Biphasic and monophasic repair: comparative implications for biologically equivalent dose calculations in pulsed dose rate brachytherapy of cervical carcinoma

Objective:

To consider the implications of the use of biphasic rather than monophasic repair in calculations of biologically-equivalent doses for pulsed-dose-rate brachytherapy of cervix carcinoma.

Methods:

Calculations are presented of pulsed-dose-rate (PDR) doses equivalent to former low-dose-rate (LDR) doses, using biphasic vs monophasic repair kinetics, both for cervical carcinoma and for the organ at risk (OAR), namely the rectum. The linear-quadratic modelling calculations included effects due to varying the dose per PDR cycle, the dose reduction factor for the OAR compared with Point A, the repair kinetics and the source strength.

Results:

When using the recommended 1 Gy per hourly PDR cycle, different LDR-equivalent PDR rectal doses were calculated depending on the choice of monophasic or biphasic repair kinetics pertaining to the rodent central nervous and skin systems. These differences virtually disappeared when the dose per hourly cycle was increased to 1.7 Gy. This made the LDR-equivalent PDR doses more robust and independent of the choice of repair kinetics and α/β ratios as a consequence of the described concept of extended equivalence.

Conclusion:

The use of biphasic and monophasic repair kinetics for optimised modelling of the effects on the OAR in PDR brachytherapy suggests that an optimised PDR protocol with the dose per hourly cycle nearest to 1.7 Gy could be used. Hence, the durations of the new PDR treatments would be similar to those of the former LDR treatments and not longer as currently prescribed.

Advances in knowledge:

Modelling calculations indicate that equivalent PDR protocols can be developed which are less dependent on the different α/β ratios and monophasic/biphasic kinetics usually attributed to normal and tumour tissues for treatment of cervical carcinoma.The use of low-dose-rate (LDR) brachytherapy (BT) for cervical cancer is being phased out and replaced by either high-dose-rate (HDR) or pulsed-dose-rate (PDR) BT [1–4]. At the Christie Hospital in Manchester, UK, PDR has been implemented in place of LDR for the BT component of a combined external beam (EB) and BT treatment of cervical carcinoma [4]. The Groupe Europeen de Curietherapie–European Society for Radiotherapy & Oncology (GEC-ESTRO) recommendations [5] were used to calculate the equivalent prescribed doses of PDR BT compared with those of the formerly used LDR-BT protocol [6]. Those guidelines use generic values of linear-quadratic parameters and monophasic repair kinetics. For the organs at risk (OARs), biphasic repair has become a more accurate characterisation of the repair kinetics. This is based on clinical evidence of a slow repair component for skin telangiectasia [7], oral mucosa [8] and subcutaneous fibrosis [9]. There is also more detailed knowledge of the two fast and slow components for clonogenic cells in mouse kidney [10], rat spinal cord paralysis [11], mouse pneumonitis [12,13] and pig skin early reactions [14].PDR BT uses cycles (or pulses) of 0.5–1.0 Gy given usually at 1–1.5-h intervals, and dose distributions using PDR or LDR can be made virtually identical [15]. It was shown that 1 Gy cycles at intervals of 1–3 h (varied among animal studies) resulted in similar biological effects from the same total doses delivered continuously at 0.50–0.75 Gy per hour. Higher doses per cycle and different cycle intervals resulted in deviations from equivalence because of biphasic repair, in particular for late-reacting tissues [16,17]. The therapeutic ratio of PDR vs LDR depends on cycle dose size and interval and tissue repair characteristics [α/β ratios and repair half-times (T_1/2)]. In normal tissues with a T_1/2<0.5-h component, PDR may be more damaging than LDR [18], but the effect should be reduced if the dose per cycle is <1 Gy [16,19].The present study reports calculations of LDR-equivalent PDR doses using biphasic vs monophasic repair kinetics for both the tumour and for the OAR, and the consequent implications.     

The challenge of segmental small bowel motility quantitation using MR enterography

Objective:

Analysis of “cine” MRI using segmental regions of interest (ROIs) has become increasingly popular for investigating bowel motility; however, variation in motility in healthy subjects both within and between scans remains poorly described.

Methods:

20 healthy individuals (mean age, 28 years; 14, males) underwent MR enterography to acquire dynamic motility scans in both breath hold (BH) and free breathing (FB) on 2 occasions. Motility data were quantitatively assessed by placing four ROIs per subject in different small bowel segments and applying two measures: (1) contractions per minute (CPM) and (2) Jacobian standard deviation (SD) motility score. Within-scan (between segment) variation was assessed using intraclass correlation (ICC), and repeatability was assessed using Bland–Altman limits of agreement (BA LoA).

Results:

Within-scan segmental variation: BH CPM and Jacobian SD metrics between the four segments demonstrated ICC R = 0.06, p = 0.100 and R = 0.20, p = 0.027 and in FB, the CPM and Jacobian SD metrics demonstrated ICC R = −0.26, p = 0.050 and R = 0.19, p = 0.030. Repeatability: BH CPM for matched segments ranged between 0 and 14 contractions with BA LoA of ±8.36 and Jacobian SD ranged between 0.09 and 0.51 with LoA of ±0.33. In FB data, CPM ranged between 0 and 10 contractions with BA LoA of ±7.25 and Jacobian SD ranged between 0.16 and 0.63 with LoA = ±0.28.

Conclusion:

The MRI-quantified small bowel motility in normal subjects demonstrates wide intersegmental variation and relatively poor repeatability over time.

Advances in knowledge:

This article presents baseline values for healthy individuals of within- and between-scan motility that are essential for understanding how this process changes in disease.Dynamic “cine” MRI acquired during MR enterography is increasingly utilized to assess bowel motility in a range of conditions, notably inflammatory bowel disease and enteric dysmotility syndromes.^1–4 Analysis of the data remains primarily subjective in clinical routine, but the ability to apply quantitative techniques makes this a potentially powerful methodology to explore gastrointestinal physiology in disease as well as an emerging application as a biomarker for drug efficacy.^5–7Despite the growing literature, a consensus has yet to be reached as to the best method of quantitatively analysing small bowel data and indeed a range of motility metrics are proposed.^2,3,8–12 The most commonly used metric is the change in luminal diameter at a fixed anatomical position through the time series. By tracking bowel diameter, a characteristic curve can be produced with the number of contractions expressed per minute (CPM) to give an intuitive and broadly accepted metric for small bowel motility (SBM).^{2–4,9,11,13–15} To date, several studies have reported a relationship between CPM and dysmotility in disease, either compared with a histopathological standard or “normal” reference bowel loops.^2–4,12 An array of additional metrics derived both from bowel diameter measures and more abstract processing techniques have further been implemented with varying degrees of effectiveness in disease and health.^{2,4,5,8,10,14,16}Although intuitively attractive, the robustness of assessing overall enteric motility using only an isolated loop of bowel has received relatively little attention to date irrespective of the precise metric applied. It is unclear how representative the selected bowel loops are of overall SBM and if normal motility intrinsically differs between bowel segments, for example, between the jejunum and ileum. Furthermore, the repeatability of single loop metrics, even in normal individuals, is not well described, knowledge of which is vital if segmental analysis is to be used to diagnose, guide treatment and monitor enteric pathology.The purpose of this study is to explore segmental variation in SBM in healthy volunteers measured using two commonly reported small bowel metrics [CPM and Jacobian standard deviation (SD)] looking at (1) within-scan motility variation between different segments and (2) between-scan variation (repeatability) across two time points.     

Quantitative analysis of contrast-enhanced ultrasonography: differentiating focal nodular hyperplasia from hepatocellular carcinoma

Objective:

To explore the potential of quantitative analysis of contrast-enhanced ultrasonography (CEUS) in differentiating focal nodular hyperplasia (FNH) from hepatocellular carcinoma (HCC).

Methods:

34 cases of FNH and 66 cases of HCC (all lesions <5 cm) were studied using CEUS to evaluate enhancement patterns and using analytic software Sonoliver® (Image-Arena™ v.4.0, TomTec Imaging Systems, Munich, Germany) to obtain quantitative features of CEUS in the region of interest. The quantitative features of maximum of intensity (IMAX), rise slope (RS), rise time (RT) and time to peak (TTP) were compared between the two groups and applied to further characterise both FNH and HCC with hypoenhancing patterns in the late phase on CEUS.

