Appendiceal Neoplasms Research Articles

Survival among 148 patients with an incidentally detected appendiceal tumours at surgery for acute appendicitis: a population-based cohort follow-up study.

To investigate the long-term prognosis of appendiceal tumours incidentally detected at appendicectomy for suspicion of benign appendicitis. A retrospective register-based single centre cohort study was carried out, using data from the local acute appendicectomy quality register of cases operated on at the Department of Surgery, South General Hospital, Stockholm, Sweden. The local colorectal cancer register was also used to identify appendix tumours. The study period was between January 2004 and January 2023. Survival was calculated according to the Kaplan-Meier method. A total of 11,888 patients were registered in the acute acute appendicectomy register, 54% males and 46% females, median age 32 (Q1 = 21, Q3 = 47) (with 33.7% were 41 years or older). From the appendicectomy and colorectal registers 148 (1.2% of the total cohort) appendiceal tumours were found; 60% in females and 40% in males, median age 56 (Q1 = 43, Q3 = 70) (with 78.4% being 41 years or older). Tumours found were: Low grade Appendiceal Mucinous Neoplasms (LAMN, N = 64); Neuroendocrine Tumours (NET N = 24); adenocarcinomas or other form of carcinomas (N = 57); and adenomas (N = 3). The overall 5-year survival in patients operated for LAMN was 96.8%, for NET 93.3% and for adenocarcinoma 69.7%. The overall 5-year survival for all tumour patients was 85.7%. For the younger patients (< 51 years) with LAMN and NET, almost all survived to the end of follow-up. Survival of patients in the carcinoma group was statistically significantly lower than for the LAMN and NET groups, especially in females 51 years or older. In the group of tumour patients undergoing surgery (n = 146), primary surgery was laparoscopic in 47% and open in 52%. Two patients did not undergo surgery due to widespread disease. In 64% of cases operation was acute, whereas it was delayed and/or planned in 34%. Most procedures were laparoscopic appendicectomy 36%, followed by open appendicectomy 30%, right-sided hemicolectomy 14.6% (open 11.6% and laparoscopic 3%, acute operation 5.5%), ileocaecal resection 5% (acute operation 3.4%), and staging laparoscopy 7%. In 38% of the operated patients the tumour was discovered incidentally at histopathology examination. Two patients had CRS and HIPEC as the initial operation. Forthy-three per cent of the 146 tumour patients operated underwent a second procedure: CRS and HIPEC in 23.3% and right-sided hemicolectomy in 13.6% (laparoscopic 8.2% open 5.4%). Survival was high for patients with incidentally detected appendiceal LAMN or NET, but not so for carcinoma. Survival was lower in the carcinoma group older than 50 years, especially those sick and females.

Appendiceal goblet cell adenocarcinoma newly classified by WHO 5th edition: a case report (a secondary publication)

BackgroundAppendiceal goblet cell adenocarcinoma (AGCA) is a newly proposed cancer type in the 5th edition of the WHO Classification of Tumours in 2019. We experienced this rare form of appendiceal primary neoplasm.Case presentationAn 85-year-old male presented a positive fecal occult blood test. A series of imagings revealed a type 1 tumor, located on the appendiceal orifice. The subsequent biopsy made the diagnosis of signet-ring cell carcinoma. Consequently, he underwent the laparoscopic-assisted ileocecal resection. Initially, the tumor was suspected to be a Goblet cell carcinoid (GCC). There was a discrepancy between the histological and immunostaining findings: the tumor cells exhibited morphological similarities to GCCs, however displayed limited staining upon immunostaining. Ultimately, we concluded that the tumor should be classified as AGCA, by following WHO 5th Edition. AGCA represents a newly categorized subtype of adenocarcinomas. Because of our preoperative suspicion of malignancy, we performed tumor resection with regional lymph node dissection, despite the fact that most appendiceal malignant tumors are typically identified after an appendectomy.ConclusionWe experienced a case that provides valuable insights into the comprehension of AGCA, a recently established pathological entity in the WHO 5th Edition. This article is an acceptable secondary publication of a case report that appeared in Azuma et al. (J Jpn Surg Assoc 83:1103–1108, 2022)

Clinical Significance of Circulating Tumor Cells in Epithelial Appendiceal Neoplasms with Peritoneal Metastases.

