Developmental Dysplasia of the Hip: An Audit of the Ultrasound Screening Programme.

Aims Developmental dysplasia of the hip (DDH) is an important cause of disability in children and young adults. Early diagnosis and treatment can help avoid more invasive interventions and long-term morbidity. This study examines the ultrasound screening programme conducted in University Hospital Waterford (UHW), and the outcomes for infants with DDH in the Southeast of Ireland. Methods We conducted an audit of all the DDH screening ultrasounds performed in UHW in the year 2020, a total of 992 infants. Data included referral and ultrasound times, screening results, interventions, and outcomes. Results Of those screened, 255 (26%) were referred to the Orthopaedic clinic, with a significant female majority of nearly 3:1. At the time of writing, only two infants were ultimately referred for further management of persistent DDH, the rest being successfully treated by less invasive interventions such as harnessing and bracing. There were no babies scanned within the recommended 6 weeks who later presented with a dislocated hip or required tertiary referral for DDH management. Conclusion The ultrasound screening programme in UHW is shown to be successful in the prompt diagnosis and early treatment of DDH. This plays a significant role in avoiding the lifelong disabling outcomes of untreated DDH, and the invasive surgical procedures required in the management of late-stage disease.

Gallbladder disease and pancreatic cancer risk: a multicentric case-control European study.

BACKGROUND AND AIMS: The overall evidence on the association between gallbladder conditions (GBC: gallstones and cholecystectomy) and pancreatic cancer (PC) is inconsistent. To our knowledge, no previous investigations considered the role of tumour characteristics on this association. Thus, we aimed to assess the association between self-reported GBC and PC risk, by focussing on timing to PC diagnosis and tumour features (stage, location, and resection). METHODS: Data derived from a European case-control study conducted between 2009 and 2014 including 1431 PC cases and 1090 controls. We used unconditional logistic regression models to estimate odds ratios (ORs) and corresponding 95% confidence intervals (CIs) adjusted for recognized confounders. RESULTS: Overall, 298 (20.8%) cases and 127 (11.6%) controls reported to have had GBC, corresponding to an OR of 1.70 (95% CI 1.33-2.16). The ORs were 4.84 (95% CI 2.96-7.89) for GBC diagnosed <3 years before PC and 1.06 (95% CI 0.79-1.41) for ≥3 years. The risk was slightly higher for stage I/II (OR = 1.71, 95% CI 1.15-2.55) vs. stage III/IV tumours (OR = 1.23, 95% CI 0.87-1.76); for tumours sited in the head of the pancreas (OR = 1.59, 95% CI 1.13-2.24) vs. tumours located at the body/tail (OR = 1.02, 95% CI 0.62-1.68); and for tumours surgically resected (OR = 1.69, 95% CI 1.14-2.51) vs. non-resected tumours (OR = 1.25, 95% CI 0.88-1.78). The corresponding ORs for GBC diagnosed ≥3 years prior PC were close to unity. CONCLUSION: Our study supports the association between GBC and PC. Given the time-risk pattern observed, however, this relationship may be non-causal and, partly or largely, due to diagnostic attention and/or reverse causation.

Risk of pancreatic cancer associated with family history of cancer and other medical conditions by accounting for smoking among relatives.

Background: Family history (FH) of pancreatic cancer (PC) has been associated with an increased risk of PC, but little is known regarding the role of inherited/environmental factors or that of FH of other comorbidities in PC risk. We aimed to address these issues using multiple methodological approaches. Methods: Case-control study including 1431 PC cases and 1090 controls and a reconstructed-cohort study (N = 16 747) made up of their first-degree relatives (FDR). Logistic regression was used to evaluate PC risk associated with FH of cancer, diabetes, allergies, asthma, cystic fibrosis and chronic pancreatitis by relative type and number of affected relatives, by smoking status and other potential effect modifiers, and by tumour stage and location. Familial aggregation of cancer was assessed within the cohort using Cox proportional hazard regression. Results: FH of PC was associated with an increased PC risk [odds ratio (OR) = 2.68; 95% confidence interval (CI): 2.27-4.06] when compared with cancer-free FH, the risk being greater when ≥ 2 FDRs suffered PC (OR = 3.88; 95% CI: 2.96-9.73) and among current smokers (OR = 3.16; 95% CI: 2.56-5.78, interaction FHPC*smoking P-value = 0.04). PC cumulative risk by age 75 was 2.2% among FDRs of cases and 0.7% in those of controls [hazard ratio (HR) = 2.42; 95% CI: 2.16-2.71]. PC risk was significantly associated with FH of cancer (OR = 1.30; 95% CI: 1.13-1.54) and diabetes (OR = 1.24; 95% CI: 1.01-1.52), but not with FH of other diseases. Conclusions: The concordant findings using both approaches strengthen the notion that FH of cancer, PC or diabetes confers a higher PC risk. Smoking notably increases PC risk associated with FH of PC. Further evaluation of these associations should be undertaken to guide PC prevention strategies.

