Proliferative myositis of the latissimus dorsi presenting in a 20-year-old male athlete.

We describe the case of a 20-year-old rower presenting with an uncommon condition of Proliferative Myositis (PM) affecting the Latissimus Dorsi (LD). PM is a rare, benign tumour infrequently developing in the upper back. Its rapid growth and firm consistency may mistake it for sarcoma at presentation. Therefore, careful multidisciplinary work-up is crucial, and should involve appropriate radiological and histopathological investigations. Here, we propose the aetiology of LD PM to be persistent myotrauma induced by repetitive rowing motions. Symptoms and rate of progression ultimately determine the management which includes surveillance and/or conservative resection. There have been no documented cases of recurrence or malignant transformation.

An International Multicenter Review of the Malignancy Rate of Excised Papillomatous Breast Lesions.

BACKGROUND: Papillary lesions of the breast are a relatively rare, but heterogeneous group ranging from benign to atypical and malignant. Debate exists regarding the optimal management of these lesions. In the absence of more accurate risk-stratification models, traditional management guidelines recommend surgical excision, despite the majority of lesions proving benign. This study sought to determine the rate of malignancy in excised breast papillomas and to elucidate whether there exists a population in which surgical excision may be unnecessary. METHODS: A multicenter international retrospective review of core biopsy diagnosed breast papillomas and papillary lesions was performed between 2009 and 2013, following institutional ethical approval. Patient demographics, histopathological, and radiological findings were recorded. All data was tabulated, and statistical analysis performed using Stata. RESULTS: A total of 238 patients were included in the final analysis. The age profile of those with benign pathology was significantly younger than those with malignant pathology (p < 0.001). Atypia on core needle biopsy was significantly associated with a final pathological diagnosis of malignancy (OR = 2.73). The upgrade rate from benign core needle biopsy to malignancy on the final pathological sample was 14.4 %; however, only 3.7 % had invasive cancer. CONCLUSIONS: This international dataset is one of the largest in the published literature relating to breast papillomas. The overall risk of malignancy is significantly associated with older age and the presence of atypia on core needle biopsy. It may be possible to stratify higher-risk patients according to age and core needle biopsy findings, thereby avoiding surgery on low-risk patients.

Immune privilege or inflammation? Insights into the Fas ligand enigma.

Fas ligand (FasL) has become an enigmatic molecule: some evidence indicates that it contributes to immune privilege in tissues and tumors, whereas other data demonstrates that FasL can elicit inflammation. New findings may begin to reconcile the paradoxical effects of FasL.

Bcl-x(L) expression in vivo in rheumatoid synovium.

To examine the expression of the apoptosis regulatory protein, Bcl-x(L), in the synovium of patients with rheumatoid arthritis (RA) and osteoarthritis (OA). Immunohistochemistry for Bcl-x(L) was carried out on synovial samples from patients with RA and OA. Reverse transcriptase polymerase chain reaction (RT-PCR) and Western blot analysis were performed to qualitatively examine the expression of Bcl-x(L). Bcl-x(L) expression was detected in the lining, endothelium and inflammatory cells of both RA (n=20) and OA (n=10) samples. However, there was significantly more expression in the lining of RA synovium compared to OA (77 vs 61%, p<0.05). Many of the positive cells in the RA subsynovium were noted to be plasma cells. There was a significant correlation between Bcl-x(L) expression and the number of inflammatory cells in the subsynovium of RA and OA patients (r (s)=0.376, p<0.05, n=30). Age and disease duration did not correlate with Bcl-x(L) expression in rheumatoid patients. Bcl-x(L) may play a role in the extended survival of synoviocytes and inflammatory cells in rheumatoid synovium.

When pathological and radiological correlation is achieved, excision of fibroadenoma with lobular neoplasia on core biopsy is not warranted.

