Low grade appendiceal mucinous neoplasm metastatic to the ovary: A case report and intraoperative assessment guide.

INTRODUCTION: Incidence of low grade appendiceal mucinous neoplasm is increasing. Preoperatively, it may present similarly to primary ovarian malignancy. This case report describes a case of presumed ovarian malignancy with final pathologic diagnosis of low grade appendiceal mucinous neoplasm. We also propose several surgical strategies to approach this conundrum. PRESENTATION OF CASE: A postmenopausal woman with abdominal pain was found to have a 30 cm abdominopelvic mass with elevated CA-125 and CEA presumably a primary ovarian malignancy. During surgical staging, intraoperative findings were notable for an appendiceal mass. Intraoperative surgical oncology consultation recommended appendectomy for diagnostic purposes. Following primary surgery and final pathologic diagnosis, she underwent cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. DISCUSSION: Low grade appendiceal mucinous neoplasm should be within the differential diagnosis of gynecologic surgeons when presented with a patient with large volume ascites and biopsy of acellular mucin. Intraoperatively, an abnormal appearing appendix with normal appearing gynecologic structures should trigger suspicion for appendiceal rather than ovarian origin. Preoperative symptoms, imaging studies, tumor markers, and frozen section pathology may not be able to differentiate between appendiceal and epithelial ovarian malignancies. CONCLUSION: A recognition of mucinous material and abnormal appearing appendix should prompt the surgeon to consider performing an appendectomy to obtain primary pathologic diagnosis. A high level of suspicion could better optimize the patient for a joint case with the appropriate surgeons. Given the documented disguise of low grade appendiceal mucinous neoplasm as primary ovarian cancer and its increasing incidence, diagnosis and general understanding of treatment should be understood.

Role of Tumor-informed Personalized Circulating Tumor DNA Assay in Informing Recurrence in Patients With Peritoneal Metastases From Colorectal and High-grade Appendix Cancer Undergoing Curative-intent Surgery.

OBJECTIVE: To investigate the role of a personalized, tumor-informed circulating tumor DNA (ctDNA) assay in informing recurrence in patients with peritoneal metastases (PM) from colorectal (CRC) and high-grade appendix (HGA) cancer after curative cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC). BACKGROUND: Over 50% of patients with CRC/HGA-PM recur after optimal CRS-HIPEC. The limited sensitivity of axial imaging and diagnostic biomarkers is a significant cause of delay in the detection of recurrence and initiation of further therapies. Plasma ctDNA has a promising role in monitoring response to treatment and/or recurrence after primary cancer resection. METHODS: Patients with CRC/HGA-PM who underwent curative CRS-HIPEC and serial postresection ctDNA assessments were included. Patients with rising postoperative ctDNA levels were compared with those with stable, undetectable ctDNA levels. Primary outcomes were the percentage of patients with recurrence and disease-free survival (DFS). Secondary outcomes were overall survival, ctDNA sensitivity, lead time, and performance of ctDNA compared with carcinoembryonic antigen. RESULTS: One hundred thirty serial postresection ctDNA assessments [median 4, interquartile range (IQR), 3 to 5] were performed in 33 patients (n = 13 CRC, n = 20 HGA) who underwent completeness of cytoreduction-0/1 CRS with a median follow-up of 13 months. Of the 19 patients with rising ctDNA levels, 90% recurred versus 21% in the stable ctDNA group (n = 14, < 0.001). Median DFS in the rising ctDNA cohort was 11 months (IQR, 6 to 12) and not reached in the stable ( P = 0.01). A rising ctDNA level was the most significant factor associated with DFS (hazard ratio: 3.67, 95% CI: 1.06-12.66, P = 0.03). The sensitivity and specificity of rising ctDNA levels in predicting recurrence were 85% and 84.6%, respectively. The median ctDNA lead time was 3 months (IQR, 1 to 4). Carcinoembryonic antigen was less sensitive (50%) than ctDNA. CONCLUSIONS: This study supports the clinical validity of serial ctDNA assessment as a strong prognostic biomarker in informing recurrence in patients with CRC/HGA-PM undergoing curative resection. It also holds promises for informing future clinical trial designs and further research.

