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Background/Aim: The present study utilized the three-dimensional histoculture drug response assay (HDRA) to determine the efficacy of recombinant methioninase (rMETase) on tumor tissue resected from patients with late-stage cancer, as a functional biomarker of sensitivity to methionine restriction therapy. Patients and Methods: Resected peritoneal-metastatic cancer, including colorectal cancer, pancreatic cancer, ovarian cancer, and pseudomyxoma were placed on Gelform in RPMI 1640 medium for seven days and treated with rMETase from 2.5 U/ml to 20 U/ml. Cell viability was determined using the MTT assay. A total of 48 patients with late-stage cancer underwent testing for rMETase responsiveness using the HDRA. Results: Colorectal cancer and pseudomyxoma had the highest sensitivity to rMETase. Pancreatic and ovarian cancer also responded to rMETase, but to a lesser degree. Conclusion: Patients with tumors with at least 40% sensitivity to rMETase in the HDRA are being considered as candidates for methionine restriction therapy, which includes the use of rMETase in combination with a low-methionine diet. [ABSTRACT FROM AUTHOR]

Simple Summary: The 5th edition of the World Health Organization (WHO) classification system for digestive system tumors identifies four types of appendiceal tumors (ATs): serrated lesions and polyps, mucinous neoplasms, adenocarcinomas, and neuroendocrine neoplasms (NENs). Diagnosing ATs poses significant challenges in the medical field due to their uncommon nature and the scarcity of data from large-scale, randomized controlled studies. These tumors are often discovered in tissue samples from appendectomies performed for acute appendicitis. Despite advancements in the treatment of abdominal cancers over recent years, managing and treating ATs effectively remains difficult. This review aims to cover the diagnostic approaches, molecular diagnostics, staging, treatment differences, and prognostic indicators related to ATs. The 5th edition of the World Health Organization (WHO) classification of tumors of the digestive system distinguishes four categories of appendiceal tumors (ATs): serrated lesions and polyps, mucinous neoplasms, adenocarcinomas, and neuroendocrine neoplasms (NENs). The differential diagnosis of ATs can be challenging in medical practice, due to their rarity and lack of data from randomized controlled trials on a large, diverse group of patients. ATs are usually noted in specimens obtained during appendectomies due to clinical acute appendicitis. In the European population, most ATs (65%) occur over the age of 50 and among women (56.8%). According to histological type, 54.6% are neuroendocrine tumors (NETs); 26.8% cystic, mucinous, and serous neoplasms; and 18.6% adenocarcinoma not otherwise specified (NOS). On pathologic analysis, most AT findings are benign lesions or small NENs that do not require further therapeutic measures. The presence of appendiceal mucinous neoplasm (AMN) can lead to pseudomyxoma peritonei (PMP). While the multimodal treatment for abdominal malignancies has evolved over the past several decades, the clinical workup and treatment of ATs remain a challenge. Therefore, this review aims to describe the diagnostic possibilities, molecular-based diagnosis, staging, differences in the treatment process, and prognostic factors associated with ATs. [ABSTRACT FROM AUTHOR]

Background: The presence of lymph node (LN) metastasis is a known negative prognostic factor in appendix cancer (AC) patients. However, currently the minimum number of LNs required to adequately determine LN negativity is extrapolated from colorectal studies and data specific to AC is lacking. We aimed to define the lowest number of LNs required to adequately stage AC and assess its impact on oncologic outcomes. Methods: Patients with stage II–III AC from the National Cancer Database (NCDB 2004–2019) undergoing surgical resection with complete information about LN examination were included. Multivariable logistic regression assessed the odds of LN positive (LNP) disease for different numbers of LNs examined. Multivariable Cox regressions were performed by LN status subgroups, adjusted by prognostic factors, including grade, histologic subtype, surgical approach, and documented adjuvant systemic chemotherapy. Results: Overall, 3,602 patients were included, from which 1,026 (28.5%) were LNP. Harvesting ten LNs was the minimum number required without decreased odds of LNP compared with the reference category (≥ 20 LNs). Total LNs examined were < 10 in 466 (12.9%) patients. Median follow-up from diagnosis was 75.4 months. Failing to evaluate at least ten LNs was an independent negative prognostic factor for overall survival (adjusted hazard ratio 1.39, p < 0.01). Conclusions: In appendix adenocarcinoma, examining a minimum of ten LNs was necessary to minimize the risk of missing LNP disease and was associated with improved overall survival rates. To mitigate the risk of misclassification, an adequate number of regional LNs must be assessed to determine LN status. [ABSTRACT FROM AUTHOR]

