinomas focally showing some serrated appearances, and the predominant component of one carcinoma was a poorly differentiated medullary growth with inflammatory stroma. Rapid progression to invasive carcinoma from SSA/P was suggested for the carcinoma with proper muscle invasion whereas one submucosally invasive carcinoma was considered to progress over 7 years. Immunohistochemically, it was suggested that with or without hMLH1 protein loss, alterations of p53 and/or Wnt signaling pathway can be involved in the cancerization through SSA/Ps. The carcinomas irregularly imitated the mucin expression of the SSA/Ps (positive for MUC5AC and MUC2, and MUC6 expression in crypt bases), which was lost with progression of the carcinomas. Analyses of small SSA/P lesions with cancerization would facilitate the understanding of the mode of progression of SSA/Ps and their early detection.     

An investigation of the spread of gentamicin resistance in a district general hospital

A cluster of infections caused by gentamicin-resistant gram-negative bacilli in a District General Hospital was investigated. The plasmids coding for gentamicin resistance in the infecting organisms and in isolates obtained from the ward environment and from the faeces of patients and staff were characterised. Six plasmids encoding gentamicin resistance were recognised amongst the organisms causing infection. Two of the plasmids were found in different serotypes of the same species and one plasmid was found in different genera. Three of the plasmids present in the organisms causing the infections were also present in the inanimate environment or in the bowel flora of patients and these also were found in different serotypes of the same species and in different genera.     

Colonic intra-epithelial carcinoma occurring in a hyperplastic polyp via a serrated adenoma

We present a case of intra-epithelial carcinoma occurring in a serrated adenoma of the colon. The pedunculated polyp, which measured 12 x 10 x 6 mm, was endoscopically removed from the ascending colon of a 78-year-old woman. Histologically, the polyp mainly consisted of serrated adenomatous glands, and had foci of intra-epithelial carcinoma at the top. Hyperplastic (metaplastic) areas were also present in both borders between the serrated adenomatous area and the surrounding normal mucosa. A sequential increase in the degree of dysplasia, and in the number of nuclei positively reactive for Ki-67 and p53 was evident from the hyperplastic areas toward the foci of carcinoma. The polyp described here may represent a carcinogenic potential of hyperplastic polyp via serrated adenoma.     

Large cell neuroendocrine carcinoma arising in a sessile serrated adenoma: a novel observation

A 68-year-old woman underwent polypectomy of 2 right-sided colonic polyps identified by screening colonoscopy. Histologic examination of both polyps showed features of sessile serrated adenoma. The larger polyp harbored an invasive tumor composed of large, high-grade cells arranged in nests and cords without tumoral mucin production. Immunohistochemistry demonstrated synaptophysin, cdx-2, cytokeratin 7, and cytokeratin 20 positivity. Both invasive carcinoma and sessile serrated adenoma showed a decreased expression level to focal negative expression of hMLH-1 by immunohistochemistry. Combined morphologic and immunohistochemical features favored large cell neuroendocrine carcinoma arising in a sessile serrated adenoma. Specific carcinoma subtypes and special histologic features (eg, tumor-infiltrating lymphocytes) have been previously reported in carcinomas arising from sessile serrated adenomas. Large cell neuroendocrine carcinoma has not yet been reported in association with sessile serrated adenomas, with this case suggesting a rare but potentially novel end point for the microsatellite instability pathway.     

SHORT COMMUNICATION: GIFT and IUI in the district general hospital

Recent reports on gamete intra-Fallopian transfer (GIFT) inhospitals without IVF support have been encouraging. We reporton the use of GIFT and intrauterine insemination (IUI) at NorthamptonGeneral Hospital, where capital costs for setting up the programmehave been low. To date seven IUI and three GIFT treatments havebeen completed, resulting in three IUI positive pregnancy tests.One miscarried after several positive -HCGs and one GIFT pregnancywas achieved.     

Incidence of anaphylaxis in the emergency department of a general hospital in Milan.

OBJECTIVE: To evaluate incidence and causes of anaphylactic reactions in the emergency room (E.R.) of a general hospital in Milan during a 2-year period. Methods: We retrospectively studied the computerized records of patients discharged from an E.R. with a diagnosis of anaphylactic reaction. Anaphylaxis was established on the presence of at least two cutaneous, respiratory, gastrointestinal or cardiovascular system symptoms. Results: During 1997 and 1998, out of 38 685 patients referred to the E.R., 13 had severe anaphylaxis with loss of consciousness (LOC) and 127 had anaphylactic symptoms, without LOC. Of the 13 patients with LOC, a possible cause was identified in 12 (five foods, six drugs, one hair dye). In the other 127 patients anaphylaxis was related to foods in 49 cases (38.5%), drugs in 44 (34.6%), unknown causes in 29 (22.8%), hymenoptera stings in two (1.5%), and other causes in three (2.3%). Conclusion: The incidence of anaphylactic reactions was 0.4% and mainly affected females and atopic subjects. Foods, particularly fruits and vegetables, appeared to be the most important cause; other important causes were non steroidal antiinflammatory drugs and beta-lactam antibiotics.