Mucinous Neoplasms Of The Appendix Research Articles

The robotic future of minimally invasive cytoreduction and hyperthermic intraperitoneal chemotherapy for peritoneal surface malignancies.

Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) has been increasingly utilized for peritoneal surface malignancies. This has been commonly utilized for a variety of neoplasms, but, especially mucinous neoplasms of the appendix, ovarian cancer, gastric cancer, colorectal cancer and mesothelioma. Traditionally, CRS/HIPEC has been performed as an open, extensive operation associated with prolonged hospitalization. However, when the peritoneal carcinomatosis index (PCI) is small (<10), minimally invasive approaches can be considered. Such less invasive approaches may be associated with improved postoperative recovery, less complications while preserving oncologic outcomes. The robotic platform offers distinct advantages over laparoscopy with superior visualization and ergonomics which account for its increased utilization in oncologic surgery. Herein, we review available data on minimally invasive approaches to CRS/HIPEC procedures, focusing on patient selection and comparative studies to open CRS/HIPEC. We summarize the existing initial studies on robotically assisted CRS/HIPEC and provide technical insights about our approach to robotically assisted CRS/HIPEC. Current data suggests that treatment of peritoneal surface malignancies with minimally invasive CRS/HIPEC is feasible in selected cases and is associated with improved postoperative recovery. The robotically assisted platform for CRS/ HIPEC deserves further investigation and may improve outcomes after this procedure in the future for carefully selected patients with low PCI.

Gelatinous peritoneal disease secondary to appendiceal mucinous adenocarcinoma: a case study and review of the literature

Pseudomyxoma peritonei also referred to as gelatinous ascites, is a rare disorder, described for the first time by R. Wyerth in 1884. It is characterized by the presence of mucous disseminated throughout the peritoneal cavity generally arising from the rupture of an appendicular mucocele. Pseudomyxoma peritonei can be asymptomatic, discovered during a laparotomy. The most common symptom is abdominal distension associated with diffuse abdominal pain. An abdominal CT scan is the most specific diagnostic tool. It shows pathognomonic signs of gelatinous ascites. Mucinous neoplasms of the appendix are the most frequent cause of pseudomyxoma peritonei accounting for 90% of cases. Pseudomyxoma peritonei needs to be considered as a borderline malignant disease because of its inevitable persistence and progression without an adapted therapeutic approach: cytoreductive surgery combined with perioperative intraperitoneal chemotherapy in specialized centers. The principal prognostic factors are the prior surgical history, the completeness of cytoreduction and especially the histopathologic grade. We report the case of pseudomyxoma peritonei secondary to appendiceal mucinous adenocarcinoma.

ASO Visual Abstract: Validation of a Nomogram to Predict Recurrence in Patients with Mucinous Neoplasms of the Appendix with Peritoneal Dissemination after Cytoreductive Surgery and HIPEC.

ASO Visual Abstract: Validation of a Nomogram to Predict Recurrence in Patients with Mucinous Neoplasms of the Appendix with Peritoneal Dissemination after Cytoreductive Surgery and HIPEC.

Validation of a Nomogram to Predict Recurrence in Patients with Mucinous Neoplasms of the Appendix with Peritoneal Dissemination After Cytoreductive Surgery and HIPEC.

Survival of patients affected by mucinous appendiceal neoplasms with peritoneal dissemination (PD) is mainly related to histopathological features. However, prognostic stratification is still a concern, as the clinical course of the disease is often unpredictable. The aim of this study is to construct and externally validate a nomogram predicting disease-free survival (DFS) in mucinous appendiceal neoplasms with PD treated by cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC). Patients treated in two referral centers were included: Hospital General Universitario Gregorio Marañón, Madrid, Spain (derivation cohort) and Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy (validation cohort). Cox regression analysis identified factors associated with shorter DFS in the derivation cohort. The nomogram performance was externally evaluated in the validation cohort using concordance index and calibration plots. Histology was classified according to the Peritoneal Surface Oncology Group International (PSOGI). The derivation cohort included 95 patients, and the validation cohort 348. Five-year DFS rates were 51.5 and 62%, respectively. Cox regression analysis (derivation cohort) identified PSOGI histology of the peritoneal components, number of preoperative elevated tumor marker, and peritoneal disease extent, as assessed by peritoneal carcinomatosis index, to be predictors of DFS. The model's predictive capacity was higher than that of PSOGI classification alone, with respective concordance indexes of 0.702 ± 0.023 and 0.610 ± 0.018 (validation cohort). The nomogram approximated the perfect model in the calibration plots at 3- and 5-year DFS. An easy-to-use model that provides better prognostic stratification than histopathological features has been constructed. This nomogram may help clinicians in individualized survival predictions and informed clinical decision-making.

