Preoperative predictors of nonhome discharge after fenestrated-branched endovascular repair of complex abdominal and thoracoabdominal aortic aneurysms.

BACKGROUND: Nonhome discharge (NHD) has significant implications for patient counseling and discharge planning and is frequently required following fenestrated-branched endovascular aortic repair (FB-EVAR) of complex abdominal aortic aneurysms (CAAA) and thoracoabdominal aortic aneurysms (TAAA). We aimed to identify preoperative predictors of NHD after elective FB-EVAR for CAAA and TAAA and develop a risk calculator able to predict NHD. METHODS: A retrospective review of prospectively collected data on all patients undergoing FB-EVAR between January 2007 and December 2021 at a single institution was performed. Exclusion criteria were admission from a nonhome setting, emergency and repeat FB-EVAR, and discharge to an unknown destination. The cohort was randomly split into separate development (70% of patients) and validation (30%) cohorts to develop a predictive calculator for NHD. Independent variables associated with NHD were assessed in a series of logistic regression analyses from 100 bootstrapped samples of the development set, and a model was developed using the most predictive variables. Resulting parameter estimates were applied to data in the validation set to assess model discrimination and calibration. RESULTS: From the initial cohort of 712 FB-EVAR patients, 644 were included in the study (74% male; mean age, 75.4 ± 7.6 years), including 452 with CAAA (70%) and 192 with TAAA (30%). Early mortality occurred in eight patients (1.2%; 5 in CAAA and 3 in TAAA) and the median hospital stay was 5 days (4 for CAAA and 7 for TAAA). Ninety-seven patients (15%) had a NHD. On multivariable analysis, older age (per year, odds ratio [OR], 1.08; P < .001), female gender (OR, 3.03; P < .001), smoking (OR, 2.86; P = .01), congestive heart failure (OR, 3.05; P = .004), peripheral artery disease (OR, 1.81; P = .07), and extent I (OR, 3.17), II (OR, 2.84), and III (OR, 2.52; all P = .08) TAAAs were associated with an increased likelihood of NHD in the development set. Based on these factors, the risk calculator was developed which accurately predicts NHD in the validation set with an area under the curve of 0.7. CONCLUSIONS: Older, female smokers with congestive heart failure and peripheral artery disease and more extensive aneurysms are at highest risk of NHD after FB-EVAR. Using only preoperative factors, our risk calculator can predict accurately who will have a NHD, allowing enhanced preoperative patient counselling and accelerated hospital discharge.

Advances from targeted therapy for non-metastatic HER2-positive inflammatory breast cancer.

Among inflammatory breast cancer (IBC) patients, over one-third have HER2-overexpressing (HER2+) tumors. Pathologic complete response (pCR) rates to neoadjuvant targeted and chemotherapy for patients with HER2+ non-metastatic IBC now apporach 60% and favorable long-term survival rates are being reported for those with a pCR. Immune mechanisms contributing to this phenomenon include antibody-mediated immune activation and induction of memory T-cell reponses which may explain the sustained antitumor response seen after discontinuation of targeted therapies.

Distinct presentation of melanoma in Black patients may inform strategies to improve outcomes.

INTRODUCTION: Melanoma guidelines stem largely from data on non-Hispanic White (NHW) patients. We aimed to identify features of melanoma within non-Hispanic Black (NHB) patients to inform strategies for earlier detection and treatment. METHODS: From 2004 to 2019 Surveillance, Epidemiology, and End Results (SEER) data, we identified nonmetastatic melanoma patients with known TN category and race. Kaplan-Meier cancer-specific survival (CSS) estimates and multivariable Cox proportional hazard modeling analyses were performed. RESULTS: Of 492 597 patients, 1499 (0.3%) were NHB, who were younger (21% vs. 17% age <50) and more commonly female (54% vs. 41%) than NHW, both p < 0.0005. For NHBs, lower extremity was the most common site (52% vs. 15% for NHWs, p < 0.0001), T category was higher (55% Tis-T1 vs. 82%; 27% T3-T4 vs. 8%, p < 0.0001) and stage at presentation was higher (19% Stage III, vs. 6%, p < 0.0001). Within the NHB cohort, males were older, and more often node-positive than females. Five-year Stage III CSS was 42% for NHB males versus 71% for females, adjusting for age and clinical nodal status (hazard ratio 2.48). CONCLUSIONS: NHB melanoma patients presented with distinct tumor characteristics. NHB males with Stage III disease had inferior CSS. Focus on this high-risk patient cohort to promote earlier detection and treatment may improve outcomes.

Impact of proton pump inhibitors on pathologic response rates following fluoropyrimidine-based neoadjuvant chemotherapy in pancreatic cancer patients.

