Case report: A novel case of paraneoplastic voltage gated calcium channel antibodies secondary to appendiceal adenocarcinoma.

Voltage gated calcium channels (VGCCs) play a critical role in neural transmission. Antibodies that target these ion channels can disrupt cellular signal transmission resulting in various clinical presentations. VGCC antibodies are most commonly associated with paraneoplastic syndromes such as Lambert-Eatons myasthenic syndrome. Here, we report a 47-year-old female with Stage IV appendiceal adenocarcinoma status post appendectomy and right hemicolectomy, who presented with progressive memory impairment, aphasia, ataxia, weakness, and headache. Neurologic exam was notable for right-sided parietal drift, decreased right arm swing, and ataxia of the bilateral upper extremities, more prominent on the right side. MRI of the brain with and without contrast was unremarkable. Cerebrospinal fluid (CSF) was notable for an elevated myelin basic protein (4.9 ng/mL, normal reference 0.0-3.7 ng/mL) with normal cell count, flow cytometry, and cytology. An extensive serum autoimmune neurology antibody evaluation revealed elevated VGCC autoantibodies (observed value: 96.1 pmol/L, normal range 0.0-30.0 pmol/L). A diagnosis of paraneoplastic voltage gated calcium channel antibodies secondary to appendiceal adenocarcinoma was made. The patient was treated with five exchanges with plasmapheresis over 10 days with significant clinical improvement in her symptoms. Upon literature review, this would be the first reported case of VGCC antibodies associated with appendiceal adenocarcinoma.

Surgical outcomes and predictors of overall survival of stage I-III appendiceal adenocarcinoma: Retrospective cohort analysis of the national cancer database.

BACKGROUND: This study aimed to determine predictors of overall survival (OS) after surgical treatment of stage I-III appendiceal adenocarcinoma and compare the outcomes of partial colectomy and hemicolectomy. METHODS: A retrospective analysis of the U.S. National Cancer Database (NCDB) including patients who underwent surgery for stage I-III appendiceal adenocarcinoma between 2005 and 2019 was conducted. A propensity-score matched analysis was undertaken to compare the outcomes of partial and hemicolectomy and multivariate analysis was performed to determine predictive factors of OS. The main outcome was OS and its independent predictors. RESULTS: 2607 patients (51.6 % male) with a mean age of 61.6 ± 13.9 years were included. 61.7 % of patients underwent hemicolectomy while 31.7 % underwent partial colectomy. After matching, partial colectomy, and hemicolectomy had similar OS (117.3 vs 117.2 months; p = 0.08), positive resection margins, short-term mortality, and 30-day readmission. The hemicolectomy group was associated with more examined lymph nodes and longer hospital stays. Older age (HR: 1.047, p < 0.0001), rural residence area (HR: 3.6, p = 0.025), higher Charlson score (HR: 1.6, p = 0.016), signet-ring cell carcinoma (HR: 2.37, p = 0.009), adjuvant systemic treatment (HR: 1.55, p = 0.015), positive surgical margins (HR: 1.83, p = 0.017), positive lymph nodes number (HR: 1.09, p < 0.0001), and examined lymph nodes number (HR: 0.962, p = 0.001) were independent predictors of OS. CONCLUSIONS: Partial colectomy and hemicolectomy had similar OS and clinical outcomes. Older age, rural residence, higher Charlson score, signet-ring pathology, adjuvant systemic treatment, positive surgical margins, positive lymph node number, and examined lymph node number were independent predictors of OS.

Which is the appropriate surgical procedure for appendiceal adenocarcinoma: appendectomy, partial colectomy or right hemicolectomy?

