The effects of CCR5 inhibition on regulatory T-cell recruitment to colorectal cancer.

BACKGROUND: Regulatory T cells (Treg) are enriched in human colorectal cancer (CRC) where they suppress anti-tumour immunity. The chemokine receptor CCR5 has been implicated in the recruitment of Treg from blood into CRC and tumour growth is delayed in CCR5-/- mice, associated with reduced tumour Treg infiltration. METHODS: Tissue and blood samples were obtained from patients undergoing resection of CRC. Tumour-infiltrating lymphocytes were phenotyped for chemokine receptors using flow cytometry. The presence of tissue chemokines was assessed. Standard chemotaxis and suppression assays were performed and the effects of CCR5 blockade were tested in murine tumour models. RESULTS: Functional CCR5 was highly expressed by human CRC infiltrating Treg and CCR5(high) Treg were more suppressive than their CCR5(low) Treg counterparts. Human CRC-Treg were more proliferative and activated than other T cells suggesting that local proliferation could provide an alternative explanation for the observed tumour Treg enrichment. Pharmacological inhibition of CCR5 failed to reduce tumour Treg infiltration in murine tumour models although it did result in delayed tumour growth. CONCLUSIONS: CCR5 inhibition does not mediate anti-tumour effects as a consequence of inhibiting Treg recruitment. Other mechanisms must be found to explain this effect. This has important implications for anti-CCR5 therapy in CRC.

A pilot study of extralevator abdominoperineal excision for primary melanoma of the anorectum.

Melanoma of the anorectum represents <2 % of all anorectal cancers and 0.3 % of all primary melanomas. Prognosis is poor, and optimal surgical management is controversial. This series details the surgical management of patients with anorectal melanoma presenting between 2002 and 2013 to the Queen Elizabeth Hospital in Birmingham, UK, a tertiary referral centre for colorectal disease. A retrospective review of patient notes, histology reports, and clinical letters was used to assess perioperative course and long-term outcome of all surgical methods. Eight patients with a median age of 65.5 presented with primary anorectal melanoma during the study period. Six cases were staged as T4 pre-operatively, with two referred as incompletely excised polyps. All eight patients underwent abdominoperineal excision of the rectum (APER), with the most recent four cases undergoing extralevator APER. Clear resection margins were achieved in three out of the four patients in the extralevator APER group with no nodal spread detected at histological assessment. Extralevator APER appears to be feasible and safe in the treatment of melanoma of the anorectum, with 75 % medium-term survival (median 38 months) in selected patients. As it is known that clear margins at surgery are associated with disease-free survival, the wider excision margin at the level of the pelvic floor offered by extralevator APER could result in more favourable surgical outcomes in this prognostically poor malignancy.

Evaluation of serum lysyl oxidase as a blood test for colorectal cancer.

AIMS: Lysyl oxidase (LOX) expression is elevated in colorectal cancer (CRC) tissue and associated with disease progression. A blood test may form a more acceptable diagnostic test for CRC although LOX has not previously been measured in the serum. We therefore sought to determine the clinical usefulness of a serum LOX test for CRC in a symptomatic population. METHODS: Adult patients referred to a hospital colorectal clinic with bowel symptoms completed a questionnaire and provided a blood sample for serum LOX measurement. Associations between presenting symptoms, serum LOX concentrations and outcomes of investigations were tested by univariate and multivariate analyses to determine if serum LOX was clinically useful in the prediction of CRC. LOX expression in CRC and adjacent colon biopsies was evaluated by ELISA and immunohistochemistry. RESULTS: Thirty-one cases of colorectal cancer and 16 high-risk polyps were identified from a total of 962 participants. There was no association between serum LOX concentration and the presence of CRC, high-risk polyps or cancers at any site. LOX expression was significantly increased in CRC tissue compared to adjacent colon. CONCLUSION: Despite overexpression of LOX in CRC tissue, elevated serum levels could not be demonstrated. Serum LOX measurement is therefore not a clinically useful test for CRC.

