Comparison of the efficacy of enfortumab vedotin between patients with metastatic urothelial carcinoma who were treated with avelumab or pembrolizumab: real-world data from a multi-institutional study in Japan.

OBJECTIVES: Enfortumab vedotin (EV) is a novel antibody-drug conjugate approved for metastatic urothelial carcinoma (UC) refractory to prior treatment with immune checkpoint inhibitors (ICIs). However, the difference in efficacy of EV after each ICIs and prognostic factors are not well known. We aimed to compare the efficacy of EV in patients with metastatic UC who were treated with avelumab or pembrolizumab and to identify the prognostic factors. METHODS: The records of 100 patients with advanced metastatic UC who received EV after the administration of either avelumab or pembrolizumab were retrospectively collected from five academic hospitals in Japan. RESULTS: The median follow-up period was 6.7 months. The median overall survival (OS) and progression-free survival (PFS) in the EV after avelumab/pembrolizumab group were not reached/14.7 months (p = 0.17) and 10.4/5.2 months (p = 0.039), respectively. The objective response rates (ORR) were 66.6% and 46.8% in EV after avelumab and EV after pembrolizumab groups, respectively (p = 0.14). Multivariate analysis identified histological variants, liver metastasis, low serum albumin levels, and high serum CRP level as significant poor prognostic factors. The median OS and PFS of cachexia patients with both low serum albumin levels and high serum CRP levels were 6.0 months and 0.93 months, respectively. CONCLUSION: PFS was superior in patients treated with EV after avelumab to EV after pembrolizumab. However, OS showed no significant difference between the two groups. Because the prognosis of patients with cachexia is extremely poor, the initiation of EV should be discussed in these patients.

Transplantation of autologous bone marrow-derived mononuclear cells into cerebrospinal fluid in a canine model of spinal cord injury.

Introduction: Spinal cord injury (SCI) is associated with severe dysfunction of nervous tissue, and repair via the transplantation of bone marrow-derived mononuclear cells (BM-MNCs) into cerebrospinal fluid yields promising results. It is essential to understand the underlying mechanisms; therefore, this study aimed to evaluate the regenerative potential of autologous BM-MNC transplantation in a canine model of acute SCI. Methods: Six dogs were included in this study, and SCI was induced using an epidural balloon catheter between L2 and L3, particularly in the area of the anterior longitudinal ligament. BM-MNC transplantation was performed, and T2-weighted magnetic resonance imaging (MRI) was conducted at specific time points (i.e., immediately after inducing SCI and at 1, 2, and 4 weeks after inducing SCI); moreover, the expression of growth-associated protein 43 (GAP-43) was evaluated. Results: MRI revealed that the signal intensity reduced over time in both BM-MNC-treated and control groups. However, the BM-MNC-treated group exhibited a significantly faster reduction than the control group during the early stages of SCI induction (BM-MNC-treated group: 4.82 ± 0.135 cm [day 0], 1.71 ± 0.134 cm [1 week], 1.37 ± 0.036 cm [2 weeks], 1.21 cm [4 weeks]; control group: 4.96 ± 0.211 cm [day 0], 2.49 ± 0.570 cm [1 week], 1.56 ± 0.045 cm [2 weeks], 1.32 cm [4 weeks]). During the early stages of treatment, GAP-43 was significantly expressed at the proximal end of the injured spinal cord in the BM-MSC-treated group, whereas it was scarcely expressed in the control group. Conclusions: In SCI, transplanted BM-MNCs can activate the expression of GAP-43, which is involved in axonal elongation (an important process in spinal cord regeneration). Thus, cell therapy with BM-MNCs can provide favorable outcomes in terms of better regenerative capabilities compared with other therapies.

[Branched Thoracic Endovascular Aortic Repair for Aortic Arch Aneurysm Following Severe Combined Valvular Disease:Report of a Case].

A 79-years-old frail man with severe combined valvular disease was referred to our hospital. Furthermore, chest computed tomography( CT) showed a saccular aneurysm in the aortic arch. We chose two staged repairs for risk reduction. As a first stage double valve replacement and tricuspid annuloplasty were performed. Three months later, we performed successful branched thoracic endovascular aortic repair( TEVAR) used physician modified Najuta which had hydrogel-reinforced fenestrations to provide a more secure connection with the bridging graft than fenestrations alone. Staged surgery with branched TEVAR used physician modified Najuta is a useful strategy in patients who have complex cardiac disease combined with aortic arch aneurysm.