Objective The purpose of this study was to explore the appropriate surgical procedure and clinical decision for appendiceal adenocarcinoma. Methods A total of 1,984 appendiceal adenocarcinoma patients from 2004 to 2015 were retrospectively identified from the Surveillance, Epidemiology, and End Results (SEER) database. All patients were divided into three groups based on the extent of surgical resection: appendectomy (N = 335), partial colectomy (N = 390) and right hemicolectomy (N = 1,259). The clinicopathological features and survival outcomes of three groups were compared, and independent prognostic factors were assessed. Results The 5-year OS rates of patients who underwent appendectomy, partial colectomy and right hemicolectomy were 58.3%, 65.5% and 69.1%, respectively (right hemicolectomy vs appendectomy, P < 0.001; right hemicolectomy vs partial colectomy, P = 0.285; partial colectomy vs appendectomy, P = 0.045). The 5-year CSS rates of patients who underwent appendectomy, partial colectomy and right hemicolectomy were 73.2%, 77.0% and 78.7%, respectively (right hemicolectomy vs appendectomy, P = 0.046; right hemicolectomy vs partial colectomy, P = 0.545; partial colectomy vs appendectomy, P = 0.246). The subgroup analysis based on the pathological TNM stage indicated that there was no survival difference amongst three surgical procedures for stage I patients (5-year CSS rate: 90.8%, 93.9% and 98.1%, respectively). The prognosis of patients who underwent an appendectomy was poorer than that of those who underwent partial colectomy (5-year OS rate: 53.5% vs 67.1%, P = 0.005; 5-year CSS rate: 65.2% vs 78.7%, P = 0.003) or right hemicolectomy (5-year OS rate: 74.2% vs 53.23%, P < 0.001; 5-year CSS rate: 65.2% vs 82.5%, P < 0.001) for stage II disease. Right hemicolectomy did not show a survival advantage over partial colectomy for stage II (5-year CSS, P = 0.255) and stage III (5-year CSS, P = 0.846) appendiceal adenocarcinoma (AU)

Which is the appropriate surgical procedure for appendiceal adenocarcinoma: appendectomy, partial colectomy or right hemicolectomy?

OBJECTIVE: The purpose of this study was to explore the appropriate surgical procedure and clinical decision for appendiceal adenocarcinoma. METHODS: A total of 1,984 appendiceal adenocarcinoma patients from 2004 to 2015 were retrospectively identified from the Surveillance, Epidemiology, and End Results (SEER) database. All patients were divided into three groups based on the extent of surgical resection: appendectomy (N = 335), partial colectomy (N = 390) and right hemicolectomy (N = 1,259). The clinicopathological features and survival outcomes of three groups were compared, and independent prognostic factors were assessed. RESULTS: The 5-year OS rates of patients who underwent appendectomy, partial colectomy and right hemicolectomy were 58.3%, 65.5% and 69.1%, respectively (right hemicolectomy vs appendectomy, P < 0.001; right hemicolectomy vs partial colectomy, P = 0.285; partial colectomy vs appendectomy, P = 0.045). The 5-year CSS rates of patients who underwent appendectomy, partial colectomy and right hemicolectomy were 73.2%, 77.0% and 78.7%, respectively (right hemicolectomy vs appendectomy, P = 0.046; right hemicolectomy vs partial colectomy, P = 0.545; partial colectomy vs appendectomy, P = 0.246). The subgroup analysis based on the pathological TNM stage indicated that there was no survival difference amongst three surgical procedures for stage I patients (5-year CSS rate: 90.8%, 93.9% and 98.1%, respectively). The prognosis of patients who underwent an appendectomy was poorer than that of those who underwent partial colectomy (5-year OS rate: 53.5% vs 67.1%, P = 0.005; 5-year CSS rate: 65.2% vs 78.7%, P = 0.003) or right hemicolectomy (5-year OS rate: 74.2% vs 53.23%, P < 0.001; 5-year CSS rate: 65.2% vs 82.5%, P < 0.001) for stage II disease. Right hemicolectomy did not show a survival advantage over partial colectomy for stage II (5-year CSS, P = 0.255) and stage III (5-year CSS, P = 0.846) appendiceal adenocarcinoma. CONCLUSIONS: Right hemicolectomy may not always be necessary for appendiceal adenocarcinoma patients. An appendectomy could be sufficient for therapeutic effect of stage I patients, but limited for stage II patients. Right hemicolectomy was not superior to partial colectomy for advanced stage patients, suggesting omission of standard hemicolectomy might be feasible. However, adequate lymphadenectomy should be strongly recommended.

Use of early postoperative intraperitoneal 5-fluorouracil with index cytoreduction improves survival with secondary cytoreductive surgery.

