Multi-detector CT: Liver protocol and recent developments.

Multi-detector computed tomography is today the workhorse in the evaluation of the vast majority of patients with known or suspected liver disease. Reasons for that include widespread availability, robustness and repeatability of the technique, time-efficient image acquisitions of large body volumes, high temporal and spatial resolution as well as multiple post-processing capabilities. However, as the technique employs ionizing radiation and intravenous iodine-based contrast media, the associated potential risks have to be taken into account. In this review article, liver protocols in clinical practice are discussed with emphasis on optimisation strategies. Furthermore, recent developments such as perfusion CT and dual-energy CT and their applications are presented.

Eye on the B-ALL: B-cell receptor repertoires reveal persistence of numerous B-lymphoblastic leukemia subclones from diagnosis to relapse.

The strongest predictor of relapse in B-cell acute lymphoblastic leukemia (B-ALL) is the level of persistence of tumor cells after initial therapy. The high mutation rate of the B-cell receptor (BCR) locus allows high-resolution tracking of the architecture, evolution and clonal dynamics of B-ALL. Using longitudinal BCR repertoire sequencing, we find that the BCR undergoes an unexpectedly high level of clonal diversification in B-ALL cells through both somatic hypermutation and secondary rearrangements, which can be used for tracking the subclonal composition of the disease and detect minimal residual disease with unprecedented sensitivity. We go on to investigate clonal dynamics of B-ALL using BCR phylogenetic analyses of paired diagnosis-relapse samples and find that large numbers of small leukemic subclones present at diagnosis re-emerge at relapse alongside a dominant clone. Our findings suggest that in all informative relapsed patients, the survival of large numbers of clonogenic cells beyond initial chemotherapy is a surrogate for inherent partial chemoresistance or inadequate therapy, providing an increased opportunity for subsequent emergence of fully resistant clones. These results frame early cytoreduction as an important determinant of long-term outcome.

Multidetector CT of pancreatic ductal adenocarcinoma: Effect of tube voltage and iodine load on tumour conspicuity and image quality.

OBJECTIVES: To compare a low-tube-voltage with or without high-iodine-load multidetector CT (MDCT) protocol with a normal-tube-voltage, normal-iodine-load (standard) protocol in patients with pancreatic ductal adenocarcinoma (PDAC) with respect to tumour conspicuity and image quality. METHODS: Thirty consecutive patients (mean age: 66 years, men/women: 14/16) preoperatively underwent triple-phase 64-channel MDCT examinations twice according to: (i) 120-kV standard protocol (PS; 0.75 g iodine (I)/kg body weight, n = 30) and (ii) 80-kV protocol A (PA; 0.75 g I/kg, n = 14) or protocol B (PB; 1 g I/kg, n = 16). Two independent readers evaluated tumour delineation and image quality blindly for all protocols. A third reader estimated the pancreas-to-tumour contrast-to-noise ratio (CNR). Statistical analysis was performed with the Chi-square test. RESULTS: Tumour delineation was significantly better in PB and PA compared with PS (P = 0.02). The evaluation of image quality was similar for the three protocols (all, P > 0.05). The highest CNR was observed with PB and was significantly better compared to PA (P = 0.02) and PS (P = 0.0002). CONCLUSION: In patients with PDAC, a low-tube-voltage, high-iodine-load protocol improves tumour delineation and CNR leading to higher tumour conspicuity compared to standard protocol MDCT. KEY POINTS: • Low-tube-voltage high-iodine-load MDCT improves pancreatic cancer conspicuity compared to a standard protocol. • The pancreas-to-tumour attenuation difference increases significantly by reducing the tube voltage. • The radiation exposure dose decreases by reducing the tube voltage.

Computed tomography staging of pancreatic cancer: a validation study addressing interobserver agreement.

