Diagnostic value of 68 Ga-DOTATATE PET-CT imaging for staging of ER+ /PR+ HER2- breast cancer patients with metastatic disease: Comparison with conventional imaging with bone scan, diagnostic CT and 18 F-FDG PET-CT in a prospective pilot trial.

INTRODUCTION: 18 F-Fludeoxyglucose PET-CT (FDG) is increasingly used to stage breast cancer. Most breast cancers express the Oestrogen Receptor (ER) and Progesterone Receptor (PR), and this subtype demonstrates lower activity on FDG imaging. Somatostatin receptors (SSTR) offer a potentially improved radiotracer target for ER+ /PR+ breast cancer. We present the first in vivo clinical study comparing 68 Ga-DOTATATE PET-CT (DOTA) to FDG and conventional imaging (bone scan and diagnostic CT), in metastatic ER+ /PR+ human epidermal growth factor receptor 2 (HER2) negative breast cancer. METHODS: Patients with clinically progressive metastatic ER+ /PR+ HER2- breast cancer underwent restaging with DOTA, FDG and conventional imaging. Scans were analysed visually, and semi-quantitatively. Wilcoxon-Rank Scoring was used to assess significance. RESULTS: Ten women (mean age 57 years) underwent imaging. 8/10 demonstrated disease on both DOTA and FDG. 2/10 positive on conventional imaging, but DOTA- /FDG- , and had no disease progression at 1-year follow-up. Heterogeneity of uptake was seen between DOTA and FDG with 5 bone lesions DOTA+ /FDG- and 1 bone lesion FDG+ /DOTA- . Twenty-one visceral lesions were FDG+ /DOTA- (2 patients), with 10/21 identified on conventional imaging. Maximum standard uptake values (SUV max) of DOTA were greater than FDG (10.9 vs. 6.6, P = ns). Four sites were biopsied (3 patients). 3/4 had high ER/PR expression (mean DOTA SUV max 9.4) and 1/4 low ER/PR expression (DOTA SUV max 3.1). CONCLUSION: Whilst we have not demonstrated DOTA to be superior to FDG in staging of ER+ /PR+ breast cancers, DOTA may have a role in assessing HR status and treatment decisions; further evaluation of this is warranted.

Prospective evaluation of the impact of human papilloma virus status and small node size on the diagnostic accuracy of 18F-fluorodeoxyglucose positron emission tomography/computed tomography for primary head and neck squamous cell carcinoma.

BACKGROUND: Fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) is well validated in the staging of pre-treatment head and neck squamous cell carcinoma (HNSCC), although the impact of human papilloma virus (HPV) status and node size on accuracy remains unclear. The aim of this study was to assess the diagnostic accuracy of PET/CT based on HPV status and node size and determine the effects of maximum standardized uptake value thresholds on sensitivity, specificity and positive predictive value. METHODS: A total of 38 patients with primary HNSCC were recruited. All patients underwent primary tumour resection and cervical node dissection following FDG-PET/CT. RESULTS: A total of 38 patients including 68 dissected necks, representing 353 nodal levels and a total of 2701 lymph nodes were included. Histopathological analysis revealed lymph node metastases in 4.3% (116/2701) of dissected lymph nodes. Forty-four percent of patients had HPV-positive tumours. Sixty-four percent of involved lymph nodes were <1 cm. The sensitivity and specificity for HPV-positive nodes were 67.2% and 99.3% versus 35.6% and 98.2% in HPV-negative nodes, respectively (P < 0.001). Mean maximum standardized uptake value in HPV-positive nodes was 6.3 versus 3.5 in HPV-negative nodes (P < 0.001). Sensitivity and specificity were 30.7% and 99.2% in <1 cm nodes versus 90.2% and 84.8% in ≥1 cm nodes, respectively (P < 0.001). CONCLUSION: FDG-PET/CT has significantly higher diagnostic accuracy in determining nodal metastases in HPV-positive HNSCC versus HPV-negative disease. Accuracy was lower in <1 versus ≥1 cm nodes.

