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Purpose: High-grade appendiceal adenocarcinomas (HGAA) with peritoneal metastases (PMs) are associated with poor survival. Hyperthermic intraperitoneal chemotherapy (HIPEC) is a novel treatment approach for unresectable HGAA-PM. However, its influence on immunogenomic profiles has not yet been fully explored., Materials and Methods: We obtained 79 samples of metastatic peritoneal tumor deposits from patients diagnosed with HGAA and performed whole-exome sequencing, RNA sequencing, and immunoprofiling before and after HIPEC. Tumor biopsies were subjected to immunogenomic profiling to detect mutational signatures and immune populations associated with oncologic outcomes., Results: Fifteen patients with HGAA-PMs were included in the study. The median progression-free survival (PFS) was 6.7 months (2.7-25.3) and the median overall survival was 11.4 months (4.7-42). Mucin-associated genes ( MUC16 , MUC3A , and MUC5AC ) and titin ( TTN ) had the highest mutation frequencies. Mutational signatures such as single-base substitution 29 and doublet-base substitution 11 were present in >50% of single-base and double-base mutations. Higher PD-L1 coexpression on CD8 + T cells demonstrated a higher PFS both intratumorally ( P = .019) and at the margin ( P = .025)., Conclusion: HIPEC-associated mutational signatures were identified in HGAA-PMs. Elevated PD-L1+ cytotoxic T-cell populations after HIPEC had better PFS, offering valuable insights for prognostication in the context of HIPEC treatment.

Background: Plasma circulating tumor DNA (ctDNA) is a promising biomarker for metastatic colorectal cancer (mCRC); however, its role in characterizing recurrence sites after mCRC resection remains poorly understood. This single-institution study investigated the timing of ctDNA detection and its levels in the context of recurrence at different sites after mCRC resection., Study Design: Patients who underwent optimal resection of CRC metastases involving the peritoneum, distant lymph nodes, or liver, with serial postoperative tumor-informed ctDNA assessments (Signatera) were included. Recurrence sites, as defined by surveillance imaging or laparoscopy, were categorized as peritoneal-only and other distant sites (liver, lung, lymph nodes, or body wall)., Results: Among the 31 included patients, ctDNA was detected in all 26 (83.4%) patients with postoperative recurrence and was persistently undetectable in 5 patients who did not experience recurrence. At 3 months postsurgery, ctDNA was detected in 2 (25%) of 8 patients with peritoneal-only recurrence and 17 (94.4%) of 18 patients with distant recurrence (p < 0.001). Beyond 3 months, ctDNA was detected in the remaining 6 patients with peritoneal-only disease and 1 patient with distant disease. ctDNA detection preceded the clinical diagnosis of recurrence by a median of 9 weeks in both groups. At recurrence, peritoneal-only recurrent cases exhibited lower ctDNA levels (median 0.4 mean tumor molecules/mL, interquartile range 0.1 to 0.8) compared with distant recurrence (median 5.5 mean tumor molecules/mL, interquartile range 0.8 to 33.3, p = 0.004)., Conclusions: Peritoneal-only recurrence was associated with delayed ctDNA detection and low levels of ctDNA after optimal resection for mCRC. ctDNA testing may effectively characterize recurrence sites and may help guide subsequent treatments specific to the disease sites involved., (Copyright © 2024 by the American College of Surgeons. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: Conventional surveillance methods are poorly sensitive for monitoring appendiceal cancers (AC). This study investigated the utility of circulating tumor DNA (ctDNA) in evaluating systemic therapy response and recurrence after surgery for AC., Methods: Patients from two specialized centers who underwent tumor-informed ctDNA testing (Signatera) were evaluated to determine the association between systemic therapy and ctDNA detection. In addition, the accuracy of ctDNA detection during surveillance for the diagnosis of recurrence after complete cytoreductive surgery (CRS) for grade 2-3 ACs with peritoneal metastases (PM) was investigated., Results: In this cohort of 94 patients with AC, most had grade 2-3 tumors (84.0%) and PM (84.0%). Fifty patients completed the assay in the presence of identifiable disease, among which ctDNA was detected in 4 of 7 (57.1%), 10 of 16 (62.5%), and 19 of 27 (70.4%) patients with grade 1, 2, and 3 diseases, respectively. Patients who had recently received systemic chemotherapy had ctDNA detected less frequently (7 of 16 [43.8%] v 26 of 34 [76.5%]; odds ratio, 0.22 [95% CI, 0.06 to 0.82]; P = .02). Among 36 patients with complete CRS for grade 2-3 AC-PM, 16 (44.4%) developed recurrence (median follow-up, 19.6 months). ctDNA detection was associated with shorter recurrence-free survival (median 11.3 months v not reached; hazard ratio, 14.1 [95% CI, 1.7 to 113.8]; P = .01) and showed high accuracy for the detection of recurrence (sensitivity 93.8%, specificity 85.0%). ctDNA was more sensitive than carcinoembryonic antigen (62.5%), CA19-9 (25.0%), and CA125 (18.8%) and was the only elevated biomarker in four (25%) patients with recurrence., Conclusion: This study revealed a reduced ctDNA detection frequency after systemic therapy and accurate recurrence assessment after CRS. These findings underscore the role of ctDNA as a predictive and prognostic biomarker for grade 2-3 AC-PM management.

