From the Operating Room to Online: Medical Student Surgery Education in the Time of COVID-19.

BACKGROUND: On March 17, 2020 the Association of American Medical Colleges recommended dismissal of medical students from clinical settings due to the COVID-19 pandemic. Third-year (M3) and fourth-year (M4) medical students were at home, M4s were interested in teaching, and residents and faculty had fewer clinical responsibilities due to elective surgery cancellations. To continue M3 access to education, we created a virtual surgery elective (VSE) that aimed to broaden students' exposure to, and elicit interest in, general surgery (GS). METHODS: Faculty, surgical residents, and M4s collaborated to create a 2-wk VSE focusing on self-directed learning and direct interactions with surgery faculty. Each day was dedicated to a specific pathology commonly encountered in GS. A variety of teaching methods were employed including self-directed readings and videos, M4 peer lectures, case-based learning and operative video review with surgery faculty, and weekly surgical conferences. A VSE skills lab was also conducted to teach basic suturing and knot-tying. All lectures and skills labs were via Zoom videoconference (Zoom Video Communications Inc). A post-course anonymous survey sent to all participants assessed changes in their understanding of GS and their interest in GS and surgery overall. RESULTS: Fourteen M3s participated in this elective over two consecutive iterations. The survey response rate was 79%. Ninety-one percent of students believed the course met its learning objectives "well" or "very well." Prior to the course, 27% reported a "good understanding" and 0% a "very good" understanding of GS. Post-course, 100% reported a "good" or "very good" understanding of GS, a statistically significant increase (P = 0.0003). Eighty-two percent reported increased interest in GS and 64% reported an increase in pursuing GS as a career. CONCLUSIONS: As proof of concept, this online course successfully demonstrated virtual medical student education can increase student understanding of GS topics, increase interest in GS, and increase interest in careers in surgery. To broaden student exposure to GS, we plan to integrate archived portions of this course into the regular third-year surgery clerkship and these can also be used to introduce GS in the preclinical years.

Sustained Clinical Performance During Surgical Rotations Predicts NBME Shelf Exam Outcomes.

OBJECTIVE: To determine if longitudinal, excellent clinical performance reflected in subjective evaluations during a surgery clerkship would be associated with a greater likelihood of National Board of Medical Examiners Surgery Shelf Exam ("shelf exam") success. DESIGN: We retrospectively reviewed medical students' surgical clerkship performance from 2014 to 2019. Clinical evaluations for each rotation were abstracted and students were stratified by performance: excellent performers and non-excellent performers. The rotation performance grades were then combined to classify overall clerkship performance: sustained excellent performers, improved performers, worsened performers, and sustained non-excellent performers. We compared the shelf exam scores between performer class for each clinical rotation and the overall clerkship. Using logistic regression, we also sought to determine if clinical performance predicted passing the shelf exam. SETTING: Emory University School of Medicine in Atlanta, Georgia. PARTICIPANTS: Third-year medical students (N = 674) who completed a surgery clerkship. RESULTS: Excellent performers scored higher than non-excellent performers on the shelf exam during both clinical rotations (all p < 0.01). Sustained excellent performers had the highest exam scores out of all the clerkship performance groups (p < 0.0001). Excellent performers for both rotations were associated with increased odds of passing the shelf exam. Sustained excellent performers had the greatest odds (OR 3, 95% confidence interval 1.5-6.3, p = 0.003) of passing the exam. CONCLUSIONS: Clinical performance during the surgical clerkship and individual rotations correlates with shelf exam scores. Students should be encouraged to excel on the wards to maximize the educational experience and improve their odds of passing the exam.

The Intersection of Age and Tumor Biology with Postoperative Outcomes in Patients After Cytoreductive Surgery and HIPEC.