In patients with disseminated appendiceal cancer (dAC) who underwent cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC), characterizing and predicting those who will develop early recurrence could provide a framework for personalizing follow-up. This study aims to: (1) characterize patients with dAC that are at risk for recurrence within 2 y following of CRS ± HIPEC (early recurrence; ER), (2) utilize automated machine learning (AutoML) to predict at-risk patients, and (3) identifying factors that are influential for prediction. A 12-institution cohort of patients with dAC treated with CRS ± HIPEC between 2000 and 2017 was used to train predictive models using H2O.ai's AutoML. Patients with early recurrence (ER) were compared to those who did not have recurrence or presented with recurrence after 2 y (control; C). However, 75% of the data was used for training and 25% for validation, and models were 5-fold cross-validated. A total of 949 patients were included, with 337 ER patients (35.5%). Patients with ER had higher markers of inflammation, worse disease burden with poor response, and received greater intraoperative fluids/blood products. The highest performing AutoML model was a Stacked Ensemble (area under the curve = 0.78, area under the curve precision recall = 0.66, positive predictive value = 85%, and negative predictive value = 63%). Prediction was influenced by blood markers, operative course, and factors associated with worse disease burden. In this multi-institutional cohort of dAC patients that underwent CRS ± HIPEC, AutoML performed well in predicting patients with ER. Variables suggestive of poor tumor biology were the most influential for prediction. Our work provides a framework for identifying patients with ER that might benefit from shorter interval surveillance early after surgery. [ABSTRACT FROM AUTHOR]

Background: Neoplastic lesions of the vermiform appendix are still considered to be rare, some studies suggest that appendix cancer may be on the rise, with an estimated incidence of 0.08–0.1% of all appendiceal specimens. The lifetime incidence of malignant appendiceal tumors ranges from 0.2 to 0.5%. Patients and Methods: Our study is applied at the Department of General Surgery at tertiary training and research hospital; 14 patients who had appendectomy or right hemicolectomy between December 2015 and April 2020 were evaluated. Results: The mean age of the patients was 52.3 ± 15.1 (range, 26–79) years. Gender of the patients were: five (35.7%) men and nine (64.3%) women. The clinical diagnosis was appendicitis without suspected findings in 11 (78.6%), appendicitis with suspected findings (appendiceal mass, etc.) in three (21.4%) of the patients, and there is no patient with asymptomatic or other rare findings. Surgeries applied for the patients were: nine (64.3%) underwent open appendectomy, four (28.6%) underwent laparoscopic appendectomy, and one (7.1%) underwent open right hemicolectomy. Histopathologic results were as follows: five (35.7%) neuroendocrine neoplasm, eight (57.1%), noninvasive mucinous neoplasm, and one (7.1%) adenocarcinoma. Conclusion: While diagnosis and management of appendiceal pathology, surgeons should be familiar with suspected findings of appendiceal tumors and discuss them with patients to the possibility of histopathologic results. [ABSTRACT FROM AUTHOR]

This article, published in the Journal of Gastrointestinal Surgery, compares the effectiveness of doublet and triplet systemic chemotherapy regimens for patients with high-grade appendiceal adenocarcinoma and peritoneal metastases. The study analyzed data from patients at a single center from 2013-2020 who received either an oxaliplatin or irinotecan-based regimen as their first-line systemic treatment. The results showed that there was no significant difference in overall survival, recurrence-free survival, or progression-free survival between the doublet and triplet groups. The authors suggest that larger, randomized studies are needed to determine the optimal chemotherapy regimen for this patient population. [Extracted from the article]

In this case report, a man presenting with a rare symptom of appendix cancer is dis- cussed. Hematuria, which was the key diagnostic feature in this patient, has never been re- ported as a presenting feature of appendix cancer which may explain why this patient has been experiencing this symptom for months and yet have not get the proper di- agnosis. As we discussed in the case report, although appendiceal cancer is a potentially life-threatening issue, it is frequently missed in patients. Therefore, we believe report- ing this key symptom in this journal would help physicians to make a more accurate diagnosis in this matter.