Appendiceal tumors are uncommon and, at times, discovered incidentally during histological examination. The histopathological classification of the disease is complex and has generated some controversy. The analysis of circulating tumor cells can be used for the early detection of metastatic potential. The aim of the present study was to examine the prognostic value of circulating tumor cells in patients with appendiceal tumors and peritoneal metastases. To our knowledge, this is the first study to examine CTCs in appendiceal tumors. We performed a prospective cohort study of consecutive patients treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy between 2015 and 2019 at a HIPEC referral center. In total, 31 patients were included in the analysis, and circulating tumor cells were detected in 15 patients (48%). CTC positivity was not associated with overall or recurrence-free survival, nor was it correlated with PCI score or histopathological grading. Surprisingly, however, CTCs were found in almost half the patients. The presence or quantities of these cells did not, on their own, predict systemic metastatic potential during the observed time, and they did not appear to significantly correlate with the oncological outcomes recorded.

Visualizing the landscape of appendiceal tumor research after 2010: A bibliometric study.

Despite the rarity of appendiceal tumors, research in this field has intensified, resulting in a growing number of studies and published papers. Surprisingly, no comprehensive bibliometric analysis has specifically addressed appendiceal tumors. To offer a thorough analysis of the current landscape and future trends in appendiceal tumor research. In our bibliometric analysis studies, we explored the Web of Science Core Collection database. The bibliographic details of the chosen publications were automatically converted and analyzed using the bibliometric package in the R environment. Additionally, we employed VoSviewer to create cooperation network maps for countries, institutions, and authors, as well as clustering maps for keywords. Furthermore, CiteSpace, another software tool, was utilized to build dual-map overlays of journals and analyze references with citation bursts. Our study included 780 English-language articles published after 2010. The number of related publications and citations has increased in the past decade. The United States leads in this area, but there is a need to improve cooperation and communication among countries and institutions. Co-occurrence analysis also revealed close collaboration among different authors. Annals of Surgical Oncology was the most influential journal in this field. Analysis of references with high co-citations and references with citation bursts, consistent with analysis of keywords and hotspots, indicated that current research primarily centers on the classification and management of appendiceal mucinous neoplasms and consequent pseudomyxoma peritonei. Despite the abundance of clinical studies, a greater number of in-depth basic research studies should be conducted. Current research on appendiceal tumors focuses on classification and management of appendiceal mucinous neoplasms and pseudomyxoma peritonei. Enhanced collaboration and basic research are vital for further advancement.

Appendiceal neoplasms derived from appendiceal tip remnants following appendectomy: a report of two cases

BackgroundNeoplasms derived from remnant appendix are rarely described, with most cases arising from the appendiceal “stump”. Here, we present two surgical cases of appendiceal neoplasms derived from appendiceal “tip” remnants.Case presentationThe first patient was a 71-year-old man who had undergone laparoscopic appendectomy for acute appendicitis 12 years prior. During appendectomy, the appendiceal root was ligated, but the appendix was not completely removed due to severe inflammation. At the most recent presentation, computed tomography (CT) was performed to examine choledocholithiasis, which incidentally revealed a cystic lesion of approximately 90 mm adjacent to the cecum. A retrospective review revealed that the cystic lesion had increased in size over time, and laparoscopic ileocecal resection was performed. Pathology revealed no continuity from the appendiceal orifice to the cyst, and a diagnosis of low-grade appendiceal mucinous neoplasm (LAMN) was made from the appendiceal tip remnant. The patient was discharged without complications. The second patient was a 65-year-old man who had undergone surgery for peritonitis due to severe appendicitis 21 years prior. During this operation, the appendix could not be clearly identified due to severe inflammation; consequently, cecal resection was performed. He was referred to our department with a chief complaint of general fatigue and loss of appetite and a cystic lesion of approximately 85 mm close to the cecum that had increased over time. CT showed irregular wall thickening, and malignancy could not be ruled out; therefore, laparoscopic ileocecal resection with D3 lymph node dissection was performed. The pathological diagnosis revealed mucinous adenocarcinoma (TXN0M0) arising from the remnant appendiceal tip. The patient is undergoing follow-up without postoperative adjuvant chemotherapy, with no evidence of pseudomyxoma peritonei or cancer recurrence for 32 months postoperatively.ConclusionsIf appendicitis-associated inflammation is sufficiently severe that accurate identification of the appendix is difficult, it may remain on the apical side of the appendix, even if the root of the appendix is ligated and removed. If the appendectomy is terminated incompletely, it is necessary to check for the presence of a residual appendix postoperatively and provide appropriate follow-up.

Immunoglobulin G4-related disease mimicking an appendiceal neoplasm: a case report.