Mucinous Neoplasms of the Appendix: Our Clinical Experience and Review of the Literature

Mucinous Neoplasms of the Appendix: Our Clinical Experience and Review of the Literature

An unusual case of pseudomyxoma peritonei associated with synchronous primary mucinous tumors of the ovary and appendix: A case report.

Pseudomyxoma peritonei (PMP) is a rare disease that usually originates from mucinous neoplasms of the appendix and, less commonly, from extra-appendiceal tumors, but it may also be caused by synchronous primary mucinous tumors of the ovary and appendix. The current study discusses the case of a 73-year-old female who presented with progressively worsening indigestion and abdominal distension. Magnetic resonance imaging of the pelvis revealed a large cystic mass with a thin enhancing septa arising from the right ovary and ascites with scalloping of the liver surface. On laparotomy, the patient was observed to have a large ruptured mass on the right ovary and a partially amputed distended appendix filled with mucin. The subsequent pathology report confirmed a borderline mucinous tumor of the right ovary and a low-grade appendiceal mucinous neoplasm associated with PMP. Immunohistochemical examination demonstrated the ovarian tumor stained strongly positive for cytokeratin (CK)-7, and negatively for CK-20 and homeobox protein CDX-2 (CDX2), whereas the appendiceal tumor stained negative for CK-7 and positive for CK-20 and CDX2. This study presents a rare case of PMP caused by synchronous primary mucinous tumors of the ovary and appendix in a postmenopausal female.

A mutation spectrum that includes GNAS, KRAS and TP53 may be shared by mucinous neoplasms of the appendix

Appendiceal mucinous tumors (AMTs) are classified as low-grade appendiceal mucinous neoplasms (LAMNs) or mucinous adenocarcinomas (MACs), although their carcinogenesis is not well understood. As somatic activating mutations of GNAS are considered to be characteristic of LAMNs while TP53 mutations have been shown to be specific to MACs, MACs are unlikely to result from transformation of LAMNs. However, emerging evidence also shows the presence of GNAS mutations in MACs. We examined 16 AMTs (11 LAMNs and 5 MACs) for genetic alterations of GNAS, KRAS, BRAF, TP53, CTNNB1, and TERT promoter in order to elucidate the possibility of a shared genetic background in the two tumor types. Extensive histological examination revealed the presence of a low-grade component in all cases of MAC. GNAS mutations were detected in two LAMNs and in one MAC, although the GNAS mutation in this MAC was a nonsense mutation (Q227X) expected not to be activating mutation. TP53 mutations were detected in three LAMNs; they were frequently detected in MACs. KRAS mutations were detected in three LAMNs and three MACs, and CTNNB1 mutations were detected in two LAMNs. KRAS mutation and activating mutation of GNAS occurred exclusively in AMTs. BRAF and TERT mutations were not detected. Overexpression of p53 was observed in only two MACs, and p53 immunostaining clearly discriminated the high-grade lesion from a low-grade component in one. These findings suggest that p53 overexpression plays an important role in the carcinogenesis of AMTs and that, in addition to mutations of GNAS, KRAS and TP53 alterations might be shared by AMTs, thus providing evidence for the possible progression of LAMNs to MAC.

Abstract 5191: Genome-wide mutational analysis reveals core signaling pathways in mucinous neoplasms of the appendix

Abstract Mucinous Neoplasm of the Appendix (MNA) is a rare malignancy often diagnosed after metastasis to the peritoneal surfaces resulting in Mucinous Carcinomatosis Peritonei (MCP). Genetic alterations in MNA are poorly characterized due to its low incidence, the hypo-cellularity of MCPs and a lack of relevant pre-clinical models. As such, application of targeted therapies to this disease is limited to those developed for colorectal cancer (CRC) and not based on molecular rationale. We sequenced the whole exomes of 10 MCPs to identify genome-wide somatic mutations and copy number aberrations and validated significant findings in 19 additional cases using deep sequencing and microdroplet PCR. These studies demonstrate that MNA has a different molecular makeup than CRC. Most tumors have co-existing oncogenic mutations in KRAS (26/29) and GNAS (21/29) and are characterized by cAMP-PKA pathway activation. High-grade tumors are GNAS wild-type (5/6), suggesting they do not progress from low-grade tumors. MNAs do share some genetic alterations with CRC including gain of 1q (5/10), Wnt and TGFβ pathway alteration. In contrast, mutations in TP53 (1/10) and APC (0/10), common in CRC, are rare in MNA. Coincident activation of the Ras-Raf-MEK-ERK and cAMP-PKA signaling pathways appears to be shared with pancreatic intraductal papillary mucinous neoplasm. Thus, MNA genome-wide mutational analysis reveals genetic alterations distinct from CRC, in support its unique pathophysiology and suggests MEK and PKA inhibition as new therapeutic opportunities. Citation Format: Hakan Alakus, Michele Babicky, Pradipta Ghosh, Shawn Yost, Kristen Jepsen, Yang Dai, Angelo Arias, Michael Samuels, Evangeline Mose, Michael Peterson, Andrew Lowy, Kelly Frazer, Olivier Harismendy. Genome-wide mutational analysis reveals core signaling pathways in mucinous neoplasms of the appendix. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5191. doi:10.1158/1538-7445.AM2014-5191

