A New Era in Perforator Flap Surgery for Breast Reconstruction: A Comparative Study of Robotic versus Standard Harvest of Bilateral Deep Inferior Epigastric Artery Perforator Flaps.

BACKGROUND: Traditional deep inferior epigastric artery perforator (DIEP) flap harvest splits the anterior sheath, weakening the abdominal wall and predisposing patients to bulge or hernia. Abdominal wall morbidity may be decreased using minimally invasive techniques. We refined a transabdominal approach to the robotic harvest of bilateral DIEP flaps. METHODS: A retrospective medical record study involving all patients who underwent bilateral or bipedicled robotic DIEP (rDIEP) or standard DIEP (sDIEP) flap harvest between July 2021 and September 2022. Outcomes included abdominal wall morbidity, total operative time, length of stay (LOS), and complications. RESULTS: Forty-seven patients were included (48 sDIEP flaps, 46 rDIEP flaps) with no significant difference in patient characteristics. Fascial incision length in the rDIEP group was shorter (4.1 vs. 11.7 cm, p < 0.001). Mesh reinforcement of the abdominal wall was used in 13/24 sDIEP and none in rDIEP patients (p < 0.001). Operative time was longer in the rDIEP cohort (739 vs. 630 minutes, p = 0.013), although subanalysis showed no difference in the second half of the cohort. The average robotic dissection time was 135 minutes, which decreased significantly with the surgeon's experience. There were no intraoperative complications from using the robot. LOS was shorter with rDIEP but not statistically significant (3.9 vs. 4.3 days, p = 0.157). CONCLUSION: This study represents the most extensive cohort analysis of bilateral rDIEP flap harvest, offering a comprehensive comparison to traditional sDIEP. The initial results underscore the viability of robotic techniques for flap harvesting, highlighting potential advantages including reduced fascial incision length and decreased abdominal disruption. Furthermore, using robotics may obviate the necessity for fascial reinforcement with mesh.

Prospective implementation of a standardized screening protocol for deep venous thrombosis in abdominal surgical oncology patients.

BACKGROUND AND OBJECTIVES: Venous thromboembolism (VTE) remains a major cause of perioperative morbidity and mortality despite implementation of prophylaxis guidelines. We sought to identify risk factors for occult deep venous thrombosis (DVT) following abdominal surgery for cancer and measure the clinical impact of a prospectively implemented standardized postoperative DVT screening protocol. METHODS: Patients undergoing abdominal surgery for malignant indication were screened with early postoperative lower extremity duplex to identify DVT. Clinical and pathologic factors associated with DVT were identified. RESULTS: Among 255 patients meeting study criteria, 25 (9.8%) had occult lower extremity DVT on routine postoperative screening. Prior history of VTE and lower preoperative hemoglobin were independently associated with DVT (OR, 9.05; P = 0.004; and OR, 1.27; P = 0.025, respectively). Preoperative chemotherapy within 1 year and thrombocytopenia were associated with DVT in univariate analyses only. Five patients developed postoperative pulmonary emboli (2.0%); three following negative duplex and two following positive duplex for distal DVT for which the patients were not therapeutically anticoagulated due to a contraindication. There were no pulmonary emboli in duplex-positive patients who were anticoagulated or who had vena cava filter placed. CONCLUSION: Despite prophylaxis, the prevalence of occult DVT in abdominal oncologic surgery patients is considerable. Postoperative screening duplex can identify these events to guide management.

A retrospective evaluation of radiation dose associated with low dose FDG protocols in whole-body PET/CT.

The objective of the study is to retrospectively measure patient radiation dose resulting from whole body X-ray CT and FDG PET studies using a low-dose protocol performed on the Siemens Biograph mCT scanner. A total of 483 patient studies were reviewed. For each, the CT dose-length product was used to estimate radiation dose to the patient as a result of the whole body X-ray CT component of the PET/CT study. The net injected FDG dose was used to calculate the whole body effective dose based on ICRP recommendations. Dose calculations were also modified to take into account individual patient weight. The total effective dose received by each patient was taken as the sum of the PET and CT components of the study. The mean effective dose from the CT component of the diagnostic study was found to be 8.2 mSv (3.4-23.4 mSv), for a CT protocol of 120 kV(p) and effective tube current-time product of 80 mAs with automatic exposure control. For an average injected FDG activity of 304 MBq the mean PET effective dose was found to be 6.3 mSv when using the ICRP standard models, or 6.0 mSv when scaling effective dose to individual patient weight or patient blood volume. The average total effective dose across the entire patient cohort for a combined PET/CT study was found to be ~14.5 mSv (9.6-29.8 mSv). Low-dose protocols for whole-body PET/CT scanning result in an effective radiation dose to the patient of approximately 14.5 mSv. Additional reductions through the use of iterative CT reconstruction and optimized low-dose FDG protocols could see total effective doses for whole-body PET/CT fall to below 10 mSv.