Palliative Care and Characterization of Symptoms in Patients Undergoing Cytoreductive Surgery/Hyperthermic Intraperitoneal Chemotherapy.

INTRODUCTION: Palliative care for advanced cancer patients has been associated with improvements in symptom management and quality of life (QoL). Patients with peritoneal metastases undergoing cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) often report symptoms adversely affecting QoL. We characterized and compared symptoms elucidated by palliative care versus surgical providers in this setting. METHODS: CRS/HIPEC patients who saw both surgical oncology and palliative care providers from 2016 to 2020 at a tertiary care center were identified from a retrospective database. Documentation of QoL-associated symptoms in surgical oncology and palliative care visits was recorded and analyzed. RESULTS: A total of 118 patients were included in this study. The most common primary histologies were appendiceal (36.4%) and colorectal (28.8%). Symptoms most frequently reported by palliative care were pain (60.2%) and fatigue (54.2%). The median number of symptoms documented was three (2, 5) in palliative care notes and two (0, 3) in surgical oncology notes (P < 0.001). Palliative care providers documented most symptoms statistically more frequently than surgical oncology providers. CONCLUSIONS: Patients who underwent CRS/HIPEC experienced various QoL-associated symptoms. Palliative care providers elicited more symptoms than surgical oncology providers. Additional studies are needed to explore the impact on outcomes of perioperative palliative care in this challenging patient population.

Mutational profiles and prognostic impact in colorectal and high-grade appendiceal adenocarcinoma with peritoneal metastases.

BACKGROUND: Next-generation sequencing (NGS) personalizes cancer treatments. In this study, we analyze outcomes based on NGS testing for colorectal cancer (CRC) and high-grade appendiceal adenocarcinoma (HGA) with peritoneal metastases. METHODS: Retrospective review of genomic analyses and outcomes in patients with CRC or HGA with peritoneal metastases at a high-volume center from 2012 to 2019. RESULTS: Ninety-two patients (57 CRC, 35 HGA) were identified. Overall survival was longer for CRC (52.8 vs. 30.5 months, p = 0.03), though rates of cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) were similar. Multiple genes were more frequently mutated in CRC, including KRAS (51% vs. 29%, p = 0.04), TP53 (47% vs. 20%, p < 0.01), and APC (46% vs. 6%, p < 0.01). For CRC, multivariate regression showed an increased hazard ratio (HR) with increasing peritoneal cancer index (1.06 [1.01-1.11], p = 0.02) and a decreased HR following CRS/HIPEC (0.30 [0.11-0.80], p = 0.02). PIK3CA mutation associated with significantly increased HR (3.62 [1.06-12.41], p = 0.04), though only in non-CRS/HIPEC patients. Multivariate analysis in the HGA group showed a benefit following CRS/HIPEC (0.18 [0.06-0.61], p = 0.01) and for mucinous disease (0.38 [0.15-0.96], p = 0.04), while there was an increased HR with TP53 mutation (6.89 [2.12-22.44], p < 0.01). CONCLUSION: CRC and HGA with peritoneal spread have distinct mutational profiles. PIK3CA and TP53 mutations are associated with survival for CRC or HGA with peritoneal metastases, respectively.

Insurance Authorization Barriers in Patients Undergoing Cytoreductive Surgery and HIPEC.