Introduction: Venous thromboembolism (VTE) is a common complication in patients with abdominal malignancies. Despite known associations between pleural mesothelioma and increased VTE risk, the characteristics of VTE in patients with peritoneal mesothelioma (PeM) remain undescribed., Methods: Patients treated for PeM were retrospectively identified from our institutional database. The frequency of VTE was assessed and logistic regression modeling was employed to assess VTE risk factors. The association between VTE and overall survival was also ascertained. Recommended thromboprophylaxis for patients who underwent surgery at our institution comprised a single preoperative dose of prophylactic anticoagulation, followed by daily dosing for four weeks postoperatively., Results: Among 120 PeM patients, 26 (21.7%) experienced VTE, including 19/91 (20.9%) surgical patients, 4/23 (17.4%) patients who received systemic therapy, and 3/6 (50%) patients who underwent observation (p = 0.21). Most events were symptomatic (n = 16, 62%) and were attributable to pulmonary emboli (n = 16, 62%). The 90-day postoperative VTE rate was 4.4% (4/91), including 1 of 60 patients who underwent index surgical intervention at our institution and 3 patients with surgery elsewhere. A low serum albumin concentration was associated with VTE in non-surgical patients (odds ratio 0.12, confidence interval [CI] 0.02-0.72; p = 0.03). No significant difference in overall survival was observed between patients with and without VTE (median 46.0 months [CI 24.9-67.0] vs. 55.0 months [CI 27.5-82.5]; hazard ratio 0.98 [CI 0.54-1.81], p = 0.98)., Conclusions: A high risk of VTE was observed in PeM patients, warranting suspicion throughout the disease trajectory. Postoperative VTE rates were within acceptable limits with 4-week thromboprophylaxis., (© 2024. Society of Surgical Oncology.)

Background: Imaging of peritoneal malignancies using conventional cross-sectional imaging is challenging, but accurate assessment of peritoneal disease burden could guide better selection for definitive surgery. Here we demonstrate feasibility of high-resolution, high-contrast magnetic resonance imaging (MRI) of peritoneal mesothelioma and explore optimal timing for delayed post-contrast imaging., Methods: Prospective data from inpatients with malignant peritoneal mesothelioma (MPM), imaged with a novel MRI protocol, were analyzed. The new sequences augmenting the clinical protocol were (I) pre-contrast coronal high-resolution T2-weighted single-shot fast spin echo (COR hr T2w SSH FSE) of abdomen and pelvis; and (II) post-contrast coronal high-resolution three-dimensional (3D) T1-weighted modified Dixon (COR hr T1w mDIXON) of abdomen, acquired at five delay times, up to 20 min after administration of a double dose of contrast agent. Quantitative analysis of contrast enhancement was performed using linear regression applied to normalized signal in lesion regions of interest (ROIs). Qualitative analysis was performed by three blinded radiologists., Results: MRI exams from 14 participants (age: mean ± standard deviation, 60±12 years; 71% male) were analyzed. The rate of lesion contrast enhancement was strongly correlated with tumor grade (cumulative nuclear score) (r=-0.65, P<0.02), with 'early' delayed phase (12 min post-contrast) and 'late' delayed phase (19 min post-contrast) performing better for higher grade and lower grade tumors, respectively, in agreement with qualitative scoring of image contrast., Conclusions: High-resolution, high-contrast MRI with extended post-contrast imaging is a viable modality for imaging peritoneal mesothelioma. Multiple, extended (up to 20 min post-contrast) delayed phases are necessary for optimal imaging of peritoneal mesothelioma, depending on the grade of disease., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-23-13/coif). H.L.K. has received consulting fees from AstraZeneca and is on the advisory board of Tempus, Bluestar Genomics, and Sanofi. R.M.E. receives royalties and licensing fees for computer-aided diagnosis technologies through the University of Chicago. A.O. has received funding from NIH and the Sanford J. Grossman Charitable Trust, has received payment for expert testimony, and is a co-owner of Quantitative MR Imaging Solutions (QMIS). S.G.A. is a past president of the International Mesothelioma Interest Group. K.K.T. has received consulting fees from Merck for unrelated work. The other authors have no conflicts of interest to declare., (2024 Quantitative Imaging in Medicine and Surgery. All rights reserved.)

