Metabolic nodal response as a prognostic marker after neoadjuvant therapy for oesophageal cancer.

BACKGROUND: The ability to predict recurrence and survival after neoadjuvant chemotherapy (NAC) and surgery for oesophageal cancer remains elusive. This study evaluated the role of [18 F]fluorodeoxyglucose (FDG) PET-CT in assessing tumour and nodal response as a prognostic marker. METHODS: This was a single-centre UK cohort study. From 2006 to 2014, patients with oesophageal cancer staged with PET-CT before NAC, and restaged by CT or PET-CT before resection, were included. Pathological tumour response was evaluated using Mandard regression grades. Metabolic tumour and nodal responses (mTR and mNR respectively) were quantified using absolute and threshold reductions. RESULTS: Among 294 included patients, mTR and mNR independently predicted prognosis before surgery. After surgery, mNR (but not mTR), pathological tumour response, resection margin status and pathological node category predicted prognosis. Patients with FDG-avid nodal disease after NAC were at high risk of recurrence/death at 1 and 2 years (43 and 71 per cent respectively; P = 0·030 and P = 0·025 versus patients without avid nodes), and had a worse prognosis than patients with non-avid nodal metastases: hazard ratio 4·19 (95 per cent c.i. 1·87 to 9·40) and 2·11 (1·12 to 3·97) respectively versus patients without nodal metastases. Considering mTR and mNR response separately improved prognostication. CONCLUSION: mNR is a novel prognostic factor, independent of conventional N status. Primary and nodal tumours may respond discordantly and patients with FDG-avid nodes after NAC have a poor prognosis.

Pragmatic staging of oesophageal cancer using decision theory involving selective endoscopic ultrasonography, PET and laparoscopy.

BACKGROUND: Following CT, guidelines for staging oesophageal and gastro-oesophageal junction (GOJ) cancer recommend endoscopic ultrasonography (EUS), PET-CT and laparoscopy for T3-T4 GOJ tumours. These recommendations are based on generic utilities, but it is unclear whether the test risk outweighs the potential benefit for some patients. This study sought to quantify investigation risks, benefits and utilities, in order to develop pragmatic, personalized staging recommendations. METHODS: All patients with a histological diagnosis of oesophageal or GOJ cancer staged between May 2006 and July 2013 comprised a development set; those staged from July 2013 to July 2014 formed the prospective validation set. Probability thresholds of altering management were calculated and predictive factors identified. Algorithms and models (decision tree analysis, logistic regression, artificial neural networks) were validated internally and independently. RESULTS: Some 953 patients were staged following CT, by [(18) F]fluorodeoxyglucose PET-CT (918), EUS (798) and laparoscopy (458). Of these patients, 829 comprised the development set (800 PET-CT, 698 EUS, 397 laparoscopy) and 124 the validation set (118 PET-CT, 100 EUS, 61 laparoscopy). EUS utility in the 71.8 per cent of patients with T2-T4a disease on CT was minimal (0.4 per cent), its risk exceeding benefit. EUS was moderately accurate for pT1 N0 disease. A number of factors predicted metastases on PET-CT and laparoscopy, although none could inform an algorithm. PET-CT altered management in 23.0 per cent, and laparoscopy in 7.1 per cent, including those with T2 and distal oesophageal tumours. CONCLUSION: Although EUS provided additional information on T and N category, its risk outweighed potential benefit in patients with T2-T4a disease on CT. Laparoscopy seemed justified for distal oesophageal tumours of T2 or greater.

Intraosseous schwannoma in schwannomatosis.

This study investigates the clinical, radiological, and pathological features of two cases of intraosseous schwannoma that arose in patients with multiple soft tissue schwannomas. In both cases, the patients were adult females and the tibial bone was affected. Vestibular schwannomas were not identified, indicating that these were not cases of neurofibromatosis 2 (NF2). Radiographs showed a well-defined lytic lesion in the proximal tibia; in one case, this was associated with a pathological fracture. Histologically, both cases showed typical features of benign schwannoma. Molecular analysis of one of the excised tumors showed different alterations in the NF2 gene in keeping with a diagnosis of schwannomatosis. Our findings show for the first time that intraosseous schwannomas can occur in schwannomatosis.

