Appendiceal Carcinoma Research Articles

Appendiceal actinomycosis mimicking malignant tumor: a rare case report

Introduction: Actinomycosis is an uncommon bacterial infection caused by Actinomyces bacteria that typically progresses slowly and leads to the formation of masses. Although it commonly affects the cervicofacial area, about 20% of cases occur in the abdominopelvic region. Because the disease can be mistaken for a tumour due to its infiltrative mass-like nature on imaging, over 90% of cases are only diagnosed following surgery and histological confirmation. This report describes a case of an appendicular mass, initially suspected to be a malignant tumour, but eventually diagnosed as appendiceal actinomycosis. Presentation of case: Upon initial presentation, a 53-year-old woman with type II diabetes mellitus and no prior surgical history, displayed abnormal appendiceal uptake during a PET-computed tomography (CT) scan conducted for a suspected spinal tumour. Colonoscopy did not indicate any notable observations, and the patient chose to defer immediate action. Several months later, a CT scan revealed an increased mass-like appearance of the appendix compared to the previous PET-CT scan. After multidisciplinary discussions, a right laparoscopic hemicolectomy was recommended due to suspected malignancy. However, histological staining on microscopy confirmed actinomycosis originating from the appendix. Discussion: Chronic appendicitis with radiologic features similar to appendiceal carcinoma, or abdominal masses located in the ileocecal area, in patients with or without a previous surgical history should raise suspicion of actinomycosis. Conclusion: Appendiceal actinomycosis should be considered in the differential diagnosis in the aetiology of chronic appendicitis mimicking appendiceal carcinoma. Awareness and accurate diagnosis of appendiceal actinomycosis can prevent unnecessary extended surgery as was performed in this case.

Tofacitinib to prevent anti-drug antibody formation against LMB-100 immunotoxin in patients with advanced mesothelin-expressing cancers.

LMB-100 is a mesothelin (MSLN)-targeting recombinant immunotoxin (iTox) carrying a Pseudomonas exotoxin A payload that has shown promise against solid tumors, however, efficacy is limited by the development of neutralizing anti-drug antibodies (ADAs). Tofacitinib is an oral Janus Kinase (JAK) inhibitor that prevented ADA formation against iTox in preclinical studies. A phase 1 trial testing LMB-100 and tofacitinib in patients with MSLN-expressing cancers (pancreatic adenocarcinoma, n=13; cholangiocarcinoma, n=1; appendiceal carcinoma, n=1; cystadenocarcinoma, n=1) was performed to assess safety and to determine if tofacitinib impacted ADA formation. Participants were treated for up to 3 cycles with LMB-100 as a 30-minute infusion on days 4, 6, and 8 at two dose levels (100 and 140 µg/kg) while oral tofacitinib was administered for the first 10 days of the cycle (10 mg BID). Peripheral blood was collected for analysis of ADA levels, serum cytokines and circulating immune subsets. The study was closed early due to occurrence of drug-induced pericarditis in 2 patients. Pericarditis with the combination was not reproducible in a transgenic murine model containing human MSLN. Two of 4 patients receiving all 3 cycles of treatment maintained effective LMB-100 levels, an unusual occurrence. Sustained increases in systemic IL-10 and TNF-α were seen, a phenomenon not observed in prior LMB-100 studies. A decrease in activated T cell subsets and an increase in circulating immunosuppressive myeloid populations occurred. No radiologic decreases in tumor volume were observed. Further testing of tofacitinib to prevent ADA formation is recommended in applicable non-malignant disease settings. https://www.clinicaltrials.gov/study/NCT04034238.

Morphologic Heterogeneity of Carcinoma with Signet Ring Cell Features at Different Primary Sites

Introduction: Signet ring cells (SRCs) may be observed in carcinomas from multiple primary sites. Elucidating unknown primaries from metastases with SRCs represents a diagnostic challenge. This study examined morphologic characteristics of adenocarcinomas with SRCs from stablished primary sites and described objective features, which can aid in identifying the site of origin. Methods: The series encompasses 257 cases of adenocarcinomas with SRCs from gastroesophageal junction (GEJ, n = 38), stomach (n = 48), pancreatobiliary system (n = 16), colorectum (n = 40), appendix (n = 32), breast (n = 41), and lung (n = 42). H&E sections were examined and scored using architectural and cytologic criteria. Morphometric analysis was performed using QuPath software. Results: Extracellular mucin was more abundant in GEJ, colorectal, and appendiceal carcinomas. Poorly cohesive morphology was the most frequent pattern in gastric and breast carcinomas. The cytoplasmic mucin/vacuole was predominantly clear and targetoid in breast carcinomas. Breast and gastric carcinomas showed the highest nuclear to cytoplasmic (N/C) ratio, whereas appendiceal carcinoma the lowest. Conclusion: Morphological evaluation (extracellular mucin, architectural patterns, and the nature of cytoplasmic mucin/vacuole) represents an important step to determine the cancer site of origin in adenocarcinomas with SRCs and guides further ancillary studies. Cytological morphometry may help further refine morphological criteria and facilitate the construction of digital-pathology algorithms.