Appendiceal cancer is rare and encompasses a diverse group of tumours ranging from low-grade appendiceal mucinous neoplasms to high-grade adenocarcinomas. Appendiceal cancers often spread to the peritoneal cavity causing extensive mucinous dissemination and peritoneal metastases. Prognosis varies with histological subtype. Cytoreductive surgery and heated intraperitoneal chemotherapy is well-established as the most effective treatment achieving long-term survival in some patients. Chemotherapy regimens used to treat appendiceal cancer are extrapolated from the colorectal cancer setting, but disease biology differs and outcomes are inferior. The role of chemotherapy in the treatment of appendiceal cancer remains poorly defined. There is an urgent need to develop novel tailored treatment strategies in the perioperative and unresectable setting. This review aims to evaluate the literature for patients who received intraperitoneal and systemic chemotherapy for appendiceal cancers. [ABSTRACT FROM AUTHOR]

Appendiceal cancer is rare and is often diagnosed incidentally in patients undergoing appendectomy for acute appendicitis. However, patients with appendiceal cancer are at increased risk of synchronous malignancy. In this case report, we present a 58-year-old man initially diagnosed with acute appendicitis after presenting to the emergency department with abdominal pain. He had an appendectomy and was discharged the following day. Unexpectedly, the postoperative histopathologic examination showed a primary adenocarcinoma in the appendix. A computed tomography scan showed rectal wall thickening and the patient was referred to colonoscopy where an experienced endoscopist found a rectal tumor during the digital rectal examination prior to the colonoscopy. The tumor was initially missed by the newly qualified doctor who examined the patient during his first admittance to hospital. The patient’s two primary cancers were treated with a laparoscopic right hemicolectomy for the appendiceal cancer and a low anterior resection for the rectal cancer. This case supports the importance of a full colorectal workup in patients with appendiceal cancer. It also emphasizes the value of a thorough digital rectal examination and the need for improved focus on teaching and practice of the procedure.

Abstract Comparing genetic mutations of first‐degree relatives with appendiceal pseudomyxoma peritonei may explain clinical outcomes and disease pathogenesis. Molecular profiling of mucinous tumors may identify improved treatments to traditional chemotherapy.

Appendiceal cancer is rare and is often diagnosed incidentally in patients undergoing appendectomy for acute appendicitis. However, patients with appendiceal cancer are at increased risk of synchronous malignancy. In this case report, we present a 58-year-old man initially diagnosed with acute appendicitis after presenting to the emergency department with abdominal pain. He had an appendectomy and was discharged the following day. Unexpectedly, the postoperative histopathologic examination showed a primary adenocarcinoma in the appendix. A computed tomography scan showed rectal wall thickening and the patient was referred to colonoscopy where an experienced endoscopist found a rectal tumor during the digital rectal examination prior to the colonoscopy. The tumor was initially missed by the newly qualified doctor who examined the patient during his first admittance to hospital. The patient’s two primary cancers were treated with a laparoscopic right hemicolectomy for the appendiceal cancer and a low anterior resection for the rectal cancer. This case supports the importance of a full colorectal workup in patients with appendiceal cancer. It also emphasizes the value of a thorough digital rectal examination and the need for improved focus on teaching and practice of the procedure.

The peritoneum is a common site for the dissemination of digestive malignancies, particularly gastric, colorectal, appendix, or pancreatic cancer. Other tumors such as cholangiocarcinomas, digestive neuroendocrine tumors, or gastrointestinal stromal tumors (GIST) may also associate with peritoneal surface metastases (PSM). Peritoneal dissemination is proven to worsen the prognosis of these patients. Cytoreductive surgery (CRS), along with systemic chemotherapy, have been shown to constitute a survival benefit in selected patients with PSM. Furthermore, the association of CRS with hyperthermic intraperitoneal chemotherapy (HIPEC) seems to significantly improve the prognosis of patients with certain types of digestive malignancies associated with PSM. However, the benefit of CRS with HIPEC is still controversial, especially due to the significant morbidity associated with this procedure. According to the results of the PRODIGE 7 trial, CRS for PSM from colorectal cancer (CRC) achieved overall survival (OS) rates higher than 40 months, but the addition of oxaliplatin-based HIPEC failed to improve the long-term outcomes. Furthermore, the PROPHYLOCHIP and COLOPEC trials failed to demonstrate the effectiveness of oxaliplatin-based HIPEC for preventing peritoneal metastases development in high-risk patients operated for CRC. In this review, we discuss the limitations of these studies and the reasons why these results are not sufficient to refute this technique, until future well-designed trials evaluate the impact of different HIPEC regimens. In contrast, in pseudomyxoma peritonei, CRS plus HIPEC represents the gold standard therapy, which is able to achieve 10-year OS rates ranging between 70 and 80%. For patients with PSM from gastric carcinoma, CRS plus HIPEC achieved median OS rates higher than 40 months after complete cytoreduction in patients with a peritoneal cancer index (PCI) ≤6. However, the data have not yet been validated in randomized clinical trials. In this review, we discuss the controversies regarding the most efficient drugs that should be used for HIPEC and the duration of the procedure. We also discuss the current evidence and controversies related to the benefit of CRS (and HIPEC) in patients with PSM from other digestive malignancies. Although it is a palliative treatment, pressurized intraperitoneal aerosolized chemotherapy (PIPAC) significantly increases OS in patients with unresectable PSM from gastric cancer and represents a promising approach for patients with PSM from other digestive cancers.