Protocol for the PRIMARY clinical trial, a prospective, multicentre, cross-sectional study of the additive diagnostic value of gallium-68 prostate-specific membrane antigen positron-emission tomography/computed tomography to multiparametric magnetic resonance imaging in the diagnostic setting for men being investigated for prostate cancer.

OBJECTIVES: Primary objectives: To determine the additive value of gallium-68 prostate-specific membrane antigen (PSMA) positron emission topography (PET)/computed tomography (CT) when combined with multiparametric magnetic resonance imaging (mpMRI) detecting clinically significant prostate cancer (csPCa) in men undergoing initial biopsy for suspicion of PCa, and to determine the proportion of men who could have avoided prostate biopsy with positive mpMRI (PI-RADS ≥3) but negative PSMA-PET/CT. Secondary objectives: To determine the proportion of men who had csPCa detected only by PSMA-PET/CT or only by systematic prostate biopsy; to compare index lesions by template biopsies vs targeted lesions identified on mpMRI or PSMA-PET/CT; to assess whether there may be health economic benefit or harm if PSMA-PET/CT is incorporated into the diagnostic algorithm; and to develop a nomogram which combines clinical, imaging and biomarker data to predict the likelihood of csPCa. PATIENTS AND METHODS: The PRIMARY trial is a multicentre, prospective, cross-sectional study that meets the criteria for level 1 evidence in diagnostic test evaluation. PRIMARY will investigate if a limited (pelvic-only) PSMA-PET/CT in combination with routine mpMRI can reliably discriminate men with csPCa from those without csPCa. We conducted a power calculation based on pilot data and will recruit up to 600 men who will undergo PSMA-PET/CT (the index test), mpMRI (standard test) and transperineal template + targeted (PSMA-PET/CT and/or mpMRI) biopsies (reference test). The conduct and reporting of the mpMRI and PSMA-PET/CT will be blinded to each other. RESULTS: The PRIMARY trial will measure and compare sensitivity, specificity, positive predictive value and negative predictive value of both mpMRI and PSMA-PET/CT vs targeted prostrate biopsy. The results will be used to determine the proportion of men who could safely avoid biopsy without compromising detection of csPCa. Furthermore, we will assess whether there is a health economic benefit in incorporating PSMA-PET/CT into the diagnostic algorithm. CONCLUSIONS: This trial will provide robust prospective data to determine the diagnostic ability of PSMA-PET/CT used in addition to mpMRI. It will establish if certain patients can avoid biopsy in the investigation of PCa.

Survival outcomes of hepatic resections in Bismuth-Corlette type IV cholangiocarcinoma.

BACKGROUND: Surgical resection for Bismuth-Corlette type IV (BC-IV) hilar cholangiocarcinomas, also termed Klatskin tumours are technically challenging and were once considered unresectable tumours. Following advances in hepatobiliary imaging and surgical techniques, emerging evidence suggests that surgical resection is a viable avenue for long-term survival. We aimed to identify factors affecting survival outcomes of hepatic resections for BC-IV cholangiocarcinomas. METHOD: A systematic review was performed across multiple databases and several clinical trial registries. Two reviewers independently screened and selected papers that contained survival data on BC-IV cholangiocarcinoma after hepatic resections. RESULTS: Of 13 499 papers from our search result, 21 papers satisfied the inclusion criteria. The median post-operative survival was 30.8 months. The average 1- and 5-year post-operative survivals were 61.6 and 33.3%, respectively. Predictors of long-term survival included achievement of R0 margins, minimisation of operative time and reduction intra-operative blood loss. CONCLUSION: Our analysis demonstrates improving post-operative outcomes and survival in surgical resection of BC-IV cholangiocarcinoma and suggests that radical surgical resection is a valid treatment option for the disease.

3-Year Freedom from Progression After 68Ga-PSMA PET/CT-Triaged Management in Men with Biochemical Recurrence After Radical Prostatectomy: Results of a Prospective Multicenter Trial.