A systems approach identifies time-dependent associations of multimorbidities with pancreatic cancer risk.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is usually diagnosed in late adulthood; therefore, many patients suffer or have suffered from other diseases. Identifying disease patterns associated with PDAC risk may enable a better characterization of high-risk patients. METHODS: Multimorbidity patterns (MPs) were assessed from 17 self-reported conditions using hierarchical clustering, principal component, and factor analyses in 1705 PDAC cases and 1084 controls from a European population. Their association with PDAC was evaluated using adjusted logistic regression models. Time since diagnosis of morbidities to PDAC diagnosis/recruitment was stratified into recent (<3 years) and long term (≥3 years). The MPs and PDAC genetic networks were explored with DisGeNET bioinformatics-tool which focuses on gene-diseases associations available in curated databases. RESULTS: Three MPs were observed: gastric (heartburn, acid regurgitation, Helicobacter pylori infection, and ulcer), metabolic syndrome (obesity, type-2 diabetes, hypercholesterolemia, and hypertension), and atopic (nasal allergies, skin allergies, and asthma). Strong associations with PDAC were observed for ≥2 recently diagnosed gastric conditions [odds ratio (OR), 6.13; 95% confidence interval CI 3.01-12.5)] and for ≥3 recently diagnosed metabolic syndrome conditions (OR, 1.61; 95% CI 1.11-2.35). Atopic conditions were negatively associated with PDAC (high adherence score OR for tertile III, 0.45; 95% CI, 0.36-0.55). Combining type-2 diabetes with gastric MP resulted in higher PDAC risk for recent (OR, 7.89; 95% CI 3.9-16.1) and long-term diagnosed conditions (OR, 1.86; 95% CI 1.29-2.67). A common genetic basis between MPs and PDAC was observed in the bioinformatics analysis. CONCLUSIONS: Specific multimorbidities aggregate and associate with PDAC in a time-dependent manner. A better characterization of a high-risk population for PDAC may help in the early diagnosis of this cancer. The common genetic basis between MP and PDAC points to a mechanistic link between these conditions.

Comparison of CT volumetric measurement with RECIST response in patients with lung cancer.

PURPOSE: To examine the correlations between uni-dimensional RECIST and volumetric measurements in patients with lung adenocarcinoma and to assess their association with overall survival (OS) and progression-free survival (PFS). MATERIALS AND METHODS: In this study of patients receiving chemotherapy for lung cancer in the setting of a clinical trial, response was prospectively evaluated using RECIST 1.0. Retrospectively, volumetric measurements were recorded and response was assessed by two different volumetric methods at each followup CT scan using a semi-automated segmentation algorithm. We subsequently evaluated the correlation between the uni-dimensional RECIST measurements and the volumetric measurements and performed landmark analyses for OS and PFS at the completion of the first and second follow-ups. Kaplan-Meier curves together with log-rank tests were used to evaluate the association between the different response criteria and patient outcome. RESULTS: Forty-two patients had CT scans at baseline, after the first follow up scan and second followup scan, and then every 8 weeks. The uni-dimensional RECIST measurements and volumetric measurements were strongly correlated, with a Spearman correlation coefficient (ρ) of 0.853 at baseline, ρ=0.861 at the first followup, ρ=0.843 at the 2nd followup, and ρ=0.887 overall between-subject. On first follow-up CT, partial responders and non responders as assessed by an "ellipsoid" volumetric criteria showed a significant difference in OS (p=0.008, 1-year OS of 70% for partial responders and 46% for non responders). There was no difference between the groups when assessed by RECIST criteria on first follow-up CT (p=0.841, 1-year OS rate of 64% for partial responders and 64% for non responders). CONCLUSION: Volumetric response on first follow-up CT may better predict OS than RECIST response. CLINICAL RELEVANCE STATEMENT: Assessment of tumor size and response is of utmost importance in clinical trials. Volumetric measurements may help to better predict OS than uni-dimensional RECIST criteria.

Daily online bony correction is required for prostate patients without fiducial markers or soft-tissue imaging.