BACKGROUND/OBJECTIVES: Ductal adenocarcinoma in the head of the pancreas (PDAC) is usually unresectable at the time of diagnosis due to the involvement of the peripancreatic vessels. Various preoperative classification algorithms have been developed to describe the relationship of the tumor to these vessels, but most of them lack a surgically based approach. We present a CT-based classification algorithm for PDAC based on surgical resectability principles with a focus on interobserver variability. METHODS: Thirty patients with PDAC undergoing pancreaticoduodenectomy were examined by using a standard CT protocol. Nine radiologists, representing three different levels of expertise, evaluated the CT examinations and the tumors were classified into four categories (A-D) according to the proposed system. For the interobserver agreement, the Intraclass Correlation Coefficient (ICC) was estimated. RESULTS: The overall ICC was 0.94 and the ICCs among the trainees, experienced radiologists, and experts were 0.85, 0.76, and 0.92, respectively. All tumors classified as category A1 showed no signs of vascular invasion at surgery. In category A2, 40% of the tumors had corresponding infiltration and required resection of the superior mesenteric vein/portal vein (SMV/PV). One of two tumors in category B2 and two of three in category C required SMV/PV resection. All six patients in category D had both arterial and venous involvement. CONCLUSION: There is almost perfect agreement among radiologists with different levels of expertise in regards to the local staging of PDAC. For tumors in a more advanced preoperative category, an increased risk for vascular involvement was noticed at surgery.

Preoperative pancreas CT/MRI characteristics predict fistula rate after pancreaticoduodenectomy.

BACKGROUND: Pancreatic fistula (PF) is considered to be the main cause of morbidity after pancreaticoduodenectomy (PD). A recent study from our institution suggested the risk for pancreatic fistula after distal pancreatectomy to be closely related to the pancreatic remnant volume (PRV). The hypothesis was formulated that after PD the PRV is an important determinant of the risk for PF formation. METHOD: All patients undergoing PD between September 2007 and November 2010 at the Karolinska University Hospital Stockholm were included. Preoperative multidetector computed tomography (CT) or magnetic resonance imaging (MRI) was used to calculate the PRV and the pancreatic duct width (PDW) at the alleged resection line. RESULTS: A total of 182 patients (median age 67 years) undergoing PD were included. The diagnosis was malignant in 144 patients (79.1 %) and benign in 38 (20.9 %). Pancreatic fistula defined according to the International Study Group on Pancreatic Fistula (ISGPF) criteria was diagnosed in 37 patients (20.3 %). The median PRV was 35.2 cm(3) and the median PDW was 3.9 mm. In a univariate analysis a large calculated volume of the pancreatic remnant increased the subsequent risk of PF (odds ratio [OR], 3.71; 95% confidence interval [95% CI], 1.58-8.71; P < 0.01), as did a small duct width (OR, 8.46; 95% CI, 3.11-23.04; P < 0.01). According to the multivariate analysis, the size of the pancreatic remnant and the width of the pancreatic duct maintained their impact on leakage risk. CONCLUSIONS: A large pancreatic volume and small pancreatic duct increase the risk of PF. Preoperative CT and/or MRI therefore are useful in predicting fistula formation before pancreaticoduodenectomy.

Non-invasive detection of apoptosis using magnetic resonance imaging and a targeted contrast agent.

The C2 domain of synaptotagmin I, which binds to anionic phospholipids in cell membranes, was shown to bind to the plasma membrane of apoptotic cells by both flow cytometry and confocal microscopy. Conjugation of the protein to superparamagnetic iron oxide nanoparticles allowed detection of this binding using magnetic resonance imaging. Detection of apoptotic cells, using this novel contrast agent, was demonstrated both in vitro, with isolated apoptotic tumor cells, and in vivo, in a tumor treated with chemotherapeutic drugs.

Studies to assess if pizotifen prophylaxis improves migraine beyond the benefit offered by acute sumatriptan therapy alone.