Immunoglobulin G4-related disease (IgG4-RD) is a fibroinflammatory condition characterized by chronic activation of the immune system and a tendency to form tumorous lesions. IgG4-RD is frequently characterized by the presence of tumor-like masses affecting multiple organs and is easily mistaken for a malignant neoplasm. However, IgG4-RD affecting the appendix is extremely rare, with only seven cases reported previously. We report the case of a woman in her early 60s who presented with insidious abdominal pain and radiological findings mimicking appendiceal neoplasms. After diagnosing appendiceal neoplasms, surgery was performed. The patient had a serum IgG4 concentration of <1.35 g/L, which did not satisfy one of the three revised comprehensive diagnostic criteria for IgG4-RD. A pathological examination was conducted, and the patient was diagnosed with appendiceal IgG4-RD. To the best of our knowledge, there have been no previously reported cases of IgG4-RD affecting the appendix in patients with low serum IgG4 concentrations. This report may prove beneficial for the future understanding of IgG4-RD and for the revision of diagnostic and treatment strategies.

Prognostic indicators of recurrence after surgical resection in non-pancreatic gastrointestinal neuroendocrine tumors.

e16287 Background: The incidence of gastrointestinal neuroendocrine tumors (GI-NETs) has continued to increase over the last two decades. In patients with locoregional disease, surgical resection of the primary tumor without additional therapies is considered standard of care. The frequency and risk factors associated with recurrence and survival in patients with non-pancreatic GI-NETs are poorly defined. We aimed to evaluate clinical and pathological factors associated with recurrence and survival in patients with resected non-pancreatic GI-NETs. Methods: We conducted a retrospective review of patients who presented to the Johns Hopkins Hospital between 2000-2019 with locoregional small bowel, colon, appendiceal, and rectal neuroendocrine tumors who underwent surgical resection with curative intent. We collected clinical and pathological data including tumor primary site, tumor differentiation, grade using Ki-67 labeling index (grade 1, 2, or 3), margin involvement, perineural or vascular invasion, time of recurrence, patterns of recurrence, and death. Patients with metastatic disease at the time of diagnosis and insufficient follow up were excluded. Results: A total of 133 patients met inclusion criteria. Most patients had tumors originating from the small bowel (n = 87, 66%), followed by the appendix (n = 19, 15%), rectum (n = 18, 14%), and colon (n = 7, 5%). With a median follow-up of 35 months, 23 patients (17%) had tumor progression after curative-intent surgery, with the liver (n = 13, 57%) as the most common site. In the majority of patients, tumors were well-differentiated (n = 118, 97%) and grade 1 (n = 78, 75%). Intermediate/high grade tumors (grade 2/3) occurred in 26 (25%) of patients. Median progression-free survival was 226 months (18.8 years). Age (greater than 60) and intermediate/high grade tumors (grade 2 or 3) were associated with worse overall survival HR = 5.5 (95% CI: 1.5, 19.6), p = 0.009, and HR = 3.3 (95% CI: 1.1, 10.2), p = 0.034, respectively. Tumor grade (2 or 3) and positive nodes were associated with worse progression-free survival HR = 4.5 (95% CI: 2.0, 10.1), p = 4e-04, and HR = 3.1 (95% CI: 1.4, 6.8), p = 0.009, respectively. Conclusions: A significant number of patients (17%) with non-pancreatic GI-NETs had tumor progression after curative-intent surgery. Risk factors for recurrence include intermediate/high-grade tumors and positive lymph nodes. Further studies are needed to evaluate the role of adjuvant therapy in patients at higher risk of recurrence following surgical resection for non-pancreatic GI-NETs.

Critical reappraisal of prognostic indicators for 949 mucinous appendiceal neoplasm patients.

The standard of care for treatment of an appendiceal mucinous neoplasm with peritoneal dissemination is cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC). These two treatments are combined in the operating room. A crucial requirement for benefit long-term is proper patient selection. Clinical and histopathologic prognostic indicators are used, along with the patient's fitness for surgery, to select patients to receive CRS and HIPEC. This study seeks to identify the reliable prognostic indicators for four different groups of patients. They are (1) the low-grade appendiceal mucinous neoplasms (LAMN) with a complete CRS, (2) the mucinous appendiceal adenocarcinomas (MACA) with complete CRS, (3) MACA with lymph node metastases (MACA-LN) with complete CRS, and (4) all histologic subtypes with incomplete cytoreduction. The prognostic indicators were evaluated for their impact on overall survival in these four groups of patients. The completeness of cytoreduction (CC) score statistically significantly showed survival differences in all three histologic subtypes. The peritoneal cancer index (PCI) showed significance with LAMN and MACA-LN but not with MACA and not with incomplete CRS. The prior surgical score (PSS) was a prognostic indicator that predicted the outcome with LAMN, MACA-LN, and incomplete CRS patients but not with the MACA group. Patients who were symptomatic or who had extensive systemic chemotherapy before CRS had a significantly reduced survival. The utility of prognostic indicators varied greatly within our four different groups of appendiceal mucinous neoplasms. CC score was always a reliable prognosticator. Surprisingly, PCI was not.

