Successful surgical management of a suspected high-flow inferior mesenteric artery aneurysm in a patient with chronic celiac and superior mesenteric artery occlusions.

Inferior mesenteric artery (IMA) aneurysms account for approximately 1% of visceral artery aneurysms and can occur secondary to high flow because of occlusive disease in other mesenteric arteries. We describe the case of a 79-year-old man who presented with a 3.3-cm IMA aneurysm and chronic total occlusions of the celiac artery and superior mesenteric artery (SMA). After an unsuccessful attempt at endovascular SMA recanalization, he underwent an uncomplicated retrograde aorta to SMA bypass and antegrade aorta to IMA bypass. We propose that an aorta to IMA bypass after SMA revascularization is safe and effective to treat suspected high-flow IMA aneurysms.

Pyramidal Decision Support Framework Leverages Subspecialty Expertise across Enterprise to Achieve Superior Cancer Outcomes and Personalized, Precision Care Plans.

The complexity of cancer care requires integrated and continuous support to deliver appropriate care. An expert network with complementary expertise and the capability of multidisciplinary care is an integral part of contemporary oncology care. Appropriate infrastructure is necessary to empower this network to deliver personalized precision care to their patients. Providing decision support as cancer care becomes exponentially more complex with new diagnostic and therapeutic choices remains challenging. City of Hope has developed a Pyramidal Decision Support Framework to address these challenges, which were exacerbated by the COVID pandemic, health plan restrictions, and growing geographic site diversity. Optimizing efficient and targeted decision support backed by multidisciplinary cancer expertise can improve individual patient treatment plans to achieve improved care and survival wherever patients are treated.

Integrating Academic and Community Practices in the Management of Colorectal Cancer: The City of Hope Model.

Colorectal cancer (CRC) management continues to evolve. In metastatic CRC, several clinical and molecular biomarkers are now recommended to guide treatment decisions. Primary tumor location (right versus left) has been shown to predict benefit from anti-epidermal growth factor receptors (EGFRs) in rat sarcoma viral oncogene homologue (RAS) and v-raf murine sarcoma viral oncogene homolog B1 (BRAF) wild-type patients. Anti-EGFR therapy has not resulted in any benefit in RAS-mutated tumors, irrespective of the primary tumor location. BRAF-V600E mutations have been associated with poor prognosis and treatment resistance but may benefit from a combination of anti-EGFR therapy and BRAF inhibitors. Human epidermal growth factor receptor 2 (HER-2) amplification was recently shown to predict relative resistance to anti-EGFR therapy but a response to dual HER-2 targeting within the RAS wild-type population. Finally, the mismatch repair (MMR)-deficient subgroup benefits significantly from immunotherapeutic strategies. In addition to the increasingly complex biomarker landscape in CRC, metastatic CRC remains one of the few malignancies that benefits from metastasectomies, ablative therapies, and regional hepatic treatments. This treatment complexity requires a multi-disciplinary approach to treatment and close collaborations between various stakeholders in large cancer center networks. Here, we describe the City of Hope experience and strategy to enhance colorectal cancer care across its network.

Unintended Consequences: Perils of Renal Revascularization for Severe Hypertension.

Revascularization of atherosclerotic renal artery stenosis may cure hypertension, but paradoxically, improvement in systemic blood pressure in response to successful revascularization may precipitate ischemia in other organs affected by previously silent atherosclerotic disease. We describe bowel ischemia secondary to preexisting celiac artery stenosis after revascularisation. Prior knowledge of multivessel disease facilitated prompt diagnosis and management of this condition.

Internal iliac coverage during endovascular repair of abdominal aortic aneurysms is a safe option: A preliminary study.

Endovascular aneurysm repairs lacking suitable common iliac artery landing zones occasionally require graft limb extension into the external iliac artery, covering the internal iliac artery origin. The purpose of this study was to assess incidence of type II endoleak following simple coverage of internal iliac artery without embolization during endovascular aneurysm repair. Three hundred eighty-nine endovascular aneurysm repairs performed by a single surgeon (2004-2015) were reviewed. Twenty-seven patients underwent simple internal iliac artery coverage. Type II endoleak was assessed from operative reports and follow-up computed tomography imaging. No patient suffered type II endoleak from a covered internal iliac artery in post-operative computed tomography scans. Follow-up ranged from 0.5 to 9 years. No severe pelvic ischemic complications were observed. In conclusion, for selected cases internal iliac artery coverage without embolization is a safe alternative to embolization in endovascular aneurysm repairs, where the graft must be extended into the external iliac artery.

