Melanoma of the rectum： A rare entity

A 41-year-old man presented with a 6-mo history of changed defecation and rectal bleeding. A 3-cm polypoid tumor of the lower rectum was found at rectosigmoidoscopy, which proved to be a leiomyosarcoma upon biopsy. Dissemination studies did not show any metastases. He was underwent to an abdomino-perineal resection （APR）. Histopathology of the specimen showed a melanoma （S-100 stain positive）. Two years after the resection, metastases in the abdomen and right lung were found. He died one and half years later. Primary anorectal melanoma is a rare and very aggressive disorder. According to current data, one should always perform a S-100 stain when anorectal sarcoma is suspected. A positive S-100 stain suggests the tumour to be most likely a melanoma. Subsequently, thorough dissemination studies need to be performed. Depending on the outcome of the dissemination studies, a surgical resection has to be performed. Nowadays, a sphincter-saving local excision combined with adjuvant loco-regional radiotherapy should be preferred in case of small tumors. The same loco-regional control is achieved with less ＂loss of function＂ compared to non-sphincter saving surgery. Only in the case of large and obstructing tumors an abdomino-perineal resection is the treatment of choice.     

CCK receptor antagonist loxiglumide alters uptake of CCK in perfused liver and pancreatic acini of the rat

The aim of the present study was to analyze the effect of the specific cholecystokinin (CCK) receptor antagonist loxiglumide on hepatic and pancreatic processing of CCK-8 and the CCK analogue cerulein. Rat liver perfusion was performed in a non-recirculating system. CCK concentrations were measured by radioimmunoassay in perfusates from the inflow cannula (portal vein) and the outflow cannula (hepatic vein). In rat pancreatic acini, the effect of loxiglumide on internalization and surface-binding of radiolabelled CCK-8 was determined. Cerulein (20 nM, 2 nM) was extracted in a single pass through the liver by 29.7 and 25.4%, respectively. The hepatic uptake of CCK-8 (50 pM, 2 nM) was more than 90 and 89.9%, respectively. Loxiglumide drastically inhibited hepatic extraction of both peptides and reduced internalization of 125I-CCK-8 in pancreatic acini dose dependently by 39-93%. These results demonstrate that the potent CCK receptor antagonist loxiglumide significantly decreased CCK uptake by the liver and pancreas.     

Differential effects of atropine and a cholecystokinin receptor antagonist on pancreatic secretion

The present study evaluates the effect of atropine and of the cholecystokinin receptor antagonist loxiglumide on feedback regulation of basal pancreatic secretion in 6 healthy volunteers. The intraduodenal instillation of the protease inhibitor camostate reduced enzymatic activities of trypsin and chymotrypsin by 80%. This was accompanied by a strong increase in amylase and lipase output. The intravenous infusion of atropine (5 micrograms/kg.h) completely abolished the stimulatory effect of camostate on enzyme output. The infusion of loxiglumide (10 mg/kg.h) caused no changes in camostate-induced stimulation of enzyme output. Plasma levels of cholecystokinin were not altered after intraduodenal instillation of camostate whether atropine, loxiglumide, or saline were infused. We suggest that the protease inhibitor camostate, by inhibition of the enzymatic activity of trypsin and chymotrypsin, interferes with feedback regulation of basal pancreatic secretion in humans, and this mechanism is predominantly mediated by the cholinergic system.     

Variation in hospital mortality after pancreatoduodenectomy is related to failure to rescue rather than major complications: a nationwide audit

Background

In the mandatory nationwide Dutch Pancreatic Cancer Audit, rates of major complications and Failure to Rescue (FTR) after pancreatoduodenectomy between low- and high-mortality hospitals are compared, and independent predictors for FTR investigated.

Postmortem age estimation via DNA methylation analysis in buccal swabs from corpses in different stages of decomposition—a “proof of principle” study

International Journal of Legal Medicine - Age estimation based on the analysis of DNA methylation patterns has become a focus of forensic research within the past few years. However, there is...     

High resolution SNP array profiling identifies variability in retinoblastoma genome stability

Both hereditary and nonhereditary retinoblastoma (Rb) are commonly initiated by loss of both copies of the retinoblastoma tumor suppressor gene (RB1), while additional genomic changes are required for tumor initiation and progression. Our aim was to determine whether there is genomic heterogeneity between different clinical Rb subtypes. Therefore, 21 Rb tumors from 11 hereditary patients and 10 nonhereditary Rb patients were analyzed using high‐resolution single nucleotide polymorphism (SNP) arrays and gene losses and gains were validated with Multiplex Ligation‐dependent Probe Amplification. In these tumors only a few focal aberrations were detected. The most frequent was a focal gain on chromosome 2p24.3, the minimal region of gain encompassing the oncogene MYCN. The genes BAZ1A, OTX2, FUT8, and AKT1 were detected in four focal regions on chromosome 14 in one nonhereditary Rb. There was a large difference in number of copy number aberrations between tumors. A subset of nonhereditary Rbs turned out to be the most genomic unstable, while especially very young patients with hereditary Rb display stable genomes. Established Rb copy number aberrations, including gain of chromosome arm 1q and loss of chromosome arm 16q, turned out to be preferentially associated with the nonhereditary Rbs with later age of diagnosis. In contrast, copy number neutral loss of heterozygosity was detected mainly on chromosome 13, where RB1 resides, irrespective of hereditary status or age. Focal amplifications and deletions and copy number neutral loss of heterozygosity besides chromosome 13 appear to be rare events in retinoblastoma. © 2013 Wiley Periodicals, Inc.     

