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Background: Adenocarcinoma in Barrett's esophagus (BE) occurs more frequently between 12 and 3 o'clock at the gastroesophageal junction (GEJ)., Methods: BE patients were prospectively recruited from December 2013 to July 2016. Expression of p53, Ki-67, cyclin-D1, COX-2 and p21 was assessed in quadrantic biopsies from the proximal and distal margins of the BE segments. Cell cycle marker association with current or subsequent dysplasia or adenocarcinoma was examined., Results: 110 patients: median age 64 (IQR, 56-71) years; median BE segment length C4M6; and a median follow-up of 4.7 (IQR, 3.6-5.7) years. In total 13 (11.8%) had evidence of dysplasia or neoplasia (2.7% indefinite for dysplasia, 5.5% low grade, 1.8% high grade and 1.8% adenocarcinoma) at index endoscopy. Six (7%) developed dysplasia or neoplasia (1 low grade, 2 high grade and 3 adenocarcinoma) during follow-up. Ki-67 expression was highest at 3 o'clock, and overall was 49.6% higher in the 12-6 o'clock position compared to 6-12 o'clock [odds ratio (OR), 1.42 (95% confidence interval (CI), 1.00-2.12)]. A similar pattern was found with p21 [1.82 (1.00-3.47)]. There was increased expression of several markers in distal BE biopsies; cyclin-D1 [1.74 (1.29-2.34)]; Cyclo-oxygenase 2 [2.03 (1.48-2.78]) and p21 [2.06 (1.16-3.68)]. Expression of Ki-67 was lower in distal compared to proximal biopsies [0.58 (0.43-0.78)]. P53 expression had high specificity (93.8%) for subsequent low-grade dysplasia, high-grade dysplasia or adenocarcinoma., Conclusion: Increased cellular proliferation was seen at 12-6 o'clock at the GEJ. Cell-cycle marker expression was increased at the GEJ compared to the proximal BE segment. These findings mirror reflux esophagitis and suggest ongoing reflux contributes to the progression of dysplasia and malignancy in BE., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Maternity statistics of England in 2020 showed rise in Caesarean Section (CS) rate to 31%. Some studies correlated adverse gynaecological symptoms e.g. menstrual irregularities and pelvic pain to 'niche' formation at CS scar site. Niche formation was speculated to cause myometrial hypertrophy aggravating these symptoms. This was a prospective comparative histological study including 52 consecutive benign hysterectomy specimens which were categorised into 2 groups: (i) specimens with CS scar ( n  = 22), (ii) specimens with no CS scar ( n  = 30). Median (IQ range) uteri weight was 97.2grms (43.5-226) and 91.7grms (35.7-201.7) in study and control groups, respectively ( p  = .991). Mean (±SD) thickness of anterior myometrial wall was 18.7 mm (±3.6) and 19.4 mm (±4.5) in study and control groups, respectively ( p  = .58). Mean (±SD) thickness of posterior myometrial wall was 19.1 mm (±3.7) and 18.7 mm (±3.9) in study and control groups, respectively ( p  = .78). The assumption that CS scar causes myometrial hypertrophy was not demonstrated in this study.IMPACT STATEMENT What is already known on this subject? Maternity statistics world-wide show a continuous rise in the rate of Caesarean Section (CS) operation. The CS scar is assumed to be related to adverse clinical gynaecological symptoms such as intermenstrual bleeding, dysmenorrhoea, dyspareunia and chronic pelvic pain; however, the mechanism of this association is not clear. Further, little is known about the effects of CS scar on uterine wall morphology and function. What do the results of this study add? This study was the first prospective series in the literature to compare the uteri with scar with those without in respect of weight and myometrial wall thickness. It was not able to demonstrate the association between having CS scar and myometrial hypertrophy which was hypothesised to be the cause of adverse gynaecological symptoms. However, the microscopic examination of the CS scar revealed adenomyosis, haemorrhage and/or chronic inflammation in most cases. What are the implications of these findings for clinical practice and/or future research? The clinical implication of the histological changes shown in the CS scar requires large comparative clinical studies.