Abstract 15468: Factor VII Induced Coronary Thrombosis

Case Description: 69-year-old male with a history of factor VII deficiency and coronary artery disease (CAD) with a stent in the distal left anterior descending (LAD) artery, underwent diagnostic laparoscopy for suspected appendiceal carcinoma. He is a non-smoker, has good exercise tolerance and takes aspirin only three times a week, due to epistaxis. Post-surgery, he complained of 10/10 substernal chest pain. Initial troponin (TnI) was 0.11 ng/dL, peaking at >80 ng/dL in 2 hours. EKG was compatible with an anterior wall STEMI. An emergent coronary angiogram showed a patent distal LAD stent and a 99% occlusive lesion in the mid-LAD, which was treated with a drug-eluting stent. With careful clinical judgment and hematology consultation, dual antiplatelet therapy was continued despite a history of coagulopathy. On probing, it was discovered that the patient received two doses of recombinant factor VII (rVII) prior to the surgery to reduce operative bleeding. Discussion: Recombinant factor VII is known to cause serious arterial and venous thromboembolic events. This risk increases to almost 10% in patients who are elderly with concomitant vascular disease. In our patient with prior history of CAD and in the setting of acute surgical stress, exogenous factor VII unbalanced the coagulation system leading to a STEMI. Surgical teams should be aware of the detrimental consequences of administration of rVII in high cardiovascular risk patients and seek alternative hemostatic strategies. Prothrombotic agents should be used with caution and close monitoring for acute coronary syndromes, especially in patients with a high risk of CAD.

Molecular profiling and characterization of the tumor immune microenvironment (TME) in appendiceal carcinoma (AC).

3622 Background: The rarity of AC presents challenges in understanding disease pathogenesis. We previously showed that AC has higher rates of mutations in KRAS and GNAS and lower rates of TP53, APC, and PIK3CA than CRC. The appendix also has many lymphoid clusters and regulates IgA production in the large bowel, suggesting that AC may be subject to more lymphocytic regulation than CRC. We sought to characterize the molecular profile and TME across AC histopathological types. Methods: AC samples were analyzed by DNA sequencing (592 genes, NextSeq, or whole exome sequencing, NovaSeq), whole transcriptome sequencing (WTS, NovaSeq), and immunohistochemistry (IHC) for molecular profiling, including microsatellite instability (MSI), mismatch repair (MMR), PD-L1 (SP142), and tumor mutational burden (TMB). Microenvironment Cell Population-counter Quantiseq was used to quantify tumor immune contexture using WTS. AC histopathology was derived from pathology reports. Mann-Whitney U and ChiSquare tests were applied as appropriate, with P-values adjusted for multiple comparisons using Benjamini-Hochberg. Results: AC (N = 731) were grouped by histology: 5% goblet cell (GC), 6% high-grade adenocarcinoma (HGA), 14% low grade mucinous (LGM), 33% mucinous adenocarcinoma (MA), 1% pseudomyxoma peritonei (PMP), 6% signet ring cell carcinoma (SRC), and 35% adenocarcinoma not otherwise specified (NOS) (see Table). Age at collection and PD-L1+ (0-5.2%) did not differ by histopathology. Seven patients had dMMR (4 NOS and 3 MA). Median TMB was significantly higher in NOS vs. GC (4 mutations/megabase vs 2, q < 0.001), NOS vs. LGM (4 vs 3, q = 0.048), MA vs. GC (4 vs 2, q < 0.001), and MA vs. LGM (4 vs 3, q = 0.037). Distinct TME patterns were observed in NOS vs. MA (median cell fraction: dendritic cells 0.07 vs 0, q < 0.01; M2 macrophages 0.055 vs 0.042, q = 0.030; natural killer cells 0.034 vs 0.031, q = 0.011; CD4 T cells 0.006 vs 0, q = 0.044) and GC vs. MA (M1 macrophages 0.039 vs 0.057, q = 0.021; dendritic cells 0.012 vs 0, q < 0.01; B cells 0.061 vs 0.050, q = 0.013; M2 macrophages 0.074 vs 0.042, q < 0.01; natural killer cells 0.041 vs 0.031, q = 0.01; and neutrophils 0.017 vs 0.038 q = 0.045). T cell inflamed signature (TIS) and immune-oncology (IO) marker gene expression were higher in HGA and lower in LGM and MA. Somatic mutation rates differed by histopathology (see Table). Conclusions: There is significant heterogeneity in TMB, TME, and mutational profiles across AC histologies. MA has a particularly immune-cold TME shown by lower infiltration of lymphocytes, TIS, and IO gene expression. These findings are critical to identify novel biomarkers and develop new therapeutic strategies for AC. [Table: see text]