The Effects of the Affordable Care Act on Utilization of Bariatric Surgery.

INTRODUCTION: The Affordable Care Act (ACA) expanded Medicaid (ME) and instituted Essential Health Benefits (EHB) that included bariatric surgery coverage on a state-by-state opt-in basis, increasing insurance coverage of bariatric surgery. MATERIALS AND METHODS: Using a difference-in-differences framework, changes in bariatric surgery rates, defined as utilization in the population of people with obesity, before and after the ACA were evaluated in four states. Bariatric surgery procedure data were taken from the Healthcare Cost and Utilization Project's State In-patient Database 2012-2015. Adjusted multivariable regressions were run in the Medicaid and commercially insured populations. RESULTS: We identified 36,456 bariatric surgeries across the 286 Health Service Areas and time periods, with 31,732 covered by commercial insurers and 4724 covered by Medicaid. An unadjusted increase in utilization rates was seen in the Medicaid and Commercial populations in both ME- and EHB-covered states as well as non-expansion and EHB opt-out states over time. In the Medicaid population, after adjusting for confounders, there was a significant increase of 24.77 cases per 100,000 people with obesity (95% confidence interval: 12.41, 37.13) in the expansion states relative to the control and pre-period. The commercial population experienced a nonsignificant change in the rates of bariatric surgery, decreasing by 2.89 cases per 100,000 people with obesity (95% confidence interval: - 21.59, 15.81). CONCLUSIONS: There was a significant increase in bariatric surgery rates among Medicaid beneficiaries associated with Medicaid expansion, but there was no change among the commercially insured.

Evaluation of Fluorodeoxyglucose Positron Emission Tomography Scanning in the Neoadjuvant Therapy Paradigm in Pancreatic Ductal Adenocarcinoma.

OBJECTIVES: Little data exist on the utility of fluorodeoxyglucose positron emission tomography (FDG-PET) in operable pancreatic ductal adenocarcinoma (PDAC) treated with neoadjuvant (NA) therapy. METHODS: Consecutively treated patients with potentially operable PDAC were recruited from a quaternary referral center between 2015 and 2018. Data were collated on demographic, clinical, radiological, treatment, and disease-free and overall survival (OS) outcome measures, correlated with FDG-PET findings. RESULTS: Of 115 patients recruited, 61% were deemed upfront operable (n = 70), 33% borderline (n = 38), and 6% (n = 7) locally advanced. Ninety-five (83%) received NA chemotherapy with 23 (24%) sequential radiotherapy. Sixty-nine (73%) treated with NA were resected, 37 (54%) attained an R0 resection, 43 (62%) had N1 disease with median tumor viability of 50%. The median OS in the entire cohort was 30.48 months and in those who received NA chemotherapy followed by resection 37.98 months. Twelve percent (n = 13) were upstaged during NA therapy by PET. Preoperative standardized uptake value maximum of less than 5 versus 5 or greater after NA predicted for improved OS, 42.95 months versus 26.05 months, P = 0.02. CONCLUSIONS: In this real-world cohort study of PDAC, the utility of FDG-PET in informing the patient treatment pathway was meaningfully demonstrated.

Technologist Approach to Global Dose Optimization.

Nuclear medicine technologists are specialized health professionals who cover a wide range of tasks from clinical routine (including image acquisition and processing, radiopharmaceutical dispensing and administration, patient care, and radioprotection tasks) to leading clinical research in the field of nuclear medicine. As a fundamental concern in all radiation sciences applied to medicine, protection of individuals against the harmful effects of ionizing radiation must be constantly revised and applied by the professionals involved in medical exposures. The acknowledgment that nuclear medicine technologists play a prominent role in patient management and several procedural steps, both in diagnostic and in therapeutic nuclear medicine applications, carries the duty to be trained and knowledgeable on the topic of radiation protection and dose optimization. An overview on selected topics related to dose optimization is presented in this article, reflecting the similarities and particularities of dose reduction-related principles, initiatives, and practicalities from a global perspective.