Appendiceal cancer is rare and is often diagnosed incidentally in patients undergoing appendectomy for acute appendicitis. However, patients with appendiceal cancer are at increased risk of synchronous malignancy. In this case report, we present a 58-year-old man initially diagnosed with acute appendicitis after presenting to the emergency department with abdominal pain. He had an appendectomy and was discharged the following day. Unexpectedly, the postoperative histopathologic examination showed a primary adenocarcinoma in the appendix. A computed tomography scan showed rectal wall thickening and the patient was referred to colonoscopy where an experienced endoscopist found a rectal tumor during the digital rectal examination prior to the colonoscopy. The tumor was initially missed by the newly qualified doctor who examined the patient during his first admittance to hospital. The patient’s two primary cancers were treated with a laparoscopic right hemicolectomy for the appendiceal cancer and a low anterior resection for the rectal cancer. This case supports the importance of a full colorectal workup in patients with appendiceal cancer. It also emphasizes the value of a thorough digital rectal examination and the need for improved focus on teaching and practice of the procedure.

Low-grade appendiceal mucinous neoplasms (LAMN) constitute a rare subset of epithelial tumors and represent the second most common form of appendiceal cancer. LAMN typically presents as acute appendicitis, with definitive diagnosis often occurring incidentally during appendectomy surgery. While contrast-enhanced computed tomography (CECT) is the imaging of choice, misdiagnoses are common, highlighting the need for additional diagnostic modalities that are often underutilized. There is ongoing debate about treatment recommendations which typically involve a simple appendectomy, but controversy persists regarding the intraoperative necessity of a cecectomy, ileocecectomy, or formal right hemicolectomy. Here, we present a case featuring a 72-year-old African American female referred to our surgery clinic presenting solely with bloating and constipation rather than classical acute appendicitis, discrepancies between CT and MR imaging, and an unusual intraoperative finding of a posteriorly positioned mucocele adhered to the cecum, necessitating right hemicolectomy., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Hillock et al.)

To determine the effect of signet ring cell (SRC) histopathology in appendix cancer with peritoneal dissemination on overall survival (OS) in patients undergoing cytoreductive surgery (CRS) and heated intraperitoneal chemotherapy (HIPEC). Retrospective cohort study from a prospectively maintained database of patients that underwent CRS/HIPEC for appendix cancer from April 1999 to December 2019. 255 patients were identified. 174 had high-grade disease with no SRC component, 35 with a low count of SRC and 46 with a high count of SRC. Median OS without SRC was 93.8 months vs 58.2 months for low count SRC and 23.7 months for high count SRC (P < 0.001). 5-year OS was 60% for patients with no SRC, 35.5% and 10% in those with low count and high count SRC respectively. On multivariate analysis, presence of SRC and complete cytoreduction score were identified as independent factors that affect OS. The presence of SRC in appendix cancer with peritoneal dissemination is associated with worse OS when compared to an absence of SRC in patients undergoing CRS/HIPEC. [ABSTRACT FROM AUTHOR]

Comparing genetic mutations of first‐degree relatives with appendiceal pseudomyxoma peritonei may explain clinical outcomes and disease pathogenesis. Molecular profiling of mucinous tumors may identify improved treatments to traditional chemotherapy. [ABSTRACT FROM AUTHOR]