BACKGROUND: Indications for cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) exist across multiple histologies, but little data exist on the impact of insurance authorization on access to these therapies. Given the evolving role of CRS/HIPEC, we sought to characterize insurance approval and delays in patients undergoing these therapies. PATIENTS AND METHODS: A retrospective review was performed at a high-volume tertiary center of patients who received CRS/HIPEC from 2017 to 2021. Collected data included patient demographics, tumor histologic characteristics, insurance type, approval/denial history, and time to prior authorization approval. Descriptive statistics were performed. RESULTS: In total, 367 patients received CRS/HIPEC during the study period. They had a median age of 59 (IQR 49-67) years, 35% were male, and 76% were white. Of the patients requiring prior authorization, 14 of 104 (13%) patients were denied prior authorization and required appeal. Median time between authorization request and approval was 33 (IQR 28-36) days. These cases generated 410 insurance authorization requests, 94 (23%) of which were not initially approved and required appeal. The rate of upfront denial was 21.1% in patients with public insurance compared with 23.4% in patients with private insurance. Gastric cancer was the most common histology among denied cases (55%), followed by colorectal, appendiceal, and gynecologic malignancies. CONCLUSIONS: Despite the broadening indications for and data supporting CRS/HIPEC, a significant proportion of patients still face hurdles in attaining insurance approval and coverage for these therapies. Addressing barriers to insurance approval is imperative to decrease therapeutic delay and improve access to data-driven care.

Extended postoperative thromboprophylaxis after pancreatic resection for pancreatic cancer is associated with decreased risk of venous thromboembolism in the minimally invasive approach.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is associated with increased venous thromboembolism (VTE). We sought to compare rates of bleeding complications and VTE in patients receiving extended postoperative thromboprophylaxis (EPT) to those who did not, and identify risk factors for VTE after pancreatectomy for PDAC. METHODS: This is a retrospective review of pancreatectomies for PDAC. EPT was defined as 28 days of low molecular weight heparin. Multivariable analysis (MVA) was performed to identify independent risk factors of VTE. RESULTS: Of 269 patients included, 142 (52.8%) received EPT. Of those who received EPT, 7 (4.9%) suffered bleeding complications, compared to 6 (4.7%) of those who did not (p = 0.938). There was no significant difference in VTE rate at 90 days (2.8% vs. 2.4%, p = 0.728) or at 1 year (6.3% vs. 7.9%, p = 0.624). On MVA, risk factors for VTE included worse performance status, lower preoperative hematocrit, R1/R2 resection, and minimally invasive (MIS) approach. Among those who received EPT, there was no difference in VTE rate between MIS and open approach. CONCLUSIONS: EPT was not associated with a difference in VTE risk or bleeding complications. MIS approach was associated with a higher risk of VTE; however, this was significantly lower among those who received EPT.

Phase II Prospective, Open-Label Randomized Controlled Trial Comparing Standard of Care Chemotherapy With and Without Sequential Cytoreductive Interventions for Patients with Oligometastatic Foregut Adenocarcinoma and Undetectable Circulating Tumor Deoxyribose Nucleic Acid (ctDNA) Levels.

BACKGROUND: Metastatic adenocarcinomas of foregut origin are aggressive and have limited treatment options, poor quality of life, and a dismal prognosis. A subset of such patients with limited metastatic disease might have favorable outcomes with locoregional metastasis-directed therapies. This study investigates the role of sequential cytoreductive interventions in addition to the standard of care chemotherapy in patients with oligometastatic foregut adenocarcinoma. METHODS: This is a single-center, phase II, open-label randomized clinical trial. Eligible patients include adults with synchronous or metachronous oligometastatic (metastasis limited to two sites and amenable for curative/ablative treatment) adenocarcinoma of the foregut without progression after induction chemotherapy and having undetectable ctDNA. These patients will undergo induction chemotherapy and will then be randomized (1:1) to either sequential curative intervention followed by maintenance chemotherapy versus routine continued chemotherapy. The primary endpoint is progression-free survival (PFS), and a total of 48 patients will be enrolled to detect an improvement in the median PFS in the intervention arm with a hazard ratio (HR) of 0.5 with 80% power and a one-sided alpha of 0.1. Secondary endpoints include disease-free survival (DFS) in the intervention arm, overall survival (OS), ctDNA conversion rate pre/post-induction chemotherapy, ctDNA PFS, PFS2, adverse events, quality of life, and financial toxicity. DISCUSSION: This is the first randomized study that aims to prospectively evaluate the efficacy and safety of surgical/ablative interventions in patients with ctDNA-negative oligometastatic adenocarcinoma of foregut origin post-induction chemotherapy. The results from this study will likely develop pertinent, timely, and relevant knowledge in oncology.

