Estimating the Prevalence of Pseudomyxoma Peritonei in Europe Using a Novel Statistical Method.

BACKGROUND: The determination of the incidence and prevalence of rare diseases is important for economists and health-care providers. Pseudomyxoma peritonei (PMP) is a rare, slow-growing abdominal cancer that represents a substantial burden on both patients and health-care systems. The incidence rate was previously approximated at 1-2 people per million per year; this incidence has never been challenged, and the prevalence has not been estimated. METHODS: Epidemiological data from Norway and England were obtained and analysed to calculate a minimum incidence rate based on the number of patients having a first surgical intervention for PMP. A novel method was then used to determine a prevalence rate for PMP, incorporating incidence, death, and cure rates in a multi-year analysis that accounted for the increasing population of Europe over a 10-year period. RESULTS: An incidence rate of 3.2 people per million per year was calculated, with a corresponding estimated prevalence rate of 22 people per million per year. By this calculation, 11,736 people in Europe were estimated to be living with PMP in 2018. CONCLUSION: Incidence and prevalence are essential tools for assessment of the financial and human cost of a disease. For rare diseases, such as PMP, the lack of accurate registries presents a particular challenge in determining such health-related statistical parameters. Based on our calculations, a significant number of people are living with PMP in Europe, underlining the need for appropriate resource allocation to ensure that adequate health-care measures are provided.

Role of Epithelial-Mesenchymal Plasticity in Pseudomyxoma Peritonei: Implications for Locoregional Treatments.

The mechanisms by which neoplastic cells disseminate from the primary tumor to metastatic sites, so-called metastatic organotropism, remain poorly understood. Epithelial-mesenchymal transition (EMT) plays a role in cancer development and progression by converting static epithelial cells into the migratory and microenvironment-interacting mesenchymal cells, and by the modulation of chemoresistance and stemness of tumor cells. Several findings highlight that pathways involved in EMT and its reverse process (mesenchymal-epithelial transition, MET), now collectively called epithelial-mesenchymal plasticity (EMP), play a role in peritoneal metastases. So far, the relevance of factors linked to EMP in a unique peritoneal malignancy such as pseudomyxoma peritonei (PMP) has not been fully elucidated. In this review, we focus on the role of epithelial-mesenchymal dynamics in the metastatic process involving mucinous neoplastic dissemination in the peritoneum. In particular, we discuss the role of expression profiles and phenotypic transitions found in PMP in light of the recent concept of EMP. A better understanding of EMP-associated mechanisms driving peritoneal metastasis will help to provide a more targeted approach for PMP patients selected for locoregional interventions involving cytoreductive surgery and hyperthermic intraperitoneal chemotherapy.

Clinicopathologic Features of Low-grade Appendiceal Mucinous Neoplasm: A Single-institution Experience of 117 Cases.

Low-grade appendiceal mucinous neoplasm (LAMN) is an enigmatic tumor that lacks the capacity for classic invasion but can dissect through the appendiceal wall, causing pseudomyxoma peritonei (PMP). Most large studies of the histologic spectrum of LAMN and its rate of associated PMP include cases submitted from outside institutions, potentially skewing their findings. We identified 117 cases of LAMN at our institution. Hematoxylin and eosin-stained slides from each were reviewed, and clinical and pathologic parameters were noted. The patients were 76 females and 41 males, with a mean age of 60 years. Presenting symptoms were available for 113 patients; the majority (56%) were symptomatic, typically with abdominal pain. Ninety-one tumors (78%) were grossly dilated, and the entire appendix was submitted in 88 (75%) cases. Median lesion size was 5.5 cm. Ninety-two cases (79%) demonstrated epithelial denudation; these were often markedly dilated and contained intraluminal or mural microcalcifications. Thirty-two (27%) had a mucosal Schwann cell proliferation. On the basis of the American Joint Committee on Staging eighth edition cancer staging manual, of 117 cases, 66% were staged as pTis, 9% as pT3, 24% as pT4a, and 2% as pT4b. Ten cases (9%) were associated with histopathologic evidence of disseminated PMP. Only 1 patient died of disease, while 3 were alive with disease at last follow-up. Previous LAMN studies have utilized both departmental and extradepartmental material; our single-institution review demonstrated lower rates of PMP than some prior studies. Some LAMNs may be markedly dilated with extensive denudation, making the diagnosis difficult to confirm microscopically and ultimately requiring submission of the entire appendix for histologic evaluation.