We report a case of a 76-year-old man presenting with a 12-month history of a solitary lesion on his scalp. The histopathology was consistent with a grade 2/3 osteosarcoma extending to the subcutis. Full-body imaging excluded any involvement of the underlying bony tissue or solid organ malignancy, thus a diagnosis of primary cutaneous osteosarcoma (PCO) was made. Given the exceedingly rare nature of PCO, we discuss the clinico-pathological features of this case and those previously reported in the literature., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Although the over-expression of angiogenic factors is reported in diffuse large B-cell lymphoma (DLBCL), the poor response to anti-VEGF drugs observed in clinical trials suggests that angiogenesis in these tumours might be driven by VEGF-independent pathways. We show that sphingosine kinase-1 (SPHK1), which generates the potent bioactive sphingolipid sphingosine-1-phosphate (S1P), is over-expressed in DLBCL. A meta-analysis of over 2000 cases revealed that genes correlated with SPHK1 mRNA expression in DLBCL were significantly enriched for tumour angiogenesis meta-signature genes; an effect evident in both major cell of origin (COO) and stromal subtypes. Moreover, we found that S1P induces angiogenic signalling and a gene expression programme that is present within the tumour vasculature of SPHK1-expressing DLBCL. Importantly, S1PR1 functional antagonists, including Siponimod, and the S1P neutralising antibody, Sphingomab, inhibited S1P signalling in DLBCL cells in vitro. Furthermore, Siponimod, also reduced angiogenesis and tumour growth in an S1P-producing mouse model of angiogenic DLBCL. Our data define a potential role for S1P signalling in driving an angiogenic gene expression programme in the tumour vasculature of DLBCL and suggest novel opportunities to target S1P-mediated angiogenesis in patients with DLBCL.

A 38-year-old woman presented to casualty with bilateral red eyes associated with a recent upper respiratory tract infection. This was initially diagnosed as conjunctivitis, however systemic review revealed an erythematous facial and skin rash, mildly swollen lips and mild swallowing difficulties. The patient was referred for an urgent medical assessment, by which time she was found to have erythema affecting 54% of her body surface area and diagnosed with suspected toxic epidermal necrolysis (TEN). She rapidly deteriorated over 24 hours with a spreading blistering skin rash and airway compromise requiring urgent intubation and admission to the intensive treatment unit (ITU). Subsequent skin biopsies confirmed the diagnosis of TEN, attributed to recent use of ibuprofen. Treatment included broad-spectrum antibiotics and high-dose corticosteroids. The patient had a prolonged hospital stay and developed severe scarring of the ocular surface. She was discharged home and remains under continuing outpatient follow-up with ophthalmology and dermatology teams., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2018. No commercial re-use. See rights and permissions. Published by BMJ.)