Does Perceived Resident Operative Autonomy Impact Patient Outcomes?

OBJECTIVE: We investigated the association of perceived trainee autonomy with patient clinical outcomes following colorectal surgery. DESIGN: This was a prospective multi-institutional study that consisted of surgery trainees completing a survey tool immediately after participating in colorectal resections to rate their self-perceived autonomy and case characteristics. Self-perception of autonomy was classified as observer, assistant, surgeon, or teacher. The completed trainee surveys were linked with patient information available through each hospital's internal NSQIP directory. The primary outcome was death and serious morbidity (DSM) and secondary outcome was 30-day readmissions. Separate mixed effects regression models were used to examine the association between perceived trainee autonomy and DSM or 30-day readmissions. Fixed effects were used to control for the effects of the training environment. The models were constructed to adjust for patient and trainee characteristics associated with each outcome independently. SETTING: This study was conducted at 7 general surgery training programs (5 academic medical centers and 2 independent training programs) with general surgery or colorectal surgery services. PARTICIPANTS: This study included a total of 63 residents and fellows rotating on surgery services that performed colorectal resections at the included 7 general surgery training programs from January until March 2016. RESULTS: The 63 trainees that participated in this study completed 417 surveys with over a 95% response rate. National Surgical Quality Improvement Program (NSQIP) patient records were available for 67% (n = 273) of completed surveys. The clinical year of the trainees were 6.1% PGY 1/2, 36% Post graduate year (PGY) 3, 40.9% PGY 4/5, and 17% fellows. Residents perceived their participation in the case to be that of an observer in 9.2% of surveys, an assistant in 51.6% of surveys, and the surgeon/teacher in 39.3% of surveys. About 50% of patients were male, 80% were White, the majority had an American Society of Anesthesiologists classification of 3, almost half had prior abdominal surgery, and over 80% of surgeries were elective. The primary operation types performed were laparoscopic (40.3%) and open (35.9%) partial colectomies. The rate of DSM in patients was approximately 24% when trainees perceived their role as observers, 23% when trainees perceived their role as assistants, and 18% when trainees perceived their role as surgeons/teachers. After adjustment for patient, trainee, and training environment, we found that the perceived level of trainee autonomy of a surgeon/teacher was associated with a 4-fold lower rate of DSM (odds ratio: 0.23, confidence of interval: 0.05-0.97, p = 0.045) compared to observers. The rate of readmissions was approximately 20% when trainees perceived their role as observers, 14% when trainees perceived their role as assistants and 9% when trainees perceived their role as surgeons/teachers. After adjustment for patient, trainee, and training environment, we found that the perceived level of trainee autonomy of a surgeon/teacher was significantly associated with a 10-fold lower rate of 30-day readmissions (odds ratio: 0.09, confidence of interval: 0.01-0.70, p = 0.022) compared to observers. CONCLUSIONS: There was an association between increased perceived trainee autonomy and improved patient outcomes, suggesting that when trainees identify with an increased role in the operation, patients may have improved care. Further research is needed to understand this association further.

Objective analysis of whole lung and lobar ventilation/perfusion relationships in pulmonary embolism.

PURPOSE: Lung scintigraphy using single photon emission computed tomography (SPECT) allows accurate regional measurement of the ventilation/perfusion (V/Q) relationship. Objective V/Q analysis has been shown to be useful in the diagnosis of pulmonary embolism (PE). By using anatomical information provided by co-registered computed tomography, we describe methodology for determining the extent of V/Q heterogeneity at a lobar level. We investigate this methodology using simulated data, and demonstrate its potential application in the clinical setting of PE. METHODS: Data representing an incremental perfusion defect involving the right lung, together with an unaffected ventilation dataset, were modelled using Monte Carlo simulation. For each increase in the size of the perfusion defect, the whole lung V/Q relationship was objectively determined. In addition, using an image mask of the pulmonary lobes, lobar V/Q relationships were also determined. V/Q heterogeneity was characterized using the log(10) standard deviation of the V/Q ratio (log SDVQR), ventilation (log SDV) and perfusion (log SDQ) distributions. Finally, this methodology was explored in clinical cases. RESULTS: As an increasing number of segments were involved by perfusion defects, there was a progressive increase in all objective parameters of V/Q heterogeneity. The relative change was greatest for log SDV. Analysis of both the simulated and clinical studies demonstrated sensitive changes in the lobar V/Q profiles to the presence of PE. CONCLUSIONS: Segmentation and analysis of SPECT ventilation-perfusion scintigraphy at a lobar level can be used to quantify regional V/Q relationships. This objective methodology is sensitive to the presence of PE, and may be useful in a clinical setting.