Adenocarcinoma de apéndice con extensión extraapendicular: Análisis clínico-quirúrgico e histológico de 27 casos / Adenocarcinoma of the appendix with extra-appendicular spread: Clinico-surgical and histologic analysis of 27 cases

Fundamento y objetivos: La neoplasia apendicular con extensión extraapendicular puede mostrarse con diferentes patrones clínicos, entre ellos el pseudomixoma peritoneal (PMP). Analizamos los resultados de una serie clínica tratada en nuestro centro. Material y métodos: Estudio retrospectivo de pacientes con carcinomatosis peritoneal apendicular (desde enero de 2012 hasta mayo de 2015). Resultados: Veintisiete pacientes consecutivos. Edad mediana 63 años (26-73), 14 varones. Índice de carcinomatosis peritoneal=16±8 (3-31). El origen tumoral supuesto preoperatoriamente fue el apéndice en 23, el ovario en 3 y urotelial en uno. Mortalidad postoperatoria 2 pacientes (7,4%). El 36% de los restantes presentó morbilidad. Morbilidad mayor (Clavien-Dindo grados 3 y 4) en 3 pacientes (12%). Conclusiones: Los adenocarcinomas mucinosos extraapendiculares pueden manifestarse como PMP con ascitis mucinosa, carcinomatosis nodular gelatinosa sin ascitis, carcinomatosis nodular o placas desmoplásicas sin masas/nódulos gelatinosos. La histología no se correlaciona con la forma de presentación. La sospecha preoperatoria de cáncer de ovario mucinoso en el contexto de carcinomatosis peritoneal obliga a descartar que se trate de metástasis ováricas apendiculares (AU)

Background and objectives: Appendiceal neoplasms with extra-appendiceal spread may show different clinical patterns with pseudomyxoma peritonei (PMP) being one of them. We analyse the results in a series of patients treated in our center. Material and methods: Retrospective study of patients operated on for appendiceal peritoneal carcinomatosis from January 2012 to May 2015. Results: Twenty-seven consecutive patients were included. Median age 63 years (26-73); 14 were men. Peritoneal carcinomatosis index=16±8 (3-31). The suspected preoperative origins were appendix in 23, ovary in 3 and urothelial in one. Postoperative mortality in 2 patients (7.4%). The remaining 36% presented morbidity. Major morbidity (Clavien-Dindo grades 3 and 4) occurred in 3 patients (12%). Conclusions: Mucinous adenocarcinomas with extra-appendiceal spread may present as PMP with mucinous ascites, jelly-nodular carcinomatosis without ascites, nodular or desmoplasic plates carcinomatosis without jelly mass/nodules. Histology is not correlated to clinical picture. Preoperative diagnosis of mucinous ovarian cancer in peritoneal carcinomatosis scenario may increase the doubt of their ovarian origin and force an appendiceal origin to be ruled out (AU)

Survey on the incidence and management of pseudomyxoma peritonei in Japan.

PURPOSE: Pseudomyxoma peritonei(PMP)is a rare condition characterized by massive ascites accumulation due to mucinous tumor dissemination in the peritoneal cavity. More recently, Sugarbaker has defined radical cytoreductive surgery and intraperitoneal chemotherapy as standardized therapy for PMP. The objective of this study was to investigate the incidence of PMP and the recent therapeutic approaches for this condition in Japan. METHODS: Questionnaires answered by PMP patients between 2006 and 2010 were evaluated in this study. The study included 1, 084 gastroenterological surgery and gynecology institutions in Japan. RESULTS: Data from 379 institutions were analyzed(response rate: 35. 0%). The mean number of diffuse PMP cases at a single institution in 5 years was 0. 78. Of 266 diffuse cases, surgery was performed in 232 cases(87. 2%)and chemotherapy was administered in 138 cases(51. 9%). However, complete cytoreduction was achieved in only 31 of 232 operated cases(13. 4%)and intraperitoneal chemotherapy was administered to only 45 of 138 patients receiving chemotherapy( 32. 6%). CONCLUSION: Despite the limited data, our results suggest that PMP occurs rarely in Japan, similar to the trend reported in Western countries. Further, the Sugarbaker procedure was not widely used in Japanese institutions.

Treatments and outcomes of peritoneal surface tumors through a centralized national service (United kingdom).