Results:

The sensitivity and specificity of CEUS for diagnosis of FNH were 67.6% and 93.9%, respectively. For quantitative analysis, IMAX and RS in FNHs were significantly higher than those in HCCs (p<0.05), while RT and TTP in FNHs were significantly shorter (p<0.05). Both the 11 FNHs and 62 HCCs with hypo-enhancing patterns in the late phase were further characterised with their quantitative features, and the sensitivity and specificity of IMAX for diagnosis of FNH were 90.9% and 43.5%, RS 81.8% and 80.6%, RT 90.9% and 71.0%, and TTP 90.9% and 71.0%, respectively.

Conclusion:

The quantitative features of CEUS in FNH and HCC were significantly different, and they could further differentiate FNH from HCC following conventional CEUS.

Advances in knowledge:

Our findings suggest that quantitative analysis of CEUS can improve the accuracy of differentiating FNH from HCC.Dynamic contrast-enhanced ultrasonography (CEUS) has noticeably improved the detection and characterisation of focal liver lesions during the past decade [1]. The enhancement patterns of the lesion are evaluated in three vascular phases (the hepatic arterial, portal venous and late phases), where the hepatic arterial phase provides information on the degree and pattern of vascularity and the portal venous and late phases provide important information on the differention between benign and malignant liver lesions [1]. A previous study has shown that CEUS using SonoVue® (Bracco, Milan, Italy) and spiral-CT provides similar diagnostic accuracy in the characterisation of focal liver lesions [2].The typical enhancement of focal nodular hyperplasia (FNH) on CEUS showed hyperenhancement in the three vascular phases with a stellate vascular and centrifugal enhancement in the arterial phase or a hypoenhancing central scar in the late phase [1, 3–5]. However, these features have not been observed in all cases of FNH, particularly in small lesions. A study on FNH showed that 3 out of 13 lesions (23.1%) were hypoenhancing in the late phase [6] and 3 out of 10 lesions <3 cm had spoke-wheel patterns and 2 had central scars [4]. There is also a broad variation of stellate vascular enhancement in FNHs with a range from 27.3% to 73.3% and of central scar with a range from 36.4% to 63.3% [3–5]. Thus, it can be difficult to differentiate atypical FNHs from other hypervascular malignant tumours, such as hepatocellular carcinoma (HCC), and hypervascular metastases [3]. Furthermore, a hypoenhancing central scar has been described in fibrolamellar HCC and sclerosing or scirrhous HCC [7, 8], and a central feeding artery with spoke-wheel sign has also been described in two scirrhous HCCs [8]. Hence, a comprehensive approache rather than simply estimating the haemodynamics could be beneficial for differential diagnosis.The current low-mechanical-index techniques for CEUS are capable of real-time demonstration of continuous haemodynamic changes in both the liver and hepatocellular nodules, from which time–intensity curves can be obtained by means of analytic software and then a series of semi-quantitative perfusion measurements extracted and analysed [9–11]. This method has shown a possible benefit in diagnosing FNH by enabling analysis of the quantitative parametric curves of the five types of hypervascular liver lesions [9]. In the present study, CEUS was applied to evaluate enhancing patterns of FNH and HCC; quantitative features of CEUS in the two groups were generated with the analytic software Sonoliver® (TomTec Imaging Systems, Germany) and compared to explore their potential in the differential diagnosis. Furthermore, the quantitative analysis of CEUS was used to characterise both FNH and HCC with hypoenhancing patterns in the late phase on CEUS.     

Obscure gastrointestinal bleeding: diagnostic performance of 64-section multiphase CT enterography and CT angiography compared with capsule endoscopy

Objective:

To compare the diagnostic capabilities between capsule endoscopy (CE) and multislice CT (MSCT) enterography in combination with MSCT angiography for assessment of obscure gastrointestinal bleeding (OGIB).

Methods:

A total of 127 patients with OGIB were looked at in this study. 82 patients (aged 42.7 ± 19.1 years; 34 males) were assigned to receive MSCT diagnosis and 67 patients to (aged 53.9 ± 16.2 years; 28 males) receive CE diagnosis. Among them, 22 patients (aged 54.1 ± 19.1 years; 12 males) received both examinations. Oral isotonic mannitol and intramuscular injection of anisodamine were performed; non-ionic contrast (iopromide, 370 mg I ml⁻¹) was intravenously administered; and then multiphase scanning was conducted at arterial, small intestinal and portal venous phases in MSCT. The results were compared with findings of reference standards including double balloon enteroscopy, digital subtraction angiography, intraoperative pathological examination and/or clinical diagnosis.

Results:

Administration of anisodamine markedly increased the satisfaction rate of bowel filling (94.67% vs 28.57%; p < 0.001) but not the diagnostic yield (p = 0.293) of MSCT. Compared with MSCT, CE showed an improved overall diagnostic yield (68.66% vs 47.56%; p = 0.010), which was also observed in overt bleeding patients (i.e. patients with continued passage of visible blood) (76.19% vs 51.02%; p = 0.013) and in patients aged younger than 40 years of age (85% vs 51.28%; p = 0.024). However, CE had similar positive rates to MSCT (p > 0.05). Among the 22 cases in whom both examinations were conducted, CE showed no significantly different diagnostic capability compared with MSCT (p = 0.4597).

Conclusion:

Both CE and MSCT are safe and effective diagnostic methods for OGIB.

Advances in knowledge:

CE is preferred for overt bleeding or patients aged younger than 40 years. The combined use of CE and MSCT is recommended in OGIB diagnosis.Obscure gastrointestinal bleeding (OGIB), which accounts for approximately 5% of all gastrointestinal haemorrhage cases,¹ is defined as persistent or recurring gastrointestinal bleeding without an obvious aetiology after gastroduodenoscopy and colonoscopy.^2,3 Based on the presence or absence of clinically evident bleeding, OGIB could be divided into occult (no visible blood) and overt (continued passage of visible blood, such as haematemesis, melaena or haematochezia) bleeding.^3,4 OGIB frequently occurs in the small bowel and is caused by small bowel diseases such as intestinal erosions, ulcers, vascular anomaly, gastrointestinal tumours and inflammatory bowel and parasitic diseases.^5,6Multiple diagnostic techniques have been developed to elucidate the causes of OGIB. Among them, two non-invasive technologies, capsule endoscopy (CE) and multislice CT (MSCT) markedly improved the ability to determine the causes of OGIB by allowing the visualization of the gastrointestinal tract.^2,3,6 CE is able to obtain direct visualization of mucosal surface of the entire small intestine.^4,7,8 However, capsule retention remains a major risk of CE diagnosis.^4,9–11 In addition, the visual field restriction limits the value of CE in diagnosis of umbilicate or extraluminal lesions, since the small bowel is difficult to evaluate owing to its large length and tortuous course.^4,10 Conversely, MSCT, including MSCT angiography (MSCTA), MSCT enteroclysis and MSCT enterography (MSCTE), has full capacity to depict the extraintestinal lesions, owing to the combination of the advantages of enteral volume challenge with the ability of cross-sectional imaging.^4,12 Yet, substantial patient radiation exposure is one of the major disadvantages of MSCT diagnosis.^3,13 Careful preparation is also needed before examination.¹⁴ Considering that both CE and MSCT have advantages and disadvantages, a limited number of published data have compared the two diagnostic tools in patients with OGIB.^4,6,15–17 However, most of these studies did not refer to MSCTA, and apparently different results were obtained owing to the advancement of the two technologies. Thus, an updated and comprehensive comparison is required.Hence, we compared the diagnostic capability of MSCTE in combination with MSCTA with CE in patients suffering from OGIB. In this study, MSCTE and MSCTA technologies performed with a 64-slice spiral CT scanner were combined by non-contrast-enhanced scanning after oral administration of a neutral enteric contrast material (isotonic mannitol, 2.5%) and the intramuscular injection of anisodamine to restrain enterocinesia, and the following multiphase scanning at arterial, small intestinal and portal venous phases followed the intravenous infusion of non-ionic iodinated contrast material (iopromide, 370 mg I ml⁻¹). In addition, the influences of the clinical bleeding pattern and age on the diagnostic capability were also investigated.     

Femoral neck shaft angle width is associated with hip-fracture risk in males but not independently of femoral neck bone density

Objective:

To investigate the specificity of the neck shaft angle (NSA) to predict hip fracture in males.