Generation of planar images from lung ventilation/perfusion SPECT.

OBJECTIVE: To develop a method of producing lung ventilation and perfusion (V/Q) planar images using forward projection of reconstructed single-photon emission computed tomography (SPECT) images through approximate attenuation (micro) maps generated from the lung emission scans alone, as transmission-based micro maps may not be routinely available. METHODS: Synthetic micro maps are derived from (99m)Tc photopeak and "scatter" windows for the attenuation correction of the SPECT images. The attenuation-corrected SPECT images are forward projected at appropriate angles to give the equivalent of planar images. This method allows high-count planar images, as well as the SPECT images, to be produced from a single SPECT acquisition. In addition, isolated "single lung" views of lateral and medial projections without "shine-through" from the contra-lateral lung, which have not been available previously, can be formed. RESULTS: Comparison of reprojected images produced from CT-derived or synthetic micro maps displayed similar detail and radiopharmaceutical distribution. In a blinded comparison of "true" planar images with those from reprojecting the SPECT data using the synthetic micro maps, no difference in mismatched defect detection was found, and hence it was confirmed that the reprojected planar images could replace true planar images with no loss in planar diagnostic sensitivity. CONCLUSIONS: The reprojected planar images provide high-count, high-quality images, which are comparable with conventional 2D images.

Disparities in operative outcomes in patients with comorbid mental illness.

BACKGROUND: Patients with mental health disorders have worse medical outcomes and experience excess mortality compared with those without a mental health comorbidity. This study aimed to evaluate the relationship between mental health comorbidities and surgical outcomes. METHODS: This retrospective cohort study used the National Inpatient Sample (2009-2011) to select patients who underwent one of the 4 most common general surgery procedures (cholecystectomy and common duct exploration, colorectal resection, excision and lysis of peritoneal adhesions, and appendectomy). Patients with a concurrent mental health diagnosis were identified. Multivariable logistic regression examined outcomes, including prolonged length of stay, in-hospital mortality, and postoperative complications. RESULTS: Of the 579,851 patients included, 38,702 patients (6.7%) had a mental health diagnosis. Mood disorders were most prevalent (58.7%), followed by substance abuse (23.8%). After adjustment for confounders, including sex, race, number of comorbidities, admission status, open operations, insurance, and income quartile, we found that having a mental health diagnosis conferred a 40% greater odds of including prolonged length of stay (OR 1.41, P < .001) and increased odds of any complication (OR 1.18, P < .001). Odds of death were slightly less in the mental health diagnosis cohort. CONCLUSIONS: General surgery patients with comorbid mental disease experience a greater incidence of postoperative complications and longer hospitalizations. Recognizing these disparate outcomes is the first step in understanding how to optimize care for this frequently marginalized population.

Association of Surgical Practice Patterns and Clinical Outcomes With Surgeon Training in University- or Nonuniversity-Based Residency Program.