BACKGROUND: Patient age is a significant factor in preoperative selection for major abdominal surgery. The association of age, tumor biology, and postoperative outcomes in patients undergoing cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) remains ill-defined. METHODS: Retrospective analysis was performed for patients who underwent a CCR0/1 CRS/HIPEC from the US HIPEC Collaborative Database (2000-2017). Age was categorized into < 65 or ≥ 65 years. Primary outcome was postoperative major complications. Secondary outcomes were non-home discharge (NHD) and readmission. Analysis was stratified by disease histology: non-invasive (appendiceal LAMN/HAMN), and invasive (appendiceal/colorectal adenocarcinoma). RESULTS: Of 1090 patients identified, 22% were ≥ 65 (n = 240), 59% were female (n = 646), 25% had non-invasive (n = 276) and 51% had invasive (n = 555) histology. Median PCI was 13 (IQR 7-20). Patients ≥ 65 had a higher rate of major complications (37 vs 26%, p = 0.02), NHD (12 vs 5%, p < 0.01), and readmission (28 vs 22%, p = 0.05), compared to those < 65. For non-invasive histology, age ≥ 65 was not associated with major complications or NHD on multivariable analysis. For invasive histology, when accounting for PCI and CCR, age ≥ 65 was associated with major complications (OR 2.04, 95% CI 1.16-3.59, p = 0.01). When accounting for major complications, age ≥ 65 was associated with NHD (OR 2.54, 95% CI 1.08-5.98, p = 0.03). Age ≥ 65 was not predictive of readmission for any histology when accounting for major complications. CONCLUSIONS: Age ≥ 65 years is an independent predictor for postoperative major complications and non-home discharge for invasive histology, but not non-invasive histology. These data inform preoperative counseling, risk stratification, and early discharge planning.

Association of ABO blood group with survival following pancreatoduodenectomy for pancreatic ductal adenocarcinoma.

BACKGROUND: Existing research suggests patients with blood group O are less likely to develop pancreatic ductal adenocarcinoma (PDAC) compared to those with non-O blood groups, and that survival from PDAC may be affected by ABO blood type. This study assessed survival outcomes in PDAC patients who underwent pancreatoduodenectomy (PD) in one health system. METHODS: From 2010 to 2017, demographic, operative, chemotherapy and survival data for patients undergoing PD at Emory Healthcare were reviewed. Patients with blood type AB were excluded due to small sample size. The relationship between ABO blood group and survival was analyzed using Kaplan-Meier survival curves and multivariate cox proportional regression analysis. RESULTS: Of 449 PDAC patients assessed, 204 (45.4%), 60 (13.4%) and 185 (41.2%) were blood groups A, B and O, respectively. Patients were well matched in clinicopathologic characteristics. Median survival did not differ by blood group (p = 0.82), and this relationship remained insignificant on cox regression analysis (p = 0.15). On multivariate analysis, lymph node positivity (p < 0.001) and increasing age (p = 0.001) were associated with reduced survival. CONCLUSION: In contrast to recent reports, this larger study found that blood group did not impact overall survival among patients undergoing PD for PDAC.

Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Gastric Cancer.

The management of peritoneal metastases from gastric cancer origin has evolved considerably over the last three decades with the establishment of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) as efficacious therapies in carefully selected patients. Other approaches such as the use of prophylactic/adjuvant HIPEC in patients who are considered high-risk and those with positive peritoneal cytology will benefit from additional data before being adopted into routine clinical practice. Lastly, there are new and emerging intraperitoneal chemotherapy techniques such as early post-operative intraperitoneal chemotherapy (EPIC) for residual microscopic disease, and pressurized intraperitoneal aerosolized chemotherapy (PIPAC) for patients with advanced unresectable peritoneal carcinomatosis, which are currently under evaluation in clinical trials. The following review outlines the natural history of gastric cancer, currently available neoadjuvant and adjuvant therapies for resectable disease, and existing evidence supporting various approaches to CRS and intraperitoneal chemotherapy.

Duodenal neuroendocrine tumors: Somewhere between the pancreas and small bowel?

