Paz‐Fumagalli, Ricardo

Abstract Acinar cell carcinoma of the pancreas (ACC) is an uncommon malignancy, accounting for less than 1% of all pancreatic neoplasms. Because of its rarity, only a few retrospective studies are available to help guide management. We previously reported the case of a patient with metastatic ACC who achieved prolonged survival with doxorubicin as a result of personalized treatment designed in part on the basis of molecular and in-vitro data collected on analysis of the tumor and primary cells in culture developed from the liver metastasis. We now report the characterization of a patient derived xenograft (PDX) mouse model originating from this patient's ACC liver metastasis tissue. Antitumor activity of multiple drugs (5-FU, irinotecan, oxaliplatin, gemcitabine, bevacizumab, erlotinib, doxorubicin and imatinib) used as single agent therapy is demonstrated. Of the targeted and cytotoxic therapies used, oxaliplatin produced a dramatic and prolonged response to therapy even after withdrawal of treatment. Bevacizumab produced a significant response, as well. Serum lipase and tissue amylase levels correlated with the antitumor response to therapy. Thus, we have developed and characterized an ACC PDX model that may be used in drug discovery for the treatment of this rare cancer for which no standard of care exists. Note: This abstract was not presented at the meeting. Citation Format: Laura A. Marlow, Adam C. Mathias, Louis K. Dawson, William F. Durham, Kenneth A. Meshaw, Robert J. Mullin, Aidan J. Synnott, Ricardo Paz-Fumagalli, Murli Krishna, Daniel Von Hoff, Daniel L. Small, Gerardo Colon-Otero, John A. Copland. Therapeutic responses in a novel patient-derived xenograft mouse model for rare acinar cell pancreatic carcinoma. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1475. doi:10.1158/1538-7445.AM2015-1475

Purpose: To investigate the natural history of dilated common iliac arteries (CIA) exposed to pulsatile blood flow after endovascular abdominal aortic aneurysm repair (EVAR) and the suitability of ectatic iliac arteries as sealing zones using flared iliac limbs. Methods: Follow-up computed tomograms of 102 CIAs in 60 EVAR patients were investigated. Diameter changes in CIAs ≤16 mm (group 1) were compared with changes in vessels where a dilated segment >16 mm in diameter continued to be exposed to pulsatile blood flow (group 2). Within group 2, cases in which the stent terminated proximal to the dilated artery segment (2a) were compared with those that had been treated with a flared limb (2b). Results: The mean CIA diameter increased by 1.0±1.0 mm in group 1 (p<0.001 versus immediately after EVAR) and by 1.5±1.7 mm in group 2 (p<0.001 versus immediately after EVAR) within an average follow-up of 43.6±18.0 months. Diameter increase was more pronounced in dilated CIAs (p=0.048), and it was not significantly different between groups 2a and 2b (p=0.188). No late distal type I endoleak or stent-graft migration associated with CIA ectasia was observed. Conclusion: Dilatation of the CIA is significant after EVAR, and it is more pronounced in ectatic iliac arteries. Although ectatic iliac arteries appear to be suitable sealing zones in the short term, continued follow-up is mandatory.

The purpose of this study was to evaluate the incidence and durability of additional proximal cuffs during endovascular abdominal aortic aneurysm repair (EVAR). A retrospective review of 90 EVAR patients was conducted. Postoperative survival, proximal sealing zone–related complications, and secondary procedures were analyzed. Additional proximal cuffs were used in 11%. Their use did not affect postoperative survival ( p = .58), type I endoleak rate (4.4%; p = .19), or the need for sealing zone–related secondary procedures (6.3%; p = .38) compared with patients without cuff placement but was related to a higher cumulative graft migration rate (2.2% overall p = .02). Two patients (2.5%; p = .79) underwent conversion to open surgery, both for proximal sealing zone–related complications. Application of proximal cuffs appears to be an effective intraoperative adjunctive procedure to achieve a proximal seal during EVAR, with favorable midterm results. However, the risk of late endograft migrations may be elevated in this group.

The purpose of this study was to review the outcome of endovascular abdominal aortic aneurysm repair (EVAR) using custom-made aortouni-iliac (AUI) devices with femorofemoral bypass. Between June 1999 and March 2001, 23 consecutive patients (1 female, 22 male) at high risk of open aortic aneurysm repair underwent EVAR with custom devices in an AUI configuration. The mean follow-up was 37 months (range 2–72 months), and the mean age was 76.8 years (range 67.5–88.7 years). Increased surgical risk was evidenced by 92% and 69% of patients with significant pulmonary or cardiac disease, respectively. The preoperative mean aneurysm diameter ( n = 23) 62 ± 8.2 mm was significantly greater than the postoperative diameter, ( n = 23) 54 ± 16.4 mm. Ten endoleaks occurred. Migration of the stent graft occurred in 9% ( n = 2). Secondary interventions were necessary in 23%, whereas tertiary interventions were required in 9%. Patients at high risk of open aneurysm repair received sufficient protection from aneurysm rupture with custom-made AUI devices.