Role of positron emission tomography-computed tomography in predicting survival after neoadjuvant chemotherapy and surgery for oesophageal adenocarcinoma.

BACKGROUND: Positron emission tomography combined with computed tomography (PET-CT) is increasingly being used in the staging of oesophageal cancer. Some recent reports suggest it may be used to predict survival. None of these studies, however, reported on the prognostic value of PET-CT performed before neoadjuvant chemotherapy and surgery. The aim of this study was to determine whether pretreatment PET-CT could predict survival. METHODS: Consecutive patients with oesophageal adenocarcinoma who underwent PET-CT before neoadjuvant chemotherapy and resection were included. Maximum standardized uptake value (SUV(max)), fluorodeoxyglucose (FDG)-avid tumour length and the presence of FDG-avid local lymph nodes were determined for all patients. Kaplan-Meier survival analysis was performed and multivariable analysis used to identify independent prognostic factors. RESULTS: A total of 121 patients were included (mean age 63 years, 97 men) of whom 103 underwent surgical resection. On an intention-to-treat basis, overall survival was significantly worse in patients with FDG-avid local lymph nodes (P < 0·001). SUV(max) and FDG-avid tumour length did not predict survival (P = 0·276 and P = 0·713 respectively). The presence of FDG-avid local lymph nodes was an independent predictor of poor overall survival (hazard ratio (HR) 4·75, 95 per cent confidence interval 2·14 to 10·54; P < 0·001) and disease-free survival (HR 2·97, 1·40 to 6·30; P = 0·004). CONCLUSION: The presence of FDG-avid lymph nodes, but not SUV(max) or FDG-avid tumour length, was an independent adverse prognostic factor.

Exploring the pattern and neural correlates of neuropsychological impairment in late-life depression.

BACKGROUND: Neuropsychological impairment is a key feature of late-life depression, with deficits observed across multiple domains. However, it is unclear whether deficits in multiple domains represent relatively independent processes with specific neural correlates or whether they can be explained by cognitive deficits in executive function or processing speed. METHOD: We examined group differences across five domains (episodic memory; executive function; language skills; processing speed; visuospatial skills) in a sample of 36 depressed participants and 25 control participants, all aged ≥ 60 years. The influence of executive function and processing speed deficits on other neuropsychological domains was also investigated. Magnetic resonance imaging correlates of executive function, processing speed and episodic memory were explored in the late-life depression group. RESULTS: Relative to controls, the late-life depression group performed significantly worse in the domains of executive function, processing speed, episodic memory and language skills. Impairments in executive function or processing speed were sufficient to explain differences in episodic memory and language skills. Executive function was correlated with anisotropy of the anterior thalamic radiation and uncinate fasciculus; processing speed was correlated with anisotropy of genu of the corpus callosum. Episodic memory was correlated with anisotropy of the anterior thalamic radiation, the genu and body of the corpus callosum and the fornix. CONCLUSIONS: Executive function and processing speed appear to represent important cognitive deficits in late-life depression, which contribute to deficits in other domains, and are related to reductions in anisotropy in frontal tracts.

Metabolic response at repeat PET/CT predicts pathological response to neoadjuvant chemotherapy in oesophageal cancer.