BACKGROUND: In patients with appendiceal mucinous neoplasm with peritoneal dissemination, a cytoreductive surgery (CRS) with perioperative chemotherapy may result in long-term survival. Disease progression may require secondary cytoreductive surgery (SCRS) and other treatments in selected patients to improve survival and preserve an optimal quality of life. METHODS: The clinical- and treatment-related variables associated with the index CRS and SCRS were statistically assessed for impact on survival after SCRS. RESULTS: A total of 186 of 687 complete CRS patients (27.1%) had SCRS. Median follow-up was 10 years and median survival was 12 years. In 95 males (51%) the median age was 45.0 years. Survival benefit with SCRS was observed if early postoperative intraperitoneal chemotherapy (EPIC) with 5-fluorouracil (EPIC 5-FU) or hyperthermic intraperitoneal chemotherapy (HIPEC) plus EPIC 5-FU was used with the index CRS (hazard ratio [HR]: 0.6, p = 0.0360; HR: 0.4, p = 0.0004, respectively). By propensity matching of 51 pairs of patients, EPIC 5-FU used with index CRS caused a survival advantage compared to HIPEC alone (p = 0.0100) with index CRS (p = 0.0100). CONCLUSIONS: Use of EPIC 5-FU at a complete index CRS was a prognostic variable that improved survival in patients requiring SCRS. Further investigations into the benefits of antiadhesion treatments with CRS and HIPEC are warranted.

Determinants of Outcome with Reoperative Surgery for Pseudomyxoma Peritonei in 186 Patients.

Objective: To describe the long-term survival and clinical- and treatment-related variables that determine the outcome of repeat cytoreductive surgery (CRS) for mucinous appendiceal neoplasms with peritoneal dissemination. Summary Background: After patients with peritoneal dissemination of an appendiceal mucinous neoplasm have a CRS, disease progression may require secondary cytoreductive surgery (SCRS) and other treatments performed in a timely manner to prolong survival and help preserve an optimal quality of life. Methods: The clinical- and treatment-related variables associated with the index CRS and the SCRS were statistically assessed for their impact on survival. Results: One hundred eighty-six of 687 complete CRS patients (27.1%) had SCRS. The median follow-up was 10 years and the median survival was 12 years. There were 95 males (51%) and the median age was 45.0 years. Survival benefit was associated with the index CRS by use of early postoperative intraperitoneal chemotherapy (EPIC) with 5-fluorouracil [Hazard ratio (HR), 0.4; P = 0.0004]. Also, survival of low-grade mucinous appendiceal neoplasms versus mucinous appendiceal adenocarcinoma (HR, 2.8; P < 0.0001) was improved. The interval between index CRS and SCRS was significant at ≤12 months versus 12-36 months versus >36 months (P < 0.0001). Change in peritoneal cancer index and disease distribution as focal or diffuse was significant by univariant and multivariant analyses. Conclusions: If the CRS was complete, the use of EPIC 5-fluorouracil, the interval between the index CRS and the SCRS, the histologic grade of the mucinous neoplasm, and the extent of recurrent disease were prognostic variables that should be used to help select patients for SCRS.

Increased Incidence of Liver Metastases in Colorectal Versus Appendiceal Adenocarcinoma Peritonectomy Patients Despite Equivocal Survival.

BACKGROUND/AIM: Colorectal adenocarcinoma (CRAdenoCa) and appendiceal adenocarcinoma (AAdenoCa) are diseases of the same histopathological type that metastasise to the liver and peritoneum. In selected subgroups, peritonectomy and heated intraperitoneal chemotherapy (HIPEC) may be indicated as part of the multimodal treatment plan. However, literature comparing the survival outcomes and preoperative tumour activity and burden of CRAdenoCa and AAdenoCa peritonectomy patients without synchronous liver metastases (sLM) is scarce. Little is also known about the comparative incidence of sLM and metachronous LM (mLM) between CRAdenoCa and AAdenoCa peritonectomy patients. This study aimed to clarify the above. PATIENTS AND METHODS: A retrospective cohort study of 684 CRAdenoCa and AAdenoCa primary peritonectomy patients between 2001-2021 was conducted at St George Hospital in Sydney, Australia. RESULTS: Median overall survival (years) was equivocal between CRAdenoCa and AAdenoCa peritonectomy patients (1.7 vs. 1.9, p=0.35). Peritoneal cancer index and preoperative carcinoembryonic antigen (CEA) were significantly elevated (25 vs. 9, p<0.0001 and 7.9 vs. 5, p=0.0080) in AAdenoCa versus CRAdenoCa peritonectomy patients without sLM. The incidence of sLM and mLM was increased in CRAdenoCa peritonectomy patients (24% vs. 3.1%, p<0.0001 and 26% vs. 10%, p=0.0001). CONCLUSION: This study demonstrates similar survival outcomes between CRAdenoCa and AAdenoCa peritonectomy patients. Despite elevated preoperative tumour burden and biological activity in AAdenoCa patients, CRAdenoCa patients had higher rates of sLM and mLM. Further studies are warranted to validate and identify cellular and molecular targets that increase CRAdenoCa's ability to metastasise to the liver.