[Endovascular Treatment of a Ruptured Mediastinal Bronchial Artery Aneurysm].

Case 1:A 73-year-old man was transported to our hospital for evaluation of sudden onset of chest pain, back pain, and dyspnea. We initially misdiagnosed him with advanced esophageal cancer accompanied by mediastinal metastasis;however, subsequent multi-detector row computed tomography (MDR-CT) confirmed the diagnosis. We performed coil embolization of a bronchial artery aneurysm and thoracic endovascular aortic repair( TEVAR) to seal the root of the bronchial artery. Case 2:An 81-year-old woman with a one-week history of fever and cervical pain was diagnosed with a ruptured infected thoracic aneurysm. She underwent the same treatment as described in Case 1. Physicians should consider it as a differential diagnosis of mediastinal hematoma.

Endovascular Aortic Repair for a Symptomatic Mycotic Aneurysm With Listeria monocytogenes: A Case Report.

PURPOSE: To report a case of successful endovascular aortic repair for a symptomatic mycotic abdominal aortic aneurysm infected with Listeria monocytogenes. CASE REPORT: We report the case of an 88-year-old woman who presented with acute abdominal pain and vomiting. Approximately a year prior to her presentation, the patient was diagnosed with a mycotic abdominal aortic aneurysm with Listeria monocytogenes and was treated conservatively for more than 2 months at another hospital. At our hospital, contrast-enhanced computed tomography revealed an abdominal aortic aneurysm and an aneurysm of the left internal iliac artery. Endovascular aortic repair was performed successfully. At 16 months after the surgery, the patient remained asymptomatic on long-term antibiotics, and there was no enlargement of the aneurysm. CONCLUSION: Endovascular aortic repair and lifelong antibiotics may be an alternative therapy for mycotic abdominal aortic aneurysms. However, the risk of recurrent infection is high and warrants long-term follow-up.

Aligning Orifice of the Renal Artery with Fish-Mouth FIXation Technique During Endovascular Aortic Aneurysm Repair for Hostile Neck Anatomy.

Background: As the success of endovascular aortic aneurysm repair (EVAR) depends on sufficient proximal fixation of the endograft to the aortic wall, the proximal hostile neck anatomy (HNA) is the major potential treatment-limiting factor in EVAR. The Aorfix endovascular stent graft was designed to operate on highly angulated aortic necks. The Aligning Orifice of the Renal artery with fish-mouth FIXation (AORFIX) technique uniquely and accurately aligns the trough part of the proximal stent end with the orifice of the lower renal artery and is used to optimize the proximal fish-mouth design for maximum proximal seal use. Herein, we aimed to evaluate the usefulness of the AORFIX technique for EVAR in patients with HNA. Methods: Eighty-one consecutive patients who underwent EVAR with the AORFIX technique (+AORFIX technique group, n = 16) and without (standard group, n = 65) were evaluated. The HNA was defined as any of the following: neck angulation ≥60°, neck length ≤15 mm, or neck thrombus or calcification ≥50% of the circumference and conical neck. Results: Each HNA criterion was similar between the two groups. However, the average number of HNA criteria was significantly higher in the +AORFIX technique group (1.9 ± .2 vs. 1.3 ± .1; P < .01). The two groups showed 100% procedural success. The concurrent renal angioplasty and stenting rates (88% vs. 4.6%; P < .01) were significantly higher in the +AORFIX technique group. There were no 30-day deaths in either group and no in-hospital device-related events in the +AORFIX technique group. The median follow-up period was 39 months, and there was no significant between-group difference in freedom from reintervention rate (+AORFIX group vs. standard group, 100% vs. 91.0%; P = .327). Conclusion: EVAR using the AORFIX technique might be useful even in patients with more complex HNA.

Multibranched endovascular repair using a modified endograft with hydrogel-reinforced fenestrations.