AIM: To compare online position verification strategies with offline correction protocols for patients undergoing definitive prostate radiotherapy. MATERIALS AND METHODS: We analysed 50 patients with implanted fiducial markers undergoing curative prostate radiation treatment, all of whom underwent daily kilovoltage imaging using an on-board imager. For each treatment, patients were set-up initially with skin tattoos and in-room lasers. Orthogonal on-board imager images were acquired and the couch shift to match both bony anatomy and the fiducial markers recorded. The set-up error using skin tattoos and offline bone correction was compared with online bone correction. The fiducial markers were used as the reference. RESULTS: Data from 1923 fractions were analysed. The systematic error was ≤1 mm for all protocols. The average random error was 2-3mm for online bony correction and 3-5mm for skin tattoos or offline-bone. Online-bone showed a significant improvement compared with offline-bone in the number of patients with >5mm set-up errors for >10% (P<0.001) and >20% (P<0.003) of their fractions. CONCLUSIONS: Online correction to bony anatomy reduces both systematic and random set-up error in patients undergoing prostate radiotherapy, and is superior to offline correction methods for those patients not suitable for fiducial markers or daily soft-tissue imaging.

Is there under-treatment of pancreatic cancer? Evidence from a population-based study in Ireland.

Although clinical trials suggest that chemotherapy can improve survival for both resected and unresected pancreatic cancer patients, the extent to which it is used in routine clinical practice is unclear. We conducted a population-based investigation of treatment patterns and factors influencing treatment receipt and mortality for pancreatic cancer. We included 3173 patients with primary invasive pancreatic cancer, diagnosed in 1994-2003, from the National Cancer Registry (Ireland). Analysis was done by joinpoint regression, logistic regression and Cox proportional hazards. Propensity score methods were used to compare mortality in those who received chemotherapy and in 'matched' patients who did not. Seven percent of patients had a resection and 12% received chemotherapy. The resection rate did not change significantly over time and less than a quarter of patients with localised disease underwent resection. Chemotherapy use increased by 20% per annum, reaching 20% among unresected and 39% among resected patients in 2002-2003. Forty two percent of patients were untreated, and this percentage was unchanged over time. After adjusting for clinical factors, patient characteristics were significantly associated with treatment receipt; older and unmarried patients were less likely to be treated. Among resected patients, risk of death fell by 10% per annum. Chemotherapy receipt was associated with significantly reduced mortality among both surgical (hazard ratio (HR)=0.50, 95% confidence intervals (CIs) 0.27-0.91) and non-surgical patients (HR=0.48, 95% CI 0.38-0.61). Our findings suggest that there may be potential for extended dissemination of chemotherapy, and possibly also for greater utilisation of curative resection, in routine practice which, in turn, has potential to improve survival at the population level.

Screening with breast ultrasound in a population at moderate risk due to family history.

OBJECTIVE: To perform a pilot study to compare ultrasound and mammographic screening with particular respect to specificity, in a cohort of women at moderate family history risk of breast cancer. MATERIAL AND METHODS: High resolution ultrasound of both breasts was undertaken in 149 women at moderate risk of breast cancer who were referred for mammographic screening. The two tests were read blind to the other. Core biopsy was undertaken for solid lesions found on ultrasound. RESULTS: 149 Patients, mean age 42.15 years, were screened with bilateral ultrasound. 90 Examinations were normal. 46 Women had cysts, two had lesions previously biopsied and found to be benign, and one had a lymph node. 10 Focal solid lesions were biopsied on account of their ultrasound findings, 6.7% (95% confidence intervals (95% CIs) 2.7% to 10.7%). All but one of the 149 mammograms were normal. In this case both mammography and ultrasound showed a focal solid lesion that at core biopsy was found to be a fibroadenoma. Histology showed seven fibroadenomata, two areas of fibrocystic change, and one adenoid cystic carcinoma. Positive predictive value for biopsy was 10%. Mean follow up was 13.7 months. There was one interval cancer. CONCLUSION: Screening with breast ultrasound, in a cohort of women at moderate risk of breast cancer due to family history, has an acceptable biopsy rate. Screening with ultrasound and mammography in patients with an increased risk of breast cancer may be beneficial and a randomised study to examine issues of acceptability, reproducibility, and cost effectiveness is apt.

Lobular carcinoma in situ on core biopsy-what is the clinical significance?