The Clinical Significance of CEA, CA19-9, and CA125 in Management of Appendiceal Adenocarcinoma.

Importance: Serum tumor markers CEA, CA19-9, & CA125 have been useful in the management of gastrointestinal and gynecological cancers, however there is limited information regarding their utility in patients with appendiceal adenocarcinoma. Objective: Assessing the association of serum tumor markers (CEA, CA19-9, and CA125) with clinical outcomes, pathologic, and molecular features in patients with appendiceal adenocarcinoma. Design: This is a retrospective study with results reported in 2023. The median follow-up time was 43 months. Setting: Single tertiary care comprehensive cancer center. Participants: Under an approved Institutional Review Board protocol, the Palantir Foundry software system was used to query the MD Anderson internal patient database to identify patients with a diagnosis of appendiceal adenocarcinoma and at least one tumor marker measured at MD Anderson between 2016 and 2023. Results: A total of 1,338 patients with appendiceal adenocarcinoma were included, with a median age of 56.5 years. The majority of the patients had metastatic disease (80.7%). CEA was elevated in more than half of the patients tested (56%), while CA19-9 and CA125 were elevated in 34% and 27%, respectively. Individually, elevation of CEA, CA19-9, or CA125 were associated with worse 5-year survival; 82% vs 95%, 84% vs 92%, and 69% vs 93% elevated vs normal for CEA, CA19-9, and CA125 respectively (all p<0.0001). Quantitative evaluation of tumor markers increased prognostic ability. Patients with highly elevated (top 10th percentile) CEA, CA19-9 or CA125 had markedly worse survival with 5-year survival rates of 59%, 64%, and 57%, respectively (HR vs. normal : 9.8, 6.0, 7.6, all p<0.0001). Although metastatic tumors had higher levels of all tumor markers, when restricting survival analysis to 1080 patients with metastatic disease elevated CEA, CA19-9 or CA125 were all still associated worse survival (HR vs. normal : 3.4, 1.8, 3.9, p<0.0001 for CEA and CA125, p=0.0019 for CA19-9). Interestingly tumor grade was not associated with CEA or CA19-9 level, while CA-125 was slightly higher in high relative to low-grade tumors (18.3 vs. 15.0, p=0.0009). Multivariable analysis identified an incremental increase in the risk of death with an increase in the number of elevated tumor markers, with a 11-fold increased risk of death in patients with all three tumor markers elevated relative to those with none elevated. Mutation in KRAS and GNAS were associated with significantly higher levels of CEA and CA19-9. Conclusions: These findings demonstrate the utility of measuring CEA, CA19-9, and CA125 in the management of appendiceal adenocarcinoma. Given their prognostic value, all three biomarkers should be included in the initial workup of patients diagnosed with appendiceal adenocarcinoma.

A case report of appendiceal adenocarcinoma extending from the retroperitoneum to the psoas muscle.

INTRODUCTION: Invasive appendiceal adenocarcinoma is rare. We describe the first reported case of appendiceal adenocarcinoma invading the psoas muscle in a 27-year-old man. CASE PRESENTATION: The patient presented with lower right quadrant pain, persisting since the last two months. Computed tomography revealed a retroperitoneal mass with a central calcified focus in the right iliac fossa, with a mass effect on the adjacent iliopsoas muscle and apparent invasion of the cecal wall. CLINICAL DISCUSSION: Magnetic resonance imaging showed a retrocecal appendicular mass with central necrosis. Colonoscopy showed an extra luminal mass effect that caused bulging of the ileocecal valve. Biopsy revealed lymphoid hyperplasia of the mucosa of the terminal ileum, with no malignant changes. An elective right hemicolectomy was done along with ileotransverse anastomosis. Histopathology examination of the surgical specimen revealed a moderately differentiated adenocarcinoma (Stage IV). Hence, adjuvant chemotherapy followed by hyperthermic intraperitoneal chemotherapy was employed. CONCLUSION: Non-specific symptoms and difficulties in reaching a diagnosis pre-operatively, may contribute to underreporting of appendiceal adenocarcinomas. Besides, few therapeutic options are available due to the rarity of this tumor. Complete surgical excision and/or chemotherapy may be lifesaving.