In the recent years, maternity statistics world-wide show a continuous rise in the rate of Caesarean Section (CS) operation. Many CS deliveries are conducted despite having no clear obstetric indications. The CS scar is assumed to be related to many adverse clinical gynaecological symptoms such as intermenstrual bleeding, dysmenorrhoea, dyspareunia and chronic pelvic pain; however, the mechanism of this relation is not clear. Further, little is known about the effects of CS scar on uterine wall morphology, function or patho-physiology. We hypothesize that: (i) the CS scar causes myometrial hypertrophy (myohypertrophy) of the anterior uterine wall above the scar, and (ii) the scar-induced morphological changes in the uterine wall causes adverse clinical gynaecological symptoms such as intermenstrual bleeding, dysmenorrhoea, dyspareunia and chronic pelvic pain. This article discusses the hypothesis and its clinical implications, as well as presents supportive preliminary data and the emerging research to prove it., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Aims: Inadequate endometrial biopsy comprises a dilemma for gynaecologists and histopathologists alike. This study was conducted to assess the clinical merit of classifying scant endometrial biopsy into inadequate and unassessable using McCluggage criteria., Methods: We retrospectively classified 268 endometrial biopsies, initially reported as inadequate, into inadequate (n=74) and unassessable (n=174) using McCluggage criteria after excluding 20 cases; all taken from patients aged ≥50 years with abnormal uterine bleeding attending Sandwell and West Birmingham Hospitals, UK from 1 January 2007 until 30 September 2012. The electronic clinical records were reviewed to find out the consequent clinical decisions and final outcomes. The follow-up period was 15 months after including the last patient., Results: The median age was 57 years (range: 50-97), and the median number of visits to hospital till the diagnosis was achieved was 2 (range: 1-4). The final diagnosis of endometrial hyperplasia or cancer was reported in 9 cases; 5 (7.1%) with an initial finding of inadequate and 4 with unassessable (2.4%); the difference was statistically insignificant (p=0.13). More patients in the inadequate category (82.4%) underwent further investigations when compared with the unassessable category (68.4%); the difference was statistically significant (p=0.029). There was no statistically significant difference in the inadequate to unassessable ratio when the endometrial thickness was ≥5 mm or <5 mm within the Pipelle group (p=0.46) or the curettage group (p=0.34)., Conclusions: Our findings suggest that categorising scant endometrial specimens into inadequate or unassessable has no clinical implications. The gynaecologist should interpret the histopathology report in the light of clinical scenario., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Peliosis is a rare condition of multiple blood-filled cysts within the parenchyma of a solid organ. Splenic peliosis is an extremely rare entity, although there is often a risk of spontaneous rupture. We present a case where our otherwise fairly healthy patient presented us with a diagnosis dilemma and was then found to have splenic peliosis histologically post-splenectomy. We discuss the current available literature and emphasise the importance of awareness of such a condition.

Background: Over-expression of angiogenic growth factors and their receptors, and high levels of these molecules in the blood, are a common feature of cancer although the relationships between cell expression and plasma levels are unknown. We hypothesized a significant correlation between the expression and cellular distribution of vascular endothelial growth factor (VEGF), its receptor Flt-1, and the angiopoietin receptor Tie-2 with levels of these molecules in the plasma., Methods: The tissue expression of VEGF, Flt-1, and Tie-2 were investigated by immunohistochemistry, and plasma levels assessed by enzyme-linked immunosorbent assay in 36 patients with breast cancer and 15 with benign breast disease., Results: Despite expected significant differences in plasma levels of the molecules (P<0.03 to <0.001), no significant differences were found in Tie-2, VEGF, and Flt-1 tissue expression between breast cancer and benign disease controls. No significant correlations were observed between plasma levels of their tissue expression., Conclusions: Tissue expression of Tie-2, VEGF, and Flt-1 may not be an overly sensitive tool for assessing abnormalities of coagulation, platelet activation, and angiogenesis in human cancer. Plasma markers may not be representative of tumor activity, and may not come wholly from tumor cells. Instead these markers may be indicative of endothelial dysfunction in cancer patients.

We have evaluated the clinical symptoms, hematological features, and natural history of 3 cases and 20 reported cases described as Philadelphia chromosome-positive (Ph+) essential thrombocythemia (ET). The presence of increased small mononuclear megakaryocytes in bone marrow smears and biopsy material in patients with pronounced thrombocytosis and no evidence of chronic myeloid leukemia (CML) in peripheral blood appeared to be a diagnostic clue to the diagnosis of Ph+ (essential) thrombocythemia. As compared to cases of reactive thrombocytosis, the megakaryocytes in Ph+ thrombocythemia are smaller than normal ones and typically have hypolobulated round nuclei. This contrasts with the finding of clustered mature and enlarged megakaryocytes in Ph-negative true ET. Patients diagnosed as Ph+ ET may progress to CML and show a high tendency to myelofibrosis and blastic transformation. These observations indicate that both Ph+ ET and Ph+ thrombocythemia associated with CML can be regarded as early manifestations of the chronic stable phase of CML., (Copyright 2004 Springer-Verlag)