P-327 Comparison of clinicopathological and molecular features of two rare entities: Appendiceal carcinoma and small bowel adenocarcinoma

P-327 Comparison of clinicopathological and molecular features of two rare entities: Appendiceal carcinoma and small bowel adenocarcinoma

The Prognostic Impact of Microsatellite Instability on the Outcome of Appendiceal Adenocarcinoma: a National Cancer Database Analysis

BackgroundMicrosatellite instability (MSI) is recognized as a favorable outcome predictor in colorectal cancer. However, its impact on overall survival (OS) of appendiceal carcinoma has not been thoroughly studied. This study aimed to assess the impact of MSI on OS of patients with appendiceal adenocarcinoma, stratified by disease stage, tumor histology, and patients’ demographics. MethodsThis was a retrospective cohort analysis of the colon cancer National Cancer Database (NCDB) between 2005 and 2019. Patients with appendiceal adenocarcinoma with known MSI status were included and subdivided according to MSI status into positive and negative. Primary outcome was OS stratified by MSI status. ResultsThe study included 1681 (50.1% male) patients with a mean age of 58.9±14.2 years; 211 (12.5%) had MSI-positive tumors (69 MSI low, 53 MSI high, and 89 not specified). Mean 5-year OS of patients with MSI-positive and MSI-negative carcinomas was similar (81.9 versus 78.6 months, p = 0.747). Patients with stage IV MSI-positive carcinomas had significantly longer OS than patients with MSI-negative carcinomas of the same stage (41.3 vs 26.5 months, p = 0.02). Differences in OS for patients with stages I–III were not statistically significant. Compared to MSI-negative/low carcinomas, MSI-high tumors had more advanced pathologic TNM stage (stage III: 23.9% vs 17.8%—stage IV: 41.3% vs 35.4%, p = 0.003), received more chemotherapy (56% vs 41%, p = 0.04), yet had similar OS (81.9 vs 78.9 months, p = 0.357). ConclusionsMSI status of appendiceal adenocarcinomas did not significantly impact survival, except for stage IV disease in which a survival benefit of MSI was noted.

Abstract B113: Equal opportunity for all? Does race/ethnicity predict overall survival after aggressive surgical therapy for appendiceal carcinoma?

Abstract Introduction: In select patients, appendiceal cancer with peritoneal surface involvement is managed aggressively with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC). There is limited to no data on the management and outcomes of this advanced disease across diverse patient populations. Here we report the first large-scale study evaluating the influence of racial/ethnic differences in outcomes for patients with appendiceal cancer undergoing CRS/HIPEC. Methods: The National Cancer Database (NCDB) 2019 Participant User File was queried for adult patients 18-89 years old, diagnosed with appendiceal cancer that underwent CRS/HIPEC from 2006-2018. Patients were stratified by racial/ethnic groups: non-Hispanic White, non-Hispanic Black, Hispanic, and Other. Differences in sociodemographics, treatment course, tumor characteristics, and postoperative outcomes were determined using Χ2 and Kruskal-Wallis tests. Kaplan-Meier survival analysis and Log-rank tests were conducted to assess for differences in survival. Cox Regression was used to evaluate for predictors of overall survival. Results: In total 2,532 patients were identified, of which 2,098 (82.9%) identified as White, 186 (7.3%) as Black, 127 (5.0%) as Hispanic, and 121 (4.8%) as Other. There were statistically significant differences for all sociodemographic factors across groups, including patient age, sex, insurance payor, distance traveled, treatment facility type, geographic location, and median income. There was no difference in year of diagnosis or burden of comorbidities shared by racial/ethnic group. Days from diagnosis to surgery, tumor grade, surgical margins, hospital length of stay, and rates of readmission were similar between all groups. There was also no difference in 30-day or 90-day mortality with similar lengths of follow-up. However, overall survival was found to be significantly different between all groups (p=0.0029) with Black patients having the shortest median survival of 106.7 months compared to Hispanic patients of 145.9 months (p=0.0093). Median survival for White patients was higher at 136.3 months. On multivariate analysis, race/ethnicity was found to be an independent significant predictor of overall survival. Black and White patients compared to Hispanic patients have increased risk of death after CRS/HIPEC for appendiceal cancer (HR: 2.117 [1.306, 3.431], p=0.0023 and HR: 1.549 [1.007, 2.383], p=0.0463, respectively). Conclusions: Racial/ethnic disparities are strikingly apparent in sociodemographics and overall survival for patients with appendiceal cancer that undergo CRS/HIPEC. Despite having similar tumor and treatment characteristics, long-term survival diverged with Hispanic patients having a survival advantage, whereas non-Hispanic Black individuals had worse overall survival. Disparities in survivorship are not fully explained by social determinants of health, thus different underlying biologic and genomic influences that have yet to be determined may be at play in how this disease progresses. Citation Format: Devon C. Freudenberger, Luke Wolfe, Andrea N. Riner, Vignesh Vudatha, Kelly M. Herremans, Leopoldo J. Fernandez, Jose G. Trevino. Equal opportunity for all? Does race/ethnicity predict overall survival after aggressive surgical therapy for appendiceal carcinoma? [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr B113.