Methods:

We consecutively studied 228 males without fracture and 38 with hip fracture. A further 49 males with spine fracture were studied to evaluate the specificity of NSA for hip-fracture prediction. Femoral neck (FN) bone mineral density (FN-BMD), NSA, hip axis length and FN diameter (FND) were measured in each subject by dual X-ray absorptiometry. Between-mean differences in the studied variables were tested by the unpaired t-test. The ability of NSA to predict hip fracture was tested by logistic regression.

Results:

Compared with controls, FN-BMD (p < 0.01) was significantly lower in both groups of males with fractures, whereas FND (p < 0.01) and NSA (p = 0.05) were higher only in the hip-fracture group. A significant inverse correlation (p < 0.01) was found between NSA and FN-BMD. By age-, height- and weight-corrected logistic regression, none of the tested geometric parameters, separately considered from FN-BMD, entered the best model to predict spine fracture, whereas NSA (p < 0.03) predicted hip fracture together with age (p < 0.001). When forced into the regression, FN-BMD (p < 0.001) became the only fracture predictor to enter the best model to predict both fracture types.

Conclusion:

NSA is associated with hip-fracture risk in males but is not independent of FN-BMD.

Advances in knowledge:

The lack of ability of NSA to predict hip fracture in males independent of FN-BMD should depend on its inverse correlation with FN-BMD by capturing, as the strongest fracture predictor, some of the effects of NSA on the hip fracture. Conversely, NSA in females does not correlate with FN-BMD but independently predicts hip fractures.Hip fracture is the worst osteoporotic fracture with regard to cost^1,2 and adverse consequences,^3,4 so its prevention by checking for the related fracture risk factors is an important goal. Although low bone mineral density (BMD) is generally recognized as the main risk factor for hip fracture,^5,6 there is growing evidence that other bone characteristics, such as proximal femur geometry (PFG) parameters, are implicated in determining the risk profile for hip fracture.^7,8 This evidence, however, mainly derives from studies carried out in females,^9–13 whereas contradictory results characterize studies carried out in males.^14–20 Authors'' opinions seem to vary widely about the ability of the neck shaft angle (NSA), one of the PFG factors, to predict osteoporotic hip fractures in males,^14–16,21 whereas its association with the risk of hip fracture in females^10,11,14,22 is generally accepted. Gender differences in the hip anatomy²³ have been put forward as a possible explanation for the different relationship of NSA with the hip-fracture risk between genders, whereas geographic and racial differences²⁴ among the examined male populations have been advocated as a possible cause of authors'' discrepancies on the relationship between NSA and the hip-fracture risk in males.This topic is therefore still under debate, and further studies are required to clarify the association of the NSA with hip-fracture risk in males. The authors of the current study contribute to this topic by studying the relationship between NSA and the hip fragility fracture in a sample of white Italian males.     

Multimodality imaging of obliterative portal venopathy: what every radiologist should know

Obliterative portal venopathy (OPV) is an important cause of non-cirrhotic portal hypertension, which is often erroneously misdiagnosed as cryptogenic cirrhosis. It has a worldwide distribution with majority of cases hailing from the Asian subcontinent. However, recently the disease has gained global attention particularly because of its association with human immunodeficiency virus infection and use of antiretroviral drug therapy (didanosine). As the name suggests, the disorder is characterized by sclerosis and obliteration of the intrahepatic portal vein branches (with attendant periportal fibrosis) leading to portal hypertension amid intriguingly little liver dysfunction. It primarily affects young adults who present with clinically significant portal hypertension in the form of episodes of variceal bleed; however, contrasting liver cirrhosis, the liver function and liver structure remain normal or near normal until late in the disease process. Radiological findings during advanced disease are often indistinguishable from cirrhosis often warranting a liver biopsy. Nevertheless, recent studies have suggested that certain imaging manifestations, if present, can help us to prospectively suggest the possibility of OPV. At imaging, OPV is characterized by a wide range of intrahepatic and/or extrahepatic portal venous abnormalities with attendant changes in liver and splenic volume and stiffness. We shall, through this pictorial review, appraise the literature and illustrate the germane radiological manifestations of OPV that can be seen using different imaging modalities including ultrasonography, CT, MRI, elastography and hepatic haemodynamic studies.It is important to recognize that not all varices mean liver cirrhosis. Although liver cirrhosis constitutes the commonest cause of portal hypertension, we should be aware that portal hypertension can occur in the absence of liver cirrhosis—a condition termed as non-cirrhotic portal hypertension (NCPH).^1,2 NCPH represents a heterogeneous group of (primarily vascular) disorders where portal hypertension manifests amid absent liver cirrhosis. Pathologically, the insult is either pre- or intrahepatic involving the main portal vein or its smaller branches and/or the perisinusoidal area.^1–3Obliterative portal venopathy (OPV) represents an important cause of NCPH that is characterized by sclerosis and obliteration of the medium-sized portal venous branches leading to portal hypertension.^1–10 Liver biopsy characteristically shows phlebosclerosis and periportal and perisinusoidal fibrosis amid absent cirrhosis (Figure 1).^1–3 Although, the exact aetiology is contentious, infections and prothrombotic states have been implicated in eastern and western patients, respectively.^1,2 Additionally, xenobiotic exposure, autoimmune and genetic factors have also been incriminated.^1–4 Although the disease has a worldwide distribution, it continues to remain poorly understood primarily owing to its relative rarity.^1–3,5–8 Another potential reason is the use of diverse terminologies under which the entity has been described from various parts of the globe, such as non-cirrhotic portal fibrosis in India, idiopathic portal hypertension in Japan and hepatoportal sclerosis in the USA.Open in a separate windowFigure 1.(a) Atrophic small portal tract (arrow) showing absent portal vein [haematoxylin and eosin stain (HE), ×200]. (b) Two small portal tract (arrows) approximations (×100, HE). (c) Portal and central vein approximation (×100, HE). (d) Parenchymal extinction suggested by portal–portal and portal–central approximation (Masson''s trichrome stain, ×200).More recently, the disease has gained global attention because of escalating number of cases being reported in human immunodeficiency virus (HIV)-infected patients.^1–3,8–10 Also, US Food and Drug Administration has recently issued a warning regarding the potential association of OPV in patients with HIV on didanosine (antiretroviral therapy).³OPV primarily affects young patients usually in their third or fourth decades of life. The affected individuals typically present with clinically significant portal hypertension characterized by multiple episodes of well-controlled upper gastrointestinal (GI) bleed, massive splenomegaly and/or hypersplenism.^1–3 Advanced stages of the disease are often indistinguishable from liver cirrhosis especially on imaging. However, discrimination from cirrhosis is crucial in clinical practice because of differences in management. Management of OPV is primarily symptomatic, that is, focused on management of an acute episode of variceal bleed. The risk of rebleeding and bleeding-related mortality is low. Intriguingly, in contrast to liver cirrhosis, the liver function and liver structure remain normal or near normal until late in the disease process leading to a better prognosis and higher survival rates; the 10-year survival rate is around 86–95%.^1,2 Development of jaundice, ascites and hepatic encephalopathy is uncommon and if at all is seen only after an episode of GI bleeding.^1,2 Liver failure and the incidence of developing hepatocellular carcinoma are also much lower.^1–3,8–10 Nonetheless, in 20–33% of patients, the liver gradually atrophies and shows functional decompensation, occasionally needing liver transplantation.^1,2Although limited literature is available on the radiological manifestations of OPV, recent studies have suggested certain imaging manifestations to be more prevalent in OPV that can allow discrimination from cirrhosis. Moreover, use of newer techniques, including transient elastography, can allow prospective non-invasive diagnosis of OPV based upon the differential changes in liver and splenic stiffness. The aim of this review is to appraise the imaging findings of OPV described in the literature and illustrate them across a wide array of imaging modalities, including ultrasonography, CT, MRI and elastography, in a group of biopsy-proven cases of OPV diagnosed at our institute.     

Contrast-enhanced ultrasonography of hepatocellular carcinoma: correlation between quantitative parameters and histological grading

Objective

The quantitative parameters in the contrast-enhanced ultrasonography time–intensity curve of hepatocellular carcinoma (HCC) were studied to explore their possible implication for histological grading of HCC.