PURPOSE: Treatment of peritoneal surface malignancies with combined cytoreductive surgery and heated intraperitoneal chemotherapy may improve oncologic outcome. To better define treatment pathways, five-year results in patients referred to one of two centralized national treatment centers in the United Kingdom were analyzed. METHODS: A prospective database of patients referred to the Manchester Peritoneal Tumor Service, established in 2002, was analyzed. Outcomes were evaluated using Kaplan-Meier life tables and Cox models. RESULTS: Two hundred seventy-eight patients (median age, 56.9 (range, 16-86) years) were considered by a dedicated multidisciplinary team and tracked on seven clinical pathways. Among the 118 surgically treated, the most common diagnosis was pseudomyxoma peritonei (101 patients, 86%). Major complications occurred in 11 patients (9%); there was no 30-day mortality. Where complete cytoreduction was achieved, three-year and five-year tumor-related survival rates were 94% and 86%, respectively. In the Cox model, incompleteness of cytoreduction (P = 0.001) and high-grade tumor (P < 0.0001) were independent prognosticators of poor outcome. CONCLUSION: The establishment of a national treatment center has allowed refinement of techniques to achieve internationally recognized results. Having achieved low levels of morbidity and mortality in the treatment of mainly pseudomyxoma peritonei of appendiceal origin, the technique of cytoreductive surgery and heated intraperitoneal chemotherapy may be considered for peritoneal carcinomatosis of colorectal origin.

Pseudomyxoma peritonei. Presenting as a localized perforation of the cecum.

Pseudomyxoma peritonei (PMP), also known as jelly belly, is a rare condition with mucinous material spread throughout the abdomen. It can arise from the appendix, colon, or even a teratoma. The documented incidence is one per million per year. We present a case report of an 80-year-old female patient presenting with PMP secondary to an appendicular tumor leading to localized infiltration, and perforation of the cecal wall. A review of the literature was carried out, with emphasis on various treatment options available for this rare condition.

A study to explore the patient's experience of peritoneal surface malignancies: pseudomyxoma peritonei.

Pseudomyxoma peritonei (PMP) is a rare tumour originating from the appendix and producing extensive mucus accumulation within the abdomen and pelvis. Since UK government policy reinforces the importance of involving patients in the delivery of healthcare, it is essential to explore patients views so that service development can be fully responsive to the patients need. The primary objective of this study was to explore the impact of PMP on the lives of patients. The secondary objectives were to explore the sources of psychological support for patients, the symptoms experienced and their information concerns. In-depth interviews were conducted with a purposive sample of 13 patients. The interviews were tape recorded, with permission, transcribed in full and analysed for content and emerging themes. The emergent themes included significant uncertainty about the diagnosis and treatment of this rare condition. The difficulties associated with confirming an initial diagnosis and living with an uncertain prognosis were highlighted. Patients' choice and access to support by a specialist team were important themes. The data highlighted the particular needs of this under-researched patient group and provided evidence to further develop patient support, particularly using the Internet.

Appendiceal neoplasms and pseudomyxoma peritonei: a population based study.

BACKGROUND: Pseudomyxoma peritonei (PMP) is a rare disease with an estimated incidence of 1 per million per year, and is thought to originate usually from an appendiceal mucinous epithelial neoplasm. However it is not known exactly how often these neoplasms lead to PMP. The aim of this study is to investigate the incidence of both lesions and their relation. METHODS: The nationwide pathology database of the Netherlands (PALGA) was searched for the incidence of all appendectomies, the incidence of primary epithelial appendiceal lesions and the incidence and pathology history of patients with PMP. All regarded the 10-year period of 1995-2005. RESULTS: In the 10-year period 167,744 appendectomies were performed in the Netherlands. An appendiceal lesion was found in 1482 appendiceal specimens (0.9%). Nine percent of these patients developed PMP. Coincidentally, an additional epithelial colonic neoplasm was found in 13% of patients with an appendiceal epithelial lesion. A mucinous epithelial neoplasm was identified in 0.3% (73% benign, 27% malignant) of appendiceal specimens and 20% of these patients developed PMP. For mucocele and non-mucinous neoplasm the association with PMP was only 2% and 3%, respectively. From the nationwide database 267 patients (62 men and 205 women) with PMP were identified, which demonstrates an incidence of PMP in the Netherlands approaching 2 per million per year. The primary site was identified in 68% and dominated by the appendix (82%). CONCLUSIONS: Primary epithelial lesions of the appendix are rare. One third of these lesions are mucinous epithelial neoplasms and especially these tumours may progress into PMP. The incidence of PMP seems to be higher than thought before. Furthermore there is a considerable risk of an additional colonic epithelial neoplasm in patients with an epithelial neoplasm at appendectomy.