BACKGROUND: The diagnosis and management of lobular neoplasia (LN) including lobular carcinoma in situ (LCIS) and atypical lobular hyperplasia (ALH) remains controversial. Current management options after a core needle biopsy (CNB) with lobular neoplasia (LN) incorporating both ALH and LCIS include excision biopsy or careful clinical and radiologic follow up. METHODS: A retrospective analysis of the surgical database at Cork University Hospital was performed to identify all core needle biopsies from January 1st 2010 to 31st December 2013 with a diagnosis of FA who subsequently underwent surgical excision biopsy. All cases with associated LN including ALH and classical LCIS were selected. We excluded cases with coexistent ductal carcinoma in situ (DCIS), invasive carcinoma, LN associated with necrosis, pleomorphic lobular carcinoma in situ (PLCIS) or lesions which would require excision in their own right (papilloma, radial scar, atypical ductal hyperplasia (ADH) or flat epithelial atypia (FEA)). Cases in which the radiologic targeted mass was discordant with a diagnosis of FA were also excluded. RESULTS: 2878 consecutive CNB with a diagnosis of FA were identified. 25 cases had a diagnosis of concomitant ALH or classical LCIS. Our study cohort consisted of 21 women with a mean age 53 years (age range 41-70 years). The core biopsy diagnosis was of LCIS and FA in 16 cases and ALH and FA in 5 cases. On excision biopsy, a FA was confirmed in all 21 cases. In addition to the FA, residual LCIS was present in 14 cases with residual ALH in 2 cases. One of the twenty-one cases (4.8%) was upgraded to invasive ductal carcinoma on excision.

PATI: Patient accessed tailored information: A pilot study to evaluate the effect on preoperative breast cancer patients of information delivered via a mobile application.

OBJECTIVES: The information needs of cancer patients are highly variable. Literature suggests an improved ability to modulate personalised stress, increased patient involvement with decision making, greater satisfaction with treatment choices and reduced anxiety levels in cancer patients who have access to information. The aim of this project was to evaluate the effects of a mobile information application on anxiety levels of patients undergoing surgery for breast cancer. MATERIALS AND METHODS: An application was developed for use with Apple iPad containing information on basic breast cancer biology, different treatments used and surgical techniques. Content and face validity studies were performed. A randomized control trial was designed, with a 1:2 allocation. Data collected include basic demographics and type of surgery. Questionnaires used included: the HADS, Mini-MAC, information technology familiarity and information satisfaction. RESULTS: A total of 39 women participated. 13 women had access to an iPad containing additional information and 26 women acted as controls. The mean age was 54 and technology familiarity was similar among both groups. Anxiety and depression scores at seven days were significantly lower in control patients without access to the additional information provided by the mobile application (p = 0.022 and 0.029 respectively). CONCLUSION: Anxiety and depression in breast cancer patients is both multifactorial and significant, with anxiety levels directly correlating with reduced quality of life. Intuitively, information should improve anxiety levels, however, we have demonstrated that surgical patients with less information reported significantly lower anxiety. We advise the thorough testing and auditing of information initiatives before deployment.

Alterations in plasma magnesium concentrations during liver transplantation.

Plasma magnesium concentrations were monitored during orthotopic liver transplantation. Magnesium supplementation was not given, although intraoperative calcium, potassium, and sodium bicarbonate were given as required. We found that there were significant falls in magnesium concentration to below our laboratory lower limit of normal, occurring chiefly during the anhepatic phase of surgery. Two patients with hypomagnesemia but normal potassium and calcium ion concentrations developed ventricular extrasystoles. Magnesium is a smooth muscle relaxant, dilating coronary arteries and peripheral vessels. It also exerts an antiarrhythmic effect and may have a permissive effect on the actions of catecholamines. Magnesium supplementation may be indicated during orthotopic liver transplantation because of the potentially beneficial effects and to avoid possible deleterious effects of hypomagnesemia. However, magnesium levels need to be monitored to avoid the unwanted side effects of hypermagnesemia.

Fas ligand upregulation is an early event in colonic carcinogenesis.