Mucinous neoplasms of the appendix: A single-center experience.

368 Background: Appendiceal neoplasms are poorly understood and represent less than 0.5% of all gastrointestinal cancers. We describe the presentation, pathologic characteristics, and treatment interventions that may have affected patient (pt) outcome. Methods: This is a retrospective review of pts with appendiceal neoplasms treated at NYU Medical Center and/or NYU Cancer Center between 2002-2011. Pt demographics and medical history were collected, including pathology reports, operative findings, imaging studies, treatment and outcomes. Results: 41 consecutive pts with varying stages of appendiceal cancer were identified (70.7% female, median age 57). Most common presentations included: 15 (36.6%) gynecologic complaints, 12 (29.2%) acute appendicitis, and 11 (26.8%) abdominal symptoms. Histologic subtypes were 27 (65.9%) mucinous cystadenomas and 14 (34.1%) adenocarcinomas of which 12 (29.3%) were mucinous adenocarcinoma and 2 (4.9%) were signet cell mucinous adenocarcinoma. Distribution of stages was: 27 (65.9%) stage 0, 2 (4.9%) stage I, 2 (4.9%) stage IIA/B, 6 (14.6%) stage IVA, and 4 (9.8%) stage IVB. All pts underwent one or more of the following procedures: appendectomy (n=39), colectomy (n=9), bilateral salpingo-oophorectomy (n=4), other (n=1). 9 of 10 stage IV pts underwent debulking, of those 2 had suboptimal debulking. 1 stage II pt and 4 stage IV pts (all mucinous adenocarcinoma subtype) received hyperthermic intraperitoneal chemotherapy (HIPEC) with mitomycin-C (all female, median age 39). In contrast, 6 stage IV pts (2 signet cell adenocarcinoma, 4 mucinous adenocarcinoma subtypes) did not receive HIPEC (67% female, median age 80). 1 pt received systemic 5FU based chemotherapy in addition to HIPEC (female, age 39). Median overall survival (mOS) for all pts ≥ stage II is 32 months. mOS in pts ≥ stage II who did not receive HIPEC is 8 mo whereas mOS in pts ≥ stage II who received HIPEC has not been reached. Conclusions: Appendiceal cancer is frequently detected as an incidental finding for gynecologic and abdominal complaints or presents as acute appendicitis. Surgery is the mainstay of treatment for this disease. Additional therapy including HIPEC may be of benefit in select advanced stage patients.

Mucinous neoplasms of the appendix: a current comprehensive clinicopathologic and imaging review

Mucinous neoplasms of the appendix are a heterogeneous group of neoplasms ranging from simple mucoceles to complex pseudomyxoma peritonei. Considerable controversy exists on their pathologic classification and nomenclature. Clear understanding of the histopathologic diversity of these neoplasms helps in establishing proper communication between the radiologist, the pathologist and the surgeon. In this article, we present a brief discussion of the current taxonomy and nomenclature of mucinous neoplasms of the appendix followed by a review of their imaging features. Important points including the significance of identifying extra-appendiceal mucin at imaging, the new classification of pseudomyxoma peritonei into low- and high-grade varieties and the significance of simultaneous ovarian and appendiceal neoplasms are highlighted.

Association of interval appendectomy with risk of neoplasm.