Beyond boundaries: Feasibility of curved linear array echoendoscope in appendiceal neoplasm detection

We recently read with great interest a study by Zhang et al in the World Journal of Gastroenterology . In our practice, we focus specifically on examining appendiceal mucinous neoplasms (AMNs) with endoscopic ultrasound (EUS) using different scopes. AMNs are rare neoplastic lesions characterized by an accumulation of mucin inside a cystic dilatation of the appendix. Clinically, they can present as nonspecific acute appendicitis. AMNs can turn into a life-threatening condition, termed pseudomyxoma peritonei, in which the ruptured appendix causes accumulation of mucin in the abdomen. Therefore, accurate and rapid diagnosis of AMN is essential. EUS is able to confirm and stage AMNs; although, EUS examination was once limited to the rectal and anal regions due to the conventional oblique-view scopes. With the emergence of new forward-view linear echoendoscopes and instruments like EUS miniprobes and overtubes, the scope of examination is changing. Herein, we discuss the feasibility of using the curved linear array echoendoscopes to examine cecal and appendiceal orifice lesions.

Prevalence of, Subtypes of, and the Role of Age in Incidental Appendiceal Neoplasms in Acute Appendicitis: A Single-Institute Study from Bahrain.

Primary appendiceal neoplasms (ANs) are rare entities that can present with acute appendicitis symptoms. Accurate diagnosis of these diverse subtypes is crucial for prognosis and proper management. This descriptive retrospective study aims to determine the prevalence and pathological subtypes of incidental ANs in patients presenting with acute appendicitis symptoms at Salmaniya Medical Center (SMC) in Bahrain between the period of January 2020 and March 2024. Particular focus was placed on investigating whether advanced age is a significant risk factor for these neoplasms. The study included 38,643 patients (aged 15 years and above) who underwent appendectomy for suspected acute appendicitis during the study period. Demographic data, clinical diagnoses, preoperative imaging findings, histopathological reports, and management details were analyzed. Medical records of patients were retrieved from ISEHA system. Statistical analysis was done using Microsoft Excel. The results showed that 12 patients (0.04% per year) had different subtypes of appendiceal tumors. Neuroendocrine tumors were the most common, identified in nine patients (75%), including nine cases of well-differentiated neuroendocrine carcinoma (NEC). Other histopathological subtypes included low-grade appendiceal mucinous neoplasm (LAMN), adenocarcinoma, and goblet cell adenocarcinoma, each found in one patient. Additionally, two patients had confirmed appendiceal mucocele. The mean age of patients with ANs was 30 years (range: 19-52 years), and 66.6% were younger than 38 years. Conclusion: These findings highlight the importance of considering ANs in the differential diagnosis of acute appendicitis, especially in older patients. Further research is warranted to confirm the role of age as a risk factor and guide clinical decision-making.

Superiority of 18F-FAPI-42 PET/CT in the detection of primary tumor and management of appendiceal neoplasm to 18F-FDG PET/CT and CE-CT

BackgroundIn the present study, we investigated the value of 18F-fibroblast-activation protein inhibitor (FAPI) positron emission tomography/computed tomography (18F-FAPI-42 PET/CT) to preoperative evaluations of appendiceal neoplasms and management for patients.MethodsThis single-center retrospective clinical study, including 16 untreated and 6 treated patients, was performed from January 2022 to May 2023 at Southern Medical University Nanfang Hospital. Histopathologic examination and imaging follow-up served as the reference standard. 18F-FAPI-42 PET/CT was compared to 18F-fluorodeoxyglucose (18F-FDG) PET/CT and contrast-enhanced CT (CE-CT) in terms of maximal standardized uptake value (SUVmax), diagnostic efficacy and impact on treatment decisions.ResultsThe accurate detection of primary tumors and peritoneal metastases were improved from 28.6% (4/14) and 50% (8/16) for CE-CT, and 43.8% (7/16) and 85.0% (17/20) for 18F-FDG PET/CT, to 87.5% (14/16) and 100% (20/20) for 18F-FAPI-42 PET/CT. Compared to 18F-FDG PET/CT, 18F-FAPI-42 PET/CT detected more regions infiltrated by peritoneal metastases (108 vs. 43), thus produced a higher peritoneal cancer index (PCI) score (median PCI: 12 vs. 5, P < 0.01). 18F-FAPI-42 PET/CT changed the intended treatment plans in 35.7% (5/14) of patients compared to CE-CT and 25% (4/16) of patients compared to 18F-FDG PET/CT but did not improve the management of patients with recurrent tumors.ConclusionsThe present study revealed that 18F-FAPI-42 PET/CT can supplement CE-CT and 18F-FDG PET/CT to provide a more accurate detection of appendiceal neoplasms and improved treatment decision making for patients.