BACKGROUND/AIMS: Fas ligand (FasL) is a mediator of apoptosis via the Fas receptor (Fas/CD95/APO-1). Normal colonic epithelium expresses Fas, and appears to be relatively sensitive to Fas mediated apoptosis. Colonic adenocarcinomas coexpress FasL and Fas without undergoing widespread apoptosis. This study investigates the expression of FasL in colonic carcinogenesis from the earliest stages of the adenoma-carcinoma sequence. METHODS: FasL expression was determined in colonic adenomas (n = 38) of varying degrees of dysplasia and histological type by immunohistochemistry. Adenomas that contained areas of carcinomatous change were included (n = 12 of 38). Normal colonic epithelium (n = 10), hyperplastic polyps (n = 8), and serrated adenomas (n = 3) from patients without colonic adenocarcinomas were used for comparison. Cell death was detected in situ in adenomas using TUNEL (terminal transferase mediated dUTP nick end labelling). RESULTS: In normal colonic epithelium and hyperplastic polyps, FasL expression was restricted to the luminal surface of the crypts, where Fas-FasL coexpression was coincident with a high frequency of TUNEL positive epithelial cells. All adenomas (n = 38) had an altered distribution of positive FasL staining; FasL expression was found in most cells (> 70% of neoplastic cells). Expression of Fas was also detected throughout the adenomas, but coexpression of FasL and Fas was not associated with TUNEL positivity in most cells. CONCLUSIONS: FasL upregulation occurs early in the adenoma-carcinoma sequence of colon carcinogenesis, and is evident at the level of mild dysplasia. The lack of pronounced apoptosis in areas of adenomas coexpressing Fas and FasL suggests that colonocytes acquire resistance to Fas mediated apoptosis early in the transformation process.

Altered mechanisms of apoptosis in colon cancer: Fas resistance and counterattack in the tumor-immune conflict.

Fas (CD95/APO-1) is a cell surface "death receptor" that mediates apoptosis upon engagement by its ligand, FasL. Fas-mediated apoptosis of lymphocytes normally serves immunoregulatory roles, including tolerance acquisition, immune response termination, and maintenance of immune privilege in certain organs. Colon tumors can exploit this lymphocyte death program by expressing FasL. This may enable colon tumors to mount a "Fas counterattack" against antitumor lymphocytes, impairing antitumor immune responses. FasL-expressing colon tumor-derived cell lines can trigger Fas-mediated apoptosis of cocultured T cells in vitro. FasL expressed in esophageal cancer has been significantly associated with apoptosis and depletion of tumor-infiltrating lymphocytes (TIL) in vivo. FasL may also facilitate metastatic colonization of Fas-sensitive organs such as the liver, by inducing apoptosis of target organ cells. Normal colonic epithelial cells express Fas and are relatively sensitive to Fas-mediated apoptosis. By contrast, colon tumor-derived cell lines are usually resistant to induction of Fas-mediated apoptosis, and colon cancer cells frequently coexpress Fas and FasL. The mechanisms allowing resistance to Fas-mediated apoptosis are complex, and defects have been identified at several levels of Fas signal transduction. The "Bcl-2 rheostat" may be pitched against apoptosis in colon cancer, inasmuch as overexpression of Bcl-2, downregulation of Bak, and mutation of Bax are common defects in colon tumors. Caspase-1 is also downregulated in colon cancer. The high frequency of p53 mutations in late-stage cancers may also inhibit Fas signaling. Fundamental defects in apoptosis signaling may contribute to both immuno- and chemoresistance in colon cancer and allow expression of FasL to counterattack antitumor lymphocytes.

Porcine oocytes denuded before maturation can develop to the blastocyst stage if provided a cumulous cell-derived coculture system.