Methods

A total of 130 HCC patients (115 males and 15 females; age: 48.13±11.00 years) were studied using contrast-enhanced ultrasonography time–intensity curve and histological pathology. The quantification software Sonoliver® (TomTec Imaging Systems, Unterschleissheim, Germany) was applied to derive time–intensity curves of regions of interest in the interior of HCCs and in reference. Quantitative parameters of 115 patients were successfully obtained, including maximum of intensity (IMAX), rise time (RT), time to peak (TTP), rise slope (RS) and washout time (WT). Histological grading of HCC was performed using haematoxylin–eosin staining, and monoclonal antibodies specific for smooth muscle actin were used to observe unpaired arteries (UAs).

Results

There were significant differences among WTs in the three differentiated HCC groups (p<0.05). However, there were no significant differences among RT, TTP, RS and IMAX in the differentiated HCC groups. Moreover, the number of UAs in the differentiated HCC groups showed no statistical significance.

Conclusion

WT plays an important role in predicting well, moderately and poorly differentiated HCC.The majority of hepatocellular carcinomas (HCCs) develop through multistep hepatocarcinogenesis [1]. Various types of hepatocellular nodules are seen in cirrhotic livers. The International Working Party of the World Congress of Gastroenterology classifies hepatocellular nodules into six types: regenerative nodules, low-grade dysplastic nodules, high-grade dysplastic nodules, well-differentiated HCC, moderately differentiated HCC and poorly differentiated HCC. The histopathological grades and types constitute well-established prognostic factors [2]. Thus, early diagnosis and confirmation of the type of hepatocellular nodules present and cellular differentiation before treatment are important.Although definite differentiation among HCC by imaging is usually impossible, the relationship between tumour cellular differentiation and image findings has been studied using contrast-enhanced (CE) CT, CEMRI and CE ultrasonography (CEUS). Tumour pathological differentiation correlates well with image findings [,3−8].Dynamic CEUS during the past decade has noticeably improved the detection and characterisation of focal liver lesions [9]. A previous study showed that CEUS and spiral CT provided a similar diagnostic accuracy in the characterisation of focal liver lesion [10]. The appearance of HCC on CEUS has also been described well. Current low-mechanical-index techniques for CEUS using second-generation microbubble agents have advantages in characterising HCC, including real-time demonstration of continuous haemodynamic changes in both the liver and hepatocellular nodules. Some studies postulated that variations of enhancement patterns may be related to the pathological function of HCC [,5−8]. Moderately differentiated HCCs generally show classic enhancement features, with presence of hypervascularity in the arterial phase and washout during the portal phase, whereas well and poorly differentiated tumours account for most atypical variations in the arterial phase and portal venous phase [7].Reports assessing hepatocellular nodules have been based on visual analysis, despite the disadvantages of interobserver variability and low reproducibility of results. Although quantitative analysis CEUS perfusion provides more objective, reliable and reproducible results [11], the time–intensity curve (TIC) of CEUS has been obtained by quantification software for offline analysis [,12−14], from which a series of semi-quantitative perfusion parameters is extracted and analysed. An analysis of the parameters of TIC in HCC has proven the correlation of CEUS with unpaired arteries (UAs) in HCC [14]. In the present study, we compare the quantitative parameters in CEUS and UAs in different pathological gradings of HCCs to explore their possible implication for histological grading of HCC.     

Walking on thin ice! Identifying methamphetamine “drug mules” on digital plain radiography

Objective:

The purpose of this study was to retrospectively evaluate the sensitivity, specificity and accuracy of identifying methamphetamine (MA) internal payloads in “drug mules” by plain abdominal digital radiography (DR).

Methods:

The study consisted of 35 individuals suspected of internal MA drug containers. A total of 59 supine digital radiographs were collected. An overall calculation regarding the diagnostic accuracy for all “drug mules” and a specific evaluation concerning the radiological appearance of drug packs as well as the rate of clearance and complications in correlation with the reader''s experience were performed. The gold standard was the presence of secured drug packs in the faeces.

Results:

There were 16 true-positive “drug mules” identified. DR of all drug carriers for Group 1 (forensic imaging experienced readers, n = 2) exhibited a sensitivity of 100%, a mean specificity of 76.3%, positive predictive value (PPV) of 78.5%, negative predictive value (NPV) of 100% and a mean accuracy 87.2%. Group 2 (inexperienced readers, n = 3) showed a lower sensitivity (93.7%), a mean specificity of 86%, a PPV of 86.5%, an NPV of 94.1% and a mean accuracy of 89.5%. The interrater agreement within Group 1 was 0.72 and within Group 2 averaged to 0.79, indicating a fair to very good agreement.

Conclusion:

DR is a valuable screening tool in cases of MA body packers with huge internal payloads being associated with a high diagnostic insecurity. Diagnostic insecurity on plain films may be overcome by low-dose CT as a cross-sectional imaging modality and addressed by improved radiological education in reporting drug carriers on imaging.

Advances in knowledge:

Diagnostic signs (double-condom and halo signs) on digital plain radiography are specific in MA “drug mules”, although DR is associated with high diagnostic insecurity and underreports the total internal payload.For the past decade, significant worldwide manufacturing of amphetamine-type stimulants has been reported to the United Nations Office on Drugs and Crime, Vienna, Austria, with a predominance of methamphetamine (MA) and its derivatives, which are also known as “syabu” or “ice”, throughout East and South East Asia.¹ In this region, the use of this synthetic drug is more prevalent than that of cocaine or heroin, which are more common in relatively developed areas, such as Europe and the USA.² During the course of this development, an increase in the number of drug carriers being intercepted by law enforcement at the borders of Malaysia has been observed. Drug carriers or “drug mules” are generally referred to as a human harbouring internal illicit drug packet(s). Internal body concealment of illegal drugs is one of the methods used to smuggle this illicit drug across the border.^3,4 “Drug mules” are generally known as body packers.^5,6 However, for correct terminology, one should differentiate between the terms body packer, body pusher and body stuffer. A body packer swallows a large amount of specially prepared drug packets to smuggle the packets in their gastrointestinal tract across a national border.^5,6 A body pusher hides a few containers in easily accessible body cavities, such as the rectum or vagina. Body stuffers, including traffickers and users, ingest intentionally small amounts of loosely wrapped drug pellets (typically initially hidden in the mouth), usually immediately before an unexpected encounter with law enforcement.^5–10The generally accepted radiological examination is a plain abdominal radiograph in the supine projection.^4–6 This technique is widely available at a low cost and is a simple method of detecting drug-filled packets within the alimentary tract. Radiation exposure to the patient is relatively moderate. In the literature, the detection rate for drug-filled packets is highly variable, and sensitivities from 58.3% to 90% have been reported.^4,5,11 Hence, plain abdominal radiography is a flawed screening method for identifying “drug mules”. Examining the bowel for foreign bodies, such as drug containers with variable sizes and radiodensities, is problematic, even for an experienced radiologist because the drug-filled packets may have an appearance similar to that of stool and gas and may be superimposed. Specific appearances described in the literature, such as the “double-condom”, “halo” and “rosette” signs, may be diagnostic for drug packages but are not necessarily so.^{4–6,11–13} Other modalities employed worldwide for the identification of body packers include CT, ultrasound, MRI and low-dose linear slit digital radiography (LSDR or LODOX®; Lodox Systems, Johannesburg, South Africa).^4,5,14–18Recent research has mainly concentrated on cocaine and heroin drug trafficking, which occurs predominantly in Western countries.^{3,4,6,7,11,14,19} There is little research on the accuracy of plain abdominal radiography in MA drug carriers, although there has been a significant increase of MA in Asia, accompanied by draconian legal measures in cases of drug trafficking.^1,2 The purpose of this study was to retrospectively evaluate the sensitivity, specificity and accuracy of plain abdominal digital radiography (DRL) for identifying the internal payloads of MA in “drug mules”.     

125I particle implantation combined with chemoradiotherapy to treat advanced pancreatic cancer

Objective:

To evaluate the therapy effects of ¹²⁵I implantation combined with chemoradiotherapy on pancreatic cancer patients.