Two multi-centre studies-one double-blind, placebo-controlled (study 1) and one open (study 2)-were set up to assess if pizotifen prophylaxis improved migraine beyond the benefit offered by acute sumatriptan therapy alone. Eighty-eight patients completed the blinded study and 63 patients completed the open study. Both studies were of crossover design with patients undertaking a 4 week run-in period prior to a 12-week treatment period. Following a 4-week washout period patients commenced a second 12-week treatment period on the alternative treatment regimen. All breakthrough attacks were treated with 100 mg oral sumatriptan with an optional 2 doses available to treat any recurrence within 24 h of taking dose 1. Pizotifen was built up to a final daily dose of 1.5 mg over a 2-week period and patients remained on this dose for a further 10 weeks. Patients in the blinded study were given matching placebo tablets for one of the two treatment periods. The efficacy of sumatriptan was not affected by pizotifen. The median of the monthly attack rate experienced by patients was slightly lower whilst patients were on pizotifen and sumatriptan than while on placebo prophylaxis and sumatriptan or sumatriptan alone; study 1, 3.5 vs 3.9 attacks per month (p = 0.008); study 2, 2.9 vs. 3.2 attacks per month (p = 0.23). Also, while on pizotifen and sumatriptan more patients had a greater proportion of their time in the study migraine-free. From the results of these studies it does not appear that pizotifen reduces migraine severity; regardless of the treatment regimen the initial headache severity of most attacks was moderate. Weight gains experienced by patients while on pizotifen and sumatriptan were greater than the weight gains experienced while on placebo prophylaxis and sumatriptan or sumatriptan alone (period 1); study 1, 2.6 vs. 1.0 kg (p = 0.002); study 2, 1.6 vs. -0.8 kg (p < 0.0001). The combination of pizotifen and sumatriptan did not result in any additional adverse events other than those usually seen with each medication alone. In these studies, where the average number of migraine attacks was around 4 per month, the benefits conferred by pizotifen were at the expense of the adverse events associated with the drug, particularly weight gain. Therefore the clinical benefit of treatment with pizotifen for patients who have less than 4 attacks per month should be carefully reviewed as acute treatment with sumatriptan may be the most appropriate treatment. Pizotifen may be better reserved for those patients who have 4 of more attacks per month.

A cost analysis of Nd:YAG laser ablation versus endoscopic intubation for the palliation of malignant dysphagia.

Although endoscopic intubation is the mainstay of non-surgical palliation of malignant dysphagia, Nd:YAG laser ablation has been shown to provide good palliation with few complications. The study reported here incorporates data from published and unpublished sources into a cost model which estimates the lifetime cost of palliation with the two therapies. It is estimated that, depending on the assumptions used, laser palliation costs between 153 pounds and 710 pounds more per patient than endoscopic intubation. Sensitivity analysis is used to assess whether variation in clinical practice and in the unit costs of resources will change the conclusions of the study. This indicates that, under most alternative sets of assumptions, intubation retains its cost advantage. However, factors that might reduce, or even eliminate, this cost differential include undertaking more laser procedures as day-cases, using more expensive expanding metal stents for intubation and reducing the need for follow-up laser procedures with palliative radiotherapy.

Laser ablation of upper gastrointestinal vascular ectasias: long term results.

Forty one patients with bleeding vascular ectasias of the upper gastrointestinal tract who required blood transfusion were treated with endoscopic Nd:YAG laser photocoagulation and followed for 34 months (median). Four distinct groups of patients were identified. There was a sustained reduction in transfusion requirements after laser treatment in all those with single (nine patients) and multiple (seven patients) angiodysplasia, in 12 of 16 (75%) patients with watermelon stomachs, and in six of nine (66%) patients with hereditary haemorrhagic telangiectasia. Overall, 25 patients (61%) required minimal or no transfusion after treatment and nine (22%) whose bleeding was controlled initially, later developed recurrent bleeding which was controlled with further laser (total 34 of 41, 83%). Surgery succeeded in a further three patients (7%) in whom laser had failed (in one case possibly because of laser induced haemorrhage). Five more cases of possible laser induced haemorrhage resolved with conservative treatment. One patient sustained a treatment related perforation and died: one patient with cirrhosis died of encephalopathy within one month of starting laser treatment. In two patients transfusion requirements were unchanged despite laser. Nd:YAG laser is a safe and effective treatment for most patients with upper gastrointestinal angiodysplasia.