Background/aim: The present study utilized the three-dimensional histoculture drug response assay (HDRA) to determine the efficacy of recombinant methioninase (rMETase) on tumor tissue resected from patients with late-stage cancer, as a functional biomarker of sensitivity to methionine restriction therapy., Patients and Methods: Resected peritoneal-metastatic cancer, including colorectal cancer, pancreatic cancer, ovarian cancer, and pseudomyxoma were placed on Gelform in RPMI 1640 medium for seven days and treated with rMETase from 2.5 U/ml to 20 U/ml. Cell viability was determined using the MTT assay. A total of 48 patients with late-stage cancer underwent testing for rMETase responsiveness using the HDRA., Results: Colorectal cancer and pseudomyxoma had the highest sensitivity to rMETase. Pancreatic and ovarian cancer also responded to rMETase, but to a lesser degree., Conclusion: Patients with tumors with at least 40% sensitivity to rMETase in the HDRA are being considered as candidates for methionine restriction therapy, which includes the use of rMETase in combination with a low-methionine diet., Competing Interests: The Authors declare no competing interests regarding this work., (Copyright 2024, International Institute of Anticancer Research.)

Introduction: Appendiceal neoplasia is rare, making up about 0.5% of gastrointestinal tumors, with an incidence of 6 cases per million annually. It often goes unnoticed and is accidentally identified during appendectomies due to heterogeneous origin and nonspecific symptomatology. Case Report: A 62-year-old male patient presented with pain in the right hypochondrium and right lumbar regions, increased postprandially, and rectal bleeding with an insidious onset 2 months prior. The patient has a history of Los Angeles Grade A reflux esophagitis, gastroesophageal reflux disease, hiatal hernia, erosive acute duodenitis, hepatic steatosis, and is overweight. An abdominal ultrasound and transient elastography were performed with difficulty because of the adipose tissue, only revealing the preexistent hepatic steatosis, and a colonoscopy was recommended to further investigate. On colonoscopy, multiple colon polyps were found, and an endoscopic polypectomy was performed. Moreover, an appendix tumor was discovered, biopsies were taken, and a CT scan was ordered for staging. Circumferential thickening of the cecum and ascending colon walls and two hepatic secondary lesions were confirmed, measuring 40mm and 58mm respectively, and, while multiple nonspecific lung nodules, calcified lung nodules and a 25mmwide femoral neck lesion were also found, it is still uncertain whether they are related to the primary tumor. Laboratory findings showed elevated inflammatory markers, slightly elevated carcinoembryonic antigen levels (9.04 ng/ml), while the CA19-9 levels were not detectable. Discussions : Due to its particular nature, this case raises several imposing questions. How can we prevent further cases of appendix cancer from reaching such lengths? What type of treatment should you opt for, given its heterogenous and multiple origins? Appendectomy and chemotherapy may be performed in cases of localized tumors without metastases. In our patient's case, depending on histopathological examination, treatment may vary including cytoreductive surgery and hyperthermic intraperitoneal chemoperfusion in the case of mucinous neoplasms. Adenocarcinomas and goblet-cell adenocarcinomas often require right hemicolectomy. Small neuroendocrine tumors are managed with appendectomy, but right hemicolectomy is advised, if there's a high risk of lymphatic spread. Conclusions: This case exemplifies the importance of comprehensive evaluation in patients with atypical gastrointestinal symptoms, since they may be the main manifestations of an underlying malignant condition. A thorough personalized treatment strategy is imperative to optimize the outcome due to the rarity of this neoplasia. Also, the advanced staging of this cancer is an example of screening programs failure and underlines the importance of educating patients to seek medical advice as early as possible. [ABSTRACT FROM AUTHOR]

Adenocarcinoma ex-goblet cell carcinoid is a very rare and histologically unique appendiceal malignancy with dual glandular and neuroendocrine differentiation. There is a high incidence of this tumor among middle-aged women with metastasis to the gynecologic tract with the mode of metastasis following peritoneal spread rather than hematogenous distribution. Adenocarcinoma ex-goblet cell carcinoid can spread to any peritoneal site including ovaries or omentum. We report a 37-year-old healthy woman who initially presented with right lower quadrant abdominal pain and pseudomyxoma peritonei. Histopathology of the appendectomy specimen revealed an adenocarcinoma ex-goblet cell carcinoid, signet ring cell type. Follow-up right hemicolectomy, omentectomy, bilateral salpingo-oophorectomy, and regional peritoneal resections revealed metastatic involvement by adenocarcinoma ex-goblet cell carcinoid, signet ring cell type. In this report, we describe a case of appendiceal adenocarcinoma ex goblet cell carcinoid with metastases to Meckel's diverticulum and areas of pelvic endometriosis, which have not been previously reported. [ABSTRACT FROM AUTHOR]

