The impact of bivalent HPV vaccine on cervical intraepithelial neoplasia by deprivation in Scotland: reducing the gap.

BACKGROUND: Cervical cancer disproportionately affects women from lower socioeconomic backgrounds. A human papillomavirus (HPV) vaccination programme was introduced in Scotland in 2008 with uptake being lower and inequitable in a catch-up cohort run for the first three years of the programme compared with the routine programme. The socioeconomic differences in vaccine uptake have the potential to further increase the inequality gap in regards to cervical disease. METHODS: Vaccination status was linked to demographic, cytological and colposcopic data, which are routinely collected by the Scottish HPV surveillance system. Incidence rates and relative risk of cervical intraepithelial neoplasia (CIN) 1, 2 and 3 in unvaccinated and vaccinated women were stratified by birth year and deprivation status using Poisson regression. RESULTS: Women who received three doses of HPV vaccine have significantly decreased risk of CIN 1, 2 and 3. Vaccine effectiveness was greater in those women from the most deprived backgrounds against CIN 2 and 3 lesions. Compared with the most deprived, unvaccinated women, the relative risk of CIN 3 in fully vaccinated women in the same deprivation group was 0.29 (95% CI 0.2 to 0.43) compared with 0.62 (95% CI 0.4 to 0.97) in vaccinated women in the least-deprived group. CONCLUSIONS: The HPV vaccine is associated with significant reductions in both low-grade and high-grade CIN for all deprivation categories. However, the effect on high-grade disease was most profound in the most-deprived women. These data are welcoming and allay the concern that inequalities in cervical cancer may persist or increase following the introduction of the vaccine in Scotland.

Risk Factors and Outcomes of De Novo Cancers (Excluding Nonmelanoma Skin Cancer) After Liver Transplantation for Primary Sclerosing Cholangitis.

BACKGROUND: Patients with primary sclerosing cholangitis (PSC) may be at higher risk of malignancy after liver transplantation (LT) compared to other LT recipients. We aimed to determine the cumulative incidence of/risk factors for long-term cancer-related mortality in patients with PSC after LT. METHODS: All adult patients underwent LT for PSC without cholangiocarcinoma from 1984 to 2012, with follow-up through June 2015. We estimated cumulative incidence, risk factors, and mortality from de novo malignancies after LT. RESULTS: Two hundred ninety-three patients were identified (mean [SD] age, 47 [12] years; 63.3% males; 2.4% smoking at LT). Over a median of 11.5 years (range, 6.4-18.6 years), 64 patients (21.8%) developed 73 nonskin cancers, including 46 solid-organ cancers (renal, 11; colorectal, 11; prostate, 7; breast, 5; pancreas, 5; ovarian/endometrial/vulvar cancers, 3; and de novo cholangiocarcinoma, 4). Twenty-two patients developed hematologic malignancies (posttransplant lymphoproliferative diseases, 18; Hodgkin disease, 2; and myelodysplastic syndrome, 2). Five patients developed melanoma. The 1-, 5-, 10-, and 20-year cumulative incidences of cancer were 2.1%, 8.6%, 18.7%, and 27%, respectively. Mortality of patients with PSC who developed cancer was higher than that of patients with PSC without cancer (hazard ratio, 2.2; P < 0.01). On multivariate analysis, recipient's age and elevated pre-LT international normalized ratio were associated with increased risk of de novo (nonskin) malignancy. CONCLUSION: The 10-year cumulative risk of cancer after LT for advanced-stage PSC was 18.7%, with posttransplant lymphoproliferative diseases, colorectal cancer, and renal cell cancer being the most common. Post-LT de novo nonskin cancer decreased overall posttransplant survival. Only recipient's age and elevated international normalized ratio at LT were associated with increased nonskin cancer risk.

30-Day and 1-year mortality in emergency general surgery laparotomies: an area of concern and need for improvement?