Nurses’ perceptions towards the delivery and feasibility of a behaviour change intervention to enhance physical activity in patients at risk for cardiovascular disease in primary care: a qualitative study

Background

Self-management support is widely accepted for the management of chronic conditions. Self-management often requires behaviour change in patients, in which primary care nurses play a pivotal role. To support patients in changing their behaviour, the structured behaviour change Activate intervention was developed. This intervention aims to enhance physical activity in patients at risk for cardiovascular disease in primary care as well as to enhance nurses’ role in supporting these patients. This study aimed to evaluate nurses’ perceptions towards the delivery and feasibility of the Activate intervention.

Methods

A qualitative study nested within a cluster-randomised controlled trial using semistructured interviews was conducted and thematically analysed. Fourteen nurses who delivered the Activate intervention participated.

Results

Three key themes emerged concerning nurses’ perceptions of delivering the intervention: nurses’ engagement towards delivering the intervention; acquiring knowledge and skills; and dealing with adherence to the consultation structure. Three key themes were identified concerning the feasibility of the intervention: expectations towards the use of the intervention in routine practice; perceptions towards the feasibility of the training programme; and enabling personal development.

Conclusions

Delivering a behaviour change intervention is challenged by the complexity of changing nurses’ consultation style, including acquiring corresponding knowledge and skills. The findings have increased the understanding of the effectiveness of the Activate trial and will guide the development and evaluation of future behaviour change interventions delivered by nurses in primary care.

Trial registration

ClinicalTrials.gov NCT02725203.

     

Is Current Perioperative Practice in Hepatic Surgery Based on Enhanced Recovery After Surgery (ERAS) Principles?

Background

The worldwide introduction of multimodal enhanced recovery programs has also changed perioperative care in patients who undergo liver resection. This study was performed to assess current perioperative practice in liver surgery in 11 European HPB centers and compare it to enhanced recovery after surgery (ERAS) principles.

Methods

In each unit, 15 consecutive patients (N = 165) who underwent hepatectomy between 2010 and 2012 were retrospectively analyzed. Compliance was classified as “full,” “partial,” or “poor” whenever ≥80, ≥50, or <50 % of the 22 ERAS protocol core items were met. The primary study end point was overall compliance with the ERAS core program per unit and per perioperative phase.

Results

Most patients were operated on for malignancy (91 %) and 56 % were minor hepatectomies. The median number of implemented ERAS core items was 9 (range = 7–12) across all centers. Compliance was partial in the preoperative (median 2 of 3 items, range = 1–3) and perioperative phases (median 5 of 10 items, range: 4–7). Median postoperative compliance was poor (median 2 of 9 items, range = 0–4). A statistically significant difference was observed between median length of stay and median time to recovery (7 vs. 5 days, P < 0.001).

Conclusion

Perioperative care among centers that perform liver resections varied substantially. In current HPB surgical practice, some elements of the ERAS program, e.g., preoperative counselling and minimal fasting, have already been implemented. Elements in the perioperative phase (avoidance of drains and nasogastric tube) and postoperative phase (early resumption of oral intake, early mobilization, and use of recovery criteria) should be further optimized.     

TMPRSS2-ERG Fusions Are Strongly Linked to Young Patient Age in Low-grade Prostate Cancer

Based on next-generation sequencing of early-onset prostate cancer (PCa), we earlier demonstrated that PCa in young patients is prone to rearrangements involving androgen-regulated genes—such as transmembrane protease, serine 2 (TMPRSS2)–v-ets avian erythroblastosis virus E26 oncogene homolog (ERG) fusion—and provided data suggesting that this situation might be caused by increased androgen signaling in younger men. In the same study, an accumulation of chromosomal deletions was found in cancers of elderly patients. To determine how age-dependent molecular features relate to cancer phenotype, an existing data set of 11 152 PCas was expanded by additional fluorescence in situ hybridization analyses of phosphatase and tensin homolog (PTEN), 6q15 and 5q21. The results demonstrate that the decrease in TMPRSS2–ERG fusions with increasing patient age is limited to low-grade cancers (Gleason ≤3 + 4) and that the significant increase in the deletion frequency with age was strictly limited to ERG-negative cancers for 6q15 and 5q21 but to ERG-positive cancers for PTEN. These data suggest that the accumulation of non–androgen-linked genomic alterations with advanced patient age may require an appropriate microenvironment, such as a positive or negative ERG status. The strong link of ERG activation to young patient age and low-grade cancers may help to explain a slight predominance of low-grade cancers in young patients.