OBJECTIVES: We devised a novel physician-modified endograft (PMEG) with hydrogel-reinforced fenestrations to provide a more secure connection with the bridging graft than fenestrations alone. We applied this novel PMEG in a clinical setting and evaluated the clinical and technical results. METHODS: In this study, patients with complex thoraco-abdominal aortic pathologies involving the renal, superior mesenteric or coeliac artery were included. However, patients with pararenal abdominal aneurysm were excluded. Regardless of anatomical suitability, all patients referred to our hospital were enrolled. All patients were treated via compassionate use of PMEG. All PMEGs were used following the same procedure using hydrogel-reinforced fenestrations. A retrospective analysis was conducted on consecutive patients who were treated between October 2018 and April 2021. RESULTS: Out of 40 patients, 29 and 11 were men and women, respectively. The median patient age was 73.6 (range: 49-87) years. Among the patients, 36 (90%) had true aneurysms, whereas the others had false lumen aneurysms and penetrating atherosclerotic ulcer. Despite anatomical challenges, all branches were successfully reconstructed. The mean operative time was 333 (standard deviation 98) min. Postoperative computed tomography angiography did not reveal type I and IIIc endoleaks from the hydrogel-reinforced fenestrations. The 30-day survival rate was 97.5%. One patient died due to brain haemorrhage on postoperative day 5. During follow-up, computed tomography revealed no migration of any bridging graft. CONCLUSIONS: We confirmed the effectiveness of the hydrogel as a sealing material and the secure connection between hydrogel-reinforced fenestrations and side branches in vivo. CLINICAL TRIAL REGISTRATION NUMBER: 5287.

Modified Candy-plug Device for Dilated False Lumen Occlusion: Is a Candle Better Than a Candy?

The AFX stent graft (Endologix) has an active seal mechanism that can conform to an irregular vascular lumen. We modified the candy-plug technique using an AFX VERA suprarenal extension with restricted purse-string sutures to shape it into a candle-like contraption. We treated 2 patients with patent, dilated false lumens (FLs) after central aortic repair using this technique. This plug was deployed into the FL to block retrograde blood flow proximally. Partial or complete thrombosis of the FL was observed in both patients 6 months after surgery. This technique was feasible for FL occlusion.

Localized motion imaging for monitoring HIFU therapy: Comparison of modulating frequencies and utilization of square modulating wave.

High-intensity focused ultrasound (HIFU) has been successfully used as a minimally invasive cancer therapy method. For monitoring the therapy, the amplitude-modulated (AM) localized motion imaging (LMI) method had been proposed. This paper compares the performance of AM-LMI while using different sine modulating wave frequencies and proposes the utilization of square modulating waves to gain the advantages of both high and low modulating frequencies. A single element therapy transducer with a 2 MHz central frequency was driven by sine modulating waves with different frequencies (approximate 34, 67, 102, 168, and 201 Hz) and by square modulating waves with two frequencies (34 and 67 Hz). An imaging probe with a 5 MHz central frequency and a 20 MHz sampling frequency was mounted in the center hole of the therapy transducer to acquire pulse-echo data, which were used to estimate the tissue oscillation amplitude induced by the acoustic radiation force of the HIFU beam. The decrease ratio of the oscillation amount was then utilized to estimate the coagulated lesion length during the therapy. The comparison of modulating frequencies demonstrated that a higher frequency could bring higher sensitivity to small lesions, while a lower frequency not only gives greater noise robustness but also promotes the ability to estimate lengths of larger lesions. The utilization of a square modulating wave demonstrated its utility to produce tissue oscillation with multiple frequencies and gain the advantages of both high and low modulating frequencies.

Genome-wide association study of gastric cancer- and duodenal ulcer-derived Helicobacter pylori strains reveals discriminatory genetic variations and novel oncoprotein candidates.

Genome-wide association studies (GWASs) can reveal genetic variations associated with a phenotype in the absence of any hypothesis of candidate genes. The problem of false-positive sites linked with the responsible site might be bypassed in bacteria with a high homologous recombination rate, such as Helicobacter pylori, which causes gastric cancer. We conducted a small-sample GWAS (125 gastric cancer cases and 115 controls) followed by prediction of gastric cancer and control (duodenal ulcer) H. pylori strains. We identified 11 single nucleotide polymorphisms (eight amino acid changes) and three DNA motifs that, combined, allowed effective disease discrimination. They were often informative of the underlying molecular mechanisms, such as electric charge alteration at the ligand-binding pocket, alteration in subunit interaction, and mode-switching of DNA methylation. We also identified three novel virulence factors/oncoprotein candidates. These results provide both defined targets for further informatic and experimental analyses to gain insights into gastric cancer pathogenesis and a basis for identifying a set of biomarkers for distinguishing these H. pylori-related diseases.