Prolonged Survival in Peritoneal Metastatic Appendiceal Carcinoma Patients Treated With Combined Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy

IntroductionPrimary treatment for peritoneal dissemination of appendiceal cancer is the combination of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. The endpoints were overall survival and evaluation of prognostic factors. MethodsClinicopathological and treatment-related factors were obtained from a prospective database. A total of 84 patients, 55 (65%) primary and 29 (35%) recurrent malignant appendiceal carcinomas with synchronous and metachronous peritoneal metastases, underwent multimodal treatment between 2011 and 2021. The endpoints of the study were overall survival and evaluation of prognostic factors. ResultsThe median follow-up was 4.8 y; the mean age was 54.5 y (range 25-77), with a sex distribution of 69% female and 31% male. The mean peritoneal cancer index was 11.3. The proportion of mucinous, intestinal-type, signet ring cell, and goblet cell carcinoma was 56%, 23%, 11%, and 10%, respectively. The 5-y survival rate of the whole cohort was 56.7%. In primary and recurrent diseases, the overall median survival was 8.4 and 4.9 y. Significantly improved survival was detected after complete cytoreduction resection (hazard ratio [HR] for CCR-2 versus CCR-0: 9.388, 95% confidence interval [CI] 3.026-29.124, P = 0.001) and initial local operation with undelayed admission to the center (HR 0.262, 95% CI 0.089-0.773; P = 0.015). The five independent factors in Kaplan–Meier analysis and univariable Cox regression analysis associated with significant adverse survival were cancer antigen (CA) 19-9 over 37 IU/mL, signet ring cell and intestinal-type histology, positive nodal status, grading, and peritoneal cancer index >20. Neoadjuvant chemotherapy administration did not impact survival (HR 1.220, 95% CI 0.612-2.432, P = 0.571). ConclusionsWith multimodal treatment, prolonged survival is attainable in stage IV primary and recurrent appendiceal carcinoma with peritoneal dissemination. Direct referral to specialized centers after confirmation of peritoneal metastasis is recommended because prompt definitive treatment may significantly improve survival.

Disseminated Intravascular Coagulation from Intraperitoneal Oxaliplatin for Appendiceal Carcinoma: A Case Report

This is a case of a 65-year-old female diagnosed with appendiceal carcinoma, who underwent cytoreductive surgery with hyperthermic intraperitoneal chemotherapy. Profuse bleeding through the peritoneal drains, with hemodynamic instability, warranted a re-exploration on the fourth postoperative day. Intraoperatively, there was 500 mL of blood clots mostly on the right upper quadrant, diffuse muscle oozing along the previously-stripped right hemidiaphragm and right paracolic gutter, and a non-expanding hematoma on the right anterior abdominal wall. Bleeding parameters were checked postoperatively, and derangements pointing to a disseminated intravascular coagulation were noted. The patient was managed with multiple blood transfusions of packed red blood cells, fresh frozen plasma, platelet concentrates, and cryoprecipitate. Dexamethasone and tranexamic acid were given intravenously. The patient was discharged well on postoperative day 14 after clinical resolution of the bleeding. Eight days after discharge, however, patient succumbed to myocardial infarction. Key words: disseminated intravascular coagulation, oxaliplatin, hyperthermic intraperitoneal chemotherapy

S2046 High-Grade Mucinous Adenocarcinoma of the Appendix With Signet Features and Omental Metastasis