BACKGROUND: While sub-2 cm pancreatic neuroendocrine tumors (NETs) are often observed, small bowel-NETs undergo resection and lymphadenectomy regardless of size. Aim was to define the natural history of duodenal (D-NETs), determine the role of resection, and define the factors associated with overall survival (OS) after resection. METHODS: National Cancer Database (2004-2014) was queried for the patients with nonmetastatic/nonfunctional D-NETs. Local resection (LR): local excision/polypectomy/excisional biopsy. Anatomic resection (AR): radical surgery. Tumor size was divided into less than 1 cm, 1 to 2 cm, and ≥2 cm. Propensity score weighting was used to create balanced resection and no-resection cohorts. The primary endpoint was OS. RESULTS: Among 5502 patient, the median age was 65 years. The median follow-up was 49 months. The median tumor size was 0.8 cm. Resection was performed in 72% (n = 3954; LR: 61%, AR: 39%). Lymph node (LN) resection was performed in 26% (43% had metastasis). A total of 74% had negative margins. Resection and no-resection cohorts were propensity score weighted for age/sex/race/Charlson-Deyo score/tumor grade (all independently associated with OS on multivariable analysis). Resection was associated with improved median OS compared to no resection in all sizes (<1 cm: median not reached vs 194 months; 1-2 cm: median not reached vs 56 months; >2 cm: median not reached vs 90 months; all P < .01). Subset analysis of each resection size cohort demonstrated that neither type of resection, LN retrieval, LN positivity, or margin status was associated with OS (all P > .05). CONCLUSION: Patients with nonmetastatic and nonfunctional D-NETS should be considered for resection regardless of tumor size. Given the lack of prognostic value, the resection type and extent of LN retrieval should be tailored to each patient's clinical picture and safety profile.

Perioperative anxiety and depression in patients undergoing abdominal surgery for benign or malignant disease.

BACKGROUND AND OBJECTIVES: Etiologies, levels, and associated factors of psychological distress in cancer patients facing surgery are poorly defined. We conducted a prospective comparative study of perioperative anxiety and depression in patients undergoing abdominal surgery for either malignant or benign disease. METHODS: With Institutional Review Board approval, patients consenting for surgery at our institution were enrolled. Surveys were completed at a preoperative visit and within 2 weeks of a postoperative appointment. Participants listed their top three sources of anxiety, and completed the Patient Health Questionnaire-9 and the General Anxiety Disorder-7. RESULTS: A total of 79 patients completed the preoperative assessment and 44 (58.7%) finished the postoperative survey. Forty-one were male (51.9%), 12 (15.2%) had a psychiatric comorbidity (PSYHx), and 47 (59.5%) had cancer. Perioperative anxiety and depression did not differ by malignancy status. Patients were most concerned about surgery (22.5%) preoperatively and finances (27.9%) postoperatively. PSYHx, frailty, insurance status, and opioid use were all associated with perioperative psychological distress. CONCLUSIONS: Cancer patients did not have significantly higher levels of perioperative psychological distress compared with benign controls. Socioeconomic worries are prevalent throughout the perioperative period, and efforts to alleviate distress should focus on providing adequate counseling.

Post-hepatectomy hyperbilirubinemia: The point of no return.

BACKGROUND: Post-hepatectomy hyperbilirubinemia is associated with liver insufficiency and failure. The highest survivable peak total bilirubin (ptbili) is not defined. This study aimed to identify the postop ptbili beyond which survival is improbable or impossible. METHODS: An institutional database of major hepatectomies (≥3 segments, no biliary resections), 2000-2012 was reviewed. Data were analyzed to find ptbili in the first 45 postop days. Factors associated with 90-day mortality (90 DM) and those predictive of ptbili were determined. RESULTS: 603 pts were analyzed with 90DM of 4.5%. 90 DM for a ptbili ≥ 18 (n = 15) was 86.6%, but only 2.5% for a ptbili < 18. All 6 pts with a ptbili ≥ 30 died. On multivariate analysis, postop ptbili ≥ 18 (HR34.95, CI 3.8-324; p = 0.002) and cirrhosis (HR6.4, CI 1.2-33.2; p = 0.027) were associated with 90DM. Factors associated with a ptbili ≥ 18 were age >65 (HR14.24, CI 2.9-70.5; p = 0.001), preop chemotherapy (HR4.77, CI 1.3-18.2; p = 0.02) and postop FFP (HR12.5, CI 2.6-56.2; p = 0.001). CONCLUSION: Postop ptbili ≥ 18 after major hepatectomy has an 86.6% risk of 90DM; there are no survivors for tbili ≥ 30. These values may guide postop counseling for prognosis. Future studies may evaluate tbili ≥ 18 as an indication for hepatic replacement therapy.