Background: Appendix adenocarcinomas (AAs) are rare tumours that often present late, with a propensity for peritoneal metastases (PMs). This study aimed to evaluate outcomes of AA patients undergoing cytoreductive surgery (CRS) with curative intent and determine the role of systemic chemotherapy., Materials and Methods: Data were collected from a prospective database and classified according to World Health Organization (WHO) 2019 classification. Tumour clearance from CRS was described using a completeness of cytoreduction (CC) score ranging from 0 [no residual disease (RD)] to 3 (>2.5 cm RD). Patients with CC0-2 CRS received hyperthermic intraperitoneal chemotherapy (HIPEC). Systemic chemotherapy was categorised as 'prior' (>6 months before), 'neoadjuvant' (<6 months before), 'adjuvant' (<6 months after CC0-1 CRS) or 'palliative' (after CC2-3 CRS). Analyses used Kaplan-Meier and Cox regression methods., Results: Between January 2005 and August 2021, 216 AA patients were identified for inclusion. Median age was 59 years (21-81 years). CRS/HIPEC was carried out in 182 (84%) patients, of whom 164/182 (76%) had mitomycin C HIPEC. CC0-1 was achieved in 172 (80%) patients. Systemic chemotherapy was given to 97 (45%) patients from the whole cohort and to 37/46 (80%) patients with positive nodes. Median overall survival (OS) was 122 months (95% confidence interval 61-182 months). After multivariate analysis, patients with acellular and lower-grade PM had similar OS to those with localised (M0) disease (P = 0.59 and P = 0.19). For patients with positive nodes, systemic chemotherapy was associated with reduced risk of death compared to no chemotherapy (P < 0.0019)., Conclusion: This study identifies AA patients with positive lymph nodes derive the most benefit from systemic chemotherapy. We confirm the prognostic importance of stage and peritoneal grade, with excellent outcomes in patients with acellular mucin and lower-grade PM., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

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 10 th 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.

Appendectomy is one of the most common surgeries performed in the emergency department The preoperative diagnosis of appendix cancer is rarely performed and only obtained after the specimen has passed through the lens of the pathologist. Treatment will depend on the tumor type, size and involvement of other structures, and may range from simple appendectomy to right hemicolectomy. Methodology: A retrospective case series using database of the Hospital Universitario del Caribe from 2007 to 2009 was made. Results: A total of 711 specimens were reviewed. We found three cases of appendix cancer: a woman in the fourth decade of life with a diagnosis of carcinoid tumor and two men diagnosed with adenocarcinoma, one in the fourth decade of life and another in the seventh. Conclusions: Appendix cancer is a very rare disease with a very low incidence, preoperative diagnosis is made with extreme rarity and it is finally obtained with pathologic examination. The treatment of this disease remains controversial. RESUMENLa apendiceptomía es una de las cirugías realizadas con mayor frecuencia en los servicios de urgencias. El diagnóstico preoperatorio de cáncer de apéndice rara vez se realiza y únicamente se obtiene una vez la pieza quirúrgica ha pasado por el lente del patólogo. Su tratamiento dependerá del tipo del tumor, tamaño, y compromiso de otras estructuras, y puede ir desde la simple apendiceptomía hasta la hemicolectomía derecha. Metodología: Estudio retrospectivo tipo serie de casos utilizando como fuente de información la base de datos del Hospital Universitario del Caribe entre los años 2007 a 2009. Revisión de todos los reportes de patología que incluyeran en la pieza quirúrgica el apéndice cecal. Se determinó en cuantos casos se encontró como diagnostico cáncer de apéndice. Resultados: Se examinó un total de 711 especímenes. Se encontraron tres casos de cáncer de apéndice: una mujer en la cuarta década de vida con diagnóstico de tumor carcinoide y dos hombres con diagnóstico de adenocarcinoma, uno en la cuarta y otro en la séptima década de vida. Conclusiones: El cáncer de apéndice es una patología sumamente rara y su diagnóstico prequirúrgico se realiza raramente y gracias al estudio anatomopatológico. El tratamiento de esta patología continua siendo controvertido