Obesity and overweight are associated with worse survival in early-onset colorectal cancer

BackgroundObesity and its associated lifestyle are known risk factors for early-onset colorectal cancer and are associated with poor postoperative and survival outcomes in older patients. We aimed to investigate the impact of obesity on the outcomes of early-onset colorectal cancers. MethodsRetrospective review of all patients undergoing primary resection of colon or rectal adenocarcinoma at our institution between 2015–2022. Patients who had palliative resections, resections performed at another institution, appendiceal tumors, and were underweight were excluded. The primary endpoint was survival according to the patient's body mass index: normal weight (18–24.9 kg/m2), overweight (25–29.9 kg/m2), and obesity (≥30 kg/m2). Patient and tumor characteristics and survival were compared between the three groups. ResultsA total of 279 patients aged <50 years with colorectal cancer were treated at our hospital; 120 were excluded from the analysis for the following reasons: main treatment or primary resection performed at another hospital (n = 97), no resection/palliative resection (n = 23), or body mass index <18 kg/m2 (n = 2). Of these, 157 patients were included in the analysis; 61 (38.9%) were overweight and 45 (28.7%) had obesity. Except for a higher frequency of hypertension in the overweight (P = .062) and obese (P = .001) groups, no differences in patient or tumor characteristics were observed. Mean overall survival was 89 months with normal weight, 92 months with overweight, and 65 months with obesity (P = .032). Mean cancer-specific survival was 95 months with normal weight, 94 months with overweight, and 68 months with obesity (P = .018). No statistically significant difference in disease-free survival (75 vs 70 vs 59 months, P = .844) was seen. ConclusionIndividuals with early-onset colorectal cancer who are overweight or obese present with similar tumor characteristics and postoperative morbidity to patients with normal weight. However, obesity may have a detrimental impact on their survival. Addressing obesity as a modifiable risk factor might improve early-onset colorectal cancer prognosis.

Retrospective analysis of the incidence of appendiceal neoplasm and malignancy in patients treated for suspected acute appendicitis

BackgroundNonoperative management of uncomplicated appendicitis is currently being promoted as treatment option, albeit 0.7–2.5% of appendectomies performed due to suspected acute appendicitis show histologically malignant findings. The purpose of this study was to investigate the incidence of neoplasm and malignancy of the appendix in patients presenting with suspected acute appendicitis in real world setting.MethodsThis is a retrospective single-centre investigation of 457 patients undergoing appendectomy between the years 2017–2020. The patients’ demographics, symptoms and diagnosis, intraoperative findings, and histopathological results were analysed.ResultsIn 3.7% (n = 17) histological analysis revealed neoplasms or malignancies. Median age was 48 years (20–90 years), without sex predominance. Leukocytes (11.3 ± 3.7 G/l) and C-reactive protein (54.2 ± 69.0 mg/l) were elevated. Histological analysis revealed low-grade mucinous appendiceal neoplasia (n = 3), sessile serrated adenoma of the appendix (n = 3), neuroendocrine tumours (n = 7), appendiceal adenocarcinoma of intestinal type (n = 3), and goblet cell carcinoma (n = 1). Additional treatment varied between no treatment or follow-up due to early tumour stage (n = 4), follow-up care (n = 3), additional surgical treatment (n = 8), or best supportive care (n = 2).ConclusionsPreoperative diagnosis of appendiceal tumours is difficult. Nonoperative management of patients with acute, uncomplicated appendicitis potentially prevents the correct diagnosis of malignant appendiceal pathologies. Therefore, close follow-up or surgical removal of the appendix is mandatory.