Adenocarcinoma ex-goblet cell carcinoid (appendiceal-type crypt cell adenocarcinoma) is a morphologically distinct entity with highly aggressive behavior and frequent association with peritoneal/intra-abdominal dissemination: an analysis of 77 cases.

High-grade versions of appendiceal goblet cell carcinoids ('adenocarcinoma ex-goblet cell carcinoids') are poorly characterized. We herein document 77 examples. Tumors occurred predominantly in females (74%), mean age 55 years (29-84), most with disseminated abdominal (77% peritoneal, 58% gynecologic tract involvement) and stage IV (65%) disease. Many presented to gynecologic oncologists, and nine had a working diagnosis of ovarian carcinoma. Metastases to liver (n=3) and lung (n=1) were uncommon and none arose in adenomatous lesions. Tumors had various histologic patterns, in variable combinations, most of which were fairly specific, making them recognizable as appendiceal in origin, even at metastatic sites: I: Ordinary goblet cell carcinoid/crypt pattern (rounded, non-luminal acini with well-oriented goblet cells), in variable amounts in all cases. II: Poorly cohesive goblet cell pattern (diffusely infiltrative cords/single files of signet ring-like/goblet cells). III: Poorly cohesive non-mucinous cell (diffuse-infiltrative growth of non-mucinous cells). IV: Microglandular (rosette-like glandular) pattern without goblet cells. V: Mixed 'other' carcinoma foci (including ordinary intestinal/mucinous). VI: goblet cell carcinoid pattern with high-grade morphology (marked nuclear atypia). VII: Solid sheet-like pattern punctuated by goblet cells/microglandular units. Ordinary nested/trabecular ('carcinoid pattern') was very uncommon. In total, 33(52%) died of disease, with median overall survival 38 months and 5-year survival 32%. On multivariate analysis perineural invasion and younger age (<55) were independently associated with worse outcome while lymph-vascular invasion, stage, and nodal status trended toward, but failed to reach, statistical significance. Worse behavior in younger patients combined with female predilection and ovarian-affinity raise the possibility of hormone-assisted tumor progression. In conclusion, 'adenocarcinoma ex-goblet cell carcinoid' is an appendix-specific, high-grade malignant neoplasm with distinctive morphology that is recognizable at metastatic sites and recapitulates crypt cells (appendiceal crypt cell adenocarcinoma). Unlike intestinal-type adenocarcinoma, it occurs predominantly in women, is disguised as gynecologic malignancy, and spreads along peritoneal surfaces with only rare hematogenous metastasis. It appears to be significantly more aggressive than appendiceal mucinous neoplasms.

Symptomatic presentation as a predictor of recurrence in gastroenteropancreatic neuroendocrine tumors: A single institution experience over 15 years.