Patients newly diagnosed with ulcerative colitis receive earlier treatment in surgical clinics.

AIM: The diagnosis and treatment of ulcerative colitis (UC) is traditionally the realm of gastroenterologists. However, the symptoms of UC overlap with those of bowel cancer and patients may be initially referred to colorectal surgery clinics. The aims of this study were to define which specialty most frequently diagnoses UC and to determine if there were differences in management between the two specialities. METHOD: The demographics, presenting symptoms and clinical management of patients with newly diagnosed UC were determined and compared by speciality clinic of initial referral. Histopathology reports and clinic letters were reviewed to identify patients newly diagnosed with UC at a large university teaching hospital from January 2007 to January 2012. RESULTS: Patients were more commonly referred to colorectal surgeons (74 vs 41 patients) than gastroenterologists. Patients referred to gastroenterology were younger (36.0 vs 59.6 years, P < 0.01) but there were no significant differences in gender, presenting symptoms or disease extent. Rigid sigmoidoscopy ± biopsy was more commonly performed in colorectal clinic (93.2 vs 31.7%, P < 0.01). There was a significantly shorter delay in starting disease-specific treatment for those patients referred initially to colorectal surgery (13.8 vs 33.6 days, P = 0.01). Performing rigid sigmoidoscopy in clinic was associated with starting disease-specific treatment at this visit. CONCLUSION: Patients with first presentation UC are more commonly seen in colorectal surgery clinics where rigid sigmoidoscopy is more frequently undertaken, allowing earlier commencement of UC treatment.

Ocean enemy's lasting sting: chronic cutaneous reaction after Cnidarian attack.

Cnidaria stings cause a wide range of cutaneous and systemic symptoms, normally occurring shortly after the venomous insult (1). We report a case of worsening cutaneous reaction over an eight-year period following a Cnidaria attack sustained whilst maritime swimming. The lesion was characterised by severe, ulcerating chronic inflammation that required wide local excision and skin grafting. Prevention and early identification of Cnidaria envenomation is important for those treating maritime swimmers.

The sensitivity of needle core biopsy in combination with other investigations for the diagnosis of phyllodes tumours of the breast.

BACKGROUND: The sensitivity of needle-core biopsy (NCB) in diagnosing phyllodes tumours has only been addressed by a handful of small studies. The aim of this study was to analyse the sensitivity of NCB in the diagnosis of phyllodes tumours and to compare this to the sensitivity of other commonly performed investigations. A secondary aim was to assess the effect of various patient and disease factors on the rate of false negative test results. METHODS: Pathology databases were interrogated to identify all patients with the SNOMED term M-9020 or the word phyllodes in specimen reports. Excisional specimen reports were matched to prior FNAC reports, NCB reports and imaging reports. RESULTS: Ninety-one patients had a confirmed phyllodes tumour on excision. The sensitivity of FNAC, NCB and imaging for diagnosing phyllodes tumours was 40%, 63% and 65% respectively. The sensitivity of imaging and NCB was greater for borderline and malignant lesions. Combining cytohistological and radiological tests improved sensitivity to 76%. A younger age was associated with a greater false negative rate for all tests. Borderline and malignant phyllodes tumours were significantly associated with advancing age and greater lesion size on imaging and histology. CONCLUSIONS: This is the largest report to date assessing the sensitivity of NCB in the diagnosis of phyllodes tumours. Increased sensitivity in the diagnosis of phyllodes tumours can be achieved by combining cytohistological and radiological test results. The novel association between younger age and false negative results warrants further investigation. The most likely explanation is a reluctance to diagnose phyllodes tumours in young women given the increased prevalence of cellular fibroadenomas in this age group.

Wnt signalling in adenomas of familial adenomatous polyposis patients.