Introduction: Primary adenocarcinoma of the appendix is an uncommon malignancy of the gastrointestinal tract. It was first described in 1882 and constitutes around 0.12 to 2.6 cases per one million people per year. In addition, signet-ring cell carcinoma of the appendix is extremely rare, it constitutes approximately 4% of all primary appendiceal neoplasms. There are few reported cases of primary signet cell appendiceal carcinoma. In this present report, we describe a rare case of primary signet ring cell carcinoma of the appendix with omental metastases in an 81-year-old male who underwent laparoscopic appendectomy. Case Description/Methods: We present a case of an 81-year-old male who had prior negative esophagogastroduodenoscopy (EGD) and colonoscopy in 2017 who presented to an urgent care in January 2021 with abdominal pain. Lab work was unremarkable, and the patient was sent home with instructions to visit the emergency department (ED) if he experienced fever, increased abdominal pain, or blood in the stool. Patient presented to the emergency department with increased abdominal pain in April 2021, and Computed Tomography (CT) scan of abdomen and pelvis with intravenous contrast showed a cystic appendiceal lesion with right peritoneal nodularity suspicious for peritoneal carcinomatosis. Therefore, the patient underwent appendectomy the following day revealing poorly differentiated, high-grade appendiceal adenocarcinoma with signet ring features, pT4a disease. Patient had a diagnostic laparoscopy in June 2021 and was found to have diffuse peritoneal carcinomatosis. Multiple biopsies were obtained and came back positive with high-grade mucinous adenocarcinoma with signet ring features. Patient agreed to pursue systemic chemotherapy. He was initiated on Capecitabine (Xeloda) 2000 mg tab PO, twice daily for 14 days and off for 7 days. Bevacizumab (Avastin) 7.5 mg IV infusion every 3 weeks (Figure). Discussion: Patients with appendiceal neoplasms may have vague lower abdominal pain but are usually asymptomatic with incidental diagnosis on imaging or appendectomy. Signet ring adenocarcinoma of the appendix typically secretes mucin leading to metastasis throughout the peritoneum and eventual obstruction. Treatment is based on stage and histology. Surgical resection and peritoneal debulking is possible. High-grade tumors require further prospective trials to evaluate treatment, but treatment options include surgical management, HIPEC, and systemic chemotherapy.Figure 1.: Histologic examination showing a signet cell carcinoma of the appendix infiltrating the peritoneum and diaphragm. (A) right lower quadrant peritoneum biopsy, (H&E stain 100x): High grade mucinous carcinoma peritonei with signet ring cells. Pool of mucin with a cluster of epithelium that shows signs of metastatic carcinoma (enlarged nuclei, atypia, pleomorphic changes). (B, C, and D) Right diaphragm peritoneum biopsy. High grade mucinous carcinoma peritonei with signet ring cells. Image B at 100x, C at 200x, and D at 400x. (E & F) immunohistochemical cytokeratin stain (AE1/AE3) shows strong positivity of high grade carcinoma. E at 100x, and F at 400x.

Case of an Low Grade Appendical Mucinous Neoplasia (LAMNS) Presenting as a Right Ovarian Mass

Appendiceal carcinoma has an incidence of 0.12 cases per 1,000,000 people per year [1]. Of all intestinal tumors, malignant tumors of appendix are less than 0.5%. They are classified into three groups: carcinoid tumors, mucinous cystadenocarcinomas and adenocarcinomas, based on architectural and cytologic features [2]. Appendiceal carcinoma present with acute right abdominal pain, and can also present as a palpable abdominal mass, acute intestinal obstruction or ascites. Most of them are diagnosed unexpectedly from histopathologycal analysis after a simple appendectomy. That is why it is important for gynecologists and general surgeons to consider appendiceal mucinous cystadenomas in their differential diagnosis for a pelvic mass, because early recognition can prevent iatrogenic rupture and subsequent spilling of potentially malignant mucin-producing cells in a peritoneal cavity. In our case report, we present a low grade mucinous appendical tumor, diagnosed during surgery in an operating room.

Accidental discovery of appendiceal carcinoma in gynecological surgery : a case report and literature review

Objective: To introduce the common diagnosis and treatment of appendix cancer. Methods: The discovery process and treatment plan of a patient with mucinous adenocarcinoma of appendix accidentally found in gynecological surgery in the Affiliated Hospital of Jining Medical College in May 2021 were summarized. Results: The patient was treated for right lower abdominal pain and considered as ovarian tumor. Preoperative abdominal enhanced CT showed that the appendix was thickened. Cancer was found in the exploration of the appendix during gynecological surgery. The right colon was removed. After surgery, he received chemotherapy. At present, he has recovered well. Conclusion: The incidence rate of appendiceal carcinoma is very low. Preoperative diagnosis is difficult. It is often found in operation or after operation. Preoperative examination and early evaluation of clinical manifestations are particularly important.