[Selective Branch Embolization and Thoracic Endovascular Aortic Repair for Asymptomatic Bronchial Artery Aneurysm:Report of a Case].

Bronchial artery aneurysm (BAA) is a rare disease, for which early treatment is recommended due to the risk of rupture often resulting in severe consequences. We report a case of successful treatment of an asymptomatic BAA by selective branch embolization combined with thoracic endovascular aortic repair (TEVAR). A 68-year-old man was accidentally found to have a bronchial artery aneurysm by computed tomography. The distance from the origin of the bronchial artery to the aneurysm was only 6 mm, at which branches were found. The BAA was completely excluded by selective branch coil embolization and deployment of a thoracic stent graft to cover the orifice of the BAA. Angiography confirmed that there was no endoleak. Selective branch embolization of BAA combined with TEVAR is effective to completely occlude the blood stream to BAA.

Numerical study on sector-vortex phased irradiation method using annular array transducer in High-Intensity Focused Ultrasound treatment.

Sector-vortex phased irradiation from annular array transducer was numerically studied with breast model constructed from MRI data of real patient. Phase compensation (PC) based on time reversal pre-computation was applied in order to handle phase delay caused by heterogeneity of breast tissues, and results showed great effectiveness on single-focus case, insignificant effectiveness on multi-focus cases with 4 and 8 phase-sectors, but ineffectiveness on multi-focus case with 12 phase-sectors, where enormous undesired outer ablation occurred. For single-focus case, phase compensation not only produced real focus very close to targeted site (0.1 mm deviation), but also decreased thermal peak ratio (outer/focal) largely by 30%. However, phase compensation did not increase total ablated size. For multi-focus cases with 4 and 8 phase-sectors, deformed focal shapes by tissue heterogeneity were restored by phase compensation, but the 4-phase-sector case had higher thermal peak ratio and smaller ablation than 8-phase-sector case for strong cancelling effect between phase-sector borders. Ineffectiveness of phase compensation on multi-focus case with 12 phase-sectors had three considerable reasons. 1st, inequality of piezo-element number between sectors; 2nd, heterogeneous attenuation of breast model; 3rd, insufficient number of piezo-elements per sector; where the 2nd reason originated from breast model, and other two reasons were related to array transducer. This research gave several preliminary indications. 1st, ineffectiveness of phase compensation occurs on case with large phase-sector number when using annular array transducer; 2nd, with same input energy and same irradiation time, sector-vortex phased irradiation creates smaller focal ablation, but withstands longer than single-focus irradiation free of outer ablation; 3rd, phase-difference π between neighboring phase-sectors is disadvantageous because of energy loss; 4th, phase compensation is effective on single-focus for improving pinpoint ablation but not for increasing total ablated size.

[Retrieval of the Ruptured Balloon during Transcatheter Aortic Valve Replacement without Complications:Report of a Case].

A 77-year-old man with a history of coronary artery bypass grafting underwent transcatheter aortic valve replacement(TAVR) via femoral artery for severe aortic stenosis(AS). Preoperative computed tomography(CT) showed there was mild calcification at the sino-tubular junction(STJ). Sapien 3 was implanted successfully, but at the end of full inflation, the balloon ruptured. The ruptured balloon was retrieved without any remnants or vascular injury. A transesophageal echocardiogram showed adequate valve deployment. TAVR with its less invasiveness has become an alternative treatment for high risk patients who cannot endure surgical aortic valve replacement(SAVR). Although there are several complications related to TAVR, they can be predicted in many cases by analysis of preoperative imaging. In this case, the rupture of the balloon was not predicted because there was no significant calcification at the STJ. Caution should be taken even though there seems to be low risk of complications by preoperative imaging modalities.

[Hybrid Treatment for Left Internal Thoracic Artery-Pulmonary Artery Fistula with Aneurysm Complicated with Mitral Regurgitation:Report of a Case].

A 78-year-old man with mitral regurgitation incidentally diagnosed with aneurysm of the left internal thoracic artery(LITA) and several internal thoracic artery-pulmonary artery( ITA-PA) fistulas originating from the aneurysm. To prevent rupture of the aneurysm, ITA ligation was performed during surgery for the mitral valve. Because of the complex anatomy surrounding the aneurysm, the main duct of the ITA was ligated at the peripheral and center of the aneurysm, then arterial fistulae were resected as many as possible. Postoperative computed tomography (CT), however, showed patent LITA and contrast material in the aneurysm. Second stage coil embolization procedure was performed with successful results. Intravascular treatment is effective for ITA aneurysms or ITA-PA fistulae because we can clearly visualize and confirm blood flow during operation.