Importance: Important metrics of residency program success include the clinical outcomes achieved by trainees after transitioning to practice. Previous studies have shown significant differences in reported training experiences of general surgery residents at nonuniversity-based residency (NUBR) and university-based residency (UBR) programs. Objective: To examine the differences in practice patterns and clinical outcomes between surgeons trained in NUBR and those trained in UBR programs. Design, Setting, and Participants: This observational cohort study linked the claims data of patients who underwent general surgery procedures in New York, Florida, and Pennsylvania between January 1, 2012, and December 31, 2013, to demographic and training information of surgeons in the American Medical Association Physician Masterfile. Patients who underwent a qualifying procedure were grouped by surgeon. Practice pattern analysis was performed on 3638 surgeons and 1 237 621 patients, representing 214 residency programs. Clinical outcomes analysis was performed on 2301 surgeons and 312 584 patients. Data analysis was conducted from February 1, 2017, to July 31, 2017. Exposures: NUBR or UBR training status. Main Outcomes and Measures: Inpatient mortality, complications, and prolonged length of stay. Results: No significant differences were observed between the NUBR-trained surgeons and UBR-trained surgeons in age (mean, 53.3 years vs 53.7 years), sex (female, 18.2% vs 16.9%), or years of clinical experience (mean, 16.5 years vs 16.5 years). Overall, NUBR-trained surgeons compared with UBR-trained surgeons performed more procedures (median interquartile range [IQR], 328 [93-661] vs 164 [49-444]; P < .001) and performed a greater proportion of procedures in the outpatient setting (risk difference, 6.5; 95% CI, 6.4 to 6.7; P < .001). Before matching, the mean proportion of patients with documented inpatient mortality was lower for NUBR-trained surgeons than for UBR-trained surgeons (risk difference, -1.01; 95% CI, -1.41 to -0.61; P < .001). The mean proportion of patients with complications (risk difference, -3.17%; 95% CI, -4.21 to -2.13; P < .001) and prolonged length of stay (risk difference, -1.89%; 95% CI, -2.79 to -0.98; P < .001) was also lower for NUBR-trained surgeons. After matching, no significant differences in patient mortality, complications, and prolonged length of stay were found between NUBR- and UBR-trained surgeons. Conclusions and Relevance: Surgeons trained in NUBR and UBR programs have distinct practice patterns. After controlling for patient, procedure, and hospital factors, no differences were observed in the inpatient outcomes between the 2 groups.

Quantification of Resident Work in Colorectal Surgery.

OBJECTIVE: To examine resident intraoperative participation, perceived autonomy, and communication patterns between residents and attending surgeons using a novel survey tool. DESIGN: This was a prospective multi-institutional study. Operative residents completed the survey tool immediately after each colorectal resection performed during the study period. Resident intraoperative participation was quantified including degree of involvement in the technical aspects of the case, self-perception of autonomy, and communication strategies between the resident and attending. SETTING: This study was conducted at 7 general surgery residency programs: 5 academic medical centers, and 2 independent training programs. PARTICIPANTS: Residents and fellows rotating on a colorectal surgery service or general surgery service. RESULTS: Sixty-three residents participated in this study with 417 surveys completed (range 19-79 per institution) representing a 95.4% response rate across all sites. Respondents ranged from clinical year 1 (CY1) to fellows. CY3s (35.7%) and CY5s (34.7%) were most heavily represented. Residents completed ≥50% of the skin closure in 88.7% of cases, ≥50% of the fascial closure in 87.1%, and t ≥ 50% of the anastomosis in 78.4% of the cases. Increasing resident participation was associated with advancing resident CY across all technical aspects of the case. This trend remained significant when controlling for site (p < 0.001). Resident self-perception of autonomy revealed learners of all stages: Observer (11.5%, n = 48), Assistant (53.7%, n = 224), Surgeon (33.8%, n = 141), and Teacher (0.96%, n = 4). Level of perceived autonomy increased with resident CY when controlling for site (p < 0.001). Residents who discussed the case before the day of surgery were twice as likely to rate themselves as Surgeon or Teacher (OR = 2.01) when controlling for CY (p = 0.011). CONCLUSIONS: Brief surveys can easily capture resident work in the operating room. Resident intraoperative involvement and perceived autonomy are associated with CY. Early communication with the attending is significantly associated with increased perception of autonomy regardless of CY.

Development and validation of a prediction model for patients discharged to post-acute care after colorectal cancer surgery.

BACKGROUND: As payment shifts toward bundled reimbursement, decreasing unnecessary inpatient care may provide cost savings. This study examines the association between discharge status, hospital duration of stay, and cost for colorectal operation patients without complications and uses risk factors to predict the need for post-acute care. METHODS: We used the New York Statewide Planning and Research Cooperative System and the California Healthcare Cost and Utilization Project State Inpatient Databases to identify all patients who underwent operative resection for colorectal cancer in 2009-2010 and were discharged to home or post-acute care. Patients with complications were excluded. Duration of stay and inpatient costs were calculated. Risk factors associated with discharge to post-acute care were identified using multivariable logistic regression and were incorporated into a model to predict discharge status. RESULTS: A total of 5.4% of 23,942 patients were discharged to a post-acute care facility. Duration of sty was 2 days greater and $3,823 more costly for patients discharged to post-acute care. Significant risk factors included age, number of comorbidities, emergency admission, open operation, admission in the previous year, and a new ostomy. A scoring system using these factors accurately predicted discharge to post-acute care. CONCLUSION: Admissions after colorectal operations were greater and more costly for patients discharged to post-acute care even without operative complications. Risk factors can predict the need for post-acute care early in the postoperative course, thereby potentially facilitating early discharge planning.

