IgG4-related systemic sclerosing disease – an emerging and under-diagnosed condition

Autoimmune pancreatitis was first described in 1961, although it was not more widely recognized as an autoimmune condition until 1995. It has now become apparent that this form of pancreatitis is part of a clinical syndrome that is commonly multisystem in nature. One of the most common histopathological features is the presence of IgG4+ plasma cells within involved tissues. Many terms have been proposed to describe the condition, but 'IgG4-related systemic sclerosing disease' appears most appropriate. Commonly affected extrapancreatic tissues include the biliary tract, liver, kidneys and lung, but a wide range of other sites may be involved. Histological examination reveals features that are not entirely disease-specific, but that are often sufficiently characteristic to provide useful support to a clinicopathological diagnosis. The disease often responds well to systemic steroid therapy, unlike some of the conditions that it may simulate clinically. The emergence of this disease as a specific and treatable entity has favourably altered the clinical outlook for patients in whom steroid therapy might not previously have been considered appropriate.     

Diagnosis of rectal gonorrhoea by blind anorectal swabs compared with direct vision swabs taken via a proctoscope.

Eight hundred and twenty-three examinations were carried out on 662 homosexual patients. At each examination a blind anorectal swab and a rectal swab taken via a proctoscope were inoculated on to a culture plate. From a total of 100 gonococcal infections of the rectum 96 gave positive results from blind anorectal swabs and 99 from swabs taken via a proctoscope. Blind anorectal swabs proved to be a reliable method in the diagnosis of rectal gonorrhoea.     

Autoimmune pancreatitis: clinical and radiological features and objective response to steroid therapy in a UK series

OBJECTIVE: Most cases of autoimmune pancreatitis (AIP) have been reported from Japan. We present data on a UK series, including clinical and radiological features at presentation, and longitudinal response to immunosuppression. METHODS: Over an 18-month period, all patients diagnosed in our center with AIP were studied. Endoscopic biliary stenting was performed as required, and patients were treated with prednisolone, with response assessed longitudinally. In cases of disease relapse following steroid reduction, azathioprine was instituted. RESULTS: Eleven patients met diagnostic criteria for AIP. Diffuse pancreatic enlargement was seen in eight patients (73%), and pancreatic duct strictures in all. Seven patients required biliary stents. Extrapancreatic involvement occurred in all, including intrahepatic stricturing and renal disease. Eight weeks after starting steroids, the median serum bilirubin level had fallen from 38 mumol/L to 11 mumol/L (P= 0.001), and ALT from 97 IU/L to 39 IU/L (P= 0.002). Stents were removed in all cases, with no recurrence of jaundice. Improvements in mass lesions and pancreaticobiliary stricturing occurred in all patients. During a median 18-month follow-up, six patients relapsed, four of whom responded to azathioprine. Two patients discontinued steroids and remained well. CONCLUSIONS: Extrapancreatic disease was an important feature of AIP in this UK series. Initial response to immunosuppressive therapy was excellent, but disease relapse was common. Optimal long-term management remains to be established.     

Prematurity and biliary atresia: a 30-year observational study

Aim of study

The diagnosis of biliary atresia (BA) remains challenging and delay can lead to significant morbidity with time to surgery a key factor in determining outcome. Prematurity may impact on outcome potentially delaying diagnosis. We sought to assess whether the premature BA infants (PBA) have a delayed time to surgery and as such, worse outcomes?

Methods

Review of a single-centre prospectively maintained database. Prematurity was defined as delivery?<?37/40 gestation. PBA was compared with date-matched term biliary atresia controls on a 2:1 basis. Primary outcomes were clearance of jaundice (<?20 μmol/L) and native liver survival. A retrospective assessment of liver fibrosis was made on biopsies at diagnosis and at Kasai portoenterostomy (KPE) in both premature and term cohorts. Data are quoted as median (range) unless indicated. A P value of ≤?0.05 was considered statistically significant.

Results

21 (female n?=?14, 67%) premature infants with BA were treated in the period Jan. 1988–Dec. 2016 and compared with 41 contemporaneous term BA controls. Median gestation was 33 (29–36) weeks and birth weight 1930 (948–4230)g. Twin pregnancy (n?=?10) was the leading cause for prematurity and significantly higher than the controls (48 vs. 0%; P?<?0.0001). Maternal co-morbidity was high (n?=?10, 48%) including pre-eclampsia (19%) and diabetes (14%). Liver biopsy was performed in 19 (90%) patients (all diagnostic) at a median of 57 (4–266) days. Delayed diagnosis (>?50 days) was seen in n?=?13 but not associated with parenteral nutrition use (46 vs. 33%, P?=?0.59) or phototherapy (50 vs. 83%, P?=?0.19). Both BASM (33 vs. 7.5%; P?=?0.01) and duodenal atresia (19 vs. 0%; P?=?0.01) were seen more frequently in the PBA cohort. Mean fibrosis scores (Ishak) from diagnostic biopsies were lower in the premature group than the control group (2.71 vs. 3.53, P?=?0.043) indicating less fibrosis but this equalized by time of subsequent KPE (P?=?0.17). Primary surgery was Kasai portoenterostomy (n?=?20) at an older median age than controls (65 vs. 56 days; P?=?0.06). Liver transplantation was the primary procedure in one late-presenting child. There was an increased but non-significant clearance of jaundice in the PBA group [n?=?12/20 (60%) vs 20/41 (48%); P?=?0.23] post-KPE. Native liver survival and true survival were not different (P?=?0.58 and 0.23).

Conclusions

PBA infants have similar outcomes to term infants, despite delayed diagnosis and higher frequency of the syndromic form. The high incidence of discordant twins supports the theory that epigenetic modifications could contribute to the pathogenesis of BA.

Level of evidence

IIIc Retrospective Matched Cohort Study.

     

The role of cell proliferation and crypt fission in adenoma aggressiveness: a comparison of ileoanal pouch and rectal adenomas in familial adenomatous polyposis

Aim In patients with familial adenomatous polyposis (FAP), ileoanal pouch cancer is rare whereas rectal cancer is common, despite polyp initiation at the two sites being similar at the molecular level. This study investigated whether the disparity in adenoma aggressiveness reflects underlying differences in histogenesis. Method Normal mucosal biopsies and 2–3 mm adenomas from patients with FAP were dissected into individual crypts. Crypt area, morphology, fission and mitoses were analysed for crypts from pouch, rectum and supra‐anastomotic ileum. Immunohistochemistry of similar archival samples was performed for lysozyme, β‐catenin and TP53 expression. Results The morphology of normal crypts was similar at each site, although crypt area differed. The area of normal pouch crypts was intermediate between rectum and ileum. The area of adenomatous crypts of rectum and pouch was similar, but the latter had increased asymmetrical fission. Crypt mitoses were proportional to area in all tissues, but crypt fission was reduced in adenomatous crypts from the rectum compared with the pouch. Pouch adenomas retained lysozyme expression as seen in normal ileum. Nuclear β‐catenin accumulation was similar, but TP53 expression was increased in rectal adenomas. Conclusion Diminutive polyps from rectum and pouch differ in morphology and proliferation. Aggressiveness in rectal polyps is not conferred by increased crypt proliferation, fission, or activation of the Wnt signalling pathway. Increased TP53 expression suggests other molecular mechanisms may be responsible. While crypt mitoses are proportional to crypt area, the threshold for fission may be site specific, indicating that tissue origin may influence histogenesis and thus malignant potential.