BACKGROUND AND OBJECTIVES: The prognostic implication of symptomatic presentation of gastroenteropancreatic neuroendocrine tumors (GEP-NETs) remains unclear. METHODS: Patients who underwent resection of nonfunctional GEP-NETs (2000-2014) were analyzed. Primary outcomes were overall survival (OS) and distant recurrence-free survival (RFS). RESULTS: Symptomatic presentation was seen in 208 (61%) of 339 patients and was associated with younger age (55 vs. 59 yrs, P = 0.001), higher tumor grade (38% vs. 21%, P = 0.027), presence of lymphovascular invasion (58% vs. 33%, P < 0.001), presence of perineural invasion (54% vs. 29%, P = 0.002), and advanced disease (T3/T4/N1/M1 [63% vs. 44%, P = 0.002]), but not tumor size (2.6 vs. 2.5 cm, P = 0.74). Symptomatic presentation was associated with decreased 3-yr distant-RFS (80% vs. 89%, P = 0.012), but not OS. When accounting for adverse features, symptomatic presentation remained independently associated with reduced distant-RFS (HR 3.51, P = 0.007). On subgroup-analysis of advanced disease patients, symptomatology was associated with reduced 3-yr distant-RFS (67% vs. 79%, P = 0.012) and persisted as an independent risk-factor for decreased distant-RFS (HR 3.01, P = 0.027). CONCLUSIONS: Symptomatic presentation of GEP-NETs is associated with aggressive features and worse distant-RFS. Trials assessing adjuvant therapy for advanced GEP-NETs are needed, and symptomatic presentation may be considered as one inclusion criterion. Following resection, symptomatic presentation should be taken into account when planning surveillance. J. Surg. Oncol. 2016;114:163-169. © 2016 Wiley Periodicals, Inc.

Octreoscan Versus FDG-PET for Neuroendocrine Tumor Staging: A Biological Approach.

BACKGROUND: Clinicians may order Octreoscan or positron emission tomography (PET) scan for staging patients with neuroendocrine tumors (NETs). (111)In-Octreoscan (Octreoscan) identifies tumors by radiolabeled targeting of somatostatin receptors, while 18F-fluorodeoxyglucose-positron emission tomography ((18)FDG-PET) measures differential tissue glucose transport. We assessed the sensitivity of both nuclear imaging modalities with pathologic correlation to define the best initial choice for NET staging after standard cross-sectional imaging. METHODS: We identified all patients diagnosed with NETs of gastrointestinal or pancreatic origin who underwent nuclear imaging staging by Octreoscan and/or PET from 2000 to 2013. Imaging results were correlated with tumor differentiation and grade of pathology specimens. RESULTS: Imaging and pathology results were identified for 153 patients. Of these, 131 underwent Octreoscan, 43 underwent PET, and 21 patients had both performed. Overall sensitivity of Octreoscan and PET for NET detection was similar (77 vs. 72 %; p = not significant). For well-differentiated NETs, Octreoscan (n = 124) demonstrated sensitivity of 80 vs. 60 % (p = 0.28) for PET (n = 30). For poorly-differentiated NETs, Octreoscan (n = 7) proved significantly less sensitive than PET (n = 13) (57 vs. 100 %; p = 0.02). The sensitivity of Octreoscan versus PET varied similarly when analyzed by WHO tumor grade: Grade 1 (79 vs. 52 %; p = 0.16), Grade 2 (85 vs. 86 %; p = not significant), and Grade 3 (57 vs. 100 %; p = 0.02). CONCLUSIONS: Tumor differentiation can be used to guide selection of nuclear imaging modalities for staging gastrointestinal and pancreatic NETs. Octreoscan appears more sensitive than (18)FDG-PET for well-differentiated NETs, whereas (18)FDG-PET demonstrates superior sensitivity for poorly-differentiated NETs.

Association between hospital finances, payer mix, and complications after hyperthermic intraperitoneal chemotherapy: deficiencies in the current healthcare reimbursement system and future implications.