A Novel Histone Crosstalk Pathway Important for Regulation of UV-Induced DNA Damage Repair in Saccharomyces cerevisiae.

Histone post-translational modifications play vital roles in a variety of nuclear processes, including DNA repair. It has been previously shown that histone H3K79 methylation is important for the cellular response to DNA damage caused by ultraviolet (UV) radiation, with evidence that specific methylation states play distinct roles in UV repair. Here, we report that H3K79 methylation is reduced in response to UV exposure in Saccharomyces cerevisiae This reduction is specific to the dimethylated state, as trimethylation levels are minimally altered by UV exposure. Inhibition of this reduction has a deleterious effect on UV-induced sister chromatid exchange, suggesting that H3K79 dimethylation levels play a regulatory role in UV repair. Further evidence implicates an additional role for H3K79 dimethylation levels in error-free translesion synthesis, but not in UV-induced G1/S checkpoint activation or double-stranded break repair. Additionally, we find that H3K79 dimethylation levels are influenced by acetylatable lysines on the histone H4 N-terminal tail, which are hyperacetylated in response to UV exposure. Preclusion of H4 acetylation prevents UV-induced reduction of H3K79 dimethylation, and similarly has a negative effect on UV-induced sister chromatid exchange. These results point to the existence of a novel histone crosstalk pathway that is important for the regulation of UV-induced DNA damage repair.

Outcomes of hospitalized patients undergoing emergency general surgery remote from admission.

BACKGROUND: Emergency general surgery during hospitalization has not been well characterized. We examined emergency operations remote from admission to identify predictors of postoperative 30-day mortality, postoperative duration of stay >30 days, and complications. METHODS: Patients >18 years in The American College of Surgeons National Surgical Quality Improvement Program (2011-2014) who had 1 of 7 emergency operations between hospital day 3-18 were included. Patients with operations >95th percentile after admission (>18 days; n = 581) were excluded. Exploratory laparotomy only (with no secondary procedure) represented either nontherapeutic or decompressive laparotomy. Multivariable logistic regression was used to identify predictors of study outcomes. RESULTS: Of 10,093 patients with emergency operations, most were elderly (median 66 years old [interquartile ratio: 53-77 years]), white, and female. Postoperative 30-day mortality was 12.6% (n = 1,275). Almost half the cohort (40.1%) had a complication. A small subset (6.8%) had postoperative duration of stay >30 days. Postoperative mortality after exploratory laparotomy only was particularly high (>40%). In multivariable analysis, an operation on hospital day 11-18 compared with day 3-6 was associated with death (odds ratio 1.6 [1.3-2.0]), postoperative duration of stay >30 days (odds ratio 2.0 [1.6-2.6]), and complications (odds ratio 1.5 [1.3-1.8]). Exploratory laparotomy only also was associated with death (odds ratio 5.4 [2.8-10.4]). CONCLUSION: Emergency general surgery performed during a hospitalization is associated with high morbidity and mortality. A longer hospital course before an emergency operation is a predictor of poor outcomes, as is undergoing exploratory laparotomy only.

SPECT/CT imaging using a spiral CT scanner for anatomical localization: Impact on diagnostic accuracy and reporter confidence in clinical practice.