Accidental discovery of appendiceal carcinoma in gynecological surgery: A case report and literature review

Objective: To introduce the common diagnosis and treatment of appendix cancer. Methods: The discovery process and treatment plan of a patient with mucinous adenocarcinoma of appendix accidentally found in gynecological surgery in the Affiliated Hospital of Jining Medical College in May 2021 were summarized. Results: The patient was treated for right lower abdominal pain and considered as ovarian tumor. Preoperative abdominal enhanced CT showed that the appendix was thickened. Cancer was found in the exploration of the appendix during gynecological surgery. The right colon was removed. After surgery, he received chemotherapy. At present, he has recovered well. Conclusion: The incidence rate of appendiceal carcinoma is very low. Preoperative diagnosis is difficult. It is often found in operation or after operation. Preoperative examination and early evaluation of clinical manifestations are particularly important. Keywords: Abdominal pain; Pelvic mass; Appendix carcinoma; Mucous adenocarcinoma.

An International Registry of Peritoneal Carcinomatosis from Appendiceal Goblet Cell Carcinoma Treated with Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy.

Peritoneal carcinomatosis from appendiceal goblet cell carcinoma (A-GCC) is a rare and aggressive form of appendiceal tumor. Cytoreductive surgery (CRS) and hyperthermic intra peritoneal chemotherapy (HIPEC) was reported as an interesting alternative regarding survival compared to surgery without HIPEC and/or systemic chemotherapy. Our aim was to evaluate the impact of CRS and HIPEC for patients presenting A-GCC through an international registry. A prospective multicenter international database was retrospectively searched to identify all patients with A-GCC tumor and peritoneal metastases who underwent CRS and HIPEC through the Peritoneal Surface Oncology Group International (PSOGI). The post-operative complications, long-term results, and principal prognostic factors were analyzed. The analysis included 83 patients. After a median follow-up of 47months, the median overall survival (OS) was 34.6months. The 3- and 5-year OS was 48.5% and 35.7%, respectively. Patients who underwent complete macroscopic CRS had a significantly better survival than those treated with incomplete CRS. The 5-year OS was 44% and 0% for patients who underwent complete, and incomplete CRS, respectively (HR 9.65, p < 0.001). Lymph node involvement and preoperative chemotherapy were also predictive of a worse prognosis. There were 3 postoperative deaths, and 30% of the patients had major complications. CRS and HIPEC may increase long-term survival in selected patients with peritoneal metastases of A-GCC origin, especially when complete CRS is achieved. Ideally, randomized control trials or more retrospective data are neededto confirm CRS and HIPEC as the gold standard in this pathology.

Prevalence of Carcinoma in Appendectomy Specimens for Patients Presenting With Acute Appendicitis: A Single-Center Study.

IntroductionAcute appendicitis is the most common general surgical emergency globally. Its etiology includes the presence of luminal obstruction by faecoliths, lymphoid hyperplasia, impacted stool, and rarely by appendiceal or caecal cancer. Malignancy related to acute appendicitis is usually seen in the older age group.AimTo identify the subset rate of patients operated for acute appendicitis who have appendiceal carcinoma and analyze the outcome of their post-operative management.Material and methodsA retrospective study of a cohort of 529 patients aged > 40 diagnosed with acute appendicitis with subsequent appendectomy in the period between 1 January 2014 and 31 December 2019 at Basildon and Thurrock University Hospital, Essex, United Kingdom was conducted. We analyzed the clinical data of the cohort including demographic information, diagnosis, pre-operative imaging, histological diagnosis as well as post-operative management where indicated.ResultsThe median age of patients was 54.5 years (range 40-92). The male to female ratio in the appendicectomy cohort was 1:1.1. About 45% were aged 40-49 years, 24.8% were aged 50-59 and 30.2% were ≥60 years. Post-operative histology revealed acute appendicitis in 82.4% of the group. In 11% of the patients, the histology revealed the presence of other benign pathology as mucocele of the appendix, acute diverticulitis, follicular hyperplasia, and fibrous obliteration. The diagnosis of appendicular malignancy was seen in 1.9%.ConclusionIncidental appendiceal cancers in the resected specimens after acute appendicitis are rare but may be associated with a poor prognosis. It is recommended to consider such diagnosis in particular when dealing with acute appendicitis in older patients with longer symptom history, and in presence of peri-appendicular mass.

Frequency and Risk Factors for Metastasis in Newly Diagnosed Appendiceal Carcinoma.