Successful conservative management of spontaneous spinal extradural haematoma.

A 69-year-old man developed severe neck and back pain with paraparesis which resolved within 2 h of onset. A CT myelogram demonstrated an extensive anterior extradural haematoma. This and several other cases from the literature suggest that patients with spontaneous spinal haematomas who rapidly recover from their neurological deficit do not require urgent surgical decompression.

Radiation enhancement of laser palliation for malignant dysphagia: a pilot study.

Laser therapy offers rapid relief of dysphagia for patients with cancers of the oesophagus and gastric cardia but repeat treatments are required approximately every five weeks to maintain good swallowing. To try to prolong the treatment interval, 22 elderly patients were given additional external beam radiotherapy. Nine had squamous cell carcinoma and 13 adenocarcinoma: five had documented metastases. Six received 40 Gy and 16,30 Gy in 10-20 fractions. A 'check' endoscopy was performed three weeks after external beam radiotherapy. Dysphagia was graded from 0-4 (0 = normal; 4 = dysphagia for liquids). The median dysphagia grade improved from 3 to 1 after laser treatment. This improvement was maintained in the 30 Gy group but there was a noticeable deterioration in three of those who had received the higher radiation dose. A lifelong dysphagia grade of 2 or better was enjoyed by 14 of 16 patients in the 30 Gy group but only two of six in the 40 Gy group. The dysphagia controlled interval was 9 weeks (median) after check endoscopy and subsequent endoscopic procedures were required every 13 weeks to maintain good swallowing. There were no endoscopy related complications. Combined treatment is a promising approach for reducing the frequency of endoscopic treatments. The 30 Gy dose seems more appropriate and may prolong survival. A randomised study to test these conclusions is in progress.

A prospective assessment of quality of life after endoscopic intubation and laser therapy for malignant dysphagia.

BACKGROUND: This study evaluated the effect of endoscopic treatment for malignant dysphagia on quality of life (QL) as part of a prospective comparison of Nd:YAG laser therapy and intubation. METHODS: Two QL instruments were used: the Quality of Life Index (QLI) and a Linear Analogue Self-Assessment (LASA). Only 23 of 43 patients receiving laser therapy and 15 of 30 having endoscopic intubation agreed to partake in QL assessment; serial measurements until death were obtained in 13 and 9 patients, respectively. RESULTS: Dysphagia grade (DG) as measured on a 5-point scale, correlated significantly with LASA (n = 92; r = -0.51; P less than 0.0001) and QLI (n = 92; r = -0.43; P less than 0.0001) scores. In addition, there was a strong correlation between LASA and QLI scores (r = 0.678; P less than 0.0001). All patients followed up serially until death derived significant palliation of their dysphagia with laser treatment and intubation. Such therapy resulted in a significant initial improvement in QL, with the mean best LASA and QLI scores after treatment being higher than the corresponding mean pretreatment scores (P less than 0.004). However, this improvement proved transient; QL worsened significantly as a patient's general condition deteriorated during the final stages of the illness. The mean last post-treatment LASA and QLI scores in both groups (recorded within 5 weeks of death) were less than the corresponding mean pretreatment scores (P less than 0.004). CONCLUSIONS: Endoscopic palliation of malignant dysphagia results in a significant initial improvement in QL. Subsequently, QL worsens appreciably as a patient's general condition deteriorates during the terminal phase of disease.

Recanalization of tube overgrowth: a useful new indication for laser in palliation of malignant dysphagia.

Overgrowth of an esophageal prosthesis by cancer is a late complication of insertion which presents a difficult management problem. We have treated 14 such patients; 9 had Celestin tubes and 5 Atkinson tubes in situ for a median of 7 months. The median patient age was 75 years; 3 had squamous cell carcinomas and 11 adenocarcinomas; 12 were at the lowest thoracic esophagus or cardia, and 2 were anastomotic. Eleven tubes were overgrown at the top, two at the bottom only, and one at both ends. Dysphagia was graded from 0 to 4 (0 = normal; 4 = dysphagia for liquids). All patients but one improved with treatment. The median pre-treatment grade was 4 (range, 2 to 4) and post-treatment was 2 (0 to 3). This improvement was significant (p less than 0.01) Wilcoxon-signal rank). Most patients required only one or two endoscopies. The median survival was 9 weeks from first laser session (range, 3 to 36 weeks). We feel these results justify laser treatment in most patients in whom cancer overgrowth causes blockage of an esophageal prosthesis.