AIMS: Emergency surgery is associated with poorer outcomes and higher mortality with recent studies suggesting the 30-day mortality to be 14-15%. The aim of this study was to analyse the 30-day mortality, age-related 30-day mortality and 1-year mortality following emergency laparotomy. We hope this will encourage prospective data collection, improvement of care and initiate strategies to establish best practice in this area. METHODS: This was a retrospective study of patients who underwent emergency laparotomy from June 2010 to May 2012. The primary end point of the study was 30-day mortality, age-related 30-day mortality and 1-year all-cause mortality. RESULTS: 477 laparotomies were performed in 446 patients. 57% were aged <70 and 43% aged >70 years. 30-day mortality was 12, 4% in those aged <70 years and 22% in those >70 years (p < 0.001). 1-year mortality was 25, 15% in those aged under 70 years and 38% in those aged >70 years (p < 0.001). CONCLUSIONS: Emergency laparotomy carries a high rate of mortality, especially in those over the age of 70 years, and more needs to be done to improve outcomes, particularly in this group. This could involve increasing acute surgical care manpower, early recognition of patients requiring emergency surgery, development of clear management protocols for such patients or perhaps even considering centralisation of emergency surgical services to specialist centres with multidisciplinary teams involving emergency surgeons and care of the elderly physicians in hospital and related community outreach services for post-discharge care.

A national survey of attitudes to research in Scottish General Surgery Trainees.

INTRODUCTION: Given the importance placed on awareness and participation in research by Speciality and Training organisations, we sought to survey Scottish trainee attitudes to exposure to research practice during training and research in or out of programme. METHODS: An online survey was distributed to core and specialist trainees in general surgery in Scotland. RESULTS: Over a 4-month period, 108 trainees (75 ST/SPRs and 33 CTs) completed the survey. In their current post, most were aware of ongoing research projects (77%) and 55% were aware of trial recruitment. Only 47% attend regular journal clubs. Most believe that they are expected to present (89%) and publish (82%) during training. Most (59%) thought that participation in research is well supported. 57% were advised to undertake time out of programme research, mostly by consultants (48%) and training committee (36%). Of the 57 with time out of programme research experience, most did so in early training (37%) or between ST3-5 (47%). 28 out of the 36 (78%) without a national training number secured one after starting research. Most undertook research in a local academic unit (80%) funded by small grants (47%) or internally (33%). Most research (69%) was clinically orientated (13/55 clinical, 25/55 translational). 56% of those completing time out of programme research obtained an MD or PhD. About 91% thought that research was relevant to a surgical career. CONCLUSIONS: Most trainees believe that research is an important part of training. Generally, most trainees are exposed to research practices including trial recruitment. However, <50% attend regular journal clubs, a pertinent point, given the current 'exit exam' includes the assessment of critical appraisal skills.

Massive mesenteric and portal venous thrombosis secondary to hormone replacement therapy.

Hormone replacement therapy increases risk of deep venous thrombosis (DVT) mainly in the extremities and lungs. There are reports of mesenteric ischemia secondary to oral contraceptive pills but no reports on hormone replacement therapy and mesenteric thrombosis. The authors present a case of a 44-year-old obese (BMI 32) woman, on long-term hormone replacement therapy, presented with thrombosis of portal, splenic and superior mesenteric veins. She underwent surgical resection of ischemic bowel and planned re-look laparotomies with further resections and jejuno-ileal anastomosis at final laparotomy. Thorough haematological investigations were normal. The authors conclude that hormone replacement therapy in obese patients with no other risk factors can cause a catastrophic mesenteric thrombosis. Aggressive surgical resection with re-look laparotomies and further resections can be lifesaving.

Groove pancreatitis: a case series and review of the literature.