BackgroundAppendiceal carcinoma has an insidious clinical presentation, and these tumors are rarely suspected prior to surgery, potentially leading to late diagnosis. The aim of this study is to investigate the prevalence of metastatic disease at initial presentation and potentially associated sociodemographic characteristics.MethodsPatients were identified from the Surveillance, Epidemiology, and End Results (SEER) program using the International Classification of Diseases for Oncology-3 (ICD-O-3) histology/behavior codes between 2010 and 2015. Firth logistic regression was performed to determine the association of metastasis at presentation with tumor subtype, adjusted for age, race, sex, insurance and marital status, tumor grade, and tumor and nodal stage using the 7th edition of the American Joint Committee on Cancer (AJCC) staging system.ResultsWe identified a total of 3,447 patients with known metastatic status. A total of 38.4% had metastatic disease at diagnosis. Compared to colonic-type adenocarcinoma (CA), mucinous adenocarcinoma (MA) and signet ring cell carcinoma (SC) were more likely to present with metastasis at diagnosis (OR: 2.34; 95% CI [1.80- 3.06]; OR: 1.93 [1.29-2.89], respectively), however, goblet cell carcinoma (GC) was less likely (OR: 0.59 [0.36-0.93]). Compared to tumors invading the submucosa (T1 stage), tumors invading deeper through the visceral peritoneum or nearby organs (T4 stage) were significantly more likely to present with metastatic disease (OR: 3.46 [2.24-5.51]). Tumors invading the muscularis propria (T2 stage) or deeper into the subserosa, or the mesoappendix (T3 stage) were less likely to present with metastatic disease (OR: 0.34 [0.16-0.71]); OR: 0.55 [0.34-0.91], respectively). Compared to no regional lymph node spread, four or more regional lymph node involvement (N2 stage) was more likely to present with metastatic disease (OR: 2.19 [1.53-3.16]). Men were less likely to present with metastatic disease (OR: 0.60 [0.48-0.73]). A total of 90.1% of CA, 84.2% of GC, 42.2% of MA, and 78.5% of SC patients with metastasis at diagnosis had extraperitoneal distant metastasis (M1b).ConclusionsA significant proportion of patients with newly diagnosed appendiceal carcinoma presented with metastatic disease, concerning substantial diagnostic delay and potentiating the need for aggressive treatments. Predictors of metastatic disease included female sex, histologic subtype, and significant regional lymph node involvement. Future research should focus on earlier detection and explore tumor biology.

Abstract 1057: Combination of the KRASG12C inhibitor sotorasib with targeted agents improves anti-tumor efficacy in KRAS p.G12C cancer models

Abstract KRAS is the most frequently mutated oncogene in cancer and encodes a key signaling protein in tumors. The p.G12C mutation of KRAS is present in approximately 13% of lung adenocarcinoma, 3% of colorectal cancer, and 2% of other solid tumors. Sotorasib (formerly known as AMG 510), the first KRASG12C inhibitor to reach clinical testing in humans, has demonstrated evidence of clinical activity as a single agent in patients with non-small cell lung (NSCLC), colorectal (CRC), endometrial, and appendiceal carcinoma. Preclinically, sotorasib has shown significant tumor growth inhibition as a single agent in multiple CDX and PDX models. The clinically-validated strategy of combining multiple inhibitors in the MAPK pathway suggests that combination strategies could yield even better outcomes for patients. Specifically, the combination of sotorasib and other inhibitors in the MAPK and AKT signaling pathways might further enhance tumor cell killing and overcome potential resistance. To test this hypothesis, in vitro combination experiments were conducted in multiple KRAS p.G12C cell lines with combination matrices of sotorasib and inhibitors of HER kinases, EGFR, SOS1, SHP2, MEK, PI3K, or mTOR, as well as an inhibitor of cyclin-dependent kinases 4 and 6 (CDK4/6). The combination of sotorasib with multiple agents resulted in robust synergistic cell killing of KRAS p.G12C tumor cells in vitro. To understand whether these observations translated in vivo, we assessed combinations of sotorasib with a SHP-2 inhibitor or a HER kinase inhibitor in pharmacodynamic assays and efficacy models in tumor xenografts. Consistent with the synergy observed in vitro, sotorasib in combination with a HER kinase inhibitor (afatinib) or a SHP2 inhibitor (RMC-4550) in vivo resulted in enhanced inhibition of MAPK signaling as measured by p-ERK in NCI-H358 tumors. In efficacy studies using the NCI-H358 xenograft model, significantly enhanced anti-tumor activity was observed with a minimally efficacious dose of sotorasib in combination with afatinib, RMC-4550, or a CDK4/6 inhibitor (palbociclib). Furthermore, enhanced anti-tumor activity was observed with sotorasib in combination with a MEK inhibitor or with the anti-EGFR monoclonal antibody panitumumab in a CRC KRAS p.G12C PDX model. Taken together, these data support the clinical evaluation of combination treatment of sotorasib with analogous agents in patients with KRAS p.G12C tumors. Citation Format: Karen Rex, Anne Y. Saiki, Tyler Holt, Alla Verlinsky, Patricia L. McElroy, Tao Osgood, Ji-Rong Sun, Marwan G. Fakih, Upendra P. Dahal, Bernd Bruenner, Victor J. Cee, Brian A. Lanman, Jude Canon, J. Russell Lipford. Combination of the KRASG12C inhibitor sotorasib with targeted agents improves anti-tumor efficacy in KRAS p.G12C cancer models [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1057.

