Radiology of colorectal cancer

In the past 20 years, the radiology of colorectal cancer has evolved from the barium enema to advanced imaging modalities like phased array magnetic resonance imaging (MRI), virtual colonoscopy and positron emission tomography (PET). Nowadays, primary rectal cancers are preferably imaged with transrectal ultrasound or MRI, while barium enema is still the most often used technique for imaging of colonic cancers. Virtual colonoscopy is rapidly evolving and might considerably change the imaging of colorectal cancer in the near future. The use of virtual colonoscopy for screening purposes and imaging of the colon in occlusive cancer or incomplete colonoscopies is currently under evaluation. The main role of PET is in detecting tumour recurrences, both locally and distantly. Techniques to fuse cross-sectional anatomical (computer tomography (CT) and MRI) and functional (PET) images are being developed. Apart from diagnostic imaging, the radiologists has added image-guided minimally invasive treatments of colorectal liver metastases to their arsenal. The radio-frequency ablation technique is now widely available, and can be used during laparotomy or percutaneously in selected cases.     

Infectious disease complications of simultaneous pancreas kidney transplantation

BACKGROUND: Although technical success rate of simultaneous pancreas kidney (SPK) transplantation in insulin-dependent diabetes mellitus (IDDM) patients with diabetic nephropathy has improved, morbidity remains high due to infection and rejection. The purpose of this study was to analyse infections encountered in our series of SPK transplants, using a restrictive antibiotic prophylaxis policy. METHODS: We reviewed all infectious diseases after 66 consecutive bladder-drained SPK transplantations in 64 IDDM patients with end-stage renal disease due to diabetic nephropathy. During follow-up, the perioperative antibiotic regimen was altered (from 5 days preemptive therapy with multiple drugs to 1 day prophylaxis with cefamandole), and long-term viral prophylaxis (high-dose aciclovir) was introduced. For post-operative urinary tract or opportunistic infection, no prophylaxis was given. RESULTS: Overall mean infection rate was 2.9 infections/ patient/year after a mean follow-up of 2.3 years. Surgical site infections (SSI) were seen in 30% of the patients, with Enterococci present in 47%. Logistic regression showed one day cefamandole prophylaxis to be associated with SSI, but there was no significant influence of SSI on either graft or patient survival. Forty-eight percent of all infections were lower urinary tract infections (UTI). There were 59 first UTIs (89%), probably related to long-term Foley catheter use, and 47 second UTIs (71%). Subsequent UTIs were not microbiologically related to first UTIs. Cytomegalovirus (10 patients) and other opportunistic agents did not cause mortality or graft loss. Five grafts were lost due to infection (SSI three times, post-transplant lymphoproliferative disease twice). Only one patient died because of infection (2%). CONCLUSIONS: Infectious diseases after SPK transplantation caused significant morbidity but did not influence either patient or graft survival. A change in prophylactic policy for both SSI as well as recurrent UTI, combined with earlier Foley removal, may lower incidences of these infections.      

Single-channel versus bilateral multichannel cochlear implant results: a case report.

Pre- and postoperative audiologic findings are compared in a patient who underwent three cochlear implant surgeries: an initial single-channel device in a recently deafened ear with no residual hearing, followed by a multichannel device in a congenitally deafened ear with a severe to profound loss, and subsequent explantation of the single-channel device and reimplantation with a multichannel device.     

Actigraphic multi‐night home‐recorded sleep estimates reveal three types of sleep misperception in Insomnia Disorder and good sleepers

People with Insomnia Disorder tend to underestimate their sleep compared with polysomnography or actigraphy, a phenomenon known as paradoxical insomnia or sleep‐state misperception. Previous studies suggested that night‐to‐night variability could be an important feature differentiating subtypes of misperception. This study aimed for a data‐driven definition of misperception subtypes revealed by multiple sleep features including night‐to‐night variability. We assessed features describing the mean and dispersion of misperception and objective and subjective sleep duration from 7‐night diary and actigraphy recordings of 181 people with Insomnia Disorder and 55 people without sleep complaints. A minimally collinear subset of features was submitted to latent class analysis for data‐driven subtyping. Analysis revealed three subtypes, best discriminated by three of five selected features: an individual’s shortest reported subjective sleep duration; and the mean and standard deviation of misperception. These features were on average 5.4, ?0.0 and 0.5 hr in one subtype accommodating the majority of good sleepers; 4.1, ?1.4 and 1.0 hr in a second subtype representing the majority of people with Insomnia Disorder; and 1.7, ?2.2 and 1.5 hr in a third subtype representing a quarter of people with Insomnia Disorder and hardly any good sleepers. Subtypes did not differ on an individual’s objective sleep duration mean (6.9, 7.2 and 6.9 hr) and standard deviation (0.8, 0.8 and 0.9 hr). Data‐driven analysis of naturalistic sleep revealed three subtypes that markedly differed in misperception features. Future studies may include misperception subtype to investigate whether it contributes to the unexplained considerable individual variability in treatment response.     