BACKGROUND: Proton pump inhibitors (PPIs) negatively impact fluoropyrimidine-based chemotherapy efficacy in colorectal cancer. This study assessed PPI impact on major pathologic response (mPR) rates of pancreatic adenocarcinoma (PDAC) patients receiving fluoropyrimidine-based chemotherapy. METHODS: An institutional retrospective review of resected PDAC patients receiving neoadjuvant fluoropyrimidine-based chemotherapy (98% FOLFIRINOX) from 2011 to 2021 was conducted. Outcomes were stratified by use or nonuse of PPIs within 6 months of neoadjuvant chemotherapy initiation. Primary outcome was mPR defined as complete or near complete response. RESULTS: Among 540 patients included, the median age was 64 (IQR: 60-70) years, 297 (55%) were male, and 202 (37%) were PPI users. 170 (31%) patients had mPR with similar rates among PPI users and nonusers (29% vs. 33%, p = 0.38). No difference in mPR was seen between PPI users and nonusers receiving chemoradiation (35% vs. 36%, p = 0.89) or ≥8 cycles of NAC (33% vs. 36%, p = 0.55). Median OS for PPI users was 30.9 versus 31.7 months for nonusers (p = 0.62). On multivariable analysis, PPI therapy was not associated with decreased survival. CONCLUSION: PPI usage did not significantly influence mPR or OS following neoadjuvant fluoropyrimidine-based chemotherapy in resected PDAC patients. Further analysis of all patients, not just those who underwent resection, is required.

Principles of Surgical Management of Peritoneal Mesothelioma.

Malignant peritoneal mesothelioma (MPeM) is a rare malignancy and represents 5% to 30% of malignant mesothelioma cases. The primary curative therapy for MPeM is radical cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC), with the strongest predictor of long-term survival being complete cytoreduction. There is a paucity of high-quality evidence available to guide management in MPeM; however, NCCN Guidelines for the management of MPeM were updated this year. In well-selected patients, 5-year overall survival exceeds 65%, but achieving optimal results requires careful preoperative evaluation and expert surgical management. Preoperative patient selection includes histology review and staging with cross-sectional imaging. Ideal candidates for curative intent surgery are those with epithelioid MPeM, a low peritoneal cancer index, and a good performance status. Contraindications to curative intent surgery include the sarcomatoid MPeM, distant metastases, extensive nodal metastases, and extensive small bowel serosal or mesentery involvement not amenable to complete cytoreduction. Those with biphasic histology, bicavitary disease, and metastatic lymphadenopathy may be considered for surgery following response to neoadjuvant therapy. CRS involves resection of all peritoneal disease, the extent of which varies case by case. Key aspects involve careful evaluation of all peritoneal surfaces, complete parietal peritonectomy and omentectomy, and evaluating suspicious abdominal lymph node basins. Once maximum cytoreduction is achieved, HIPEC is performed using a platinum-based perfusate. Postoperative protocols are recommended to optimize recovery and mitigate HIPEC-specific complications, namely chemotherapy-mediated nephrotoxicity and bone marrow suppression.

Distress levels in pregnant and matched non-pregnant women.

This study examined self-rated symptoms of distress (Depression Anxiety and Stress Scale-DASS-21 and Perceived Stress Scale-PSS-4) among 93 pregnant women and a comparison group of 93 non-pregnant women matched on age and educational attainment. There were no significant differences between the groups, either on mean levels of distress or on proportions above a clinical cut-off point. Overall, 22%, 31% and 16% of pregnant women reported experiencing at least moderate levels of depression, anxiety and stress, respectively. Implications for conceptualising distress in pregnancy and identifying and providing support for the substantial minority who are distressed are discussed.

Assessment of the effect of the American Society of Breast Surgery guidelines on contralateral prophylactic mastectomy rates for unilateral breast cancer.

BACKGROUND: In July 2016, the American Society of Breast Surgeons published guidelines discouraging contralateral prophylactic mastectomy for average-risk women with unilateral breast cancer. We incorporated these into practice with structured patient counseling and aimed to assess the effect of this initiative on contralateral prophylactic mastectomy rates. METHODS: We evaluated female patients with unilateral breast cancer undergoing mastectomy at our institution from January 2011 to November 2022. Variables associated with contralateral prophylactic mastectomy and trends over time were analyzed using the Wilcoxon rank sum test or χ2 analysis as appropriate. RESULTS: Among 3,208 patients, (median age 54 years) 1,366 (43%) had a unilateral mastectomy, and 1,842 (57%) also had a concomitant contralateral prophylactic mastectomy. Across all patients, contralateral prophylactic mastectomy rates significantly decreased post-implementation from 2017 to 2019 (55%) vs 2015 to 2016 (62%) (P = .01) but increased from 2020 to 2022 (61%). Immediate breast reconstruction rate was 70% overall (81% with contralateral prophylactic mastectomy and 56% without contralateral prophylactic mastectomy, P < .001). Younger age, White race, mutation status, and earlier stage were also associated with contralateral prophylactic mastectomy. Genetic testing increased from 27% pre-guideline to 74% 2020 to 2022, as did the proportion of patients with a pathogenic variant (4% pre-guideline vs 11% from 2020-2022, P < .001), of whom 91% had a contralateral prophylactic mastectomy. Among tested patients without a pathogenic variant and patients not tested, contralateral prophylactic mastectomy rates declined from 78% to 67% and 48% to 38% pre -and post-guidelines, respectively, P < .001. CONCLUSION: Implementation of specific patient counseling was effective in decreasing contralateral prophylactic mastectomy rates. While recognizing that patient choice plays a significant role in the decision for contralateral prophylactic mastectomy, further educational efforts are warranted to affect contralateral prophylactic mastectomy rates, particularly in the setting of negative genetic testing.

