Megarectum: systematic histopathological evaluation of 35 patients and new common pathways in chronic rectal dilatation.

AIMS: Megarectum is well described in the surgical literature but few contemporary pathological studies have been undertaken. There is uncertainty whether 'idiopathic' megarectum is a primary neuromuscular disorder or whether chronic dilatation leads to previously reported and unreported pathological changes. We sought to answer this question. METHODS: Systematic histopathological evaluation (in accord with international guidance) of 35 consecutive patients undergoing rectal excision surgery for megarectum (primary: n=24) or megarectum following surgical correction of anorectal malformation (secondary: n=11) in a UK university hospital with adult/paediatric surgical and gastrointestinal neuropathology expertise. RESULTS: We confirmed some previously reported observations, notably hypertrophy of the muscularis propria (27 of 35, 77.1% of patients) and extensive fibrosis (30 of 35, 85.7% of patients). We also observed unique and previously unreported features including elastosis (19 of 33, 57.6%) and the presence of polyglucosan bodies (15 of 32, 46.9% of patients). In contrast to previous literature, few patients had any strong evidence of specific forms of visceral neuropathy (5 of 35, including 3 plexus duplications) or myopathy (6 of 35, including 3 muscle duplications). All major pathological findings were common to both primary and secondary forms of the disease, implying that these may be a response to chronic rectal distension rather than of primary aetiology. CONCLUSIONS: In the largest case series reported to date, we challenge the current perception of idiopathic megarectum as a primary neuromuscular disease and propose a cellular pathway model for the features present. The severe morphological changes account for some of the irreversibility of the condition and reinforce the need to prevent ongoing rectal distension when first identified.

Solid pseudopapillary tumour of the pancreas: clinicopathological analysis.

BACKGROUND: We report on our experience of the surgical management and outcomes of 11 patients with solid pseudopapillary tumour of the pancreas (SPT). We sought to correlate the immunohistochemical staining of these tumours with that previously reported in the literature. METHODS: A retrospective analysis of the clinical presentation, radiological findings, surgical treatment, histopathological characteristics and outcomes for patients surgically managed with SPT at The Royal London Hospital. A literature search was performed to analyse the immunohistochemical stains commonly used to diagnose SPT. RESULTS: Between August 2006 and April 2016, 10 females and one male patient underwent surgery for SPT. The localization of the tumour was in the pancreatic head in two patients, one in the neck, three in the body and five in the tail. All 11 patients had localised disease. Six patients suffered post-surgical complications. Histopathology shows immunoreactivity for: ß-catenin, vimentin, CD-10, CD-56, α1-antitrypsin and negative staining for synaptophysin and chromogranin. At a median of 24 months of follow-up, the disease-free survival rate was 100% and no recurrence was noted. A literature review generated 38 suitable articles with 116 individual cases of SPT, with high expression of vimentin and neuron specific enolase throughout, and low rates of chromogranin and synatophysin positivity. CONCLUSION: SPT is rare and affects mostly young women. An accurate diagnosis is important as the relative indolent behaviour can be managed with surgical resection even when large in size, bringing excellent long-term outcomes.

Diagnosis of rare malignant tumours of the breast by FNA cytology--a report of 3 cases.

This report describes the fine needle aspiration (FNA) cytology findings in 3 cases with breast tumours. The characteristic cyto architectural pattern helped in the diagnosis of two papillary carcinomas. The predominant spindle cell pattern with scattered bizarre cells was interpreted as malignant spindle cell tumour in one case. On histopathology, this was diagnosed as metaplastic carcinoma.

Inhibition of de novo NAD(+) synthesis by oncogenic URI causes liver tumorigenesis through DNA damage.

Molecular mechanisms responsible for hepatocellular carcinoma (HCC) remain largely unknown. Using genetically engineered mouse models, we show that hepatocyte-specific expression of unconventional prefoldin RPB5 interactor (URI) leads to a multistep process of HCC development, whereas its genetic reduction in hepatocytes protects against diethylnitrosamine (DEN)-induced HCC. URI inhibits aryl hydrocarbon (AhR)- and estrogen receptor (ER)-mediated transcription of enzymes implicated in L-tryptophan/kynurenine/nicotinamide adenine dinucleotide (NAD(+)) metabolism, thereby causing DNA damage at early stages of tumorigenesis. Restoring NAD(+) pools with nicotinamide riboside (NR) prevents DNA damage and tumor formation. Consistently, URI expression in human HCC is associated with poor survival and correlates negatively with L-tryptophan catabolism pathway. Our results suggest that boosting NAD(+) can be prophylactic or therapeutic in HCC.