Pathogenesis of histologic variations of appendiceal mucinous neoplasms.

BACKGROUND: In order for peritoneal metastases from a primary appendiceal mucinous neoplasm to occur, the wall of the appendix must perforate to allow mucus with tumor cells access to the peritoneal spaces. With progression the peritoneal metastases show a broad spectrum of tumor biology varying from indolent to aggressive activity. METHODS: The histopathology of peritoneal tumor masses was determined from the clinical material resected at the time of cytoreductive surgery (CRS). All groups of patients were treated by a uniform strategy that involved complete CRS and perioperative intraperitoneal chemotherapy. Overall survival was determined. RESULTS: From a database of 685 patients, four histologic subtypes were identified and long-term survival determined. Four hundred and fifty patients (66.0%) had low-grade appendiceal mucinous neoplasm (LAMN), 37 patients (5.4%) had mucinous appendiceal adenocarcinoma of intermediate subtype (MACA-Int), 159 patients (23.2%) had mucinous appendiceal adenocarcinoma (MACA), and 39 patients (5.4%) had a mucinous appendiceal adenocarcinoma with positive lymph nodes (MACA-LN). The mean survival of the four groups was 24.5, 14.8, 11.2 and 7.4 years, respectively (p < 0.0001). These four subtypes of mucinous appendiceal neoplasms were shown to have distinct survival estimates. CONCLUSIONS: The estimated survival of these four histologic subtypes in patients having a complete CRS plus HIPEC is of value to the oncologist managing these patients. A mutations and perforations hypothesis was offered in an attempt to explain the broad spectrum of mucinous appendiceal neoplasms that exist. Inclusion of MACA-Int and MACA-LN as standalone subtypes was thought to be necessary.

Cancer embryonic antigen (CEA) levels in patients with appendiceal adenocarcinoma predict response to neo-adjuvant chemotherapy and overall survival.

BACKGROUND AND OBJECTIVES: Serum tumor markers are widely used for diagnosis, prognosis, treatment response, and surveillance. Our study evaluated cancer embryonic antigen (CEA) in patients with appendiceal adenocarcinoma. METHODS: The National Cancer Database was reviewed (2004-2011) for patients with surgical treatment for appendiceal adenocarcinoma. Patients were stratified into two groups: normal and elevated CEA. Multivariable adjusted Cox proportional hazards regression analyses were used to determine the independent effect of CEA on survival. RESULTS: Our study consisted of 2867 patients, 54.0% having elevated CEA. Patients with elevated CEA were more likely to have Stage IV disease, be female, and African American; all p < 0.001. Three-year overall survival (OS) was significantly higher with normal CEA (75.5% vs. 62.8%, p < 0.001). On multivariable analysis, elevated CEA was associated with worse survival (hazard ratio 1.49, 95% confidence interval 1.23-1.80). Patients with elevated CEA had improved 3-year OS with neo-adjuvant compared to adjuvant chemotherapy (p = 0.004), while those with normal CEA showed no difference. CONCLUSIONS: In patients with surgically treated appendiceal adenocarcinoma, preoperative elevation in CEA independently predicts decreased 3-year survival and correlates with improved OS with neo-adjuvant therapy. CEA levels should be considered in clinical decision-making regarding neo-adjuvant therapy in patients with appendiceal adenocarcinoma.

Clinicopathological spectrums and prognosis of primary appendiceal adenocarcinoma, goblet cell adenocarcinoma, and low-grade appendiceal mucinous neoplasms.