AIM: To retrospectively review the surgical histological findings in all cases where lobular carcinoma in situ(LCIS) was identified on percutaneous core biopsy (CB) performed as part of the Cambridge and Huntingdon breast screening programme. MATERIALS AND METHODS: We retrospectively reviewed all the core biopsies performed in our department for screen detected abnormalities over a 5-year period between 1 April 1994 and 31 March 1999. All patients where LCIS was identified on CB were reviewed. As the significance of LCIS on CB was unclear all went on to surgical excision. We reviewed the clinical and imaging findings, biopsy technique and subsequent surgical histology of each patient. RESULTS: During the study period 60 769 women were invited for screening, of whom 47 975 attended (attendance rate = 79%). Of these, 2330 (4.9%) were recalled for assessment and 749 (1.6%) underwent CB. A malignant diagnosis was obtained in 311 (42%), 211 invasive and 100 in situ lesions. LCIS was identified on CB in 13 (2%). LCIS was the only lesion identified in seven cases. All seven cases subsequently underwent surgical excision. Surgical histology revealed a single case of LCIS and invasive lobular carcinoma. There were two cases of LCIS and DCIS one with a probable focus of invasive ductal carcinoma. In one case LCIS was identified in association with a radial scar. In three of the seven cases LCIS was the only abnormality on both CB and surgical biopsy. CONCLUSION: Our series shows that isolated LCIS on CB following mammographic screening is an infrequent finding, and it may be associated with either an invasive cancer or DCIS. It is therefore advisable that when LCIS is identified on CB, surgical excision of the mammographic abnormality should be performed. Decisions on management should be undertaken in a multidisciplinary setting taking into account clinical and imaging findings.

Interval cancer peer review in East Anglia: implications for monitoring doctors as well as the NHS breast screening programme.

AIM: To devise a method for reviewing interval cancers that will both educate radiologists and facilitate improvement of breast screening practice. To evaluate different methods for case classification to find one that best serves this purpose. METHOD: The method of peer review and the means by which interval cancers are classified is described. The way in which cases are designated false-negative is an issue of acceptability for radiologists, and so three different methods are evaluated. Each is applied to the data set collected in this region over a 3-year period. RESULTS: For cases read by five readers, when a consensus method was used for classifying cases, the proportion of cases classified as false-negative was 14%. Using a method in which only one of the five readers had to classify a case as false-negative for it to be categorized as such, the proportion of false-negative cases rose to a maximum of 38%. The minimum proportion of cases that could be considered to be false-negative was 6% and was obtained when all five readers had to classify a case as false-negative for it to be so categorized. Consistent with its majority viewpoint, the consensus method gave results for proportions of total cases classified as false-negative which were similar to those given by methods in which cases are classified as false-negative if either three of five readers, or at least 60% of readers, classified it as such. CONCLUSION: For the peer review method to achieve its dual aims of educating radiologists and auditing performance, the participating radiologists must share ownership of the results and view the analysis as fair. The method used to classify interval cancers as false-negative will influence the number so classified. A consensus method has been found to give a result that is both fair and acceptable to our radiologist. Using this method 16% of all reviewed cases were classified as false-negative and 60% as true interval cancers. Britton, P. D. (2001). Clinical Radiology56, 44-49.

Intrathoracic lipoma masquerading as subclavian artery trauma.

A 58 year old man was admitted to the accident and emergency department following an industrial accident in which he sustained a three part fracture dislocation of his right humerus. Chest radiography revealed a large mass in the right upper hemithorax and, when the patient became hypotensive, an emergency thoracotomy was performed. The mass was found to be a massive intrathoracic lipoma. This case shows how preexisting intrathoracic lesions may be mistaken for subclavian or great vessel trauma following violent shoulder girdle injury. The differential diagnosis of traumatic and non-traumatic intrathoracic mass lesions in chest radiography should be considered carefully.

Non-deflation of Foley catheter balloon: use of transrectal ultrasound.

The problem of failed balloon deflation on removal of a Foley catheter is frequently observed. The use is reported of transrectal ultrasound with a small gauge biopsy needle to enable balloon deflation after the failure of less invasive techniques.

Biochemical evidence for osteomalacia with carbamazepine therapy.

Many anticonvulsants are known to cause osteomalacia, however, carbamazepine has not previously been studied in this regard. We studied 31 patients on carbamazepine (mean dose 758 mg +/- s.d. 468 mg per day), as a single drug for epilepsy for a duration of 20.5 +/- 10 months. Three patients (10%) had hypocalcaemia, and serum calcium was significantly lower (P less than 0.01), and serum alkaline phosphatase significantly higher (P less than 0.05) than matched control subjects. Serum phosphorus was significantly inversely correlated and serum alkaline phosphatase was positively correlated with both dose and duration, but not blood levels of carbamazepine. These findings are consistent with mild biochemical changes of osteomalacia. None of the patients were symptomatic. Serum bilirubin (mean 2.6 +/- 1.4 mumol/l) was very significantly lower (P less than 0.01) than in controls. Both the calcium and bilirubin disturbances are probably due to carbamazepine causing hepatic microsomal enzyme induction.