INTRODUCTION: Groove pancreatitis is a form of chronic pancreatitis affecting the space surrounded by the pancreatic head, duodenum and common bile duct. The clinical findings can conflict with pancreatic cancer causing diagnostic dilemma preoperatively. CASE SERIES: We describe two patients with a history of alcohol excess, who presented with a few months history of upper abdominal pain associated with weight loss and vomiting. Endoscopic and radiological investigations related duodenal narrowing, biliary dilatation and multiple pseudocysts around the head of the pancreas and duodenum. A Whipple's pancreaticoduodenectomy was carried out in both patients. Histopathology report demonstrated cystic areas in both medial and lateral walls of the duodenum microscopically consistent with groove pancreatitis. CONCLUSION: The diagnosis of groove pancreatitis should be considered in patients with duodenal stenosis and cystic lesions around the head of the pancreas associated with history of alcohol excess. Differentiation from pancreatic cancer is difficult preoperatively.

Mesenteric lipoma causing small bowel perforation: a case report and review of literature.

A lipoma of the small bowel mesentery is a rare pathological entity. It has been shown to rarely cause obstruction and volvulus of the small bowel. We report a case of a 72-year-old man who presented with lower abdominal pain and slightly raised inflammatory markers. Computerized tomography of the abdomen showed small bowel perforation and oedematous terminal ileum. At laparotomy the cause was found to be a mesenteric lipoma causing small bowel perforation. As far as the authors are aware, this presentation is not described in the English language literature.

A fully autologous co-culture system utilising non-irradiated autologous fibroblasts to support the expansion of human keratinocytes for clinical use.

Autologous keratinocytes can be used to augment cutaneous repair, such as in the treatment of severe burns and recalcitrant ulcers. Such cells can be delivered to the wound bed either as a confluent sheet of cells or in single-cell suspension. The standard method for expanding primary human keratinocytes in culture uses lethally irradiated mouse 3T3 fibroblasts as feeder cells to support keratinocyte attachment and growth. In an effort to eliminate xenobiotic cells from clinical culture protocols where keratinocytes are applied to patients, we investigated whether human autologous primary fibroblasts could be used to expand keratinocytes in culture. At a defined ratio of a 6:1 excess of keratinocytes to fibroblasts, this co-culture method displayed a population doubling rate comparable to culture with lethally irradiated 3T3 cells. Furthermore, morphological and molecular analysis showed that human keratinocytes expanded in co-culture with autologous human fibroblasts were positive for proliferation markers and negative for differentiation markers. Keratinocytes expanded by this method thus retain their proliferative phenotype, an important feature in enhancing rapid wound closure. We suggest that this novel co-culture method is therefore suitable for clinical use as it dispenses with the need for lethally irradiated 3T3 cells in the rapid expansion of autologous human keratinocytes.

Dentists in mountain rescue.

Dental practitioners often lead busy lives. It is amazing how diverse their activities can be after the surgery door has closed. This short article describes how our colleagues volunteer to serve the public in one difficult and hazardous environment - the mountainsides of Cumbria.

Cutaneous squamous cell carcinoma in a child.

Cutaneous squamous cell carcinoma in children is very rare. Of those reported cases, most arise in the context of underlying predisposing conditions such as xeroderma pigmentosum, albinism or immunosuppression. We report a rare case of cutaneous squamous cell carcinoma in a child with no history of predisposing conditions.

Supply and demand: sink regulation of sugar accumulation in sugarcane.

Sugarcane (Saccharum spp. hybrids) accumulates sucrose to high concentrations and, as a result, has been the focus of extensive research into the biochemistry and physiology of sucrose accumulation. Despite this, the relationship between source leaf photosynthetic activity and sucrose accumulation in the culm sink is not well understood. The observations that photosynthetic activity declines during culm maturation in commercial cultivars and that high-sucrose-accumulating noble ancestral genotypes (Saccharum officinarum L.) photosynthesize at rates two-thirds of those of low-sucrose ancestors (Saccharum spontaneum L.) indicate that source-sink communication may play a pivotal role in determining sucrose yield. Although maturation of the culm results in a decreased demand for sucrose, recent evidence from partial leaf shading, defoliation, and transgenic studies indicates that sugarcane cultivars are capable of further increases in sugar content. Furthermore, sugarcane leaves appear to retain the capacity to increase the supply of assimilate to culm tissues under conditions of increased assimilate demand. The relationship between source and sink tissues in sugarcane should be viewed within a supply-demand paradigm; an often neglected conceptual approach in the study of this crop. Uncoupling of the signalling pathways that mediate negative feedback between source and sink tissues may result in improved leaf assimilation rates and, consequently, lead to increased sugarcane sucrose yields.