Differences in Sociodemographic Disparities Between Patients Undergoing Surgery for Advanced Colorectal or Ovarian Cancer.

BACKGROUND: Cytoreductive surgery (CRS) for ovarian cancer with peritoneal metastases (OPM) is an established treatment, yet access-related racial and socioeconomic disparities are well documented. CRS for colorectal cancer with peritoneal metastases (CRPM) is garnering more widespread acceptance, and it is unknown what disparities exist with regards to access. METHODS: This retrospective cross-sectional multicenter study analyzed medical records from the National Cancer Database from 2010 to 2015. Patients diagnosed with CRPM or ORP only and either no or confirmed resection were included. Patient- and facility-level characteristics were analyzed using uni- and multivariable logistic regressions to identify associations with receipt of CRS. RESULTS: A total of 6634 patients diagnosed with CRPM and 14,474 diagnosed with OPM were included in this study. Among patients with CRPM, 18.1% underwent CRS. On multivariable analysis, female gender (odds ratio [95% CI] 2.04 [1.77-2.35]; P < 0.001) and treatment at an academic or research facility (OR 1.55 [1.17-2.05]; P = 0.002) were associated with CRS. Among patients with OPM, 87.1% underwent CRS. On multivariable analysis, treatment at facilities with higher-income patient populations was positively associated with CRS, while age (OR 0.97 [0.96-0.98]; P < .0001), use of nonprivate insurance (OR 0.69 [0.56-0.85]; P = 0.001), and listed as Black (OR 0.62 [0.45-0.86]; P = 0.004) were negatively associated with CRS. CONCLUSION: There were more systemic barriers to CRS for patients with OPM than for patients with CRPM. As CRS becomes more widely practiced for CRPM, it is likely that more socioeconomic and demographic barriers will be elucidated.

Assessing the domino effect: Female physician industry payments fall short, parallel gender inequalities in medicine.

BACKGROUND: Physician-industry relationships have been complex in modern medicine. Since large proportions of research, education and consulting are industry-backed, this is an important area to consider when examining gender inequality in medicine. METHODS: The Open Payments Program (OPP) database from August 2013 to December 2016 was analyzed. In order to identify physicians' genders, the OPP was matched with the National Provider Index dataset. Descriptive statistics of payments to female compared to male surgeons were obtained and stratified by payment type, subspecialty, geographic location and year. RESULTS: 3,925,707 transactions to 136,845 physicians were analyzed. Of them, 31,297 physicians were surgeons with an average payment per provider of $131,252 to male surgeons compared to $62,101 to female surgeons. Significantly fewer women received consultant, royalty/licensure, ownership and speaker payments. However, women received a higher average amount per surgeon compared to their male counterparts within research payments. Overall payments to women trended upwards over time. CONCLUSION: Gender inequality still exists in medicine, and in industry-physician payments. Industry should increasingly consider engaging women in consultancies, speaking engagements, and research.

Value of gastrografin in adhesive small bowel obstruction.