Colonoscopy in the diagnosis and management of appendiceal disease

In this editorial, we comment on the article published in the recent issue of the World Journal of Gastrointestinal Endoscopy . We focused on the understanding of appendiceal disease, and the various options for diagnosis and treatment via endoscopy. Some factors affecting the diagnosis and management of appendiceal diseases are also discussed. The existence of any organ has its natural rationality, and the appendix is such a magical organ. A growing number of experts and scholars have gradually come to a consensus that the appendix is not a useless evolutionary relic. There are many lymphocytes and lymph nodes in the appendix wall, which has a strong immune function, and this function is particularly important for children and adolescents. Many intestinal probiotics in the appendix are very helpful for maintaining the balance of the intestinal flora. With the continuous progress of endoscopic technology, endoscopic treatment involving preservation of the appendix has shown great advantages over surgery. In the diagnosis of appendiceal inflammation and neoplasms, colonoscopy, endoscopic retrograde appendicography and choledochoscopy help assess conditions of the appendix. Endoscopic retrograde appendicitis therapy, abscess drainage under colonoscopy, fenestration of abscess under colonoscopy, and endoscopic or natural orifice transluminal endoscopic surgery resection of appendiceal neoplasms are safe and effective endoscopic treatments for appendiceal disease. New breakthroughs in the application of endoscopy in the appendix are expected to occur in the near future.

State of the Art Review: Evidence based management of acute appendicitis

Introduction: Even though acute appendicitis is the world’s most common emergency general surgical operation, it remains under-researcher with wide variations in care. The aim of this review was to present current evidence on the management of acute appendicitis, focusing on risk assessment, diagnostic modalities, treatment strategies, and special considerations for specific patient populations.&#x0D; &#x0D; Methods: The writing group conducted a modified Delphi to prioritise topic areas for inclusion in this review. Consensus was achieved when each topic had &gt;70% for either important or strongly important. Scoping reviews of current and grey literature were conducted to identify relevant evidence, focussing on new publications in the last 5 years (2019-2024).&#x0D; &#x0D; Results: Validated risk scoring systems, such as the Adult Appendicitis Score and the AIRS score, aid in identifying low-risk patients suitable for ambulatory management, while imaging modalities, including CT scans and ultrasound, play a pivotal role in confirming diagnosis and guiding treatment decisions. The review highlights the efficacy of surgical intervention versus antibiotic therapy, emphasising the importance of shared decision-making and individualised treatment plans. Tailored care strategies are needed for elderly patients, pregnant women, and those with appendiceal neoplasms whilst strategies for optimising antibiotic stewardship, minimising negative appendectomy rates, and enhancing postoperative care will provide the best evidence-based care.&#x0D; &#x0D; Discussion: This review provides evidence-based practices can be integrated into routine clinical care and ongoing education for frontline clinicians. The practice recommendations are designed to be evidence based and can be tailored depending on local resources. These should form the basis of future educational packages and surgical training programmes.&#x0D;

Imaging of pediatric gastrointestinal tumors: A tertiary center experience over 19 years

PurposeGastrointestinal tract (GIT) tumors in children are rare and there is a scarcity of data on their imaging features. The purpose of this study was to determine thefrequency of various GIT tumor types in children and to identify key imaging characteristics. MethodsThis retrospective, single-center study was approved by the local ethics committee. Children with histologically proven GIT tumours (malignantand benign) who had imaging available on the institutional PACS between May 1, 2000 and Dec 31, 2019 were included. Demographic data and available imaging was reviewed by two blinded radiologists. ResultsIn total, 90 children (45 male, mean age 9.3 ± 4.3 years) with GIT tumours were included. The final diagnoses included polyps (n = 28), lymphomas/PTLD (n = 27), neuroendocrine tumours (n = 16), adenocarcinoma (n = 6), adenoma (n = 5), gastrointestinal stromal tumor (GIST) (n = 3), inflammatory myofibroblastic tumours (n = 2) and lastly leiomyoblastoma, leiomyoma and lipoma (1 each). All GIT segments were affected, but overall the small and large bowel had most lesions. Eighty-one percent children had a single lesion while remaining 19 % had multiple lesions. The neoplastic process manifested as intra-luminal lesion (58 %) or wall thickening (42 %) on imaging. Multiple cystic areas and vascular pedicle for polyps; and hypoechogenecity of the mass or wall thickening and aneurysmal dilatation for lymphomas, were the characteristic imaging features. None of the neuroendocrine tumours affecting appendix were seen on pre-resection imaging. ConclusionsVariety of benign and malignant tumors are seen throughout the childhood. Polyps, lymphomas and appendiceal neuroendocrine tumors are common lesions. Characteristic imaging features of juvenile polyps and lymphomas on ultrasound may help narrowing the differentials, and guide further work up.