Primary appendiceal adenocarcinoma (APCA), goblet cell adenocarcinoma (GCA), and low/high-grade appendiceal mucinous neoplasms (LAMN/HAMN) are distinct entities with overlapping clinical presentation and histomorphology, leading to diagnostic challenges. We retrospectively reviewed our archived cases between 2010 and 2018 for diagnosis reappraisal and comparative analysis using updated terminology and modern parameters. A total of 87 cases (22 APCA, 40 GCA, and 25 LAMN pT≥3) were included. The entire cohort had 49 women and 38 men with a median age of 59.9 (range 26-88) years. There were no statistically significant differences in age and sex among the three groups. Clinically, patients with GCA were more likely to present with acute appendicitis (65%) and more likely to have appendectomy as initial surgery (68%). Both APCA and GCA were more likely to involve the proximal appendix while LAMN was more likely to involve the distal appendix (p<0.05). All APCAs were associated with mucosal precursor lesions, most commonly tubular, tubulovillous, or villous adenoma, flat LAMN/HAMN-pTis mucinous epithelium, or mixed, which correlated with distinct histomorphology, tumour differentiation, and stage. Although polypoid precursor lesions were rare in GCA, a significant proportion of GCA showed crypt atypia associated with neoplastic cells. Immunohistochemically, APCA had more frequent ß-catenin nuclear positivity and loss of SATB2 expression (p<0.05). KRAS mutation was more common in APCA than in GCA (8/11 vs 1/7, p<0.01). We further validated the three-tiered grading system (G1, G2, G3) in GCA, which correlated well with tumour stage and patient survival. APCA had worse progression-free and disease-specific survivals than GCA and LAMN (pT≥3) with the latter being relatively indolent even when perforated with peritoneal spread. Our study is the first comprehensive comparison between all three appendiceal neoplasms. We also describe a spectrum of previously under-recognised crypt atypia in GCA, which should trigger a diligent search for GCA if present.

Association of Systemic Chemotherapy Approaches With Outcomes in Appendiceal Peritoneal Metastases.

INTRODUCTION: Many patients undergoing cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) for appendiceal adenocarcinoma peritoneal metastases (APM) undergo preoperative systemic chemotherapy. The primary aim of this study is to evaluate differences in oncologic outcomes among two popular chemotherapy approaches in patients with APM undergoing CRS-HIPEC. METHODS: We performed a multicenter retrospective review of patients who underwent CRS-HIPEC for APM due to high or intermediate grade disease between 2013 and 2019. Patients in the total neoadjuvant therapy group (TNT) received 12 cycles of preoperative chemotherapy. Patients in the "sandwich" chemotherapy group (SAND) received six cycles of preoperative chemotherapy with a maximum of six cycles of postoperative chemotherapy. The primary outcomes were overall survival (OS) and recurrence-free survival (RFS) defined as months from date of first treatment or surgery, respectively. RESULTS: A total of 39 patients were included in this analysis, with 25 (64%) patients in the TNT group and 14 (36%) patients in the SAND group. Patients in the TNT group had a median OS of 62 mo, while median OS in the SAND group was 45 mo (P = 0.01). In addition, patients in the TNT group had significantly longer RFS compared to the SAND group (35 versus 12 mo, P = 0.03). In a multivariable analysis, TNT approach was independently associated with improved OS and RFS. CONCLUSIONS: In this multicenter retrospective analysis, a TNT approach was associated with improved overall and recurrence-free survival compared to a sandwiched chemotherapy approach in patients undergoing CRS-HIPEC for high or intermediate grade APM.

Do Lymph Node Metastases Matter in Appendiceal Cancer with Peritoneal Carcinomatosis? A US HIPEC Collaborative Study.

BACKGROUND: Whether formal regional lymph node (LN) evaluation is necessary for patients with appendiceal adenocarcinoma (AA) who have peritoneal metastases is unclear. The aim of this study was to evaluate the prognostic value of LN metastases on survival in patients treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC). METHODS: A retrospective analysis of the US HIPEC collaborative, a multi-institutional consortium comprising 12 high-volume centers, was performed to identify patients with AA who underwent CRS-HIPEC with adequate LN sampling (≥ 12 LNs). RESULTS: Two hundred-fifty patients with AA who underwent CRS-HIPEC were included. Outcomes were compared between LN - and LN + disease. Baseline patient characteristics between groups were similar, with most patients undergoing complete cytoreduction (0/1: 86.0% vs. 76.8%, p = 0.08), respectively. More adverse tumor factors were found in patients with LN + disease, including poor differentiation, signet ring cells, and lymphovascular invasion. Multivariate analysis of overall survival (OS) found LN + disease was independently associated with worse OS (HR: 2.82 95%CI: 1.25-6.34, p = 0.01), even after correction for receipt of systemic therapy. On Kaplan-Meier analysis, median OS was lower in patients with LN + disease (25.9 months vs. 91.4 months, p < 0.01). LN + disease remained associated with poor OS following propensity score matching (HR: 4.98 95%CI: 1.72-14.40, p < 0.01) and in patients with PCI ≥ 20 (HR: 3.68 95%CI: 1.54-8.80, p < 0.01). CONCLUSIONS: In this large multi-institutional study of patients with AA undergoing CRS-HIPEC, LN status remained associated with worse OS even in the setting of advanced peritoneal carcinomatosis. Formal LN evaluation should be performed for most patients with AA undergoing CRS-HIPEC.