BACKGROUND: Small bowel obstruction (SBO) from adhesive disease presents great burden for the healthcare system. Some groups have reported water soluble contrast agents (WSCA) protocols, but published studies are underpowered. This study introduces a WSCA protocol to improve outcomes and streamline patient care. STUDY DESIGN: The study ran July 1, 2013-June 30, 2015, at Kaiser Permanente San Diego; protocol started July 1, 2014. Data was collected prospectively, on an intention to treat basis. We excluded patients whose SBO were not due to adhesive disease. Protocol included nasogastric tube, intravenous resuscitation, liquid docusate, and gastrografin study if symptoms persisted at 24 h. Colon contrast determined resolution vs operative consideration. Primary outcomes were operative rates and hospital length of stay (LOS). RESULTS: Seven hundred fifteen were patients admitted with SBO; after exclusions there were 261 pre-protocol and 243 protocol patients. One hundred sixty patients resolved within 24 h; 96% of remaining patients stayed on protocol (n = 154). After WSCA protocol began, 15.6% required an operation, compared to 19.8% of pre-protocol patients (NS). The WSCA protocol significantly decreased the time to surgery (2.8 vs 4.88 days, p = 0.03), and the LOS of operated patients (9.51 vs 15.78 days, p = 0.02). CONCLUSIONS: A standardized SBO protocol using WSCA significantly decreased time to operation and hospital LOS. This approach improves utilization of resources and may improve outcomes. More work should be done to investigate the positive effects of WSCA protocol for patients with SBO.

Computed Tomography Fractional Flow Reserve Can Identify Culprit Lesions in Aortoiliac Occlusive Disease Using Minimally Invasive Techniques.

BACKGROUND: Currently, the gold standard diagnostic examination for significant aortoiliac lesions is angiography. Fractional flow reserve (FFR) has a growing body of literature in coronary artery disease as a minimally invasive diagnostic procedure. Improvements in numerical hemodynamics have allowed for an accurate and minimally invasive approach to estimating FFR, utilizing cross-sectional imaging. We aim to demonstrate a similar approach to aortoiliac occlusive disease (AIOD). METHODS: A retrospective review evaluated 7 patients with claudication and cross-sectional imaging showing AIOD. FFR was subsequently measured during conventional angiogram with pull-back pressures in a retrograde fashion. To estimate computed tomography (CT) FFR, CT angiography (CTA) image data were analyzed using the SimVascular software suite to create a computational fluid dynamics model of the aortoiliac system. Inlet flow conditions were derived based on cardiac output, while 3-element Windkessel outlet boundary conditions were optimized to match the expected systolic and diastolic pressures, with outlet resistance distributed based on Murray's law. The data were evaluated with a Student's t-test and receiver operating characteristic curve. RESULTS: All patients had evidence of AIOD on CT and FFR was successfully measured during angiography. The modeled data were found to have high sensitivity and specificity between the measured and CT FFR (P = 0.986, area under the curve = 1). The average difference between the measured and calculated FFRs was 0.136, with a range from 0.03 to 0.30. CONCLUSIONS: CT FFR successfully identified aortoiliac lesions with significant pressure drops that were identified with angiographically measured FFR. CT FFR has the potential to provide a minimally invasive approach to identify flow-limiting stenosis for AIOD.

Selective cytotoxicity of pancratistatin-related natural Amaryllidaceae alkaloids: evaluation of the activity of two new compounds.

BACKGROUND: Pancratistatin (PST), a compound extracted from an Amaryllidaceae (AMD) family plant, has been shown to specifically induce apoptosis in cancer cells with no/minimal toxic effect on normal cells. A systematic synthetic approach has indicated that the minimum cytotoxic pharmacophore comprises the trans-fused b/c-ring system containing the 2, 3, 4-triol unit in the C-ring. To further explore the structure-activity relationship of this group of compounds we have investigated the anti-cancer efficacy and specificity of two PST-related natural compounds, AMD4 and AMD5. Both of these compounds lack the polyhydroxylated lycorane element of PST instead having a methoxy-substituted crinane skeleton. RESULTS: Our results indicate that AMD5 has efficacy and selectivity similar to PST, albeit at a 10-fold increased concentration. Interestingly AMD4 lacks apoptotic activity. CONCLUSION: Our results indicate that the phenanthridone skeleton in natural Amaryllidaceae alkaloids may be a significant common element for selectivity against cancer cells; furthermore, the configuration of the methoxy-side groups is responsible for higher binding affinity to the target protein/s thus making for a more efficient anti-cancer agent.