OBJECTIVES: Reports have suggested that a reduction in tumour 18F-fluorodeoxyglucose (FDG) uptake on positron emission tomography (PET) examination during or after neoadjuvant chemotherapy may predict pathological response in oesophageal cancer. Our aim was to determine whether metabolic response predicts pathological response to a standardised neoadjuvant chemotherapy regimen within a prospective clinical trial. METHODS: Consecutive patients staged with potentially curable oesophageal cancer who underwent treatment within a non-randomised clinical trial were included. A standardised chemotherapy regimen (two cycles of oxaliplatin and 5-fluorouracil) was used. PET/CT was performed before chemotherapy and repeated 24-28 days after the start of cycle 2. RESULTS: Forty-eight subjects were included: mean age 65 years; 37 male. Using the median percentage reduction in SUV(max) (42%) to define metabolic response, pathological response was seen in 71% of metabolic responders (17/24) compared with 33% of non-responders (8/24; P = 0.009, sensitivity 68%, specificity 70%). Pathological response was seen in 81% of subjects with a complete metabolic response (13/16) compared with 38% of those with a less than complete response (12/32; P = 0.0042, sensitivity 52%, specificity 87%). There was no significant histology-based effect. CONCLUSIONS: There was a significant association between metabolic response and pathological response; however, accuracy in predicting pathological response was relatively low.

Additional benefit of ¹8F-fluorodeoxyglucose integrated positron emission tomography/computed tomography in the staging of oesophageal cancer.

OBJECTIVE: ¹8F-fluorodeoxyglucose positron emission tomography (FDG PET) has been shown to improve the accuracy of staging in oesophageal cancer. We assessed the benefit of PET/CT over conventional staging and determined if tumour histology had any significant impact on PET/CT findings. METHODS: A retrospective cohort study, reviewing the results from 200 consecutive patients considered suitable for radical treatment, undergoing routine PET/CT staging comparing the results from CT and endoscopic ultrasound, as well as multi-disciplinary team records. Adenocarcinoma and squamous cell carcinoma were compared for maximum Standardised Uptake Value (SUV(max)), involvement of local lymph nodes and distant metastases. RESULTS: PET/CT provided additional information in 37 patients (18.5%) and directly altered management in 34 (17%): 22 (11%) were upstaged; 15 (7.5%) were downstaged, 12 of whom (6%) received radical treatment. There were 11 false negatives (5.5%) and 1 false positive (0.5%). SUV(max) was significantly lower for adenocarcinoma than squamous cell carcinoma (median 9.1 versus 13.5, p = 0.003). CONCLUSIONS: Staging with PET/CT offers additional benefit over conventional imaging and should form part of routine staging for oesophageal cancer. Adenocarcinoma and squamous cell carcinoma display significantly different FDG-avidity.

PET/CT in primary musculoskeletal tumours: a step forward.

Hybrid imaging with combined positron emission tomography/computed tomography (PET/CT) plays an important role in the staging and management of a wide variety of solid tumours. However, its use in the evaluation of musculoskeletal malignancy has not yet entered routine clinical practice. Cross-sectional imaging with magnetic resonance imaging (MR) and computed tomography have well-established roles but there is increasing evidence for the selective use of PET/CT in the management of these patients. The aims of this article are to review the current evidence and clinical applications of PET/CT in primary musculoskeletal tumours and discuss potential future developments using novel PET tracers and integrated PET/MR.

Sarcoid-like reaction to malignancy on whole-body integrated (18)F-FDG PET/CT: prevalence and disease pattern.

AIM: To evaluate the prevalence of sarcoid-like reaction to malignancy detected using integrated 2-[(18)F]-fluoro-2-deoxy-d-glucose (FDG) positron-emission tomography and computed tomography (PET/CT) in patients undergoing staging or restaging of solid-organ malignancy. MATERIALS AND METHODS: A systematic search was performed using the institutional radiology information system of 2048 consecutive PET/CT examinations performed in cancer patients at a tertiary-referral centre. Cases that were considered suspicious for sarcoid-like reaction were identified from the initial radiological report and were retrospectively reviewed by three experienced PET/CT reporters. RESULTS: Sarcoid-like reaction was initially suspected in 23 of the 2048 (1.1%) FDG PET/CT examinations, with the diagnosis confirmed histologically or by clinico-radiological follow-up in 13 of the 23 cases (57%). Sarcoid-like reaction was more commonly seen in patients undergoing FDG PET/CT for restaging of suspected recurrence rather than for primary tumour staging (77% versus 23%; p=0.05). The mean maximum standardized uptake value (SUV(max)) of confirmed hilar and mediastinal sarcoid-like reaction was 7.3 (range 3.1-13.6). Symmetric hilar uptake was demonstrated in 11 of the 13 (85%) and all 13 had additional mediastinal nodal uptake. Pulmonary uptake was seen in seven of the 13 cases (54%). Extra-thoracic involvement was present in eight of the 13 (61.5%), including nodal, splenic, and hepatic lesions. CONCLUSION: Sarcoid-like reaction was suspected in 1.1% of cancer patients at FDG PET/CT examination, with confirmation of the diagnosis in 0.6%. With the increasing use of FDG PET/CT in cancer patients, it is important to be aware of the prevalence of this uncommon, but important, disease entity and to consider this diagnosis in appropriate cases in order to avoid a false-positive interpretation of metastatic disease.