Altered thyrotropic and lactotropic axes regulation in Huntington’s disease

Background Recently, a loss of hypothalamic dopamine D₂ receptors was demonstrated in Huntington’s disease (HD). Activation of dopamine D₂ receptors is known to inhibit the function of both thyrotropic and lactotropic axes. Objective To assess whether the activity of the thyrotropic and lactotropic axes is disturbed in patients with HD, contributing to symptoms such as unintended weight loss. Participants and methods In nine medication‐free patients with early‐stage HD (six men, three women) and nine age‐, sex‐ and body mass index‐matched controls, we measured serum levels of thyroid‐stimulating hormone (TSH) and prolactin (men only) every 10 min for 24 h. Multiparameter auto‐deconvolution and approximate entropy analysis were applied to quantify basal, pulsatile and total TSH and prolactin secretion rates as well as the regularity of hormone release. Results Compared with controls, TSH and prolactin secretion tended to be slightly, but not significantly, higher in patients with HD (TSH: 1·13 ±0·14 vs 0·91 ± 0·19 mU/l, P = 0·40; prolactin: 213 ± 18 vs 209 ± 11 pmol/l, P = 0·87). However, in patients with HD, total T₃ levels were significantly higher (1·60 ± 0·05 vs 1·35 ± 0·09, P = 0·045), while T₄ levels tended to be higher as well (91·9 ± 3·9 vs 81·3 ± 3·1, P = 0·085). Prolactin secretion was significantly more irregular in patients with HD (Approximate entropy (ApEn): 1·06 ± 0·08 vs 0·80 ± 0·09, P = 0·037). Total T₃ levels were negatively associated with motor impairment (r = ?0·72, P = 0·030), whereas increasing free T₄ levels were associated with a larger mutant cytosine‐adenine‐guanine (CAG) repeat size (r = +0·68, P = 0·044). Conclusion: Our findings indicate a mild hyperactivity of the thyrotropic axis and a disturbed regulation of the lactotropic axis in patients with early‐stage HD.     

Loss of 50% of excess weight using a very low energy diet improves insulin-stimulated glucose disposal and skeletal muscle insulin signalling in obese insulin-treated type 2 diabetic patients

Aims/hypothesis Both energy restriction (ER) per se and weight loss improve glucose metabolism in obese insulin-treated type 2 diabetic patients. Short-term ER decreases basal endogenous glucose production (EGP) but not glucose disposal. In contrast the blood glucose-lowering mechanism of long-term ER with substantial weight loss has not been fully elucidated. The aim of this study was to investigate the effect of loss of 50% of excess weight [50% excess weight reduction (EWR)] on EGP, whole-body insulin sensitivity and the disturbed myocellular insulin-signalling pathway in ten obese insulin-treated type 2 diabetic patients. Methods A euglycaemic–hyperinsulinaemic clamp with stable isotopes ([6,6-²H₂]glucose and [²H₅]glycerol) combined with skeletal muscle biopsies was performed during a very low energy diet (VLED; 1,883 kJ/day) on day 2 and again after 50% EWR. Oral blood glucose-lowering agents and insulin were discontinued 3 weeks prior to the VLED and at the start of the VLED, respectively. Results Loss of 50% EWR (20.3 ± 2.2 kg from day 2 to day of 50% EWR) normalised basal EGP and improved insulin sensitivity, especially insulin-stimulated glucose disposal (18.8 ± 2.0 to 39.1 ± 2.8 μmol kg fat-free mass⁻¹ min⁻¹, p = 0.001). The latter was accompanied by improved insulin signalling at the level of the recently discovered protein kinase B/Akt substrates AS160 and PRAS40 along with a decrease in intramyocellular lipid (IMCL) content. Conclusions/interpretation Considerable weight loss in obese, insulin-treated type 2 diabetic patients normalises basal EGP and improves insulin sensitivity resulting from an improvement in insulin signal transduction in skeletal muscle. The decrease in IMCL might contribute to this effect.     