The physiological role of cumulus cells (CC) surrounding oocytes is particularly important for normal cytoplasmic maturation of oocytes. However, removal of CC from oocytes is inevitable for some embryo manipulation techniques, such as germinal vesicle (GV) transfer, somatic cell haploidization, and oocyte cryopreservation. The present study was designed to determine an optimal method to culture porcine denuded oocytes (DO). The results indicated CC from cumulus-oocyte complexes at the GV stage (GVCC) or at the metaphase II stage, and mural granulosa cells could not improve the maturation of DO. However, GVCC could enhance the development of matured porcine DO after fertilization; the percentage of blastocysts was increased from 1.1 to 17.2% (P < 0.05), and the relative value of the x-axis and y-axis of spindles was also increased (P < 0.05). Coculture with GVCC had no effect on the distribution of mitochondria and cortical granules. The results contribute to our understanding of the mechanisms by which CC promote oocyte maturation and contribute to optimization of protocols for in vitro maturation of DO.

Percutaneous tracheostomy.

Percutaneous dilational tracheostomy (PDT) originated in the USA and now an increasing number of UK centres are adopting the technique. It compares favourably with traditional surgical tracheostomy; PDT can be performed more satisfactorily at the bedside, avoiding the transport of critically ill patients to the operating theatre. It is a more rapid and convenient technique and evidence increasingly suggests that it is associated with significantly fewer and less severe complications. If early reports are confirmed by larger, carefully controlled trials, it is likely that PDT will largely replace conventional surgical techniques for the provision of tracheostomy in the critically ill. An improved risk-benefit ratio of PDT may favour earlier conversion of translaryngeal intubation to tracheostomy.

Schistosoma mansoni: ingestion of dextrans, serum albumin, and IgG by schistosomula.

Schistosomula of Schistosoma mansoni develop the ability to ingest and digest red blood cells after the fourth day post-transformation. Here, we have used fluorescently-labeled dextrans and two plasma proteins, albumin and IgG, to test whether day-old schistosomula can ingest and process macromolecules prior to the time that they eat red cells. Worms ingested dextrans of molecular weights 4,000, 70,000 and 2 x 10(6) in a time- and concentration-dependent manner. The dextran remained in the cecal lumen for up to 2 days after feeding. Parasites ingested both fluorescein-conjugated bovine serum albumin and rabbit IgG, but neither of these proteins remained confined to the cecum over time. Instead, fluorescence redistributed to the acetabular glands within a few hours. Thin-layer chromatography indicated that schistosomula degraded fluorescein-conjugated albumin to fluorescein-conjugated peptides approximately 10-15 amino acids long. The volume of the cecum was estimated to be 2431 microns 3 and the surface area 299 microns 2. These results demonstrate that larval schistosomes can ingest both proteins and complex carbohydrates shortly after transformation, before they can ingest red cells. Further, the gut apparently releases proteases that cleave plasma proteins, but not saccharidases that cleave dextran.

Specific binding of human low-density lipoprotein to the surface of schistosomula of Schistosoma mansoni and ingestion by the parasite.

Low-density lipoproteins (LDL) may be important in human schistosomiasis because LDL bound to the surface of the parasite inhibits the binding of anti-schistosomal antibodies. Low-density lipoproteins also may serve as a source of lipids for the parasite membrane synthesis. Here LDL fluorescently labeled with carbocyanine dye (DiI-LDL) was used to measure the specificity of binding of LDL to the surface of schistosomula of Schistosoma mansoni and to examine the distribution of the LDL particles over time. DiI-LDL binding was saturable and specific, with strong inhibition by unlabeled LDL and apoB but not by apoA1, bovine serum albumin, or IgG, and only weak inhibition by high-density lipoproteins. Half of the bound DiI-LDL was displaced by unlabeled LDL. DiI-LDL remained bound on the surface of schistosomula for up to 36 hours in culture. However parasites also ingested both DiI-LDL and a second fluorescent LDL, Bodipy-LDL. Over time, both fluorophores appeared throughout the worm tissues, suggesting the LDL particles were breaking down and that the fluorophores and lipids originally contained within the LDL particle were partitioning throughout the worm. Thus human LDL appears to bind to the surface of schistosomula specifically. Ingested LDL appears to be broken down and may serve as a source of host lipids for the parasite.