Treatment of malignant strictures of the cervical esophagus by endoscopic intubation using modified endoprostheses.

Endoscopic intubation has traditionally been considered unsuitable as a means of palliating cervical esophageal carcinomas involving or within 2 cm of the cricopharyngeus sphincter muscle because of the potential problems of foreign body sensation and proximal prosthesis migration. We attempted to palliate eight such patients, three of whom had tracheo-esophageal fistulas by the endoscopic placement of modified Celestin endoprostheses; the floppy funnel of the prosthesis was positioned above the cricopharyngeus in the hypopharynx. Prosthesis placement and fistula occlusion was possible in all patients. Six patients had a significant long-term improvement in their dysphagia, managing a semi-solid (5 patients) or liquid diet (1 patient); two patients did not improve, despite accurate prosthesis placement, because of marked tracheal aspiration. Six patients reported no foreign body sensation; one patient had minor discomfort, and another moderate throat discomfort. Distal prosthesis migration occurred in two patients (replaced in 1 patient). Endoscopic intubation of high cervical esophageal carcinomas with specially modified endoprostheses is feasible and can provide worthwhile palliation of dysphagia and symptoms due to a tracheo-esophageal fistula. Foreign body sensation and proximal prosthesis migration did not prove troublesome.

Endoscopic treatment for bleeding peptic ulcers: randomised comparison of adrenaline injection and adrenaline injection + Nd:YAG laser photocoagulation.

Forty two patients with haemorrhage from peptic ulcers with visible vessels were enrolled in a randomised study comparing endoscopic haemostasis with adrenaline (1:10,000) injections (adrenaline group) and adrenaline injection + neodymium yttrium-aluminium-garnet (Nd:YAG) laser photocoagulation (adrenaline + laser group). The two groups (21 patients each) were well matched for factors affecting outcome. Surgery was performed for continued haemorrhage uncontrolled by endoscopic treatment or rebleeding after two endoscopic treatments. Haemostasis after one treatment was similar in the two groups: adrenaline 16/21 (76%), adrenaline + laser 18/21 (86%). Haemostasis after two treatments was numerically (0.05 less than p less than 0.10) greater in the adrenaline + laser group: 21/21 (100%) v 18/21 (86%). Three patients (14%) in the adrenaline group underwent uneventful emergency surgery. There were no deaths or procedure related complications in either group. Most bleeds from peptic ulcers with visible vessels can be controlled endoscopically without the need for surgery. Both treatments in this study proved highly efficacious in securing haemostasis. Adrenaline injection treatment seems to be the treatment of choice in view of its simplicity, low cost, and availability. Additional Nd:YAG laser treatment may provide a marginal improvement in efficacy, although a much larger trial would be required to prove this.

A prospective comparison of laser therapy and intubation in endoscopic palliation for malignant dysphagia.

There is little objective long-term follow-up comparing laser therapy with intubation for palliation of malignant dysphagia. In a prospective, nonrandomized two-center trial 43 patients treated with the neodymium:yttrium-aluminum-garnet laser were compared with 30 patients treated by endoscopic intubation; the two groups were comparable for mean age and tumor position, length, and histology. Dysphagia was graded from 0 to 4 (0, normal swallowing; 4, dysphagia for liquids). Pretreatment mean dysphagia grades were similar: laser-treated group, 2.9 (SD, 0.6); intubated group, 3.2 (SD, 0.55). For thoracic esophageal tumors, the percentage of patients achieving an improvement in dysphagia grade by greater than or equal to 1 grade initially and over the long term was similar (laser, 95% and 77%; intubation, 100% and 86%). For tumors crossing the cardia, intubation was significantly better (laser, 59% and 50%; intubation, 100% and 92%, respectively; P less than 0.001). In patients palliated over a long period, however, the mean dysphagia grade over the remainder of their mean dysphagia grade over the remainder of their lives (mean survival: laser, 6.1 months; intubation, 5.1 months) was better in the laser group (1.6 vs. 2.0; P less than 0.01); 33% of laser-treated and 11% of intubated patients could eat most or all solids (P less than 0.05). For long-term palliation, laser-treated patients required on average more procedures (4.6 vs. 1.4; P less than 0.05) and days in the hospital (14 vs. 9; P less than 0.05). The perforation rate was lower in the laser-treated group (2% vs. 13%; P less than 0.02); no treatment-related deaths occurred in either group. For individual patients, the best results are likely to be achieved when the two techniques are used in a complementary fashion in specialist centers.