A patient with primary adenocarcinoma of the appendix metastasizing to the ovary.

OBJECTIVE: The aim of this work is to draw attention to the difficulty of differential dia-gnosis of rare adenocarcinoma of the appendix and the histological diversity of ovarian tumors. CASE REPORT: We present a case of a 62-year-old patient sent by an attending gynecologist for the finding of an asymptomatic adnextumor diagnosed during a routine preventive examination. Based on preoperative examinations, a malignant ovarian tumor was suspected. Standard surgery was performed including hysterectomy with bilateral adnexectomy, total omentectomy, appendectomy, pelvic and paraaortic lymphadenectomy. Definitive histopathological analysis revealed a secondary ovarian tumor, with the adenocarcinoma of the appendix appearing to be the primary site. CONCLUSION: Up to 25% of all ovarian tumors are secondary metastatic tumors. Appendix neoplasia should be considered in the differential diagnosis of right-sided adnextumors. Due to their localization, they can only mimic an ovarian tumor during imaging examinations, or they can be the primary origin of an already metastatic ovary, as in our case.

Organoids From Mucinous Appendiceal Adenocarcinomas as High-Fidelity Models for Individual Therapy.

Background: Mucinous appendiceal adenocarcinoma (MAA) is a rare, heterogeneous disease. Patients with unrespectable mucinous appendiceal adenocarcinoma presenting with peritoneal spread are treated by intraperitoneal chemotherapy, hyperthermic intraperitoneal chemotherapy, systemic chemotherapy, or targeted therapy. However, there are no guidelines for efficacious drugs against mucinous appendiceal adenocarcinoma. Therefore, relevant high-fidelity models should be investigated to identify effective drugs for individual therapy. Methods: Surgical tumor specimens were obtained from a mucinous appendiceal adenocarcinoma patient. The tissue was digested and organoid culture was established. H&E and immunohistochemistry staining as well as DNA sequencing was performed on tissue and organoid. The pathological characteristics and gene mutations of the organoid were compared to those of the original tumor. Drug sensitivity tests were performed on organoid and the patient clinical responds to chemotherapy and targeted therapy was compared. Results: Organoids were successfully established and stably passaged. Pathological characteristics of organoids including H&E staining and expression of protein markers (CK20, CDX-2, STAB2, CD7, PAX8) were consistent to those of the original tumor. Moreover, the organoids carried the same gene mutations as the primary tumor. Sensitivity of the organoids to chemotherapeutic drugs and tyrosine kinase inhibitors included: 5-FU (IC50 43.95 µM), Oxaliplatin (IC50 23.49 µM), SN38 (IC50 1.02 µM), Apatinib (IC50 0.10 µM), Dasatinib (IC50 2.27 µM), Docetaxel (IC50 5.26 µM), Regorafenib (IC50 18.90 µM), and Everolimus (IC50 9.20 µM). The sensitivities of organoid to these drugs were comparable to those of the patient's clinical responses. Conclusion: The mucinous appendiceal adenocarcinoma organoid model which retained the characteristics of the primary tumor was successfully established. Combined organoid-based drug screening and high throughput sequencing provided a promising way for mucinous appendiceal adenocarcinoma treatment.

The association between appendicitis severity and patient age with appendiceal neoplasm histology-a population-based study.