A comparison of the effect on gastric emptying of either enflurane or propofol given during maintenance of anaesthesia for minor surgery.

Twenty patients scheduled for minor gynaecological surgery were studied. Anaesthesia was induced with propofol and maintained either with enflurane/oxygen/nitrous oxide or propofol/oxygen/nitrous oxide. The rate of gastric emptying was measured indirectly by the paracetamol absorption model. The results showed that there was no significant difference in gastric emptying rate between the two groups. Recovery in the propofol group was more rapid in that paracetamol ingestion occurred earlier in the recovery period compared with the enflurane group.

A comparison of the effect on gastric emptying of alfentanil or morphine given during anaesthesia for minor surgery.

Twenty patients, scheduled for minor gynaecological surgery, were studied. Anaesthesia was induced with propofol and maintained with oxygen, nitrous oxide and enflurane. Patients were randomly allocated to two groups: group 1 were given alfentanil 0.2 mg; group 2 were given morphine 5 mg. The rate of gastric emptying was measured indirectly by the paracetamol absorption technique. The results showed that morphine caused greater delay in gastric emptying compared with alfentanil (p < 0.05). The observed effect on gastric emptying rate may potentially affect the risk of peri-operative regurgitation and aspiration. This study provides further evidence that in short day-case procedures, when oral medication may be required postoperatively, alfentanil may be preferable to morphine as an intra-operative opioid.

Fas ligand mediates immune privilege and not inflammation in human colon cancer, irrespective of TGF-beta expression.

Many cancers express Fas ligand (FasL/CD95L) in vivo, and can kill lymphoid cells by Fas-mediated apoptosis in vitro. However, overexpression of recombinant FasL in murine tumour allografts revealed a potential antitumour effect of FasL, via recruitment of neutrophils. Transforming growth factor-beta1 (TGF-beta1) could inhibit these neutrophil-stimulatory effects of FasL. In the present study, we sought to determine directly whether FasL contributes to immune privilege or tumour rejection in human colon cancers in vivo, and whether TGF-beta1 regulates FasL function. Serial tumour sections were immunostained for FasL and TGF-beta1. Neutrophils and tumour infiltrating lymphocytes (TILs) were detected by immunohistochemistry for lactoferrin and CD45, respectively. Apoptotic TIL were identified by dual staining for TUNEL/CD45. FasL expression by nests of tumour cells was associated with a mean four-fold depletion of TILs (range 1.8-33-fold, n=16, P<0.001), together with a two-fold increase in TIL apoptosis (range 1.6-2.5-fold, n=14, P<0.001), relative to FasL-negative nests within the same tumours. The overall level of neutrophils present in all tumours examined was low (mean 0.3%, n=16), with FasL expression by tumour nests associated with a mean two-fold decrease in neutrophils, irrespective of TGF-beta1 expression. Together, our results suggest that tumour-expressed FasL is inhibitory rather than stimulatory towards antitumour immune responses.

The susceptibility to Fas-induced apoptosis in normal enterocytes is regulated on the level of cIAP1 and 2.

Various members of the tumor necrosis factor receptor superfamily are implicated in the regulation of enterocyte apoptosis. Previously, we observed that human intestinal epithelial cells are rather unsusceptible to Fas-induced apoptosis. In the present study we analyzed these protective mechanisms in the human intestinal epithelial cell line HIEC, focusing on antiapoptotic molecules of the IAP family which block apoptosis at the level of the caspase cascade. HIEC expressed all key molecules required to trigger Fas-induced apoptosis. However, no apoptosis occurred after activation of Fas, whereas an upregulation of antiapoptotic cIAP1 and 2 was observed. Suppression of this upregulation with the proteasome inhibitor MG132 or the protein synthesis inhibitor cycloheximide highly sensitized HIEC toward Fas-induced apoptosis. Western blot analyses revealed that both inhibitors potently suppressed endogenously produced cIAP1 and 2. No effect was observed on XIAP expression. These data indicate that enterocytes are particularly protected against Fas-induced apoptosis on the level of executionary caspases.