BACKGROUND: Despite increasing implementation of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC), there are little data on its financial implications. We analyzed hospital cost and reimbursement data within the context of insurance provider type and postoperative complications. METHODS: Clinicopathologic variables, hospital costs, and reimbursement for all patients undergoing CRS/HIPEC at a single institution from 2009 to 2013 were analyzed. RESULTS: A total of 64 patients underwent CRS/HIPEC. Median PCI score was 19, and average operative time was 550 min. Tumor histology included appendiceal (n = 40; 62 %), colorectal (n = 16; 25 %), goblet cell (n = 5; 8 %), and mesothelioma (n = 3; 5 %). Median length-of-stay was 13 days. Complications occurred in 42 patients (66 %), including 13 (20 %) with major (Clavien grade III-IV) complications. Payer mix included 42 private insurance and 22 Medicare/Medicaid. Financial data was available for 56 patients: average total hospital cost was $49,248 and reimbursement was $63,771, for a hospital profit of $14,523/patient. Despite similar costs between Medicare/Medicaid and private-insurance patients, Medicare/Medicaid reimbursed much less ($30,713 vs $80,747; p < 0.001), resulting in a net loss of $17,342 per patient. For private-insured patients, major complications were associated with increased cost and increased reimbursement, resulting in a net profit of $36,285, compared with a net loss of $54,274 in Medicare/Medicaid patients. CONCLUSIONS: CRS/HIPEC is profitable in privately insured patients, even for those with major complications, but loses money in patients with Medicare/Medicaid. Under a future bundled-reimbursement system, complications will be negatively associated with profit. With these impending changes, hospitals must place emphasis on value, recalculate the reimbursement necessary for financial viability, and focus on decreasing costs and minimizing complications.

Management of recurrent gastrointestinal stromal tumors.

Recurrence after resection of primary gastrointestinal stromal tumor (GIST) is an unfortunately all-too-common phenomenon. The principal treatment for recurrent GIST is the first-line tyrosine kinase inhibitor (TKI) imatinib mesylate. Those who progress on, or are intolerant of imatinib, are treated with second-line TKI sunitinib malate. Cytoreductive surgery may be considered as an "adjuvant" therapy for patients with disease stabilized on imatinib, and, on an individual basis, sunitinib.

Predictive capability of near-infrared fluorescence angiography in submental perforator flap survival.

BACKGROUND: Perforator flaps have become increasingly popular in reconstructive surgery, as patients experience less donor-site morbidity than with conventional musculocutaneous flaps. Previously, the authors' laboratory described the intraoperative use of near-infrared fluorescence angiography for patient-specific perforator flap design. This study evaluates the predictive capability of near-infrared fluorescence angiography for flap survival in submental flap reconstruction. METHODS: Near-infrared angiography was performed using indocyanine green at 0, 0.5, 24, 48, and 72 hours after surgery for flap creation in 12 pigs. A single perforator artery was preserved during flap creation based on location (central or noncentral) and dominance (dominant or nondominant). Venous drainage, arterial perfusion, and perfused area as a percentage of total flap area were analyzed. Clinical assessments of perfusion were compared with those made using near-infrared imaging and histology. RESULTS: Use of near-infrared fluorescence angiography immediately after flap creation accurately predicted areas of perfusion at 72 hours (p=0.0013), compared with the initial clinical assessment (p=0.3085). Identification of necrosis by histology at 72 hours correlated with near-infrared findings of insufficient arterial perfusion immediately after flap creation. No statistically significant differences in perfusion metrics were detected based on location or dominance of the preserved perforator; however, flaps containing central perforators had a higher percentage perfused area than those with noncentral perforators. CONCLUSIONS: The use of near-infrared angiography immediately after flap creation can predict areas of perfusion at 72 hours. This predictive capability may permit intraoperative revision of compromised flaps that have a high likelihood of failure.

Real-time intra-operative near-infrared fluorescence identification of the extrahepatic bile ducts using clinically available contrast agents.