Predicting the need for vascular surgeons in Canada.

OBJECTIVE: With the introduction of direct entry (0+5) residency programs in addition to the traditional (5+2) programs, the number of vascular surgery graduates across Canada is expected to increase significantly during the next 5 to 10 years. Society's need for these newly qualified surgeons is unclear. This study evaluated the predicted requirement for vascular surgeons across Canada to 2021. A program director survey was also performed to evaluate program directors' perceptions of the 0+5 residency program, the expected number of new trainees, and faculty recruitment and retirement. METHODS: The estimated and projected Canadian population numbers for each year between 2013 and 2021 were determined by the Canadian Socio-economic Information and Management System (CANSIM), Statistics Canada's key socioeconomic database. The number of vascular surgery procedures performed from 2008 to 2012 stratified by age, gender, and province was obtained from the Canadian Institute for Health Information Discharge Abstract Database. The future need for vascular surgeons was calculated by two validated methods: (1) population analysis and (2) workload analysis. In addition, a 12-question survey was sent to each vascular surgery program director in Canada. RESULTS: The estimated Canadian population in 2013 was 35.15 million, and there were 212 vascular surgeons performing a total of 98,339 procedures. The projected Canadian population by 2021 is expected to be 38.41 million, a 9.2% increase from 2013; however, the expected growth rate in the age group 60+ years, who are more likely to require vascular procedures, is expected to be 30% vs 3.4% in the age group <60 years. Using population analysis modeling, there will be a surplus of 10 vascular surgeons in Canada by 2021; however, using workload analysis modeling (which accounts for the more rapid growth and larger proportion of procedures performed in the 60+ age group), there will be a deficit of 11 vascular surgeons by 2021. Program directors in Canada have a positive outlook on graduating 0+5 residents' skill, and the majority of programs will be recruiting at least one new vascular surgeon during the next 5 years. CONCLUSIONS: Although population analysis projects a potential surplus of surgeons, workload analysis predicts a deficit of surgeons because it accounts for the rapid growth in the 60+ age group in which the majority of procedures are performed, thus more accurately modeling future need for vascular surgeons. This study suggests that there will be a need for newly graduating vascular surgeons in the next 5 years, which could have an impact on resource allocation across training programs in Canada.

Wait times among patients with symptomatic carotid artery stenosis requiring carotid endarterectomy for stroke prevention.

BACKGROUND: Current Canadian and international guidelines suggest patients with transient ischemic attack (TIA) or nondisabling stroke and ipsilateral internal carotid artery stenosis of 50% to 99% should be offered carotid endarterectomy (CEA) ≤ 2 weeks of the incident TIA or stroke. The objective of the study was to identify whether these goals are being met and the factors that most influence wait times. METHODS: Patients who underwent CEA at the Ottawa Hospital for symptomatic carotid artery stenosis from 2008 to 2010 were identified. Time intervals based on the dates of initial symptoms, referral to and visit with a vascular surgeon, the decision to operate, and the date of surgery were recorded for each patient. The influence of various factors on wait times was explored, including age, sex, type of index event, referring physician, distance from the surgical center, degree of stenosis, and surgeon assigned. RESULTS: Of the 117 patients who underwent CEA, 92 (78.6%) were symptomatic. The median time from onset of symptoms to surgery for all patients was 79 days (interquartile range [IQR], 34-161). The shortest wait times were observed in stroke patients (49 [IQR, 27-81] days) and inpatient referrals (66 [IQR, 25-103] days). Only 7 of the 92 symptomatic patients (8%) received care within the recommended 2 weeks. The median surgical wait time for all patients was 14 days (IQR, 8-25 days). In the multivariable analysis, significant predictors of longer wait times included retinal TIA (P = .003), outpatient referrals (P = .004), and distance from the center (P = .008). Patients who presented to the emergency department had the shortest delays in seeing a vascular surgeon and subsequently undergoing CEA (P < .0001). There was no difference between surgeons for wait times to be seen in the clinic; however, there were significant differences among surgeons once the decision was made to proceed with CEA. CONCLUSIONS: Our wait times for CEA currently do not fall within the recommended 2-week guideline nor does it appear feasible within the current system. Important factors contributing to delays include outpatient referrals, living farther from the hospital, and presenting with a retinal TIA (amaurosis fugax). Our findings also suggest better scheduling practices once a decision is made to operate can modestly improve overall and surgical wait times for CEA.