Ovarian Causes of Pseudomyxoma Peritonei (PMP)-A Literature Review.

Pseudomyxoma peritonei (PMP) is a rare, progressive, slowly growing, inadequately understood neoplasm with a 5-year progression-free survival rate of as low as 48%. It is characterized by varying degrees of malignancy and the production of mucinous and gelatinous structures. Typically, the development of pseudomyxoma peritonei is associated with the rupture of appendiceal mucinous tumors and other gastrointestinal or ovarian mucinous tumors. The goal of our literature review was to identify various aspects that characterize the ovarian causes of pseudomyxoma peritonei. The authors performed an extensive literature search between 1 February 2024 and 2 March 2024 on the following databases: Pubmed, Scopus, Oxford Journals, and Reaxys, and the findings were summarized into seven main clinical and paraclinical situations. According to our research, the main instances in which pseudomyxoma peritonei can be triggered by an ovarian cause are the following: (1) mucinous cystadenoma; (2) mucinous ovarian cancer; (3) colon cancer with ovarian metastasis; (4) malignant transformation of an ovarian primary mature cystic teratoma; (5) appendiceal mucocele with peritoneal dissemination mimicking an ovarian tumor with peritoneal carcinomatosis; (6) mucinous borderline tumor developing inside an ovarian teratoma; and (7) the association between a mucinous bilateral ovarian cancer and a colonic tumor. In our study, we aimed to provide a comprehensive overview of the ovarian causes of pseudomyxoma peritonei, including its epidemiology, imagery characteristics, symptoms, current treatment, and promising future therapies, in the hopes of finding feasible solutions, as a lack of understanding of this mucus-secreting malignant disease increases the risk of delayed diagnosis or uncontrolled deterioration.

Abstract CT079: The Pseudovax trial: A novel peptide vaccine targeting mutated GNAS for pseudomyxoma peritonei

Abstract Background: Pseudomyxoma peritonei (PMP) is a rare cancer originating from appendiceal mucinous tumors, which may spread to encompass the entire peritoneal cavity. Complete surgical removal and hyperthermic intraperitoneal chemotherapy cures approximately half of the patients, but patients with recurrent or non-resectable disease have no efficacious treatment options. These patients have a high unmet need for novel treatment options, and in the Pseudovax trial we will explore a novel therapeutic concept. A main molecular driver of PMP (in up to 90% of cases) is otherwise rare mutations in the GNAS oncogene, coding for the Gsα protein. We hypothesized that mutated Gsα would be a tumor neoantigen, and in T cells isolated from peripheral blood of PMP patients, a strong T cell proliferative response was observed. In the corresponding tumors, T cells with up-regulated immune checkpoint molecules PD-1 and TIGIT were detected. Study hypotheses: Patients with GNAS-mutated PMP has a preexisting, attenuated immune response directed against mutated Gsα protein. Vaccination with mutated Gsα peptides can be combined with immune checkpoint inhibition (ICI) with acceptable toxicity. The vaccine will reactivate the immune response and ICI will restore measurable anticancer immunity in patients. Study design: The Pseudovax trial is a small (10 patients) first-in-human, proof-of-concept, prospective, open label, phase I trial. Patients with recurrent or non-resectable PMP are eligible for inclusion. During a treatment period of 12 months, a mutated Gsα peptide vaccine + adjuvant (GM-CSF) will be administered as intradermal injections. After 12 weeks, treatment with ICI will be initiated. The primary endpoints are toxicity and circulating immune response against the vaccine, measured as increase in interferon-gamma production or proliferation of circulating vaccine-specific T cells compared to pre-vaccination baseline. Secondary endpoints are progression-free survival (abdominopelvic CT scans, blood levels of carcinoembryonic antigen (CEA) and/or detection of GNAS mutation by ctDNA analysis). Citation Format: Kjersti Flatmark, Annette Torgunrud, Fleten G. Karianne, Ben Davidson, Hedvig V. Juel, Nadia Mensali, Christin Lund Andersen, Else Marit Inderberg. The Pseudovax trial: A novel peptide vaccine targeting mutated GNAS for pseudomyxoma peritonei [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT079.