High circulating thyrotropin levels in obese women are reduced after body weight loss induced by caloric restriction

CONTEXT: Previous clinical studies concerning the impact of body weight loss on single plasma TSH concentration measurements or the TSH response to TRH in obese humans have shown variable results. OBJECTIVE: The objective of this study was to investigate the effect of weight loss induced by caloric restriction on diurnal TSH concentrations and secretion in obese humans. DESIGN: This was a clinical, prospective, crossover study. SETTING: The study was conducted at the Clinical Research Center of Leiden University Medical Center. PARTICIPANTS: Eleven obese premenopausal women (body mass index, 33.3 +/- 0.7 kg/m2) were studied. INTERVENTION: The study intervention was weight loss (50% reduction overweight by caloric restriction). MAIN OUTCOME MEASURE(S): Twenty-four-hour plasma TSH concentrations (10-min intervals) and the 24-h TSH secretion rate, calculated by a waveform-independent deconvolution technique (Pulse), were determined. RESULTS: The 24-h TSH secretion rate was significantly higher in obese women than in normal weight controls, and weight loss was accompanied by diminished TSH release (before weight loss, 43.4 +/- 6.4 mU/liter.24 h; after weight loss, 34.4 +/- 5.9 mU/liter.24 h; P = 0.02). Circulating free T3 levels decreased after weight loss from 4.3 +/- 0.19 to 3.8 +/- 0.14 pmol/liter (P = 0.04). Differences in 24-h TSH release correlated positively with the decline of circulating leptin (r2 = 0.62; P < 0.01). Conclusions: Elevated TSH secretion in obese women is significantly reduced by diet-induced weight loss. Among various physiological cues, leptin may be involved in this phenomenon. The decreases in TSH and free T3 may blunt energy expenditure in response to long-term calorie restriction, thereby frustrating weight loss attempts of obese individuals.     

Two days of a very low calorie diet reduces endogenous glucose production in obese type 2 diabetic patients despite the withdrawal of blood glucose-lowering therapies including insulin

The mechanism of the blood glucose-lowering effect of a 2-day very low calorie diet (VLCD; 1890 kJ/d) in combination with the cessation of all blood glucose-lowering agents was studied in 12 (7 women, 5 men) obese (body mass index, 36.3 ± 1.0 kg/m² [mean ± SEM]) type 2 diabetic patients (age, 55 ± 4 years; HbA_1c, 7.3% ± 0.4%) undergoing insulin therapy. Endogenous glucose production (EGP) and whole body glucose disposal (6,6 ²H₂-glucose), lipolysis (²H₅-glycerol), and substrate oxidation (indirect calorimetry) rates were measured before and after the intervention in basal and hyperinsulinemic conditions.After 2 days of a VLCD and discontinuation of all blood glucose-lowering therapies, fasting plasma glucose levels did not increase (11.3 ± 1.3 vs 10.3 ± 1.0 mmol/L). Basal EGP significantly declined (14.2 ± 1.0 to 11.9 ± 0.7 μmol/kg per minute; P = .009). Basal metabolic clearance rate of glucose and rate of basal lipolysis did not change. During hyperinsulinemia, EGP (5.5 ± 0.8 to 5.2 ± 0.5 μmol/kg per minute), whole body glucose disposal (12.1 ± 0.7 to 11.3 ± 1.0 μmol/kg per minute), the metabolic clearance rate of glucose, and the rate of lipolysis did not change after the 2-day intervention.Cessation of blood glucose-lowering therapy in combination with a 2-day VLCD does not lead to hyperglycemia and is associated with a reduction in basal EGP. Insulin-stimulated whole body glucose disposal did not improve, nor did insulin suppressibility of EGP and lipolysis.     

The decline in plasma leptin in response to calorie restriction predicts the effects of adjunctive leptin treatment on body weight in humans

BACKGROUND: Plasma leptin levels decline in response to food restriction. We hypothesized that the magnitude of this decline would predict the amount of weight lost in response to exogenous leptin administration. METHODS: Thirty obese subjects were mildly energy-restricted for 21 days. Subsequently, they were randomized to receive either recombinant human leptin [rL, 10 mg s.c. once (n=15) or twice (n=6) daily] or placebo (n=9) as an adjunct to the dietary measures for 12 weeks. RESULTS: Weight loss amounted to 2.8+/-1.1, 5.2+/-0.9, and 7.9+/-1.4 kg (mean+/-standard error) (p=0.035 vs. placebo) in placebo, rL once daily, and rL b.i.d. treated subjects, respectively. The reduction in plasma leptin concentrations during the initial 21 days was positively correlated with the loss of body weight following leptin treatment (r(2)=0.24, p=0.04). Plasma leptin concentration prior to the initiation of rL therapy was inversely associated with the amount of body weight lost in response to intervention (r(2)=0.36, p=0.003). CONCLUSION: Leptin administration counteracts the adaptations that are actuated by the drop in leptin concentrations and thereby disrupts energy balance to promote weight loss.