A phase I trial combining high-dose 90Y-labeled humanized anti-CEA monoclonal antibody with doxorubicin and peripheral blood stem cell rescue in advanced medullary thyroid cancer.

UNLABELLED: This trial determined the pharmacokinetics, dosimetry, and dose-limiting toxicity of 90Y-hMN-14 IgG (humanized anticarcinoembryonic antigen [CEA, or CEACAM5] monoclonal antibody; labetuzumab), combined with doxorubicin and peripheral blood stem cell (PBSC) support in advanced medullary thyroid cancer (MTC) patients. METHODS: Fifteen patients received an infusion of 111In-hMN-14 IgG. One to 2 wk later, 14 patients received 90Y-hMN-14 IgG, starting at 740 MBq/m2, followed 24 h later with a fixed intravenous bolus dose of doxorubicin (60 mg/m2). Preharvested PBSCs were reinfused when the 90Y activity in the body was < or =111 MBq/m2. RESULTS: The mean red marrow dose estimated for the 90Y-hMN-14 IgG was 1.65 +/- 0.59 mGy/MBq (n = 11), with normal organs ranging from approximately 2.3 to 4.4 mGy/MBq. Eighty percent of all known lesions (125/156), including 78 of 79 bone and 16 putatively occult lesions, were targeted. The average radiation dose to the tumor was 15.1 +/- 10.8 mGy/MBq (55.8 +/- 39.8 cGy/mCi) 90Y-hMN-4 IgG (n = 29 tumors in 8 patients), with a majority of the lesions receiving >2,000 cGy at an administered dose of < or =1,480 MBq/m2. The average tumor-to-red marrow, tumor-to-liver, tumor-to-lungs, and tumor-to-kidneys ratios were 15.0 +/- 11.0, 5.1 +/- 3.6, 6.9 +/- 6.1, and 9.0 +/- 8.7, respectively. Cardiopulmonary toxicity was dose limiting at 1,850 MBq/m2. Minor responses were noted in 2 patients and 1 patient had a partial response (68% reduction in local and hepatic metastatic disease). CONCLUSION: This treatment combination was well tolerated with complete recovery of blood counts and reversible nonhematologic toxicities at the maximum tolerated dose of 1,480 MBq/m2. Evidence of antitumor response in these patients with advanced cancer was modest, but encouraging; this type of treatment may be more successful if applied to more limited, earlier-stage disease.

Radioimmunotherapy of non-Hodgkin's lymphoma with 90Y-DOTA humanized anti-CD22 IgG (90Y-Epratuzumab): do tumor targeting and dosimetry predict therapeutic response?