68Ga-labeled prostate-specific membrane antigen (PSMA) PET/CT is increasingly used in men with biochemical recurrence (BCR) after radical prostatectomy (RP), but its longer-term prognostic or predictive potential in these men is unknown. The aim of this study was to evaluate the predictive value of PSMA PET for a 3-y freedom from progression (FFP) in men with BCR after RP undergoing salvage radiotherapy (sRT). Methods: This prospective multicenter study enrolled 260 men between 2015 and 2017. Eligible patients were referred for PSMA PET with a rising level of prostate-specific antigen (PSA) after RP. Management after PSMA PET was recorded but not mandated. PSMA PET protocols were standardized across sites and reported prospectively. Clinical, pathologic, and surgical information; sRT; timing and duration of androgen deprivation; 3-y PSA results; and clinical events were documented. FFP was defined as a PSA rise of no more than 0.2 ng/mL above nadir after sRT, with no additional treatment. Results: The median PSA was 0.26 ng/mL (interquartile range, 0.15-0.59 ng/mL), and follow-up was 38 mo (interquartile range, 31-43 mo). PSMA PET had negative results in 34.6% (90/260), showed disease confined to the prostatic fossa in 21.5% (56/260), showed disease in the pelvic nodes in 26.2% (68/260), and showed distant disease in 17.7% (46/260). Of the patients, 71.5% (186/260) received sRT: 38.2% (71/186) to the fossa only, 49.4% (92/186) to the fossa plus the pelvic nodes, and 12.4% (23/186) to the nodes alone or stereotactic body radiation therapy. PSMA PET was highly predictive of FFP at 3 y after sRT. Overall, FFP was achieved in 64.5% (120/186) of those who received sRT, 81% (81/100) with negative results or fossa-confined findings versus 45% (39/86) with extrafossa disease (P < 0.0001). On logistic regression, PSMA PET was more independently predictive of FFP than established clinical predictors, including PSA, T stage, surgical margin status, or Gleason score (P < 0.002). Thirty-two percent of men with a negative PSMA PET result did not receive treatment. Of these, 66% (19/29) progressed, with a mean rise in PSA of 1.59 ng/mL over the 3 y. Conclusion: PSMA PET results are highly predictive of FFP at 3 y in men undergoing sRT for BCR after RP. In particular, men with negative PSMA PET results or disease identified as still confined to the prostatic fossa demonstrate high FFP, despite receiving less extensive radiotherapy and lower rates of additional androgen deprivation therapy than those with extrafossa disease.

The role of mechanical bowel preparation and oral antibiotics for left-sided laparoscopic and open elective restorative colorectal surgery with and without faecal diversion.

BACKGROUND: There is significant variation in the use of mechanical bowel preparation and oral antibiotics prior to left-sided elective colorectal surgery. There has been no consensus internationally. METHODS: This was a retrospective analysis of the 2015 American College of Surgeons National Surgical Quality Improvement Program database. Patients were divided into four groups: those who had mechanical bowel preparation with oral antibiotics, mechanical bowel preparation alone, oral antibiotics alone and no preparation. The main outcome measures included overall, superficial, deep and organ/space surgical site infections. Secondary outcomes included anastomotic leak, ileus and rate of Clostridium difficile. RESULTS: A total of 5729 patients were included for analysis. The overall surgical site infection rate (any superficial, deep or organ/space infection) was significantly lower in the mechanical bowel preparation and oral antibiotics approach when compared to no preparation (OR = 0.46, 95% CI 0.36-0.59, P < 0.0001). On multivariable logistic regression analysis, mechanical bowel preparation with oral antibiotics maintained a lower risk of overall surgical site infections. MBP and OAB also had a protective effect on anastomotic leak in both the laparoscopic and open cohorts (laparoscopic multivariable adjusted OR = 0.42 (0.19-0.94), P = 0.035; open multivariable adjusted OR = 0.3 (0.12-0.77), P = 0.012). Mechanical bowel preparation alone and oral antibiotics alone was not associated with a significant decrease in surgical site infections. There was no increase in C. difficile occurrences with the use of oral antibiotics. CONCLUSION: Mechanical bowel preparation with oral antibiotics significantly minimised surgical site infections and anastomotic leak following both laparoscopic and open left-sided restorative colorectal surgery. Mechanical bowel preparation alone did not reduce surgical site infections. There was a trend to reduction in surgical site infections with oral antibiotics alone.