BACKGROUND: Iatrogenic bile duct injuries are serious complications with patient morbidity. We hypothesized that the invisible near-infrared (NIR) fluorescence properties of methylene blue (MB) and indocyanine green (ICG) could be exploited for real-time, intraoperative imaging of the extrahepatic bile ducts during open and laparoscopic surgeries. METHODS: In all, 2.0 mg/kg of MB and 0.05 mg/kg of ICG were injected intravenously into 35-kg female Yorkshire pigs and the extrahepatic bile ducts were imaged over time using either the Fluorescence-Assisted Resection and Exploration (FLARE) image-guided surgery system (open surgery) or a custom NIR fluorescence laparoscopy system. Surgical anatomy was confirmed using x-ray cholangiography. The contrast-to-background ratio (CBR), contrast-to-liver ratio (CLR), and chemical concentrations in the cystic duct (CD) and common bile duct (CBD) were measured, and the performance of each agent was quantified. RESULTS: Using NIR fluorescence of MB, the CD and CBD could be identified with good sensitivity (CBR and CLR > or =4), during both open and laparoscopic surgeries, from 10 to 120 min postinjection. Functional impairment of the ducts, including constriction and injury were immediately identifiable. Using NIR fluorescence of ICG, extrahepatic bile ducts did not become visible until 90 min postinjection because of strong residual liver retention; however, between 90 and 240 min, ICG provided exquisitely high sensitivity for both CD and CBD, with CBR > or =8 and CLR > or =4. CONCLUSION: We demonstrate that 2 clinically available NIR fluorophores, MB fluorescing at 700 nm and ICG fluorescing at 800 nm, provide sensitive, prolonged identification of the extrahepatic bile ducts and assessment of their functional status.

Intraoperative localization of insulinoma and normal pancreas using invisible near-infrared fluorescent light.

BACKGROUND: Neuroendocrine tumors of the pancreas, such as insulinoma, are difficult to localize, and complete resection is essential for cure. Our hypothesis is that a near-infrared (NIR) fluorophore exhibiting uptake in insulinoma could provide high-sensitivity detection intraoperatively. MATERIALS AND METHODS: The optical properties of methylene blue (MB) were measured in vitro in 100% serum at 37 degrees C and in vivo after tissue uptake. MB was injected as a rapid intravenous bolus at doses ranging from 0.25 to 2 mg/kg into wildtype rats and pigs, and into insulinoma-bearing transgenic mice. The FLARE imaging system was used to acquire color video and NIR fluorescence images simultaneously and in real-time. The signal-to-background ratios (SBR) of tissues and tumors were quantified using FLARE software. RESULTS: When appropriately diluted, MB exhibits moderate NIR fluorescence emission peaking at 688 nm. At doses > or =1 mg/kg, certain normal tissues, such as pancreas, accumulate MB and remain NIR fluorescent for up to 1 h with an SBR > or = 1.6. MB spectral properties are maintained after uptake into tissue. Interestingly, insulinoma exhibits even higher MB signal than normal pancreas, resulting in insulinoma-to-pancreas ratios of 3.7 and insulinoma-to-muscle ratios of 16.2. MB permitted high-sensitivity, real-time localization of primary, multicentric, and metastatic insulinoma and permitted differentiation among tumor, normal pancreas, and other abdominal structures. CONCLUSION: A single intravenous injection of a clinically available, commonly used NIR fluorophore provides prolonged intraoperative localization of normal pancreas and insulinoma using invisible NIR fluorescent light.

Intraoperative near-infrared fluorescence imaging in perforator flap reconstruction: current research and early clinical experience.

Despite recent advances in perforator flap reconstruction, there can be significant variability in vessel size and location. Although preoperative evaluation may provide valuable information, real-time intraoperative methods have the potential to provide the greatest benefit. Our laboratory has developed the Fluorescence-Assisted Resection and Exploration (FLARE) near-infrared (NIR) fluorescence imaging system for intraoperative visualization of details of the underlying vasculature. The FLARE system uses indocyanine green, a safe and reliable NIR fluorophore already FDA-approved for other indications. The system has been optimized in large-animal models for the identification of perforator size, location, and perfusion and has also been translated to the clinic for use during breast reconstruction after mastectomy. In this article, we review our preclinical and clinical data, as well as literature describing the use of similar NIR fluorescence imaging systems in plastic and reconstructive surgery.

Submental perforator flap design with a near-infrared fluorescence imaging system: the relationship among number of perforators, flap perfusion, and venous drainage.