PURPOSE: To evaluate the incremental benefit in routine clinical practice of computed tomography (CT) scans acquired for anatomical localization on an integrated SPECT/CT which incorporates a spiral CT scanner, in comparison with conventional planar and SPECT scanning. METHODS: The first 50 studies acquired on the integrated system were evaluated by two experienced nuclear medicine physicians who were aware of the patient's clinical history. These included bone scans, gallium scans, octreotide scans, sestamibi parathyroid scans and MIBG scans. For each patient study, abnormalities were assessed on planar and SPECT images for location and provisional diagnosis and a quantitative scale was used to assess reporter confidence. The fused SPECT/CT images were then reviewed and the location and provisional diagnosis noted and reporter confidence was assessed using the same quantitative scale. RESULTS: There were 129 abnormalities detected in 50 patient studies. For localization of abnormalities, the inclusion of the CT resulted in a minor change in 16% of cases and a significant change in 11% over planar/SPECT imaging alone. The confidence of localization was improved moderately in 19% and improved significantly in 6%. For diagnosis, SPECT/CT resulted in a minor change in 10% and a significant change in 9% over planar/SPECT imaging. The confidence of diagnosis was improved moderately in 10% and improved significantly in a further 10% of cases. For the final scan interpretation, there would have been no change in 44% patients, a minor change in 30% and a significant change in 26% with the use of SPECT/CT. CONCLUSION: Use of integrated SPECT/CT with a high spatial resolution, spiral CT used for anatomical localization improves accuracy and reporter confidence in clinical practice. As a result, final reports were different in 56% of the cases, including being significantly different in 26% patients compared to reporting with planar/SPECT alone.

Lutetium-177 DOTATATE Production with an Automated Radiopharmaceutical Synthesis System.

OBJECTIVES: Peptide Receptor Radionuclide Therapy (PRRT) with yttrium-90 ((90)Y) and lutetium-177 ((177)Lu)-labelled SST analogues are now therapy option for patients who have failed to respond to conventional medical therapy. In-house production with automated PRRT synthesis systems have clear advantages over manual methods resulting in increasing use in hospital-based radiopharmacies. We report on our one year experience with an automated radiopharmaceutical synthesis system. METHODS: All syntheses were carried out using the Eckert & Ziegler Eurotope's Modular-Lab Pharm Tracer® automated synthesis system. All materials and methods used were followed as instructed by the manufacturer of the system (Eckert & Ziegler Eurotope, Berlin, Germany). Sterile, GMP-certified, no-carrier added (NCA) (177)Lu was used with GMP-certified peptide. An audit trail was also produced and saved by the system. The quality of the final product was assessed after each synthesis by ITLC-SG and HPLC methods. RESULTS: A total of 17 [(177)Lu]-DOTATATE syntheses were performed between August 2013 and December 2014. The amount of radioactive [(177)Lu]-DOTATATE produced by each synthesis varied between 10-40 GBq and was dependant on the number of patients being treated on a given day. Thirteen individuals received a total of 37 individual treatment administrations in this period. There were no issues and failures with the system or the synthesis cassettes. The average radiochemical purity as determined by ITLC was above 99% (99.8 ± 0.05%) and the average radiochemical purity as determined by HPLC technique was above 97% (97.3 ± 1.5%) for this period. CONCLUSIONS: The automated synthesis of [(177)Lu]-DOTATATE using Eckert & Ziegler Eurotope's Modular-Lab Pharm Tracer® system is a robust, convenient and high yield approach to the radiolabelling of DOTATATE peptide benefiting from the use of NCA (177)Lu and almost negligible radiation exposure of the operators.

Pulmonary hypertension leads to a loss of gravity dependent redistribution of regional lung perfusion: a SPECT/CT study.

OBJECTIVE: Pre-capillary pulmonary hypertension (PHT) is characterised by progressive pulmonary vascular obliteration and loss of vascular reserves. In health, regional lung perfusion redistributes under the influence of gravity due to the presence of recruitable vessels. We investigated a combined single photon emission computed tomography/CT (SPECT/CT) method for assessing the pulmonary circulation by quantifying the gravity dependent redistribution of lung perfusion. DESIGN: Characterisation of patients versus healthy controls. PATIENTS: 15 patients with pre-capillary PHT and 11 healthy controls. SETTING: University hospital clinic. INTERVENTION: Regional lung perfusion was measured using SPECT/CT in two different postures (supine vs upright). A perfusion redistribution index (PRI) was used to quantify the cranial-caudal shift in regional lung perfusion resulting from gravitational (postural) change. MAIN OUTCOME MEASURE: PRI was compared between cases and controls, and correlated with markers of disease severity in cases. RESULTS: Patients with pre-capillary PHT had notably reduced PRI compared to controls (0.02±0.06 vs. 0.28±0.15 normalised perfusion/cm, p<0.0001). PRI was significantly associated with prognostic parameters such as 6 min walk distance (r=0.60, p=0.018), functional class (p=0.008), and tricuspid annular plane systolic excursion (r=0.58, p=0.022). The receiver operating characteristic curve showed that PRI differentiated patients with pre-capillary PHT from controls with AUC=0.94 (p<0.001). CONCLUSIONS: With SPECT/CT, gravity dependent redistribution of lung perfusion can be quantified using the PRI derived from supine and upright perfusion analysis. The potential utility of PRI for the non-invasive detection of PHT and assessment of disease severity warrants further study.