Nutcracker syndrome due to chronic aortic dissection.

Nutcracker syndrome (NCS) is known as a status of compression of the left renal vein (LRV) between the abdominal aorta and superior mesenteric artery (SMA). We here report a case of NCS in a Marfan syndrome patient with type B aortic dissection who was presented with sudden gross hematuria. Computed tomography revealed the compression of the LRV sandwiched between the SMA and the dilated dissecting abdominal aorta. The compression was released by surgical intervention and the hematuria was promptly resolved. This report highlights that NCS should be considered as a differential diagnosis of unexplained hematuria in patients with a chronic dissecting aorta.

Safety and efficacy of the percutaneous thoracic endovascular repair with regional anesthesia.

OBJECTIVES: Thoracic endovascular aortic repair (TEVAR) is typically performed with general anesthesia (GA) and surgical cutdown (G-TEVAR). As the latest generation of TEVAR delivery systems are smaller, we introduced percutaneous TEVAR with regional anesthesia (RA) (R-TEVAR) and an arteriotomy closure device. In this study, we compare the safety and efficacy of R-TEVAR to that of the G-TEVAR. METHODS: This single-center observational study included consecutive patients who underwent either G-TEVAR between January 2015 and October 2018 (33 patients) or R-TEVAR (41 patients) between January 2018 and April 2020. RA was achieved using an ultrasound-guided nerve block. RESULTS: The mean outer diameter of the delivery device was significantly smaller in R-TEVAR (18.5 vs. 22.7 Fr; p < 0.01) and the time from arriving into the operating room to beginning of surgery (34.1 vs. 68.5 min; p < 0.01), procedural time (46.4 vs. 103.6 min; p < 0.01), and operating room stay time (108.3 vs. 194.6 min; p < 0.01) were significantly shorter. The mean rate of change in blood pressure was significantly lower in the R-TEVAR group (7.7% vs. 32.2%; p < 0.01). One case of spinal cord ischemia occurred in the G-TEVAR group (0% vs. 3.0%; p = 0.262) and one case of inadequate hemostasis and conversion to surgical cutdown without GA occurred in the R-TEVAR group (2.4% vs. 0%; p = 0.366). CONCLUSIONS: The R-TEVAR is safe and minimally invasive. Further, RA may provide additional benefits of mean blood pressure stability and early recognition of neurologic complications.

Upside-down and kissing stent graft techniques for late extravasation of a prosthetic graft implanted in the abdominal aorta.

Extravasation of prosthetic grafts is rare. Various anatomical problems after graft replacement might make standard endovascular treatment difficult. Use of a commercially available main body requires an adequate distance of the flow divider. An 86-year-old man developed extravasation of a graft that had been implanted in the infrarenal abdominal aorta 24 years previously. Endovascular repair with upside-down and kissing stent graft techniques using the contralateral leg was successfully performed.

Total endovascular repair of a mycotic thoracic aortic aneurysm in a patient with an aberrant right subclavian artery.

An aberrant right subclavian artery (ARSA) is a rare arterial anomaly. Although a few cases of total endovascular repair for the ARSA aneurysm have been previously reported, anatomical limitations and the possibility of endoleaks remained. In this case, we created 4 holes on the stent graft for each cervical branch, with reference to the preoperative computed tomography findings. This approach might enable us to repair all types of thoracic aortic aneurysms with ARSA with each anatomical feature.

Transcatheter aortic valve implantation after branched thoracic endovascular aortic repair in zone 0.

An 83-year-old woman who underwent emergent hemi-arch replacement for acute aortic dissection (Stanford Type A) and staged branched thoracic endovascular aortic repair in zone 0 was admitted for severe aortic stenosis. We performed transfemoral transcatheter aortic-valve implantation with an SAPIEN 3 valve. The interference between the stent frames of the valve and the stent grafts in the aortic arch was concerning. However, using the SAPIEN 3 valve's flex system, the valve was successfully delivered through the complex structure in the aortic arch without any aggravation. The patient's postoperative course was uneventful.