430 Background: The role of interval appendectomy after conservative management of perforated appendicitis remains controversial. Determining the etiology of perforated appendicitis is one reason to perform interval appendectomies. This study hypothesizes that there is an increased rate of neoplasm in patients undergoing interval appendectomy. Methods: This is a retrospective review of all patients over 18 years of age who underwent appendectomy for presumed appendicitis from January, 2006 to December, 2010 at a single, tertiary care institution. Demographic data, pathologic diagnosis, clinico-pathologic characteristics, interval resection rate, and complication data were collected and analyzed. Results: During the study period, 376 patients underwent appendectomy. The mean age was 41 years (range 18 to 94). Interval appendectomy was performed in 18 patients (5.0%) (age 28 to 74). Neoplasms were identified in 14 patients (3.7 %); 6 were found in patients who had undergone interval appendectomy (33%). Nine were mucinous tumors (69.2%), 5 of which were associated with interval appendectomies. Neoplasms were identified in 8.3% of patients between 35 and 55 years old. Conclusions: Mucinous neoplasms of the appendix were found in 33% of patients undergoing interval appendectomy. Interval appendectomies should be considered in all patients 35 years and older due to increased risk of appendiceal neoplasm. [Table: see text]

Muzinöse Neoplasien der Appendix vermiformis, Pseudomyxoma peritonei und die neue WHO-Klassifikation

Mucinous neoplasms of the appendix are rare tumors, some of them characterized by an enigmatic discrepancy between a benign morphologic appearance and an aggressive biologic potential, associated with a poor prognosis and high mortality. The clinical picture of pseudomyxoma peritonei is, with few exceptions, caused by mucinous appendiceal neoplasms and differs in many aspects from usual peritoneal carcinomatosis. The controversy regarding terminology, diagnostic criteria, classification and therapy of these tumors has lasted for decades. The revised edition of the World Health Organization Classification of Tumors of the Digestive System proposes a uniform reporting system for mucinous appendiceal neoplasms and the peritoneal disease associated with it, thereby creating a comparable basis for pathological diagnosis, clinical therapy and further scientific studies.

Subperitoneal adenomucinosis following proctocolectomy for ulcerative colitis

Adenomucinosis is a rare condition characterized by accumulation of large volumes of mucin, typically related to mucinous neoplasms of the appendix within the peritoneal space. Extraperitoneal adenomucinosis is an uncommon variant where mucin accumulates outside the peritoneal space and usually arises following surgery for mucinous appendiceal neoplasms. This is a case of subperitoneal adenomucinosis resulting from retention of a small fragment of rectal mucosa following proctocolectomy for ulcerative colitis 16 years prior. The patient presented with a slow-growing boggy perineal mass. Contrast-enhanced magnetic resonance imaging (MRI) showed the mass to be localized to the pelvis, without solid enhancing components, and correctly facilitated local surgical excision without the risk of peritoneal dissemination and accurately predicted benignity.

Low Grade Peritoneal Mucinous Carcinomatosis Associated with Human Papilloma Virus Infection: Case Report

Pseudomyxoma peritonei is a clinical syndrome characterized by peritoneal dissemination of a mucinous tumor with mucinous ascites. The vast majority of the pseudomyxoma peritonei are associated with mucinous neoplasms of the appendix. We describe a case of pseudomyxoma peritonei associated with mucinous adenocarcinoma of the cervix in a 60-year-old woman. The patient developed low grade mucinous peritoneal carcinomatosis 8 years after hysterectomy for cervical adenocarcinoma. No other primary mucinous tumor was identified and peritoneal carcinomatosis tested positive for high-risk human papilloma virus (HPV), showing both integrated and episomal pattern. HPV has been previously associated with development of cervical carcinomas (both squamous and mucinous) but neither has cervical adenocarcinoma nor HPV been implicated in development of pseudomyxoma peritonei. To the best of our knowledge, this is the first description of HPV-associated malignancy presenting as pseudomyxoma peritonei.

Splenic Metastases from Mucinous Neoplasms of the Appendix and Colon

Splenic metastases associated with mucinous intraabdominal tumors have been an enigma in the radiologic and oncology literature. These focal parenchymal defects from a non-metastasizing malignancy within an organ that rarely develops metastatic foci, even with high-grade cancer, were studied. Information on 9 patients who underwent splenectomy with intraparenchymal splenic masses associated with appendiceal or colorectal mucinous tumors with peritoneal dissemination was collected. The CT scan, the histopathology and the clinical parameters of these patients were studied. A literature review searching for prior reports of this subject was performed. Eight of these patients had mucinous appendiceal tumors and 1 a mucinous sigmoid colon cancer. All patients had mucinous carcinomatosis at some time in their clinical course. These splenic tumor masses had a CT image compatible with metastases and not compatible with mucinous tumor layered out of the splenic capsule. None of the patients had evidence of metastases to other sites such as liver or lymph nodes. All patients had a mucinous histopathology. Splenectomy may be associated with prolonged survival. From our review of the clinical information available on these 9 patients, these splenic lesions were thought to be an entrapment of mucinous tumor within splenic surface trabeculae, which expand into the splenic parenchyma resembling metastatic disease. These CT findings may be more accurately referred to as splenic pseudometastases.