PURPOSE: Recent studies have reported alarming appendiceal tumor rates associated with complicated acute appendicitis, especially in patients presenting with a periappendicular abscess. However, the data on histology of appendiceal tumors among acute appendicitis patients is limited, especially in patient cohorts differentiating between uncomplicated and complicated acute appendicitis. We have previously reported the association of increased appendiceal tumor prevalence with complicated acute appendicitis in this population-based study. The objective of this secondary analysis was to evaluate the association of both appendicitis severity and patient age with appendiceal tumor histology. METHODS: This nationwide population-based registry study (The Finnish Cancer Registry) was conducted from 2007 to 2013. All appendiceal tumors (n = 840) and available medical reports (n = 504) of these patients at eight study hospitals were previously evaluated, identifying altogether 250 patients with both acute appendicitis and appendiceal tumor. RESULTS: The severity of acute appendicitis was significantly associated with more malignant tumor histology. The risk of adenocarcinoma or pseudomyxoma was significantly higher among patients with periappendicular abscess (OR 15.05, CI 95% 6.98-32.49, p < 0.001) and patients presenting with perforated acute appendicitis (OR 4.09, CI 95% 1.69-9.90, p = 0.0018) compared to patients with uncomplicated acute appendicitis. Similarly, patient age over 40 years was significantly associated with the risk of adenocarcinoma and pseudomyxoma (OR 26.46, Cl 95% 7.95-88.09, p < 0.001). Patient sex was not associated with a more malignant appendiceal tumor histology (p = 0.67). CONCLUSION: More malignant appendiceal tumor histology of adenocarcinoma or pseudomyxoma was significantly associated with patient age over 40 years and complicated acute appendicitis, especially periappendicular abscess.

Progression of perforated cystadenoma of the appendix to pseudomyxoma peritonei over 18 years. A case report.

INTRODUCTION AND IMPORTANCE: In the past, mucinous appendiceal neoplasms (MAN) greater than 2 cm in diameter were treated by a right colon resection. New data shows that treatment options are to be determined by the histopathologic grade of the appendiceal tumor and the condition of the wall of the appendix (intact vs. breached). CASE PRESENTATION: A 39-year-old woman had an incidental diagnosis of a low-grade appendiceal mucinous neoplasm (LAMN) at the time of a hysterectomy. The appendiceal tumor had small quantities of mucus surrounding an enlarged appendix. No tumor cells were seen in the mucus by histologic study. The patient was placed in follow-up. Eighteen years later she required treatment for advanced pseudomyxoma peritonei. CLINICAL DISCUSSION: When 5 different histopathologic types of MAN are considered with an intact vs. perforated wall of the appendix, four different treatment options develop. With LAMN and well or moderately differentiated mucinous appendiceal adenocarcinoma (MACA), the patient does not require operative intervention if the wall of the appendix is intact. If mucus or mucus plus tumor cells are identified outside the appendix an intervention is indicated. In patients, as the one presented, in whom only small amounts of mucus are outside the appendix, surveillance may be recommended. CONCLUSIONS: In patients with a diagnosed low-grade MAN, dissemination to regional lymph nodes is rare. Dissemination to the peritoneal space places the patient at risk to develop pseudomyxoma peritonei. As this case report illustrates, if surveillance is recommended, long-term follow-up is required.

The Role of Adjuvant Chemotherapy Following Right Hemicolectomy for Non-metastatic Mucinous and Nonmucinous Appendiceal Adenocarcinoma.

BACKGROUND: Appendiceal adenocarcinoma (AA) represents a heterogenous group of neoplasms with distinct histologic features. The role and efficacy of adjuvant chemotherapy (AC) in non-metastatic disease remain controversial. The aim of this study was to ascertain the role of AC in non-metastatic AA in a national cohort of patients. METHODS: The National Cancer Database (NCDB) was queried to identify patients diagnosed with stage I-III mucinous and nonmucinous AA who underwent right hemicolectomy between 2006 and 2016. Kaplan-Meier and Cox regression analyses were used to evaluate the impact of AC on overall survival (OS) stratified by each pathologic stage. RESULTS: A total of 1433 mucinous and 1954 nonmucinous AA were identified; 578 (40%) and 722 (40%) received AC respectively. In both AC groups, there was a higher proportion of T4 disease, lymph node metastasis, pathologic stage III, and poorly/undifferentiated grade (all P<0.05). On unadjusted analysis, there was no significant association between AC and OS for stage I-III mucinous AA. For nonmucinous AA, AC significantly improved OS only for stage II and III disease. On adjusted analysis, AC was independently associated with an improved OS for stage III nonmucinous AA (HR: 0.61, 95%CI 0.45-0.84, P=0.002), while for mucinous AA, AC was associated with worse outcomes for stage I/II disease (HR: 1.4, 95%CI 1.02-1.91, P=0.038) and had no significant association with OS for stage III disease. CONCLUSION: This current analysis of a national cohort of patients suggests a beneficial role for AC in stage III nonmucinous AA and demonstrates no identifiable benefit for stage I-III mucinous AA.