BACKGROUND: Epigenetic silencing of Wnt antagonists and expression changes in genes associated with Wnt response pathways occur in early sporadic colorectal tumourigenesis, indicating that tumour cells are more sensitive to Wnt growth factors and respond differently. In this study, we have investigated whether similar changes occur in key markers of the Wnt response pathways in the genetic form of the disease, familial adenomatous polyposis (FAP). METHODS: We investigated epigenetic and expression changes using pyrosequencing and real-time RT-PCR in samples from seven patients without neoplasia, and matched normal and tumour tissues from 22 sporadic adenoma and 14 FAP patients. RESULTS: We found that 17 out of 24 (71%) FAP adenomas were hypermethylated at sFRP1, compared with 20 out of 22 (91%) of sporadic cases. This was reflected at the level of sFRP1 transcription, where 73% of FAP and 100% of sporadic cases were down-regulated. Increased expression levels of c-myc and FZD3 were less common in FAP (35 and 46% respectively) than sporadic tumours (78 and 67% respectively). CONCLUSION: Overall, the changes in expression and methylation were comparable, although the degree of change was generally lower in the FAP adenomas. Molecular heterogeneity between multiple adenomas from individual FAP patients may reflect different developmental fates for these premalignant tumours.

Angiolymphoid hyperplasia with eosinophilia (epithelioid haemangioma) occurring within multiple deep lymph nodes and presenting with weight loss and raised CA-125 levels.

We report a case of angiolymphoid hyperplasia with eosinophilia (epithelioid haemangioma) involving multiple deep mediastinal, abdominal and intramammary lymph nodes in a 52-year-old woman with weight loss and raised CA-125 levels. The unusual clinical presentation with raised CA-125 levels and its occurrence within multiple deep visceral lymph nodes has never been reported in literature.

Mesonephric hyperplasia can cause abnormal cervical smears: report of three cases with review of literature.

BACKGROUND: Hyperplastic mesonephric remnants are an incidental finding in occasional uterine or cervical surgical specimens. We describe three cases in which such remnants were postulated to be the source of abnormal glandular cells in cervical smears. CASES: In all three cases abnormal glandular cells were seen in cervical smears. Subsequent histology showed the presence of hyperplastic mesonephric remnants that communicated with the endocervical canal and were likely to be the source of the abnormal glandular cells. We believe that the key features of these cells, which may aid their distinction from other causes of glandular abnormalities, are their loose clustering, lack of significant anisocytosis and cuboidal outlines. CONCLUSION: We aim to document mesonephric hyperplasia as a possible source for abnormal glandular cells in cervical smears.

Extramammary metastatic neoplasms in the breast: a cytomorphological study of 11 cases.

The occurrence of metastatic tumours in the breast is uncommon and it is crucial for cytologists to be aware and distinguish them cytologically from primary breast tumours in fine needle aspirates. In the present retrospective study of 11 cases, over a 20-year period, we discuss the cytological features of extramammary metastatic tumours in the breast. A brief attempt has been made to discuss the past literature. The 11 metastatic tumours included four haematolymphoid neoplasms, two melanomas, two metastatic sarcomas and three metastatic carcinomas. A prior clinical diagnosis of the primary tumour was obtained in seven cases. Immunohistochemistry or histology following a cytological diagnosis confirmed all the cases. The main objective of this study was to highlight the use of cytology and at the same time caution the cytologist to be aware of the clinical/imaging findings and if necessary to utilize immunohistochemical facilities to consider/rule out the possibility of metastatic tumour in the breast.

Imaging features of breast trauma: a pictorial review.

Accidental injury to the female breast can cause symptoms and signs which may mimic carcinoma and can also be painful or disfiguring. Nine women who sustained injury to the breast are presented, illustrating some of the manifestations of traumatic injury to the female breast, the majority of which are attributable to fat necrosis. A brief discussion of the clinical and imaging features of fat necrosis is included. These cases reinforce the importance of triple assessment in any woman presenting with a breast lump, even with a clear history of trauma.