Transcriptomic landscapes of effective and failed liver regeneration in humans.

Background & Aims: Although extensive experimental evidence on the process of liver regeneration exists, in humans, validation is largely missing. However, liver regeneration is critically affected by underlying liver disease. Within this project, we aimed to systematically assess early transcriptional changes during liver regeneration in humans and further assess how these processes differ in people with dysfunctional liver regeneration. Methods: Blood samples of 154 patients and intraoperative tissue samples of 46 patients undergoing liver resection were collected and classified with regard to dysfunctional postoperative liver regeneration. Of those, a matched cohort of 21 patients were used for RNA sequencing. Samples were assessed for circulating cytokines, gene expression dynamics, intrahepatic neutrophil accumulation, and spatial transcriptomics. Results: Individuals with dysfunctional liver regeneration demonstrated an aggravated transcriptional inflammatory response with higher intracellular adhesion molecule-1 induction. Increased induction of this critical leukocyte adhesion molecule was associated with increased intrahepatic neutrophil accumulation and activation upon induction of liver regeneration in individuals with dysfunctional liver regeneration. Comparing baseline gene expression profiles in individuals with and without dysfunctional liver regeneration, we found that dual-specificity phosphatase 4 (DUSP4) expression, a known critical regulator of intracellular adhesion molecule-1 expression in endothelial cells, was markedly reduced in patients with dysfunctional liver regeneration. Mimicking clinical risk factors for dysfunctional liver regeneration, we found liver sinusoidal endothelial cells of two liver disease models to have significantly reduced baseline levels of DUSP4. Conclusions: Exploring the landscape of early transcriptional changes of human liver regeneration, we observed that people with dysfunctional regeneration experience overwhelming intrahepatic inflammation. Subclinical liver disease might account for DUSP4 reduction in liver sinusoidal endothelial cells, which ultimately primes the liver for an aggravated inflammatory response. Impact and implications: Using a unique human biorepository, focused on liver regeneration (LR), we explored the landscape of circulating and tissue-level alterations associated with both functional and dysfunctional LR. In contrast to experimental animal models, people with dysfunctional LR demonstrated an aggravated transcriptional inflammatory response, higher intracellular adhesion molecule-1 (ICAM-1) induction, intrahepatic neutrophil accumulation and activation upon induction of LR. Although inflammatory responses appear rapidly after liver resection, people with dysfunctional LR have exaggerated inflammatory responses that appear to be related to decreased levels of LSEC DUSP4, challenging existing concepts of post-resectional LR.

Technique of partial open surgical stent graft explantation with preservation of fenestrated stent graft component to treat recalcitrant type II endoleak.

Fenestrated and branched stent grafts have been used with increasing frequency for endovascular repair of complex aortic aneurysms. Endoleaks are frequently encountered after endovascular aortic aneurysm repair, with treatment indicated when associated with an enlarging aneurysm sac. When endovascular treatment fails, complex open surgical explantation will become necessary. We have reported the technique of partial graft explantation in a patient with a recalcitrant type II endoleak. Both the proximal fenestrated segment and the distal iliac limbs were preserved, and aortic control was obtained by clamping the infrarenal stent graft. This method allowed for more distal aortic cross-clamping and negated the need for visceral branch reimplantation.

Effective treatment of type IIb endoleak via targeted translumbar embolization.

After endovascular aneurysm repair, type II endoleaks are encountered frequently, and warrant intervention when associated with aneurysmal sac expansion. Thus, the contemporary vascular surgeon must be able to manage them. The presented case illustrates our approach to percutaneous translumbar selective coil embolization of individual lumbar arteries feeding the type IIb endoleak. The use of specific imaging systems allows for needle track guidance to access the endoleak pocket. Treatment of the feeding vessels with detachable coils can be achieved with a direct route via the translumbar sheath. The benefits of this approach include avoidance of graft puncture, targeted therapy, and low puncture-related complications.