Invasive appendiceal adenocarcinoma is rare. We describe the first reported case of appendiceal adenocarcinoma invading the psoas muscle in a 27-year-old man. 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. 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. 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. • Appendiceal adenocarcinoma involving the psoas muscle is extremely rare, especially in younger patients of which this may be the first report. • Appendiceal adenocarcinoma can be a challenging diagnosis often only made after appendicectomy, unless there is local invasion • Surgical resection can be potentially curative and is the management of choice [ABSTRACT FROM AUTHOR]

Background: Whereas the poor prognosis of signet ring cell adenocarcinomas of the appendix is well known, the significance of mucinous histology remains unclear. The aim of this population-based study was to evaluate if mucinous histology is an independent prognostic factor in appendiceal adenocarcinomas.Methods: Patients with stage I-III adenocarcinoma of the appendix who underwent surgery between 2004 and 2012 were identified in the Surveillance, Epidemiology, and End Results database. Overall survival (OS) and cancer-specific survival (CSS) were assessed using risk-adjusted Cox proportional hazards regression models and propensity score methods.Results: Overall, 980 patients with appendix cancer were included, of which 449 (45.8 %) had a mucinous histology. In an unadjusted analysis, the 5-year OS and CSS in patients with a mucinous adenocarcinoma (MC) was 76.8 % (95 % confidence interval (95 %CI): 72.1-81.7 %) and 81.0 % (95 %CI: 76.6-85.6 %), respectively, compared with 70.0 % (95 %CI: 65.1-75.3 %) and 76.2 % (95 %CI: 71.5-81.2 %) in patients with non-mucinous adenocarcinoma (NMC) (P = 0.082 and P = 0.368). In multivariable analysis, no impact on survival was observed for OS (HR = 1.22, 95 %CI: 0.89-1.68, P = 0.208) and CSS (HR = 1.21, 95 %CI: 0.84-1.74, P = 0.296). After propensity score matching, nearly identical survival rates were observed (OS: HR = 1.03, 95 %CI: 0.71-1.49, P = 0.881 and CSS: HR = 1.05, 95 %CI: 0.70-1.59, P = 0.803).Conclusions: The present population-based, propensity score matched analysis shows that mucinous histology does not affect survival in stage I-III appendiceal adenocarcinoma patients. Therefore, the same treatment strategies can be applied for patients with NMC and MC of the appendix. [ABSTRACT FROM AUTHOR]

Abstract: Background: Cytoreductive surgery (CRS)/hyperthermic intraperitoneal chemotherapy (HIPEC) is the procedure of choice in patients with peritoneal dissemination from appendiceal cancer. Although recurrence rates are 26%–44% after first CRS/HIPEC, the role of repeated CRS/HIPEC has not been well defined. We hypothesize that patients undergoing multiple CRS/HIPEC's have meaningful long term survival. Methods: A retrospective study of a prospective database of 294 patients with peritoneal carcinomatosis (PC) was conducted, of these 162 had PC of appendiceal origin. Twenty-six of these patients underwent 56 CRS/HIPEC. Survival and outcomes was analyzed. Results: The percentage of patients with pre-surgical PCI scores ≥20 for the first, second, and third CRS/HIPEC was 65, 65, and 25%, respectively. Complete cytoreduction (CC 0-1) at first, second, and, third surgeries was 96, 65 and 75%, respectively. The mean operating time was 10.1 h. There was no 30-day peri-operative mortality. Following the first, second, and third CRS/HIPEC 27, 42, and 50% experienced grade III complications, respectively. Mean follow up was 51, 28, and 16 months from the first, second, and third CRS/HIPEC, respectively. Overall survival rate for the first CRS/HIPEC was 100, 83, 54, and 46% at years 1, 3, 5 and 10, respectively; from the second CRS/HIPEC 91, 53, and 34% at 1, 3, and 5 years, respectively; and from the third CRS/HIPEC was 75% at one year. Conclusion: Repeat CRS/HIPEC can lead to meaningful long term survival rates in patients with appendiceal peritoneal carcinomatosis with morbidity and mortality similar to those of the initial CRS/HIPEC. [Copyright &y& Elsevier]