Coagulation, fibrinolytic and platelet function in patients on long-term therapy with aspirin 300 mg or 1,200 mg daily compared with placebo.

Aspirin has been shown to be beneficial in the prophylaxis of arterial thromboembolic disease. The rationale for its use as an antithrombotic drug lies in its inhibition of thromboxane A2-dependent platelet function. However, the effect of aspirin on coagulation and fibrinolysis during chronic therapy has not been studied. We have measured a range of haemostatic and platelet functions in 49 patients with transient ischaemic attacks randomly allocated to aspirin 300 mg a day, aspirin 1,200 mg a day or placebo. All had been taking their allocated treatment for between 9 months and 4 years prior to investigation. Bleeding time was prolonged, serum thromboxane diminished and platelet aggregation to arachidonic acid but not ADP was abolished by both 300 mg and 1,200 mg aspirin, in a non-dose dependent fashion. Serum salicylate increased with the dose of aspirin ingested. No effect was seen with either dose of aspirin on urinary thromboxane and 6-keto-PGF1 alpha excretion, or on coagulation. Patients taking 1,200 mg aspirin a day had a lower haemoglobin and packed cell volume, lower resting fibrinopeptide A concentration and lower basal plasminogen activator activity than those on placebo. Response to venous occlusion was normal in all groups. The results suggest 300 mg and 1,200 mg aspirin have an equivalent platelet inhibitory effect but 1,200 mg aspirin causes greater gastro-intestinal blood loss.

Endoscopic Nd:YAG laser treatment of rectosigmoid cancer.

Forty nine patients with rectosigmoid carcinoma considered unsuitable for surgery underwent endoscopic Nd:YAG laser treatment for palliation of symptoms and tumour eradication, if feasible. Altogether 25 (51%) of the lesions had distal margins less than 7 cm from the anus and 36 (73%) extended above the peritoneal reflection. In seven patients with tumours less than 3 cm in diameter, symptomatic improvement was achieved in all (mean follow up 16 months) and complete tumour eradication in three. In the remaining 42 patients with larger tumours (34 greater than 2/3 circumferential, mean length 5.5 cm), symptomatic improvement was achieved with repeated treatments (average 3.4) in 31 (74%) over a mean follow up of 19 weeks. Of the parameters assessed, only circumferential tumour extent proved significant in predicting functional outcome after treatment. All treatment failures (eight initial, three late) occurred in patients with extensive tumours, and only seven of these patients were considered fit for colostomy. Bowel perforation occurred in two patients (5%) but there was no treatment-related mortality. Mean stay in hospital for all laser treatments was nine days (30% were outpatient attendances). These results suggest that laser therapy may be the palliative treatment of choice in patients with rectal carcinoma unsuitable for surgery.

Relative efficacy of intravenous methylprednisolone and ACTH in the treatment of acute relapse in MS.

To compare the efficacy of high-dose intravenous methylprednisolone with intramuscular ACTH in the treatment of acute relapse in multiple sclerosis, we undertook a double-blind, randomized, controlled study involving 61 patients. There was a marked improvement in both groups in the course of the study, but no difference between them in either the rate of recovery or the final outcome. High-dose IV methylprednisolone is a safe alternative to ACTH in the management of acute relapse in MS.