Abstract 5480: Single cell and spatial transcriptomic profile of appendiceal tumour peritoneal disease

Abstract Introduction: Appendiceal tumors (AT) are rare and often develop peritoneal disease (PD), with 5 year survival of 15-63% for high grade adenocarcinomas (HG) and 46-96% for low grade mucinous neoplasms (LG). While the mainstay of treatment is cytoreductive surgery and heated intraperitoneal chemotherapy (CRS/HIPEC), the role of systemic chemotherapy is less clear with limited biological characterization of AT and its tumor microenvironment (TME). The purpose of this study was to evaluate the TME of AT PD. Here we present an atlas of AT PD cells alongside a spatially resolved transcriptomic profile comparing HG and LG. Methods: We collected tissue from 29 patients with AT PD during CRS prior to HIPEC (18 LG, nine HG and two no tumor control). We performed comprehensive single-cell RNA sequencing (38224 cells) on fresh tissue specimens from nine patients (four HG, five LG), and whole transcriptome spatial analysis (&amp;gt;18000 genes) using the GeoMx Digital Spatial Profiler on formalin-fixed paraffin-embedded tissue from 22 patients (five HG, 13 LG). In the spatial profiling, we used anti-CK20, anti-CD45 and SYTO 83 as morphology markers to select areas of interest (AOIs): tumor (CK20), immune (CD45) and stroma (non-CK20/CD45). Analyses were performed with R and a false discovery rate threshold of 0.05. Results: Single-cell RNA sequencing showed that both LG and HG have a preponderance of T-lineage cells including CD8, CD4 and NK T-cells. Both LG and HG tumors display association of mesothelial cells with cancer-associated fibroblasts (CAF), and CAF subsets expressing genes of epithelial-mesenchymal transition (EMT). LG and HG tumors display different patterns of mucin gene expression - epithelial cells of HG express the secreted mucin MUC20 in addition to MUC2 and MUC5B also expressed in LG; a subset of mesothelial cells in LG but not HG express the transmembrane mucin genes MUC1, MUC3A, MUC12 and MUC16. Spatial analysis of tumor AOIs revealed HG compared to LG had increased expression of genes associated with MYC targets, oxidative phosphorylation, anti-tumor immune pathways (IFNα/γ response, intestinal immune network for IGA production), cell cycle pathways (E2F targets, G2M checkpoint) and EMT. LG compared to HG had increased expression of genes associated with inflammation-mediated disease (TNFα signaling via NFKB, inflammatory response), regulation of tumor growth (P53), hypoxia and early cell cycle (estrogen response) and glycosylation pathways. Immune and stromal AOIs did not have significant transcriptomic differences between LG and HG. Conclusion: This study provides novel insights into the biological profile of AT PD by describing TME cell types, immune function, tumor growth and cell cycle pathways. These findings may be used to identify clinically relevant biomarkers and new therapeutic targets. Citation Format: Madeleine C. Strach, Nicole Yeung, Eva Apostolov, Tony Wang, Hui-Ming Lin, Nabila Ansari, Cherry Koh, Joo-Shik Shin, James Kench, Alexander Swarbrick, Lisa Horvath, Kate L. Mahon. Single cell and spatial transcriptomic profile of appendiceal tumour peritoneal disease [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5480.

Mortality risk prediction for primary appendiceal cancer

BackgroundAccurately predicting survival in patients with cancer is crucial for both clinical decision-making and patient counseling. The primary aim of this study was to generate the first machine-learning algorithm to predict the risk of mortality following the diagnosis of an appendiceal neoplasm. MethodsPatients with primary appendiceal cancer in the Surveillance, Epidemiology, and End Results database from 2000 to 2019 were included. Patient demographics, tumor characteristics, and survival data were extracted from the Surveillance, Epidemiology, and End Results database. Extreme gradient boost, random forest, neural network, and logistic regression machine learning models were employed to predict 1-, 5-, and 10-year mortality. After algorithm validation, the best-performance model was used to develop a patient-specific web-based risk prediction model. ResultsA total of 16,579 patients were included in the study, with 13,262 in the training group (80%) and 3,317 in the validation group (20%). Extreme gradient boost exhibited the highest prediction accuracy for 1-, 5-, and 10-year mortality, with the 10-year model exhibiting the maximum area under the curve (0.909 [±0.006]) after 10-fold cross-validation. Variables that significantly influenced the predictive ability of the model were disease grade, malignant carcinoid histology, incidence of positive regional lymph nodes, number of nodes harvested, and presence of distant disease. ConclusionHere, we report the development and validation of a novel prognostic prediction model for patients with appendiceal neoplasms of numerous histologic subtypes that incorporate a vast array of patient, surgical, and pathologic variables. By using machine learning, we achieved an excellent predictive accuracy that was superior to that of previous nomograms.