Methods:

30 patients with Stage III or IV pancreatic cancer were equally divided into two groups (control and treatment group). The patients in the treatment group (nine males, six females) received chemotherapy in the first week and ¹²⁵I implantation in the third week, followed by combined chemoradiotherapy in the fifth week. The patients in the control group (10 males, 5 females) received the same treatment except ¹²⁵I implantation. The therapy in the control group and treatment group was repeated every 4 weeks.

Results:

The median conformal radiotherapy dose in the treatment group (30.62 Gy) was significantly lower than that in the control group (47.86 Gy). The total radiation dose was 88.71 ± 27.39 Gy, and the surface activity was 0.6 mCi in the treatment group. After treatment, the average tumour size decreased both in the treatment group [9.17 cm², 95% confidence interval (CI): 5.60–12.74, p < 0.001] and in the control group (4.54 cm², 95% CI: 2.74–6.35, p < 0.001). The median survival time in the treatment group was 14 months (95% CI: 12.215–14.785) and in the control group was 12 months (95% CI: 10.884–13.116). There was no statistical significance in survival rates between the two groups (χ² = 0.908, p = 0.341).

Conclusion:

¹²⁵I implanted into tumour combined with chemoradiotherapy has higher local control rate of advanced pancreatic cancer than chemoradiotherapy.

Advances in knowledge:

We combined chemoradiotherapy with ¹²⁵I implantation to treat advanced pancreatic cancer and obtained a higher local control rate and better quality of life than when using chemoradiatherapy alone.Pancreatic cancer is currently one of the most intractable cancers with high and continually rising mortality in China.¹ The main risk factors are smoking, age and some genetic disorders, although the primary causes are poorly understood.² Pancreatic cancer causes no early symptoms, so the majority of patients are diagnosed as having advanced cancer with rapid progression when they come to the hospital.³ Thus, patients miss the opportunity for tumour resection when first diagnosed. Even if the cancer is discovered early, only 20% of patients can undergo surgical excision, whereas the other 80% cannot.² For patients who have undergone radical excision, the 5-year survival rate is just 20–25%.^4–9Advanced pancreatic cancer, according to the TNM stage of pancreatic carcinoma by the American Joint Committee on Cancer (AJCC),¹⁰ includes Stages III and IV, and pancreatectomy is not well accepted.¹¹ It is reported that approximately 40% of pancreatic cancer patients present with locally advanced, non-metastatic disease.¹² Local lesions play a vital role in a patient''s survival.^13–16 The aim of advanced pancreatic cancer treatment is to enhance local lesion control and improve the quality of life (QOL).^17,18Gemcitabine is a type of pyrimidine analogue, which acts as a ribonucleoside reductase inhibitor and destroys cells and terminates the DNA chains. It has been approved by the US Food and Drug Administration as a gold standard agent in chemotherapy¹⁹ for the treatment of cancer, especially for advanced pancreatic cancer.²⁰ Currently, the major therapy is comprehensive treatment, namely chemoradiotherapy, which is superior to either radiotherapy²¹ or chemotherapy.²² But the overall survival time is not prolonged by chemoradiotherapy in advanced pancreatic cancer compared with single-agent gemcitabine.²³ The 5-year survival rate is still <5%.²⁴ However, interstitial implantation of radioactive seeds (brachytherapy) combined with conformal radiotherapy (external beam radiation therapy) has a good effect for local control of pancreatic cancer.^{25,26 125}I particles are reported to be the most commonly used for brachytherapy because of their long half-life and short radiation distance.²⁷ Therefore, we infer that ¹²⁵I implantation combined with chemoradiation may obtain better curative effects.In this study, we compared the local control rate, pain relief and survival rate of 30 patients with advanced pancreatic cancer who were treated with or without ¹²⁵I implantation combined with chemoradiotherapy in our hospital during October 2006 to January 2012. We expected that the implantation of ¹²⁵I particles could be an efficient therapy for patients with advanced pancreatic cancer.     

Embolisation of the right gastric artery in patients undergoing hepatic arterial infusion chemotherapy using two possible approach routes

We used a retrospective non-randomised study to investigate the clinical effect of selective embolisation of the right gastric artery before hepatic arterial infusion chemotherapy (HAIC) using a port-catheter system. We evaluated whether the hepatic artery or the left gastric artery is the better approach for selecting the right gastric artery. A total of 367 patients (244 men and 123 women; mean age, 64.1 years) with unresectable advanced liver cancer underwent percutaneous implantation of a port-catheter system. In 294 of these patients, right gastric arterial embolisation with microcoils was attempted before placement of the port-catheter system to prevent gastric mucosal lesions. Approach was either through the hepatic artery (175 patients) or through the left gastric artery (119 patients), with success rates in catheterising the right gastric artery of 78.3% and 77.3%, respectively. If the attempt was unsuccessful, the catheter was redirected to the alternative approach, which increased the final success rate to 96.3%. Only seven patients experienced gastroduodenal mucosal lesions acutely after HAIC, as revealed by endoscopy. Embolisation of the right gastric artery is a feasible procedure that can reduce the incidence of gastric mucosal lesions associated with HAIC. Approach through either the hepatic artery or the left gastric artery is equally acceptable.Long-term hepatic arterial infusion chemotherapy (HAIC) via an implanted port-catheter system is a treatment option for patients with unresectable advanced liver cancer [1, 2]. In the past, such catheter placement was done by surgical laparotomy under general anaesthesia [3–6], an invasive procedure. However, recent advances in interventional techniques allow the implantation of port-catheter systems percutaneously under local anaesthesia [7–14].A frequent complication is reactive gastric or duodenal mucosal lesions, which result from chemical irritation caused by infusion of chemotherapeutic agents into adjacent organs through arteries originating from the common hepatic artery [15–24]. One such complication is a gastric mucosal lesion caused by inflow of chemotherapeutic agents into the right gastric artery [15–24]. To prevent this complication, the efficacy of selectively embolising the right gastric artery with coils at the time of implantation of the port-catheter system has been noted [21, 25–27].In many cases, however, the right gastric artery is slender and angulated, with anatomical variations [26, 28–31]. Hence, it is occasionally difficult to insert a catheter selectively into the right gastric artery by antegrade catheterisation via the site of the hepatic artery. This is the approach most commonly used by interventional radiologists. Failure to embolise the right gastric artery can result [26]. As an alternative method, a retrograde approach to the right gastric artery via the left gastric artery has been introduced [32, 33].Because HAIC with an implanted port-catheter system is performed in a relatively large number of cases in our institution, we have many opportunities to embolise the right gastric artery using both approaches. The aim of the present retrospective non-randomised study, which included a large number of subjects, was to evaluate the usefulness of right gastric arterial embolisation and to determine whether the antegrade or retrograde approach is more useful.     

Differentiating benign and malignant salivary gland tumours: diagnostic criteria and the accuracy of dynamic contrast-enhanced MRI with high temporal resolution

Objective:

To determine the optimal diagnostic criterion of dynamic contrast-enhanced MRI (DCE-MRI) for predicting salivary gland malignancy using a dynamic sequence with high temporal resolution, as well as the accuracy of this technique.

Methods:

The DCE-MRI findings of 98 salivary gland tumours (74 benign and 24 malignant) were reviewed. MR images were sequentially obtained at 5-s intervals for 370 s. Two parameters, peak time and washout ratio (WR) were determined from the time–signal intensity curve. The optimal thresholds of these parameters for differentiating benign and malignant tumours were determined, along with the diagnostic accuracy of the criterion using these thresholds.

Results:

A peak time of 150 s and a WR of 30% were identified as optimal thresholds. As the criterion for malignancy, the combination of peak time <150 s and WR <30% provided a sensitivity of 79% (19/24), specificity of 95% (70/74) and an overall accuracy of 91% (89/98). Three of the five false-negative cases were malignant lymphomas of the parotid gland.

Conclusion:

Peak time <150 s with WR <30% comprised the optimal diagnostic criterion in predicting salivary gland malignancy, providing a sensitivity of 79% and specificity of 95%. The use of high temporal resolution might improve the accuracy of DCE-MRI.