Objectives: Palliative care (PC) for patients with advanced cancer has been associated with improved symptom burden and quality of life (QoL). This study aimed to characterise postoperative symptoms of cytoreductive surgery (CRS)/hyperthermic intraperitoneal chemotherapy (HIPEC) patients and to assess PC impact by analysing symptom burden before and after PC interventions., Methods: CRS/HIPEC patients with two PC visits within 5 months postoperatively (2016-2021) at a tertiary care centre were identified from a retrospective database. For each patient, documentation of QoL-associated symptoms at the initial PC visit and changes in symptomatology at the second PC visit were recorded. Descriptive statistics were performed., Results: 46 patients were included in this study. Median age was 62.2 (range 31.9-84.6) years. Median peritoneal cancer index was 23.5 (range 0-39). The most common histologies were colorectal (32.6%) and appendiceal (30.4%). Symptoms most frequently reported were pain (84.8%), fatigue (54.3%) and appetite loss/change (52.2%). Following PC interventions, most symptoms were stable or improved. The mean number of symptoms per patient was 3.7, with an average of 3.5 improved/stable and 0.5 worse/new onset at follow-up (p<0.001)., Conclusion: CRS/HIPEC patients experienced a high QoL-associated symptom burden. Following postoperative PC interventions, significantly more symptoms were reported as improved/stable, compared with worse/new onset., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The delivery of multimodal treatment at a high-volume center is known to optimize the outcomes of gastrointestinal malignancies. However, patients undergoing cytoreductive surgery (CRS) for peritoneal metastases often must 'fragment' their surgical and systemic therapeutic care between different institutions. We hypothesized that this adversely affects outcomes., Patients and Methods: Adults undergoing CRS for colorectal or appendiceal adenocarcinoma at our institution between 2016 and 2022 were identified retrospectively and grouped by care network: 'coordinated care' patients received exclusively in-network systemic therapy, while 'fragmented care' patients received some systemic therapy from outside-network providers. Factors associated with fragmented care were also ascertained. Overall survival (OS) from CRS and systemic therapy-related serious adverse events (SAEs) were compared across the groups., Results: Among 85 (80%) patients, 47 (55%) had colorectal primaries and 51 (60%) received fragmented care. Greater travel distance [OR 1.01 (CI 1.00-1.02), p = 0.02] and educational status [OR 1.04 (CI 1.01-1.07), p = 0.01] were associated with receiving fragmented care. OS was comparable between patients who received fragmented and coordinated care in the colorectal [32.5 months versus 40.8 months, HR 0.95 (CI 0.43-2.10), p = 0.89] and appendiceal [31.0 months versus 27.4 months, HR 1.17 (CI 0.37-3.74), p = 0.55] subgroups. The frequency of SAEs (7.8% versus 17.6%, p = 0.19) was also similar., Conclusions: There were no significant differences in survival or SAEs based on the networks of systemic therapy delivery. This suggests that patients undergoing CRS at a high-volume center may safely receive systemic therapy at outside-network facilities with comparable outcomes., (© 2023. Society of Surgical Oncology.)

Objective: To elucidate the potential usage of continuous feedback regarding team satisfaction and correlations with operative performance and patient outcomes., Background: Continuous, actionable assessment of teamwork quality in the operating room (OR) is challenging. This work introduces a novel, data-driven approach to prospectively and dynamically assess health care provider satisfaction with teamwork in the OR., Methods: Satisfaction with teamwork quality for each case was assessed utilizing a validated prompt displayed on HappyOrNot Terminals placed in all ORs, with separate panels for circulators, scrub nurses, surgeons, and anesthesia providers. Responses were cross-referenced with OR log data, team familiarity indicators, efficiency parameters, and patient safety indicator events through continuous, semiautomated data marts. Deidentified responses were analyzed through logistic regression modeling., Results: Over a 24-week period, 4123 responses from 2107 cases were recorded. The overall response rate per case was 32.5%. Greater scrub nurse specialty experience was strongly associated with satisfaction (odds ratio: 2.15, 95% CI: 1.53-3.03, P < 0.001). Worse satisfaction was associated with longer than expected procedure time (odds ratio: 0.91, 95% CI: 0.82-1.00, P = 0.047), nighttime (0.67, 95% CI: 0.55-0.82, P < 0.001), and add-on cases (0.72, 95% CI: 0.60-0.86, P < 0.001). Higher material costs (22%, 95% CI: 6-37, P = 0.006) were associated with greater team satisfaction. Cases with superior teamwork ratings were associated with a 15% shorter length of hospital stay (95% CI: 4-25, P = 0.006)., Conclusions: This study demonstrates the feasibility of a dynamic survey platform to report actionable health care provider satisfaction metrics in real-time. Team satisfaction is associated with modifiable team variables and some key operational outcomes. Leveraging qualitative measurements of teamwork as operational indicators may augment staff engagement and measures of performance., Competing Interests: K.K.T. reports collecting speaking fees from Aspire Bariatrics. The remaining authors report no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)