Impact of Patient Preparation on the Diagnostic Performance of 18F-FDG PET in Cardiac Sarcoidosis: A Systematic Review and Meta-analysis.

PURPOSE: F-FDG PET/CT is a valuable diagnostic tool in the evaluation of cardiac sarcoidosis. Appropriate patient preparation is important because the diagnostic accuracy of this procedure depends on adequate suppression of physiologic glucose uptake. This systematic review and meta-analysis aims to assess the effect of different patient preparations on the diagnostic accuracy of F-FDG PET/CT in cardiac sarcoidosis. PATIENTS AND METHODS: We searched the PubMed/MEDLINE, Embase, and Cinicaltrials.gov databases. Sixteen studies (n = 559) were identified to be suitable for this systemic review. Studies were stratified according to fasting duration and means of physiologic suppression of F-FDG by cardiac tissue, which involves the use of heparin infusion or high-fat, low-carbohydrate diet before imaging. Study quality was assessed using the QUADAS-2 tool. Forest plots of sensitivity and specificity were calculated in Review Manager 5.3, and a random-effects hierarchical summary receiver operating characteristic model was created using MetaDiSc. Meta-regression was performed to investigate sources of heterogeneity. RESULTS: PET/CT had an overall Specificity of 0.75 (95% confidence interval [CI], 0.69-0.80) and specificity of 0.81 (95% CI, 0.76-0.85) for the diagnosis of cardiac sarcoidosis. This modest diagnostic accuracy was attributed to the inclusion of large single study in which a short fasting duration before scanning likely influenced its sensitivity. Its exclusion resulted in an overall sensitivity of 0.81 (95% CI, 0.76-0.86) and specificity of 0.82 (95% CI, 0.77-0.86). Meta-regression showed that the diagnostic odds ratio was significantly affected by fasting time and heparin administration before scanning (P = 0.01, 0.02) but not with high-fat, low-carbohydrate diet (P = 0.17). CONCLUSIONS: F-FDG PET/CT plays an integral role in the diagnosis of cardiac sarcoidosis. Diagnostic accuracy is affected by fasting duration and means of cardiomyocyte glucose uptake suppression before scanning.

Prospective Comparison of 18F-Fluoromethylcholine Versus 68Ga-PSMA PET/CT in Prostate Cancer Patients Who Have Rising PSA After Curative Treatment and Are Being Considered for Targeted Therapy.