UNLABELLED: A DOTA (1,4,7,10-tetraazacyclododecane-N,N',N",N"'-tetraacetic acid)-conjugated, (111)In- and (90)Y-labeled humanized antibody to CD22, epratuzumab, was studied in patients with non-Hodgkin's lymphoma (NHL) to assess biodistribution and tumor targeting, pharmacokinetics, dosimetry, and anti-antibody response. Of particular interest was to evaluate whether pretherapy targeting and tumor dosimetry could predict therapeutic responses. METHODS: Patients received a pretherapy imaging study with (111)In-DOTA-epratuzumab IgG (0.75 mg/kg), followed about 1 wk later with (90)Y-DOTA-epratuzumab starting at a dose level of 0.185 GBq/m(2) (5 mCi/m(2)) in patients who had prior high-dose chemotherapy (group 2), and at 0.370 GBq/m(2) in patients who did not have a prior transplant (group 1), with escalation in 0.185-GBq/m(2) increments. RESULTS: The effective blood half-life for (111)In-DOTA epratuzumab was 36.1 +/- 7.9 h (n = 25) compared with 35.2 +/- 7.0 h for (90)Y-DOTA-epratuzumab (n = 22). The whole-body half-life for (90)Y-DOTA-epratuzumab estimated from (111)In-DOTA-epratuzumab scintigraphy was 58.3 +/- 4.7 h (n = 20), with urine collection confirming the loss of between 2.2% and 15.9% of the injected activity over 3 d (n = 3). One-hundred sixteen of 165 CT-confirmed lesions were visualized with (111)In-DOTA-epratuzumab. Radiation-absorbed doses to liver, lungs, and kidneys averaged 0.55 +/- 0.13 (n = 17), 0.28 +/- 0.06 (n = 17), and 0.38 +/- 0.07 mGy/MBq (n = 10), respectively, with 0.14 +/- 0.02 and 0.23 +/- 0.04 mGy/MBq delivered to the whole-body and red marrow, respectively. Tumor doses (n = 14 lesions in 10 patients) ranged from 1.0 to as much as 83 mGy/MBq for a 0.5-g lesion (median, 7.15 mGy/MBq). Group 2 patients were more likely to experience significant hematologic toxicities, but doses of up to 0.370 GBq/m(2) of (90)Y-DOTA-epratuzumab were tolerated with standard support measures, whereas patients in group 1 tolerated doses of up to 0.740 GBq/m(2) with the potential for further escalation. Anti-tumor effects were seen in both indolent and aggressive NHL. The data also suggest that anti-tumor responses of potentially equal magnitude can occur irrespective of tumor targeting and tumor size. Hence, tumor response did not correlate with the radiation dose delivered or with the tumor being visualized by external imaging. An anti-antibody response to epratuzumab was detected by an enzyme-linked immunosorbent assay in only 2 of 16 patients. CONCLUSION: These results suggest that (90)Y-DOTA-epratuzmab is a promising agent for the treatment of NHL and warrants further study. There was evidence suggesting that in this system, factors other than tumor radiation dose and targeting may be involved in the success of radioimmunotherapy.

Phase I radioimmunotherapy trial with iodine-131--labeled humanized MN-14 anti-carcinoembryonic antigen monoclonal antibody in patients with metastatic gastrointestinal and colorectal cancer.

This trial was conducted to determine the pharmacokinetics, dosimetry, dose-limiting toxicity, and the maximum tolerated dose of iodine-131 humanized MN-14 immunoglobulin G (131I-hMN-14 IgG), a humanized complementary-determining region-grafted anti-carcinoembryonic antigen monoclonal antibody, in metastatic gastrointestinal and colorectal cancer patients. Patients were divided into 2 groups: group A consisted of patients who had prior external beam radiation therapy (n = 8), and group B included patients who had received standard chemotherapy (n = 13). All patients received a diagnostic infusion of 131I-hMN-14 IgG (approximately 8.0 mCi, 15 mg/m2) to study the pharmacokinetics, biodistribution, and dosimetry. One week later, 17 of 21 patients received infusional therapy of escalating radioactive doses of 131I-hMN-14 IgG. Blood pharmacokinetics and quantitative imaging were performed again after the therapeutic dose. Radiation-absorbed doses to normal organs and tumors were determined by MIRDOSE-3 algorithms. The primary dose-limiting toxicity was hematologic toxicity at 40 mCi/m2. The blood half-life (n = 20) was identical for the diagnostic and therapy infusions. The mean red marrow dose was 2.2 +/- 2.4 cGy/mCi. The mean tumor radiation dose (n = 8) was 24.2 +/- 22.6 cGy/mCi. Tumor targeting was seen in most large metastatic lesions. No objective responses were seen in these heavily pretreated and mostly advanced patients. In conclusion, 131I-hMN-14 IgG has good targeting, good tumor to normal organs radiation absorbed ratios, and an acceptable toxicity profile in advanced metastatic gastrointestinal and colorectal cancer patients.