Advances in knowledge:

Although several studies have reported the usefulness of DCE-MRI in the differential diagnosis of salivary gland tumours, the specific diagnostic criteria employed have differed widely. We determined the optimal criterion and its accuracy using a dynamic sequence with high temporal resolution.Salivary gland tumours account for approximately 3% of all tumours.¹ They can arise from any salivary gland, although the majority occur in the parotid gland.² Pre-operative differential diagnosis between benign and malignant salivary gland tumours is very important because the results strongly affect surgical treatment planning. Among various imaging techniques, MRI is now the modality of choice for evaluation of suspected salivary gland tumours.^3,4 Owing to its superb contrast resolution and multiplanar facilities, MRI can clearly identify a tumour''s exact location and extent, as well as its relationship with neighbouring structures. On the other hand, the sensitivity of conventional MRI in predicting malignancy is known to be quite low.^5–7Several researchers reported that time–signal intensity curves (TICs) obtained by dynamic contrast-enhanced MRI (DCE-MRI) were useful in the differential diagnosis of salivary gland tumours and that the TIC characterized by early enhancement and low washout was associated with malignancy.^4,8–15However, the specific criteria involved, that is, the definition of and thresholds for the time to peak enhancement and the washout ratio (WR), have varied widely among studies. Thus, the efficacy of DCE-MRI in the differential diagnosis of salivary gland tumours has not yet been fully established. To obtain accurate TICs, a dynamic MRI sequence with high temporal resolution should be used.^6,16 However, the temporal resolution in most of the previous studies was relatively low (15–60 s),^{8–12,14,17–20} which may partly explain the inconsistencies between reports.In this study, we applied DCE-MRI with a temporal resolution of 5 s to 98 cases with salivary gland tumours. Our aims were to evaluate the TICs of these cases and to determine the optimal diagnostic criteria for DCE-MRI as well as its accuracy in differentiating benign from malignant salivary gland tumours.     

Diffusion-weighted MRI in the follow-up of chronic periaortitis

Objective:

To evaluate the usefulness of diffusion-weighted MRI (DWI) for the assessment of the intraindividual follow-up in patients with chronic periaortitis (CP) under medication.

Methods:

MRI data of 21 consecutive patients with newly diagnosed untreated disease were retrospectively examined before and after medical therapy, with a median follow-up of 16 weeks. DWI parameters [b800 signal, apparent diffusion coefficient (ADC) values] of the CP and psoas muscle were analysed together with the extent and contrast enhancement. Pre- and post-treatment laboratory inflammation markers were acquired parallel to each MR examination.

Results:

Statistically significant lower b800 signal intensities (p ≤ 0.0001) and higher ADC values (p ≤ 0.0001) were observed after medical treatment within the fibrous periaortic tissue. Extent and contrast enhancement of the CP showed also a statistically significant decrease (p ≤ 0.0001) in the follow-up examinations, while the control parameters within the psoas muscle showed no differences.

Conclusion:

DWI seems to be a useful method for the evaluation of response to treatment without contrast agents. The technique may be helpful in the assessment of disease activity to guide further therapeutic strategies.

Advances in knowledge:

DWI detects significant differences in the intraindividual follow-up of CP under medical therapy.Chronic periaortitis (CP) is a proliferating fibroinflammatory disease of the perivascular retroperitoneal space and aortic wall.^1–4 Owing to adventitial inflammation, some recent theories consider CP as a large vessel vasculitis.⁵ Clinical manifestations of CP include idiopathic retroperitoneal fibrosis, inflammatory aortic aneurysm and perianeurysmal retroperitoneal fibrosis.^2,6,7 The three manifestations with very similar histopathological characteristics are distinguished by the diameter of the abdominal aorta and concomitant ureteral affection.^1,3,7Specific clinical symptoms are caused by extrinsic compression of the ureters or retroperitoneal veins, resulting in hydronephrosis, oliguria, lower extremity oedema and deep vein thrombosis.^1,8Under medical treatment with steroids, CP has a good prognosis.⁷ Today tamoxifen is suggested as a safe and effective therapeutic alternative, and immunosuppressive drugs can be considered in patients with suboptimal responses to these drugs or multiple relapses.^9–11CT and MRI are the modalities of first choice for diagnosis and follow-up of CP.^1,7,12 The fibrotic para-aortic tissue shows significant contrast uptake in gadolinium-enhanced MRI.^12–14 Dynamic contrast-enhanced MRI was suggested for the assessment of the disease activity.^15,16 However, in cases with impaired renal function (e.g. by ureteral compression), gadolinium-independent imaging methods should be preferred owing to the potential development of a nephrogenic systemic fibrosis.¹⁷Diffusion-weighted MRI (DWI) is a non-contrast MR modality that has been successfully applied for the assessment of retroperitoneal masses, inflammatory abdominal aortic aneurysms and for the differentiation between retroperitoneal fibrosis and malignant retroperitoneal neoplasms.^18–21DWI indicates restricted diffusion of water, for example caused by a high cellularity in malignant disease or active inflammation. The apparent diffusion coefficient (ADC) is a quantitative parameter for the level of restricted diffusion, which is calculated from the signals of different diffusion gradients (b-values).²²In the context of untreated CP diffusion-weighted MRI may detect restricted inflammation as a sign of high cellularity caused by active inflammation.There are no data for the evaluation of intraindividual follow-up and the response to treatment by DWI of CP so far. Therefore, the aim of the present study was to analyse differences in DWI signals during follow-up in patients with CP before and after treatment. In addition, we sought to elucidate the potential of DWI in the therapy monitoring of CP.     

Switching bipolar hepatic radiofrequency ablation using internally cooled wet electrodes: comparison with consecutive monopolar and switching monopolar modes

Objective:

To evaluate whether switching bipolar radiofrequency ablation (SB-RFA) using three internally cooled wet (ICW) electrodes can induce coagulations >5 cm in porcine livers with better efficiency than consecutive monopolar (CM) or switching monopolar (SM) modes.

Methods:

A total of 60 coagulations were made in 15 in vivo porcine livers using three 17-gauge ICW electrodes and a multichannel radiofrequency (RF) generator. RF energy (approximately 200 W) was applied in CM mode (Group A, n = 20) for 24 min, SM mode for 12 min (Group B, n = 20) or switching bipolar (SB) mode for 12 min (Group C, n = 20) in in vivo porcine livers. Thereafter, the delivered RFA energy, as well as the shape and dimension of coagulations were compared among the groups.

Results:

Spherical- or oval-shaped ablations were created in 30% (6/20), 85% (17/20) and 90% (18/20) of coagulations in the CM, SM and SB groups, respectively (p = 0.003). SB-RFA created ablations >5 cm in minimum diameter (D_min) in 65% (13/20) of porcine livers, whereas SM- or CM-RFA created ablations >5 cm in only 25% (5/20) and 20% (4/20) of porcine livers, respectively (p = 0.03). The mean D_min of coagulations was significantly larger in Group C than in Groups A and B (5.1 ± 0.9, 3.9 ± 1.2 and 4.4 ± 1.0 cm, respectively, p = 0.002) at a lower delivered RF energy level (76.8 ± 14.3, 120.9 ± 24.5 and 114.2 ± 18.3 kJ, respectively, p < 0.001).

Conclusion:

SB-RFA using three ICW electrodes can create coagulations >5 cm in diameter with better efficiency than do SM- or CM-RFA.

Advances in knowledge:

SB-RFA can create large, regular ablation zones with better time–energy efficiency than do CM- or SM-RFA.Radiofrequency (RF) tumour ablation is increasingly being utilized as an alternative option in patients with unresectable primary and secondary liver malignancies.^1,2 In the treatment of small hepatocellular carcinomas (HCCs), RF ablation (RFA) has been shown to yield satisfactory local tumour control, with one study pathologically demonstrating complete tumour necrosis in 83% of HCCs <3 cm.³ Indeed, according to the recent Barcelona Clinic Liver Cancer staging and treatment strategy guidelines for HCCs, RFA is favoured over surgical resection for very early stage HCCs (single nodule <2 cm) in patients with Child–Pugh A liver cirrhosis.⁴ Furthermore, a recent systematic review paper by Cucchetti et al⁵ reported that for very early HCCs (single nodule <2 cm) in Child–Pugh Class A patients, RFA provided similar life expectancy and quality-adjusted life expectancy at a lower cost than did surgical resection.However, for single HCCs 3–5 cm in diameter, resection was shown to provide better life expectancy and to be more cost effective than RFA owing to high local tumour progression rates after RFA.^5–12 This is in large part owing to the limited ability of currently available RFA devices in creating a sufficiently large ablation zone encompassing HCCs 3–5 cm in diameter along with a safety margin.^7,11,13,14 Therefore, an ideal RFA system would provide the capability to create coagulations >5 cm in short-axis diameter within a reasonable time frame (<30 min) for the treatment of tumours >3 cm in diameter considering a sufficient safety margin (5–10 mm in thickness). Currently, multiple overlapping ablations are often used for the treatment of liver tumours >2 cm in order to cover the complete tumour volume as well as to create a 1-cm-thick peripheral ablation margin.^15,16 However, there is considerable technical difficulty in probe repositioning during overlapping ablations, especially under ultrasound guidance, owing to gas bubble formations, ultimately resulting in incomplete ablations.^17–19Recently, multiple-electrode RFA approaches, including the switching monopolar (SM) mode, bipolar mode and multipolar mode, have been attempted with each demonstrating efficiency in creating a larger ablation zone in liver tissue than in the standard monopolar RF technique.^2,20–26 Theoretically, RFA in switching bipolar (SB) mode using multiple electrodes should further improve the thermal and electronic efficiency of RFA devices compared to conventional monopolar modes. However, until now, the efficacy of SB-RFA with internally cooled wet (ICW) electrodes, which allow simultaneous internal cooling and saline infusion, in creating 3- to 5-cm coagulation areas, have not been tested in previous in vivo studies.Therefore, the purpose of this study was to evaluate whether SB-RFA using three ICW electrodes can induce coagulations >5 cm in diameter in porcine livers with better efficiency than consecutive monopolar (CM) or SM mode.     

Diffusion-weighted imaging vs STIR turbo SE imaging: capability for quantitative differentiation of small-cell lung cancer from non-small-cell lung cancer

Objective:

To compare the capability of differentiation of small-cell lung cancer (SCLC) from non-SCLC (NSCLC) between diffusion-weighted imaging (DWI) and short tau inversion recovery (STIR) turbo spin-echo imaging.

Methods:

The institutional review board of Kobe University Hospital, Kobe, Japan, approved this study, and written informed consent was obtained from each patient. 49 patients with NSCLC (30 males and 19 females; mean age, 66.8 years) and 7 patients with SCLC (5 males and 2 females; mean age, 68.6 years) enrolled and underwent DWI and STIR. To quantitatively differentiate SCLC from NSCLC, apparent diffusion coefficient (ADC) values on DWI and contrast ratios (CRs) between cancer and muscle on STIR were evaluated. ADC values and CRs were then compared between the two cell types by Mann–Whitney''s U-tests, and the diagnostic performances were compared by McNemar''s test.

Results:

There were significant differences of mean ADC values (p < 0.001) and mean CRs (p = 0.003). With adopted threshold values, the specificity (85.7%) and accuracy (85.7%) of DWI were higher than those of STIR (specificity, 63.3%; p = 0.001 and accuracy, 66.1%; p = 0.001). In addition, the accuracy of combination of both indexes (94.6%; p = 0.04) could significantly improve as compared with DWI alone.

Conclusion:

DWI is more useful for the differentiation of SCLC from NSCLC than STIR, and their combination can significantly improve the accuracy in this setting.

Advances in knowledge:

Pulmonary MRI, including DWI and STIR, had a potential of the suggestion of the possibility as SCLC.Lung cancer is the most common cause of cancer-related death among both males and females worldwide.¹ Lung cancers are divided into non-small-cell cancer (NSCLC) and small-cell lung cancer (SCLC), and the differentiation between SCLC and NSCLC is important in clinical practice because their therapeutic strategies, clinical course and prognoses are different.² In general, SCLC is usually determined with extensive hilar and mediastinal lymphadenopathy,³ and these cancers are mainly treated by chemotherapy or chemoradiotherapy.^2,4On the other hand, 5–10% of patients with SCLC were diagnosed as having solitary pulmonary nodules.^5,6 In this situation, the assessments of distant metastases before treatment play an important role in deciding the treatment. At present, although there are some different reports for patients with NSCLC regarding the assessment of distant metastases before surgery,^7–9 it is important to assess the distant metastases of these patients with SCLC because SCLC is known for its rapid doubling time, high growth fraction and early development of metastatic disease.^10–12 If patients with SCLC are diagnosed at Stage I or possibly Stage II, clinicians consider their treatment as surgery and/or neoadjuvant chemotherapy.^13–15 Therefore, the differentiation between SCLC and NSCLC and the suggestion of the possibility of SCLC may be important in routine clinical practice. However, the differentiation of SCLC from NSCLC is difficult on CT and positron emission tomography (PET) or PET/CT,^5,6,16 and fiberoptic bronchoscopy and percutaneous biopsy are recommended, although their diagnostic sensitivities range from 67% to 100%.^17–19Recently, the image quality and diagnostic capability of chest MRI has improved because of the advancement of MR systems and sequences, and short tau inversion recovery (STIR) turbo spin-echo (SE) imaging and diffusion-weighted imaging (DWI) have been reported as useful in differentiating malignant nodules and lymph nodes from benign ones in several articles.^20–25 Meanwhile, the utilities of chest MRI, including STIR and DWI, have been reported,²⁶ and, in addition, meta-analysis report for pulmonary nodules by means of DWI have been published.²⁷ However, to the best of our knowledge, there have been only reports of chest DWI regarding the differentiation between SCLC and NSCLC,²² but no major studies have reported a direct comparison of the use of DWI and STIR in chest MRI for the assessment of differentiation between SCLC and NSCLC. We hypothesized that both DWI and STIR were useful MR sequences for differentiation of SCLC from NSCLC and their combination might improve the differentiation capabilities. The aim of this study was to evaluate the diagnostic performances of DWI and STIR for differentiating between SCLC and NSCLC.     

Evaluation of anatomical landmark position differences between respiration-gated MRI and four-dimensional CT for radiation therapy in patients with hepatocellular carcinoma

Objective

To measure the accuracy of position differences in anatomical landmarks in gated MRI and four-dimensional CT (4D-CT) fusion planning for radiation therapy in patients with hepatocellular carcinoma (HCC).

Methods

From April to December 2009, gated MR and planning 4D-CT images were obtained from 53 inoperable HCC patients accrued to this study. Gated MRI and planning 4D-CT were conducted on the same day. Manual image fusions were performed by matching the vertebral bodies. Liver volumes and three specific anatomical landmarks (portal vein conjunction, superior mesenteric artery bifurcation, and other noticeable points) were contoured from each modality. The points chosen nearest the centre of the four landmark points were compared to measure the accuracy of fusion.

Results

The average distance differences (±standard deviation) of four validation points were 5.1 mm (±4.6 mm), 5.6 mm (±6.2 mm), 5.4 mm (±4.5 mm) and 5.1 mm (±4.8 mm). Patients who had ascites or pulmonary disease showed larger discrepancies. MRI–CT fusion discrepancy was significantly correlated with positive radiation response (p<0.05).

Conclusions

Approximately 5-mm anatomical landmark positional differences in all directions were found between gated MRI and 4D-CT fusion planning for HCC patients; the gap was larger in patients with ascites or pulmonary disease.

Advances in knowledge

There were discrepancies of approximately 5 mm in gated MRI–CT fusion planning for HCC patients.Many studies have reported that the treatment response and survival of hepatocellular carcinoma (HCC) patients are related to the delivered radiation dose [1-3]. Recently, detailed information on HCC and liver motion gained from the use of advanced techniques, such as a fiducial marker combined with four-dimensional (4D) planning CT, has enabled the delivery of higher doses of radiation therapy (RT) with reduced normal liver toxicity [3-5].Although triphasic CT can provide much information about HCC, the lesion/liver contrast is higher in MRI than in CT [6,7]. To take advantage of these benefits, there have been many efforts to incorporate liver MRI in the RT planning process [8,9]. Moreover, several groups have demonstrated the feasibility of using cine-MRI and 4D-MRI to measure liver tumour motion for RT planning [10-12]. However, a consensus has not yet been reached on the best strategies to compensate for liver motion and adapt RT planning and delivery using planning 4D-CT combined with liver MRI.The primary goal of this prospective study was to evaluate the accuracy of gated MRI and 4D-CT fusion planning by measuring the discrepancies in the specific anatomical landmark points of the liver between exhale-phase images of gated liver MRI and 4D-CT. We also evaluated possible factors affecting gated liver MRI and 4D-CT fusion discrepancy and RT response.     