Frequency and risk factors for metastasis in newly diagnosed appendiceal carcinoma.

e16281 Background: Appendiceal carcinoma has an insidious clinical presentation, and these tumors are rarely suspected prior to surgery, potentially leading to late diagnosis. The aim of this study is to investigate the prevalence of metastatic disease at initial presentation and potentially associated sociodemographic characteristics. Methods: Patients were identified from the Surveillance, Epidemiology, and End Results (SEER) program using ICD-O-3 histology/behavior codes between 2010-2015. Logistic regression was performed to determine the association of metastasis at presentation with tumor subtype, adjusted for age, race, sex, insurance and marital status, grade, and tumor and nodal stage using the seventh edition of the American Joint Committee on Cancer (AJCC) staging system. Results: We identified a total of 3, 447 patients with known metastatic status. 38.4% had metastatic disease at diagnosis. Compared to colonic-type adenocarcinoma (CA), mucinous adenocarcinoma (MA) was associated with significantly higher odds of presenting with metastasis at diagnosis in unadjusted (OR 3.55; 95% CI [2.97-4.24]) and adjusted (OR 2.97 [2.26-3.89]) regression. Signet ring cell carcinoma (SC) also had higher odds in unadjusted (OR 3.91 [2.99-5.12]) and adjusted (OR 2.05 [1.33-3.15]) regression. Goblet cell carcinoma (GC) was associated with lower odds in unadjusted (OR 0.28 [0.21-0.37]) and adjusted (OR 0.58 [0.36-0.94]) regression. The table describes the association of tumor and nodal stage with metastasis at diagnosis. Women had higher odds in unadjusted (OR 1.59 [1.39-1.82]) and adjusted (OR 1.93 [1.55-2.39]) regression. 90.1% of CA, 84.2% of GC, 42.2% of MA, and 78.5% of SC patients with metastasis at diagnosis had extraperitoneal distant metastasis (M1b). Conclusions: A significant proportion of patients with appendiceal carcinoma had metastasis at diagnosis. Compared to CA, MA and SC were much more likely to present with metastasis at diagnosis, while GC was less likely. Women had almost twice the odds of presenting with metastatic disease as men. T4 and N2 stages showed much higher odds of metastasis at diagnosis compared to T1 and N0 stages, respectively. Surprisingly, T2 and T3 stages were associated with lower odds of metastasis at diagnosis than T1 stage.[Table: see text]

Appendiceal adenocarcinoma found by surgery for acute appendicitis is associated with older age

BackgroundAppendectomy for acute appendicitis is the most common procedure performed emergently by general surgeons in the United States. The current management of acute appendicitis is increasingly controversial as non-operative management gains favor. Although rare, appendiceal neoplasms are often found as an incidental finding in the setting of appendectomy. Criteria and screening for appendiceal neoplasms are not standardized among surgical societies.MethodsThe National Surgical Quality Improvement Program (NSQIP) database was queried for all patients who underwent appendectomy over a 9-year period (2010–2018). Over the same time period, patients who underwent appendectomy in two municipal hospitals in The Bronx, New York City, USA were reviewed.ResultsWe found a 1.7% incidence of appendiceal neoplasms locally and a 0.53% incidence of appendiceal tumors in a national population sample. Both groups demonstrated an increased incidence of appendiceal carcinoma by age. This finding was most pronounced after the age of 40 in both local and national populations. In our study, the incidence of appendiceal tumors increased with each decade interval up to the age of 80 and peaked at 2.1% in patients between 70 and 79 years.ConclusionsAppendiceal adenocarcinomas were identified in patients with acute appendicitis that seem to be associated with increasing age. The presence of an appendiceal malignancy should be considered in the management of older patients with acute appendicitis before a decision to embark on non-operative therapy.