Currently available aortic stent-grafts require bilateral femoral incisions for device deployment. The incidence of morbidity (infection, lymphatic complications, breakdown) of vertical, infrainguinal incisions used in endovascular aneurysm repair (EVAR) for abdominal aortic aneurysms (AAAs) was assessed, and the natural history of asymptomatic groin fluid collections following such procedures was determined. Between June 1999 and February 2001, 77 consecutive patients underwent EVAR for AAAs utilizing bilateral vertical femoral incisions. Fifty-nine (77%) bifurcated stent-grafts (BSGs), and 18 (23%) aortouniiliac (AUI) devices, with femorofemoral bypass were performed. Patients returned at 2 weeks, 1 month, and 6 months for physical examination, and 1 month and 6 months for abdominal and pelvic computed tomography (CT) scans. The presence of fluid collections was determined from the dictation report of the attending radiologist. Data are reported as (n) mean ± SE. Patient characteristics were compared using Fisher's exact test; p <0.05 considered significant. There were 72 males and 5 females, age 75 ±6.4 years and aneurysm size (77) 5.6 ±0.8 cm. There were no cases of wound breakdown or lymph fistula. Wound infections occurred in 3/150 incisions (2%), 2/34 AUI incisions (6%), and 1/1 16 BSG incisions (0.86%). There was no statistical difference (p =0.13) between graft types (BSG vs AUI). All infections were diagnosed clinically before the 1-month CT scan, treated without operative intervention or hospitalization, and resolved. There was a significant decrease in the BSG group and overall in asymptomatic wound fluid collections from 1 to 6 months postoperatively. At 1 and 6 months, respectively, the BSG group had 17 (14.6%) and 3 (2.6%) fluid collections out of 116 incisions (p = 0.003); the AUI group had 6 (17.6%) and 1 (2.9%) fluid collection(s) out of 34 incisions (p = 0. 13); and overall 23 (15.3%) and 4 (2.6%) out of 150 incisions (p = 0.004). The present study demonstrates that bilateral vertical femoral incisions used in EVAR have a wound infection rate of 2.0%. Infections are usually detected and treated clinically and empirically without the need for hospitalization or surgery. Asymptomatic groin wound fluid collections resolve significantly within 6 months without intervention. Therefore, surgical femoral artery exposure adds little morbidity to the endovascular repair of abdominal aortic aneurysms.

AbstractBackgroundThe purpose of the present study was to compare surgical and endovascular revascularization for chronic mesenteric ischemia (CMI).MethodsForty‐nine patients underwent surgical (SG) or endovascular (EG) treatment. Relief of symptoms was considered the primary endpoint; patency, morbidity, and mortality were secondary endpoints. For statistical analysis, significance was assumed if P values ≤ 0.05.ResultsTwenty‐six patients (53%) underwent surgical revascularization; 23 patients (47%), endovascular repair. Mean follow‐up was 25 ± 21 months (SG) versus 10 ± 10 (EG) months (P = 0.07). Except for body mass indices (SG 18.9 ± 2.7 versus EG 23.6 ± 4.8; P = 0.001), preoperative data were comparable. Freedom from symptoms was 100% (SG) versus 90% (EG) after intervention (P = 0.194), and 89% (SG) versus 75% (EG) at the end of follow‐up. Reocclusion or re‐stenosis occurred in 8% (SG) versus 25% (EG) (log‐rank test: P = 0.003), and mesenteric ischemia developed in 0% (SG) versus 9% (EG) (P = 0.04). Reintervention for CMI was required in 0% (SG) versus 13% (EG) (P = 0.01). Surgical patients experienced more early complications (42% versus EG 4%; P = 0.02) and longer hospital stays (11.6 ± 10.9 days versus EG 1.3 ± 0.5 days; P < 0.001). Overall mortality at the end of follow‐up was 31% (SG) versus 4% (EG) (log‐rank test: P = 0.08), including all patients with combined open mesenteric and aortic reconstruction (P = 0.001).ConclusionsSurgical treatment has superior long‐term patency and requires fewer reinterventions, but it is also more invasive with greater morbidity and mortality compared to endovascular treatment. Endovascular techniques may be preferable in patients with significant co‐morbidities, concomitant aortic disease, or indeterminate symptoms.

The purpose of this paper is to describe the intraoperative management of a type IIIb endoleak after deployment of a bifurcated endograft in a patient with narrow iliac access vessels. A 62-year-old man underwent elective endovascular repair (EVAR) of a 53 mm abdominal aortic aneurysm. After device deployment, a large IIIb endoleak, arising from the main body of the device, was visualized. Narrow iliac vessels precluded deployment of a second bifurcated graft, and the endoleak was successfully excluded with an aortomonoiliac device, followed by contralateral iliac occlusion and subsequent creation of a femorofemoral bypass. At 1-year follow-up, the aneurysm remains excluded and is decreasing in size. Type III endoleaks are a known complication of EVAR, requiring immediate treatment through their association with aneurysm enlargement and rupture. If an additional bifurcated graft cannot be used, aortomonoiliac conversion represents a feasible endovascular alternative treatment for type III endoleaks, other than conversion to open surgical repair. Therefore, aortomonoiliac converters with appropriate occluder devices should be readily available during deployment of bifurcated devices.