BACKGROUND: The submental flap is a reliable alternative to microsurgical reconstruction of facial deformities, providing an excellent cosmetic match with the contour and color of the face. In this study, the authors evaluated submental flap design by using near-infrared fluorescence angiography to identify perforator arteries. The impact of the number of preserved perforator arteries on flap perfusion and venous drainage was quantified. METHODS: Indocyanine green was injected intravenously into 18 pigs. Three groups of six animals each had one, two, or three perforator arteries preserved. The fluorescence-assisted resection and exploration near-infrared fluorescence imaging system was used for image acquisition. Images were recorded before and after flap creation, and every hour, for 6 hours. The time to maximum perfusion, the drainage ratio (an indicator of venous drainage), and the percentage of perfused flap area were analyzed statistically at each time point. RESULTS: Flaps with a single dominant perforator artery had an initial mean perfused area of 80 percent, which improved to 97 percent at 6 hours. For flaps with two and three preserved perforator arteries, perfused area at 6 hours was 99.8 percent and 100 percent, respectively. A significant increase was observed in all three metrics as more vessels were preserved. Regardless of the number of perforator arteries preserved, though, all three metrics improved over 6 hours. CONCLUSIONS: Near-infrared fluorescence angiography can reliably identify submental perforator arteries for flap design and can be used to assess flap perfusion and venous drainage in real time. Flap metrics at 6 hours were equivalent when either one or multiple perforator arteries were preserved.

Image-guided perforator flap design using invisible near-infrared light and validation with x-ray angiography.

Although perforator flaps mark an important conceptual change in reconstructive surgery, individual perforator vessels show a high degree of variability with respect to anatomic landmarks. We have developed an intraoperative imaging system that simultaneously displays surgical anatomy and otherwise invisible near-infrared images. In 22 adult pigs, perforating vessels were identified within seconds using this optical imaging system and systemic injection of indocyanine green. Perforator flaps were then designed based on these results, and vessel location confirmed by direct visualization and anatomic dissection. Since x-ray angiography remains the gold standard for identification of underlying vessels, conventional x-ray angiography was also performed in 8 pigs to verify the location of perforators. There was full correlation of all the perforators identified among near-infrared fluorescence angiography, x-ray angiography, and anatomic dissection. The technology we describe provides high-sensitivity real-time image guidance throughout perforator dissection, and permits patient-specific flap design.

Quantitative assessment of perfusion and vascular compromise in perforator flaps using a near-infrared fluorescence-guided imaging system.

BACKGROUND: Techniques currently used to determine flap perfusion are mainly subjective, with the majority of reconstructive surgeons still relying on clinical examination. In this study, the authors demonstrate the use of near-infrared fluorescence angiography to directly quantify normal and abnormal perfusion in perforator flaps. METHODS: Indocyanine green was injected intravenously into anesthetized adult pigs (n = 38). A custom near-infrared fluorescence imaging system was used for image acquisition and quantitation. Thirty-nine flaps were designed based on identified perforators, and postoperative imaging was performed for comparison. In select flaps, isolated occlusion of the arterial and venous pedicle was performed. In select flaps, vascular spasm was induced by local irrigation of the vessels with epinephrine. The fluorescence intensities of select regions of interest were quantified. From these data, the authors defined two indices for abnormal perfusion: the Tmax ratio and the drainage ratio. RESULTS: The authors identified a normal pattern of perfusion before flap elevation, composed of a distinct fluorescence intensity peak at maximal arterial inflow followed by a smooth drop representing venous drainage. Delay of this peak after flap elevation, as indicated by the Tmax ratio, identified vascular spasm and arterial occlusion (p < 0.0001). Abnormal fall of fluorescence intensities after this peak, as indicated by the drainage ratio, identified venous occlusion (p < 0.0001). CONCLUSIONS: Quantitation of fluorescence intensities by near-infrared angiography accurately characterizes arterial and venous compromise. The authors' technique can assess perfusion characteristics during the intraoperative and postoperative periods and therefore complements clinically based subjective criteria now used for flap assessment.