UNLABELLED: In prostate cancer with biochemical failure after therapy, current imaging techniques have a low detection rate at the prostate-specific antigen (PSA) levels at which targeted salvage therapy is effective. (11)C-choline and (18)F-fluoromethylcholine, though widely used, have poor sensitivity at low PSA levels. (68)Ga-PSMA (Glu-NH-CO-NH-Lys-(Ahx)-[(68)Ga-N,N'-bis[2-hydroxy-5-(carboxyethyl)benzyl]ethylenediamine-N,N'-diacetic acid]) has shown promising results in retrospective trials. Our aim was to prospectively compare the detection rates of (68)Ga-PSMA versus (18)F-fluoromethylcholine PET/CT in men who were initially managed with radical prostatectomy, radiation treatment, or both and were being considered for targeted therapy. METHODS: A sample of men with a rising PSA level after treatment, eligible for targeted treatment, was prospectively included. Patients on systemic treatment were excluded. (68)Ga-PSMA, (18)F-fluoromethylcholine PET/CT, and diagnostic CT were performed sequentially on all patients between January and April 2015, and the images were assessed by masked, experienced interpreters. The findings and their impact on management were documented, together with the results of histologic follow-up when feasible. RESULTS: In total, 38 patients were enrolled. Of these, 34 (89%) had undergone radical prostatectomy and 4 (11%) had undergone radiation treatment. Twelve (32%) had undergone salvage radiation treatment after primary radical prostatectomy. The mean PSA level was 1.74 ± 2.54 ng/mL. The scan results were positive in 26 patients (68%) and negative with both tracers in 12 patients (32%). Of the 26 positive scans, 14 (54%) were positive with (68)Ga-PSMA alone, 11 (42%) with both (18)F-fluoromethylcholine and (68)Ga-PSMA, and only 1 (4%) with (18)F-fluoromethylcholine alone. When PSA was below 0.5 ng/mL, the detection rate was 50% for (68)Ga-PSMA versus 12.5% for (18)F-fluoromethylcholine. When PSA was 0.5-2.0 ng/mL, the detection rate was 69% for (68)Ga-PSMA versus 31% for (18)F-fluoromethylcholine, and when PSA was above 2.0, the detection rate was 86% for (68)Ga-PSMA versus 57% for (18)F-fluoromethylcholine. On lesion-based analysis, (68)Ga-PSMA detected more lesions than (18)F-fluoromethylcholine (59 vs. 29, P < 0.001). The tumor-to-background ratio in positive scans was higher for (68)Ga-PSMA than for (18)F-fluoromethylcholine (28.6 for (68)Ga-PSMA vs. 9.4 for (18)F-fluoromethylcholine, P < 0.001). There was a 63% (24/38 patients) management impact, with 54% (13/24 patients) being due to (68)Ga-PSMA imaging alone. Histologic follow-up was available for 9 of 38 patients (24%), and 9 of 9 (68)Ga-PSMA-positive lesions were consistent with prostate cancer ((68)Ga-PSMA was true-positive). The lesion positive on (18)F-fluoromethylcholine imaging and negative on (68)Ga-PSMA imaging was shown at biopsy to be a false-positive (18)F-fluoromethylcholine finding ((68)Ga-PSMA was true-negative). CONCLUSION: In patients with biochemical failure and a low PSA level, (68)Ga-PSMA demonstrated a significantly higher detection rate than (18)F-fluoromethylcholine and a high overall impact on management.

Limited evidence for calcium supplementation in preeclampsia prevention: a meta-analysis and systematic review.

OBJECTIVE: This article synthesises evidence for calcium supplementation in preeclampsia prevention. METHODS: Major databases and trial registries were searched, and comparisons were made against other meta-analyses. RESULTS: Calcium supplementation reduced the overall risk of preeclampsia in 10 trials (n = 24 787; risk ratio (RR) 0.62; 95% confidence interval [CI] 0.47-0.81). Its effect was larger in two subgroups: low-baseline calcium intake (RR 0.42 [0.23-0.76]) and increased risk of developing hypertensive disorders (RR 0.36 [0.10-0.98]). This effect was not significant amongst larger studies (RR 0.93 [0.83-1.04]). Funnel plotting suggested possible publication bias. CONCLUSION: Some evidence for calcium supplementation exists, but its utility is limited by the possibility of publication bias and a lack of large trials.

Surgical safety checklists: a review.

BACKGROUND: Surgical checklists are designed to improve patient outcomes following surgery. While such checklists have been widely implemented worldwide, few studies examine surgical checklists within an Australian context. For this purpose, we have performed a literature review using data from OECD member nations to determine the effectiveness of surgical checklists in improving patient outcomes and factors that contribute to their successful implementation. METHOD: The databases, Pubmed, Medline, EMBASE, Cochrane and CINAHL were searched using the keywords ('surgical' AND 'checklist') and ( (surgical) AND checklist) AND ( (implementation) OR (utilization) OR (usage) ). Studies were limited to those written in the English language, peer-reviewed, published between January 2000 and December 2012, and including an abstract. RESULTS: Our search yielded 2242 papers, of which 72 papers were identified for their potential relevance and selected for full text review. Of these, nine papers met the inclusion criteria and were reviewed in detail. Evidence that supports the use of surgical checklists in countries with a large number of protocols already in place is limited. Adequate checklist implementation plays a central role in checklist effectiveness, which in turn is dependent on multiple factors. CONCLUSION: Although evidence from OECD member countries is non-conclusive, it does suggest that surgical checklists, when effectively implemented, have the potential to be effective at reducing complication and mortality rates following surgery. Within an Australian context, more studies are needed to fully establish the potential effectiveness of surgical checklists and to monitor checklist use compliance in order to ensure greater patient safety.