Abstract: Background: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are a combined treatment modality considered for selected patients with peritoneal carcinomatosis from colorectal and appendiceal cancer. Doxorubicin is a drug consistently used by our group in this clinical setting. The surgical and clinical factors that modify the pharmacokinetics of HIPEC may be important for the design of future perioperative chemotherapy regimens. Materials and methods: The patients included were 145 who had colorectal or appendiceal carcinomatosis resected using CRS prior to treatment with HIPEC with doxorubicin as part of a multidrug regimen. The effect of clinical and surgical factors on drug distribution after a single intraperitoneal bolus administration with doxorubicin was determined. Results: The pharmacokinetics of 145 patients treated with intraperitoneal doxorubicin showed a 78 times greater exposure to peritoneal surfaces as compared to plasma. At 90 min 12% of the drug remained in the chemotherapy solution and 88% was retained in the body. The extent of visceral resection and peritonectomy increased the clearance of doxorubicin from the peritoneal space. A major resection of visceral peritoneal surface, a contracted peritoneal space, and an incomplete cytoreduction reduced drug clearance. Conclusions: Surgical and clinical factors may require modifications of chemotherapy administration. A large visceral resection and a contracted peritoneal space caused a reduced doxorubicin clearance. Total diffusion surface is an important determinant of doxorubicin pharmacokinetics. [Copyright &y& Elsevier]

Background: Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy are a combined treatment modality considered for selected patients with peritoneal carcinomatosis from colorectal and appendiceal cancer. Mitomycin C is a drug often used in this clinical setting. The surgical and clinical factors that may influence the pharmacokinetics of hyperthermic intraperitoneal chemotherapy should be further elucidated. Materials and methods: The patients included were 145 who had colorectal or appendiceal carcinomatosis resected using cytoreductive surgery prior to treatment with hyperthermic intraperitoneal chemotherapy with mitomycin C as part of a multidrug regimen. The effect of clinical and surgical factors on drug distribution after single intraperitoneal bolus administration with mitomycin C was determined. Results: The pharmacokinetics of 145 patients treated with intraperitoneal mitomycin C showed a 27 times greater exposure to peritoneal surfaces when compared to plasma. At 90 min, 29% of the drug remained in the chemotherapy solution, 62% was retained in the body, and 9% was excreted in the urine. The extent of peritonectomy increased the clearance of mitomycin C from the peritoneal space ( p = 0.051). A major resection of visceral peritoneal surface and a contracted peritoneal space reduced drug clearance. A contracted peritoneal space significantly reduced ( p = 0.0001) drug concentrations in the plasma. Conclusions: Surgical and clinical factors may require modifications of drug dose or timing of chemotherapy administration. A large visceral resection and a contracted peritoneal space caused a reduced mitomycin C clearance. Total diffusion surface is an important determinant of mitomycin C pharmacokinetics. [ABSTRACT FROM AUTHOR]

Abstract: Background: Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy and early postoperative intraperitoneal chemotherapy is becoming an accepted treatment of carcinomatosis. Methods: Between February 2000 and January 2008, there were 101 consecutive patients with carcinomatosis who were treated with cytoreductive surgery + hyperthermic intraperitoneal chemotherapy and early postoperative intraperitoneal chemotherapy. Patient and tumor characteristics, surgical details, complications, disease-free survival (DFS), and overall survival (OS) were recorded prospectively. Results: The majority (82%) of patients, median age 49 years (range, 18–77 y), had complete macroscopic cytoreduction (completeness of cytoreduction score, 0) despite a generally extensive tumor burden. Perioperative mortality and grade III/IV morbidity rates were 4% and 39%, respectively. Preliminary median DFS and OS have not been defined for appendix tumors at a median follow-up period of 16 months (range, 1–86 mo). Median DFS and OS for colonic tumors are 8 months and 26 months, respectively, with a median follow-up period of 12 months (range, 1–48 mo). Conclusions: Combined regional treatment is feasible and holds significant promise for the treatment of peritoneal carcinomatosis. [Copyright &y& Elsevier]

This report describes a case of appendiceal adenocarcinoma presenting as an appendiceal mucocele which was diagnosed on fine needle aspiration cytology despite biopsies being non‐diagnostic. [ABSTRACT FROM AUTHOR]