Stage T3a renal cell carcinoma: staging accuracy of CT for sinus fat,perinephric fat or renal vein invasion

Objective:

To study the accuracy of CT for staging T3a (TNM 2009) renal cell carcinoma (RCC).

Methods:

Unenhanced and nephrographic phase CT studies of 117 patients (male:female = 82:35; age range, 21–86 years) with T1–T3a RCC were independently reviewed by 2 readers. The presence of sinus or perinephric fat, or renal vein invasion and tumour characteristics were noted.

Results:

Median (range) tumour size was 5.5 (0.9–19.0) cm; and 46 (39%), 16 (14%) and 55 (47%) tumours were pT1, pT2 and pT3a RCC, respectively. The sensitivity/specificity for sinus fat, perinephric fat and renal vein invasion were 71/79%, 83/76% and 59/93% (Reader 1) and 88/71%, 68/72% and 69/91% (Reader 2) with κ = 0.41, 0.43 and 0.61, respectively. Sinus fat invasion was seen in 47/55 (85%) cases with T3a RCC vs 16/55 (29%) and 33/55 (60%) for perinephric fat and renal vein invasion. Tumour necrosis, irregularity of tumour edge and direct tumour contact with perirenal fascia or sinus fat increased the odds of local invasion [odds ratio (OR), 2.5–3.7; p < 0.05; κ = 0.42–0.61]. Stage T3a tumours were centrally located (OR, 3.9; p = 0.0009).

Conclusion:

Stage T3a RCC was identified with a sensitivity of 59–88% and specificity of 71–93% (κ = 0.41–0.61). Sinus fat invasion was the most common invasive feature.

Advances in knowledge:

Centrally situated renal tumours with an irregular tumour edge, inseparable from sinus structures or the perirenal fascia and CT features of tumour necrosis should alert the reader to the possibility of Stage T3a RCC (OR, 2.5–3.9).Current guidelines¹ recommend nephron-sparing procedures (either partial nephrectomy or ablation) for Stage T1a (<4 cm) renal cell carcinomas (RCCs), but the indications for nephron-sparing procedures are widening.² Successful surgical series have been reported with Stage T1b (<4–7 cm) tumours and even Stage T2 RCCs.³ Central location is not necessarily a barrier to good clinical outcome after partial nephrectomy,³ but nephron-sparing procedures are contraindicated for stage ≥T3a renal cancers.¹ Thus, prior accurate recognition of T3a stage is important, especially with central renal masses, as any pre-operative suspicion of local invasion should contraindicate nephron-sparing surgery or ablation.In the most recent TNM iteration, Stage T1 and T2 tumours are defined by tumour diameter (T1a, ≤4 cm; T1b, 4–7 cm; T2a, 7–10 cm; and T2b, ≥10 cm) and the absence of any local invasion. Stage T3a RCC was redefined to include invasion of either renal sinus or perinephric fat.⁴ Renal vein invasion [main renal vein and/or segmental (muscle-containing) branch invasion], without caval involvement, was downgraded from Stage T3b to Stage T3a, whilst adrenal invasion was upgraded from Stage T3a to Stage T4. Size is not a governing factor with ≥T3a tumours, and some renal masses <7 cm in diameter will be locally advanced. Nearly half of all pT3a RCCs (n = 309/623) in one study were <7 cm in diameter.⁵ Other studies have confirmed the poor prognostic significance of sinus fat or venous invasion in masses <7 cm, with a 4–6 times increased risk of cancer-related death.^6,7 Centrally located masses are more likely to demonstrate local invasion with positive surgical resection margins after partial nephrectomy,^8,9 and unrecognized sinus invasion may explain the recurrence of cancer, and subsequent death from metastatic disease, in some cases of presumed T1 RCCs.⁸However, in previous studies, CT staging has been variably accurate^10–18 for RCCs, and staging inaccuracies, usually understaging, are said to be most common with Stage T3a disease.^12,17 For venous invasion, the specificity and sensitivity have ranged between 58–97% and 32–96%,^10,14–16 and for perinephric infiltration, the figures have been 32–96% and 85–93%,^14–16 respectively. The CT accuracy for sinus fat invasion has not been previously investigated. The primary aim of this study was to define the accuracy of contrast-enhanced CT for identifying any of the three defining features of Stage T3a RCC, that is, sinus or perinephric fat invasion, or renal vein invasion. Secondary study objectives were to identify any tumour characteristics that increase the odds of T3a disease and may be used as accessory CT signs to alert the reader to an increased likelihood of local invasion by RCC.     

Simultaneous integrated boost to intraprostatic lesions using different energy levels of intensity-modulated radiotherapy and volumetric-arc therapy

Objective:

This study compared the dosimetry of volumetric-arc therapy (VMAT) and intensity-modulated radiotherapy (IMRT) with a dynamic multileaf collimator using the Monte Carlo algorithm in the treatment of prostate cancer with and without simultaneous integrated boost (SIB) at different energy levels.

Methods:

The data of 15 biopsy-proven prostate cancer patients were evaluated. The prescribed dose was 78 Gy to the planning target volume (PTV78) including the prostate and seminal vesicles and 86 Gy (PTV86) in 39 fractions to the intraprostatic lesion, which was delineated by MRI or MR-spectroscopy.

Results:

PTV dose homogeneity was better for IMRT than VMAT at all energy levels for both PTV78 and PTV86. Lower rectum doses (V₃₀–V₅₀) were significantly higher with SIB compared with PTV78 plans in both IMRT and VMAT plans at all energy levels. The bladder doses at high dose level (V₆₀–V₈₀) were significantly higher in IMRT plans with SIB at all energy levels compared with PTV78 plans, but no significant difference was observed in VMAT plans. VMAT plans resulted in a significant decrease in the mean monitor units (MUs) for 6, 10, and 15 MV energy levels both in plans with and those without SIB.

Conclusion:

Dose escalation to intraprostatic lesions with 86 Gy is safe without causing serious increase in organs at risk (OARs) doses. VMAT is advantageous in sparing OARs and requiring less MU than IMRT.

Advances in knowledge:

VMAT with SIB to intraprostatic lesion is a feasible method in treating prostate cancer. Additionally, no dosimetric advantage of higher energy is observed.Randomized trials have shown a gain in biochemical relapse-free survival using dose escalation for prostate cancer.¹ However, isolated local failure is still reported in nearly one-third of patients, even with higher radiotherapy (RT) doses.¹ Local recurrence is of clinical importance because a relationship has been suggested between local control, distant metastasis and survival.² It has also been demonstrated that intraprostatic failure mainly originates at the initial tumour location as a result of intrinsic resistance of a fraction of the tumour clones, which implies that selective dose escalation to the dominant intraprostatic lesion using simultaneous integrated boost (SIB) might be beneficial.³With new RT techniques, such as intensity-modulated RT (IMRT) and volumetric-arc therapy (VMAT), SIB could be delivered without increasing acute toxicity.^4–7 Several recent studies have performed dosimetric comparison of IMRT and VMAT plans in prostate cancer;^8–10 however, dosimetric evaluation of IMRT and VMAT plans delivering SIB is rare. In these studies, target volume and organs at risk (OARs) doses may vary with different treatment planning systems. Another aspect not often addressed in these planning studies is the photon energy level.^4,8,9,11 Although higher energy photons have the potential advantage of reduced attenuation with depth, this may in turn increase the risk of secondary malignancies because of the presence of neutrons generated in the accelerator head at treatment energies >8 MV.¹²Functional imaging techniques can clearly demonstrate tumour within the prostate. MRI, MR spectroscopy (MRS) and positron emission tomography are capable of demonstrating intraprostatic lesions (IPLs).¹³ The advent of combined MRI with MRS or dynamic contrast enhanced (DCE)-MRI improves the detection rate of tumours within the prostate.^13–15The aim of the present study was to make dosimetric comparisons of VMAT and 7-field IMRT with dynamic multileaf collimators (MLCs) using the Monte Carlo algorithm with XVMC code in the treatment of prostate cancer with or without SIB, which can provide improved dose calculation accuracy and has been implemented successfully in the clinical setting.^16,17 Additionally, the impact of three photon energies on target volumes, OARs and normal tissue was evaluated in IMRT and VMAT plans.