Gallium-68 DOTATATE Production with Automated PET Radiopharmaceutical Synthesis System: A Three Year Experience.

OBJECTIVES: Gallium-68 (Ga-68) is an ideal research and hospital-based PET radioisotope. Currently, the main form of Ga-68 radiopharmaceutical that is being synthesised in-house is Ga-68 conjugated with DOTA based derivatives. The development of automated synthesis systems has increased the reliability, reproducibility and safety of radiopharmaceutical productions. Here we report on our three year, 500 syntheses experience with an automated system for Ga-68 DOTATATE. METHODS: The automated synthesis system we use is divided into three parts of a) servomotor modules, b) single use sterile synthesis cassettes and, c) a computerised system that runs the modules. An audit trail is produced by the system as a requirement for GMP production. The required reagents and chemicals are made in-. The Germanium breakthrough is determined on a weekly basis. Production yields for each synthesis are calculated to monitor the performance and efficiency of the synthesis. The quality of the final product is assessed after each synthesis by ITLC-SG and HPLC methods. RESULTS: A total of 500 Ga-68 DOTATATE syntheses (>800 patient doses) were performed between March 2011 and February 2014. The average generator yield was 81.3±0.2% for 2011, 76.7±0.4% for 2012 and 75.0±0.3% for 2013. Ga-68 DOTATATE yields for 2011, 2012, and 2013 were 81.8±0.4%, 82.2±0.4% and 87.9±0.4%, respectively. These exceed the manufacturer's expected value of approximately 70%. Germanium breakthrough averaged 8.6×10(-6)% of total activity which is well below the recommended level of 0.001%. The average ITLC-measured radiochemical purity was above 98.5% and the average HPLC-measured radiochemical purity was above 99.5%. Although there were some system failures during synthesis, there were only eight occasions where the patient scans needed to be rescheduled. CONCLUSION: In our experience the automated synthesis system performs reliably with a relatively low incident of failures. Our system had a consistent and reliable Ga-68 DOTATATE output with high labelling efficiency and purity. There is minimal operator intervention and radiation exposure. The system is GMP-compliant and has low maintenance and acceptable running costs. This system together with the recommended (68)Ge/(68)Ga generator is well suited for use in a hospital-based radiopharmacy.

Translation of Methodology Used In Human Myocardial Imaging to a Sheep Model of Acute Myocardial Infarction.

INTRODUCTION: Pre-clinical investigation of stem cells for repairing damaged myocardium predominantly uses rodents, however large animals have cardiac circulation closely resembling the human heart. The aim of this study was to evaluate whether SPECT/CT myocardial perfusion imaging (MPI) could be used for assessing sheep myocardium following an acute myocardial infarction (MI) and response to intervention. METHODS: Eighteen sheep were enrolled in a pilot study to evaluate [(99m)Tc]-sestamibi MPI at baseline, post-MI and after therapy. Modifications to the standard MPI protocols were developed. All data was reconstructed with OSEM using CT-derived attenuation and scatter correction. Standard analyses were performed and inter-observer agreement was measured using Kappa (κ). Power determined the sample sizes needed to show statistically significant changes due to intervention. RESULTS: Ten sheep completed the full protocol. Data processed was performed with pre-existing hardware and software used in human MPI scanning. No improvement in perfusion was seen in the control group, however improvements of 15%-35% were seen after intra-myocardial stem cell administration. Inter-observer agreement was excellent (К=0.89). Using a target power of 0.9, 28 sheep were required to detect a 10-12% change in perfusion. CONCLUSION: This study demonstrates the suitability of large animal models for imaging with standard MPI protocols and its feasibility with a manageable number of animals. These protocols could be translated into humans to study the efficacy of stem cell therapy in heart regeneration and repair.