18Fluorocholine PET/CT scanning with arterial phase-enhanced CT is useful for persistent/recurrent primary hyperparathyroidism: first UK case series results.

INTRODUCTION: Redo parathyroidectomy for persistent/recurrent primary hyperparathyroidism is associated with a higher risk of complications and should be planned only with convincing localisation. We assessed whether 18fluorocholine positron emission tomography/computed tomography could identify parathyroid adenoma(s) in patients with persistent/recurrent primary hyperparathyroidism and negative conventional scans. MATERIALS AND METHODS: A departmental database was used to identify patients with failed localisation attempts (sestamibi single photon emission computed tomography/computed tomography and/or computed tomography/magnetic resonance imaging and/or selective parathyroid hormone sampling) after previous unsuccessful surgery for primary hyperparathyroidism. 18Fluorocholine positron emission tomography was performed in all patients and redo surgery offered to those with positive findings. RESULTS: 18Fluorocholine positron emission tomography incorporating arterial and portal phase enhanced computed tomography was performed in 12 patients with persistent/recurrent primary hyperparathyroidism (four men and eight women). Seven patients (58%) were cured after excision of adenomas located in ectopic positions (n = 3) or in anatomical position (n = 4). Five patients (42%) had persistent hypercalcaemia and repeat 18fluorocholine scan confirmed that the area highlighted on preoperative scans was excised. The arterial phase enhancement of the computed tomography was significantly different between cured and not-cured patients (P = 0.007). All seven cured patients had either a strong or weak enhancing pattern on computed tomography. Standardised uptake value at 60 minutes in patients with successful surgery (range 2.7-15.7, median 4.05) was higher than in patients with failed surgery (range 1.8-5.8, median 3.2) but was not statistically significant (P = 0.300). DISCUSSION: 18fluorocholine scanning can identify elusive parathyroid adenomas, including those that are ectopic, and is useful in the management of patients with persistent/recurrent primary hyperparathyroidism when first-line scans are negative. The grading of the arterial phase of computed tomography can help to differentiate between true adenomas and false positive targets (lymph nodes).

The role of 18F-FDG PET/CT in the evaluation of oesophageal carcinoma.

Integrated positron-emission tomography/computed tomography (PET/CT) with 2-[fluorine-18] fluoro-2-deoxy-D-glucose (FDG) is now established in the management of oncology patients. With increasing availability and a constantly advancing body of evidence, the role of FDG PET/CT in oesophageal cancer is set to expand to include initial staging, assessment of disease response, therapy planning, and detection of disease recurrence. This article reviews the utility of FDG PET/CT in the management of oesophageal carcinoma, discussing its role and limitations in the imaging of these patients.

Asymmetric breast uptake of radioiodine in a patient with thyroid malignancy: metastases or not?

Various physiological processes can cause potentially misleading appearances in radioiodine whole body scans; proper understanding of the causes of these can therefore obviate diagnostic errors. Whole-body radioiodine scintigraphy with I131 or I123 is an accurate form of imaging used for management of differentiated thyroid carcinoma. Following thyroidectomy, any residual thyroid tissue or metastatic disease is ablated with high dose I131 and diagnostic images are acquired, demonstrating residual thyroid tissue and metastatic disease. However, atypical physiological uptake of I131 can simulate metastases.

