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1.
J Vasc Surg ; 2024 Jun 03.
Article in English | MEDLINE | ID: mdl-38838968

ABSTRACT

BACKGROUND: There is persistent controversy surrounding the merit of surgical volume benchmarks being used solely as a sufficient proxy for assessing the quality of open abdominal aortic aneurysm (AAA) repair. Importantly, operative volume quotas may fail to reflect a more nuanced and comprehensive depiction of surgical outcomes most relevant to patients. Accordingly, we herein propose a patient-centered textbook outcome (TO) for AAA repair that is analogous to other large magnitude extirpative operations performed in other surgical specialties, and test its feasibility to discriminate hospital performance using Society for Vascular Surgery (SVS) volume guidelines. METHODS: All elective open infrarenal AAA repairs (OAR) in the SVS-Vascular Quality Initiative were examined (2009-2022). The primary end point was a TO, defined as a composite of no in-hospital complication or reintervention/reoperation, length of stay of ≤10 days, home discharge, and 1-year survival rates. The discriminatory ability of the TO measure was assessed by comparing centers that did or did not meet the SVS annual OAR volume threshold recommendation (high volume ≥10 OARs/year; low volume <10 OARs/year). Logistic regression and multivariable models adjusted for patient and procedure-related differences. RESULTS: A total of 9657 OARs across 198 centers were analyzed (mean age, 69.5 ± 8.4 years; female, 26%; non-White, 12%). A TO was identified in 44% (n = 4293) of the overall cohort. The incidence of individual TO components included no in-hospital complication (61%), no in-hospital reintervention or reoperation (92%), length of stay of ≤10 days (78%), home discharge (76%), and 1-year survival (91%). Median annual center volume was 6 (interquartile range, 3-10) and a majority of centers did not meet the SVS volume suggested threshold (<10 OARs/year, n = 148 [74%]). However, most patients (6265 of 9657 [65%]) underwent OAR in high-volume hospitals. When comparing high- and low-volume centers, a TO was more likely to occur in high-volume institutions: ≥10 OARs/year (46%) vs <10 OARs/year (42%; P = .0006). The association of a protective effect for higher center volume remained after risk adjustment (odds ratio, 1.1; 95% confidence interval, 1.05-1.26; P = .003). CONCLUSIONS: TOs for elective OAR reflect a more nuanced and comprehensive patient centered proxy to measure care delivery, consistent with other surgical specialties. Surprisingly, a TO was achieved in <50% of elective AAA cases nationally. Although the likelihood of a TO seems to correlate with SVS center volume recommendations, it more importantly reflects elements which may be prioritized by patients and thus offers insights into further improving real-world AAA care.

2.
J Surg Res ; 198(2): 418-23, 2015 Oct.
Article in English | MEDLINE | ID: mdl-25940155

ABSTRACT

BACKGROUND: Primary hepatic neoplasms in children are rare tumors. All malignant and medically refractive benign primary pediatric liver tumors ultimately require surgical resection for cure. Accurate preoperative imaging including multidetector helical computerized tomography or magnetic resonance imaging (MRI) is necessary to determine resectability. In the literature intraoperative ultrasound (IOUS) has proven to be a vital adjunct to liver surgery in adults, but this is not well established in children. MATERIALS AND METHODS: Between April 2003 and November 2014, children (<18-y-old) with a primary liver neoplasm, preoperatively evaluated with multidetector helical computerized tomography or MRI, who had IOUS used at the time of surgery were retrospectively reviewed. RESULTS: Preoperative evaluation with high-resolution MRI and IOUS were discordant in 4 of 19 patients (21%). In one case, right hepatic vein involvement was not accurately assessed with MRI. Two cases showed tumor involvement in segment IV by MRI; however, IOUS revealed no medial segment involvement. The final patient had a large (>5 cm), solitary hepatic adenoma on MRI, but IOUS in this case revealed diffuse adenomatosis. The operative management was altered in three of these cases. CONCLUSIONS: Although MRI can provide a detailed view of the hepatic anatomy and is an invaluable tool for preoperative planning for the pediatric patient with a primary liver neoplasm, IOUS may provide further and more up to date delineation of tumor extent and should be considered a crucial element in operative planning for hepatectomy in children.


Subject(s)
Adenoma, Liver Cell/diagnostic imaging , Hepatoblastoma/diagnostic imaging , Liver Neoplasms/diagnostic imaging , Adenoma, Liver Cell/surgery , Adolescent , Female , Hepatoblastoma/surgery , Humans , Infant , Intraoperative Care , Liver Neoplasms/surgery , Male , Multidetector Computed Tomography , Retrospective Studies , Ultrasonography
3.
Front Immunol ; 14: 1012799, 2023.
Article in English | MEDLINE | ID: mdl-36756111

ABSTRACT

Introduction: Histotripsy is a novel focused ultrasound tumor ablation modality with potent immunostimulatory effects. Methods: To measure the spatiotemporal kinetics of local andabscopal responses to histotripsy, C57BL/6 mice bearing bilateral flank B16 melanoma or Hepa1-6 hepatocellular carcinoma tumors were treated with unilateral sham or partial histotripsy. Treated and contralateral untreated (abscopal) tumors were analyzed using multicolor immunofluorescence, digital spatial profiling, RNA sequencing (RNASeq), and flow cytometry. Results: Unilateral histotripsy triggered abscopal tumor growth inhibition. Within the ablation zone, early high mobility group box protein 1 (HMGB1) release and necroptosis were accompanied by immunogenic cell death transcriptional responses in tumor cells and innate immune activation transcriptional responses in infiltrating myeloid and natural killer (NK) cells. Delayed CD8+ T cell intratumoral infiltration was spatiotemporally aligned with cancer cell features of ferroptosis; this effect was enhanced by CTLA-4 blockade and recapitulated in vitro when tumor-draining lymph node CD8+ T cells were co-cultured with tumor cells. Inoculation with cell-free tumor fractions generated by histotripsy but not radiation or freeze/thaw conferred partial protection from tumor challenge. Discussion: We propose that histotripsy may evoke local necroptotic immunogenic cell death, priming systemic adaptive immune responses and abscopal ferroptotic cancer cell death.


Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Mice , Animals , Mice, Inbred C57BL , Cell Death , Carcinoma, Hepatocellular/therapy , Immunity
4.
J Immunother Cancer ; 8(1)2020 01.
Article in English | MEDLINE | ID: mdl-31940590

ABSTRACT

BACKGROUND: Developing the ability to use tumor-directed therapies to trigger potentially therapeutic immune responses against cancer antigens remains a high priority for cancer immunotherapy. We hypothesized that histotripsy, a novel non-invasive, non-thermal ablation modality that uses ultrasound-generated acoustic cavitation to disrupt tissues, could engender adaptive immune responses to tumor antigens. METHODS: Immunocompetent C57BL/6 mice inoculated with flank melanoma or hepatocellular carcinoma tumors were treated with histotripsy, thermal ablation, radiation therapy, or cytotoxic T lymphocyte-associated protein-4 (CTLA-4) blockade checkpoint inhibition. Lymphocyte responses were measured using flow cytometric and immunohistochemical analyses. The impact of histotripsy on abscopal immune responses was assessed in mice bearing bilateral tumors, or unilateral tumors with pulmonary tumors established via tail vein injection. RESULTS: Histotripsy ablation of subcutaneous murine melanoma tumors stimulated potent local intratumoral infiltration of innate and adaptive immune cell populations. The magnitude of this immunostimulation was stronger than that seen with tumor irradiation or thermal ablation. Histotripsy also promoted abscopal immune responses at untreated tumor sites and inhibited growth of pulmonary metastases. Histotripsy was capable of releasing tumor antigens with retained immunogenicity, and this immunostimulatory effect was associated with calreticulin translocation to the cellular membrane and local and systemic release of high mobility group box protein 1. Histotripsy ablation potentiated the efficacy of checkpoint inhibition immunotherapy in murine models of melanoma and hepatocellular carcinoma. CONCLUSIONS: These preclinical observations suggest that non-invasive histotripsy ablation can be used to stimulate tumor-specific immune responses capable of magnifying the impact of checkpoint inhibition immunotherapy.


Subject(s)
Ablation Techniques/methods , Antineoplastic Agents, Immunological/pharmacology , CTLA-4 Antigen/antagonists & inhibitors , High-Intensity Focused Ultrasound Ablation/methods , Liver Neoplasms, Experimental/therapy , Melanoma, Experimental/therapy , Animals , Combined Modality Therapy , Liver Neoplasms, Experimental/immunology , Liver Neoplasms, Experimental/pathology , Lung Neoplasms/immunology , Lung Neoplasms/secondary , Lung Neoplasms/therapy , Melanoma, Experimental/immunology , Melanoma, Experimental/pathology , Mice , Mice, Inbred C57BL
5.
Pediatrics ; 135(4): e1067-71, 2015 Apr.
Article in English | MEDLINE | ID: mdl-25802350

ABSTRACT

Paraduodenal hernias are the most common type of congenital internal hernia. Because of its overall rare incidence, this entity is often overlooked during initial assessment of the patient. Lack of specific diagnostic criteria also makes diagnosis exceedingly difficult, and the resulting diagnostic delays can lead to tragic outcomes for patients. Despite these perceived barriers to timely diagnosis, there may be specific radiographic findings that, when combined with the appropriate constellation of clinical symptoms, would aid in diagnosis. This patient first presented at 8 years of age with vague symptoms of postprandial emesis, chronic abdominal pain, nausea, and syncope. Over the span of 6 years he was evaluated 2 to 3 times a year with similar complaints, all of which quickly resolved spontaneously. He underwent multiple laboratory, imaging, and endoscopic studies, which were nondiagnostic. It was not until he developed signs of a high-grade obstruction and extremis that he was found to have a large left paraduodenal hernia that had volvulized around the superior mesenteric axis. This resulted in the loss of the entire superior mesenteric axis distribution of the small and large intestine and necrosis of the duodenum. In cases of chronic intermittent obstruction without clear etiology, careful attention and consideration should be given to the constellation of symptoms, imaging studies, and potential use of diagnostic laparoscopy. Increased vigilance by primary care and consulting physicians is necessary to detect this rare but readily correctable condition.


Subject(s)
Abdominal Pain/etiology , Chronic Pain/etiology , Duodenal Diseases/congenital , Hernia, Abdominal/congenital , Intestinal Volvulus/diagnosis , Abdominal Pain/surgery , Child , Chronic Pain/surgery , Delayed Diagnosis , Diagnostic Errors , Duodenal Diseases/surgery , Hernia, Abdominal/surgery , Humans , Intestinal Volvulus/surgery , Intestines/pathology , Intestines/surgery , Male , Necrosis , Postoperative Complications/etiology , Postoperative Complications/surgery , Reoperation , Tomography, X-Ray Computed
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