Substrate-induced phenotypical change of monocytes/macrophages into myofibroblast-like cells: a new insight into the mechanism of in-stent restenosis.

Stented coronary angioplasty is the procedure of choice to re-establish patency in obstructed coronary arteries. However, the stent implantation procedure often leads to in-stent restenosis, a process that is characterized by stent strut colonization by macrophages and smooth muscle cells and by neointima formation. The present in vitro study investigates the effect of stent materials on the phenotypical features of monocyte/macrophages. Human peripheral blood monocytes from healthy donors (n = 7) were cultured up to 7 days on substrates mimicking: (i) the stent surface (i.e., electropolished stainless steel), (ii) the de-endothelialized vessel wall (collagen-based extracellular matrix gel), and (iii) thrombus (i.e., fibrin gel). The cells were analyzed by immunocytochemistry for their ability to express alpha-actin, a typical myofibroblast marker, by ELISA to determine PDGF-BB and TGF-beta1 secretion and by PCR to evaluate hyaluronan synthase 1, 2, and 3 genes expression. Data were statistically analyzed by ANOVA (Dunnett's test) and data considered significantly different at p

Cofilin is a marker of myofibroblast differentiation in cells from porcine aortic cardiac valves.

The formation of myofibroblasts in valve interstitial cell (VIC) populations contributes to fibrotic valvular disease. We examined myofibroblast differentiation in VICs from porcine aortic valves. In normal valves, cells immunostained for alpha-smooth muscle actin (alpha-SMA, a myofibroblast marker) were rare (0.69 +/- 0.48%), but in sclerotic valves of animals fed an atherogenic diet, myofibroblasts were spatially clustered and abundant (31.2 +/- 6.3%). In cultured VIC populations from normal valves, SMA-positive myofibroblasts were also spatially clustered, abundant (21% positive cells after 1 passage), and stained for collagen type I and vimentin but not desmin. For an analysis of stem cells, two-color flow cytometry of isolated cells stained with Hoechst 33342 demonstrated that 0.5% of VICs were side population cells; none stained for SMA. Upon culture, sorted side population cells generated approximately 85% SMA-positive cells, indicating that some myofibroblasts originate from a rare population with stem cell characteristics. Plating cells on rigid collagen substrates enabled the formation of myofibroblasts after 5 days in culture, which was completely blocked by culture of cells on compliant collagen substrates. Exogenous tensile force also significantly increased SMA expression in VICs. Isotope-coded affinity tags and mass spectrometry were used to identify differentially expressed proteins in myofibroblast differentiation of VICs. Of the nine proteins that were identified, cofilin expression and phospho-cofilin were strongly increased by conditions favoring myofibroblast differentiation. Knockdown of cofilin with small-interfering RNA inhibited collagen gel contraction and reduced myofibroblast differentiation as assessed by the SMA incorporation into stress fibers. When compared with normal valves, diseased valves showed strong immunostaining for cofilin that colocalized with SMA in clustered cells. We conclude that in VICs, cofilin is a marker for myofibroblasts in vivo and in vitro that arise from a rare population of stem cells and require a rigid matrix for formation.

Changes in photosynthetic rates and gene expression of leaves during a source-sink perturbation in sugarcane.