Fluorodeoxyglucose activity associated with a cosmetic poly-L-lactide filler: a potential confounder on positron emission tomography and computed tomography.

Injectable cosmetic fillers are increasingly popular, but are not often considered as a cause of abnormal findings on imaging. We present a case of poly-L-lactic acid (PLLA) filler associated with 18-fluorodeoxyglucose (FDG) uptake, which had the potential to interfere with staging of a squamous cell carcinoma of the lateral tongue. We characterise the FDG-positron emission tomography/computed tomography (PET/CT) properties of a PLLA dermal filler, Sculptra® (Aventis), and highlight its potentially confounding appearance in the staging scans of oncological patients, particularly those with oral tumours.

Injuries of the inferior vena cava.

Injuries of the IVC, whether caused by blunt or penetrating mechanisms, are usually fatal. Patients who arrive in shock and fail to respond to initial resuscitative measures, those who are still actively bleeding at the time of laparotomy, and those with wounds of the retrohepatic vena cava have a low probability of survival. Death most commonly is caused by intraoperative exsanguination. Knowledge of the anatomy and exposure techniques for the five different segments of the intra-abdominal vena cava is very important to trauma surgeons. Although some wounds of the vena cava, especially those of the retrohepatic vena cava, are best left unexplored, most injuries inferior to this level can be exposed and repaired by lateral suture technique. Preservation of a lumen of at least 25% of normal is probably important in the suprarenal vena cava but is of no provable value inferior to the renal veins. No evidence supports the need to expose and repair vena caval wounds that have spontaneously stopped bleeding. Such wounds, especially in the retrohepatic area, may be managed expectantly provided that there is no strong suspicion of an associated injury to a major artery or hollow viscus.

Portal vein injuries.

Wounds of the portal vein are caused most commonly by penetrating trauma and carry a very high mortality rate. Most deaths are caused by exsanguination, occurring intraoperatively as surgeons struggle to control the hemorrhage from the portal vein and associated vascular injuries. A thorough knowledge of the anatomy of the area and of the likely patterns of wounding is important. At surgery, surgeons must be prepared to deal with multiple vessel wounding. Although most investigators have advocated lateral repair of the portal vein when it can be accomplished, portal ligation seems to be a safe alternative. Complex repairs are justified only when a contraindication to ligation exists. Postoperative care must recognize the need for extraordinary fluid replacement and the small risk for postoperative bowel infarction after repair or ligation of the portal vein.

Serial brain MRI at 3-6 month intervals as a surrogate marker for Alzheimer's disease.

A surrogate marker is needed for Alzheimer's disease (AD) both to aid diagnosis and to assess interventions. Despite widespread use, brain imaging markers have largely been confounded by overlap with "normal" ageing. 39 elderly subjects completed up to four serial volumetric brain MRI scans with intervals from 2.5 months to 7 months. By National Institute of Neurological and Communicative Disorders and Stroke (NINCDS) criteria, five subjects had probable AD, two possible AD and 32 were negative for AD, although this group included memory-impaired subjects. Total brain and ventricular volumes were measured for each scan, and rates of change for each interval calculated. The rate of change in ventricle-to-brain ratio was 15.6% per year (standard deviation (SD) 2.8%) for probable AD compared with 4.3% per year (SD 1.1%) for negative AD (p<0.001). There was no significant difference between these groups' mean ventricle-to-brain ratios measured at a single time point (p=0.25). Rates of change in brain or ventricular volume over time also differed between the two groups (p<0.001). Power calculations reveal that to detect a 20% reduction in the excess rate of atrophy of a probable AD cohort in just 6 months, with 90% power, 135 subjects would be required in each arm of a randomized placebo controlled trial. For a 30% reduction in the excess rate of atrophy, 61 subjects would be required. Rate of change analysis makes serial brain MRI a valuable surrogate marker for Alzheimer's disease. Since only 6 months or less is required between scans, this procedure has both clinical relevance and potential for monitoring interventions.