BACKGROUND AND AIMS: In crops other than sugarcane there is good evidence that the size and activity of carbon sinks influence source activity via sugar-related regulation of the enzymes of photosynthesis, an effect that is partly mediated through coarse regulation of gene expression. METHODS: In the current study, leaf shading treatments were used to perturb the source-sink balance in 12-month-old Saccharum spp. hybrid 'N19' (N19) by restricting source activity to a single mature leaf. Changes in leaf photosynthetic gas exchange variables and leaf and culm sugar concentrations were subsequently measured over a 14 d period. In addition, the changes in leaf gene response to the source-sink perturbation were measured by reverse northern hybridization analysis of an array of 128 expressed sequence tags (ESTs) related to photosynthetic and carbohydrate metabolism. KEY RESULTS: Sucrose concentrations in immature culm tissue declined significantly over the duration of the shading treatment, while a 57 and 88% increase in the assimilation rate (A) and electron transport rate (ETR), respectively, was observed in the source leaf. Several genes (27) in the leaf displayed a >2-fold change in expression level, including the upregulation of several genes associated with C(4) photosynthesis, mitochondrial metabolism and sugar transport. Changes in gene expression levels of several genes, including Rubisco (EC 4.1.1.39) and hexokinase (HXK; EC 2.7.1.1), correlated with changes in photosynthesis and tissue sugar concentrations that occurred subsequent to the source-sink perturbation. CONCLUSIONS: These results are consistent with the notion that sink demand may limit source activity through a kinase-mediated sugar signalling mechanism that correlates to a decrease in source hexose concentrations, which, in turn, correlate with increased expression of genes involved in photosynthesis and metabolite transport. The signal feedback system reporting sink sufficiency and regulating source activity may be a potentially valuable target for future genetic manipulation to increase sugarcane sucrose yield.

The internervous safe zone for incision of the capsule of the hip. A cadaver study.

In order to determine the potential for an internervous safe zone, 20 hips from human cadavers were dissected to map out the precise pattern of innervation of the hip capsule. The results were illustrated in the form of a clock face. The reference point for measurement was the inferior acetabular notch, representing six o'clock. Capsular branches from between five and seven nerves contributed to each hip joint, and were found to innervate the capsule in a relatively constant pattern. An internervous safe zone was identified anterosuperiorly in an arc of 45 degrees between the positions of one o'clock and half past two. Our study shows that there is an internervous zone that could be safely used in a capsule-retaining anterior, anterolateral or lateral approach to the hip, or during portal placement in hip arthroscopy.

Radial nerve contribution to brachialis in the UK Caucasian population: position is predictable based on surface landmarks.

The midline of the brachialis muscle is now regarded by many surgeons as an internervous plane, between the musculocutaneous nerve supply to the medial portion and a radial nerve contribution to the lateral portion, a principle applied in anterior approaches to the humerus. The radial nerve to brachialis has been described previously in East Asian specimens (Ip and Chang, 1968, Anat Rec 162:363-371; Mahakkanukrauh and Somsarp, 2002, Clin Anat 15:206-209). We sought to investigate the occurrence and character of this nerve in the UK Caucasian population. Dissection of the musculocutaneous nerve and radial nerve was carried out in Caucasian cadaveric arms (n = 42). The radial nerve was dissected from the spiral groove to the lateral epicondyle. Where a branch to brachialis was encountered, its course and level of origin relative to the length of the arm were noted. The musculocutaneous nerve innervated the brachialis in all specimens. Upon investigation 67% of specimens were found to have a radial nerve branch to brachialis. Sixty-one percent of these branches went straight into the muscle, 13% descended, and 26% recurred. The level of origin of the radial nerve branch to brachialis was at a mean of 23% of the distance between the lateral epicondyle and the acromion (n = 31, range 17-37%, SD = 5.3). In three specimens, two branches were observed. A radial nerve contribution to the innervation of the brachialis was present in 67% of UK Caucasian cadavers, which is less than that noted by others in East Asian specimens. The level of the origin of these branches is predictable based on surface landmarks. This fact may be of use during humeral surgery.