Mucoceles apendiculares / Mucocele of the appendix

Introducción. Los mucoceles apendiculares son una entidad infrecuente; representan sólo el 0,25% de todas las apendicectomías y un 8% de todos los tumores apendiculares. Material y métodos. Describimos 27 casos de mucoceles apendiculares tratados entre enero de 1978 y diciembre de 2006 en el Hospital Donostia. Resultados. La edad media ± desviación estándar de los pacientes fue de 54,4 ± 21,7 años (rango, 17-88). De los 27 pacientes, 15 (55,5%) eran varones y 12 (44,5%) mujeres. Fueron intervenidos de urgencia 17 pacientes (62,9%). Resultaron hallazgos operatorios en el curso de intervenciones por otra razón en 7 (25,9%) ocasiones; 3 pacientes fueron operados con diagnóstico de tumoración abdominal no filiada (11,1%). La causa principal de intervención de urgencia fue el dolor en la fosa ilíaca derecha, 14 (82,2%); obstrucción intestinal, 1 (5,8%); diagnóstico de endometriosis, 1 (5,8%), y diagnóstico de piosalpinx, 1 (5,8%). Se intervino a 3 pacientes por presentar seudomixoma peritoneal pasados 24, 36 y 41 meses. El último caso se encuentra bien tras peritonectomía y pasados 78 meses. Hemos encontrado una incidencia global de 11 casos (40,7%) de neoplasias isocronas o metacronas de otra localización en estos pacientes. Conclusiones. Recomendamos el seguimiento de todos los pacientes con mucocele apendicular porque a veces se asocian a neoplasias de otra localización y riesgo de seudomixoma peritoneal, incluso en fases más avanzadas del seguimiento (AU)

Introduction. Mucoceles of the appendix are infrequent entities and are found in only 0.25% of all appendectomies and 8% of all appendicular tumors. Material and methods. We describe 27 cases of mucocele of the appendix treated at Donostia Hospital between January 1978 and December 2006. Results. The mean age of the patients was 54.4 ± 21.7 years (range: 17­88). Of the 27 patients, 15 (55.5%) were males and 12 (44.5%) were females. Emergency surgery was performed in 17 patients (62.9%). Mucoceles were identified as operative findings during surgery for other reasons in seven patients (25.9%). Three patients (11.1%) underwent surgery because of a diagnosis of abdominal tumor. The main reason for emergency surgery was lower right abdominal pain in 14 patients (82.2%), intestinal obstruction in one (5.8%), a diagnosis of endometriosis in one (5.8%) and a diagnosis of pyosalpinx in one (5.8%). Three patients underwent surgery due to pseudomyxoma peritonei after 24, 36 and 41 months' follow-up. The third patient is asymptomatic after peritonectomy and a follow-up of 78 months. We found an overall incidence of 11 cases (40.7%) presenting with synchronous or metachronous neoplasms from other locations. Conclusions. We recommend monitoring of all patients with mucocele of the appendix, because these masses can sometimes be associated with neoplasms in other locations and there is a risk of pseudomyxoma peritonei even after a long follow-up (AU)

Pseudomyxoma peritonei syndrome of appendiceal origin: an overview.

Pseudomyxoma peritonei (PMP) syndrome is an uncommon, slowly progressive condition that usually arises from perforation of an adenoma in the appendix. PMP syndrome is characterized by mucin accumulation in the peritoneal cavity. Mucinous implants are found on all peritoneal surfaces and the omentum. PMP syndrome rarely metastasizes outside the abdominal cavity but remains a fatal illness as the space in the abdomen and pelvis required for normal function of the gastrointestinal tract becomes filled with copious amounts of the mucinous tumor. Treatment options include observation, aggressive debulking surgery, intraperitoneal chemotherapy, radiotherapy, and mucolytic agents.

[Peritoneal gelatinous ascites]. / La maladie gélatineuse du péritoine.

Pseudomyxoma peritonei or gelatinous ascites is a rare clinical entity, and its pathogenesis remains obscure. It most often follows a mucinous tumor of the appendix. An ovarian origin in woman has been suggested but remains controversial. Its onset is often insidious: an increase in the abdominal perimeter may be the first sign noted. Preoperative diagnosis is facilitated by modern imaging techniques. Ultrasonography and computed tomography provide complementary signs: septa and scalloping of the liver margins, respectively. Effusion in the lesser peritoneal cavity suggests this diagnosis. Magnetic resonance imaging, by showing the gelatinous ascites, their septa and the scalloping of liver and spleen, can strengthen the probability of the diagnosis. Only laparotomy can confirm it, however. Appendectomy is required in all cases. Recurrence is more frequent in the forms associated with malignant or bipolar tumors. Cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy is the only therapy shown to be effective in cases of recurrence or malignant forms.

Toxicity and mortality of cytoreduction and intraoperative hyperthermic intraperitoneal chemotherapy in pseudomyxoma peritonei--a report of 103 procedures.

AIMS: To report on treatment related toxicity and mortality in patients with pseudomyxoma peritonei (PMP) treated by cytoreduction in combination with intraoperative hyperthermic intraperitoneal chemotherapy (HIPEC) and to identify prognostic factors. METHODS: A review was performed of 103 procedures of cytoreduction and intraoperative HIPEC for PMP between 1996 and 2004. Toxicity was graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) classification. A surgical complication was defined as any post-operative event that needed re-intervention. Pre and peroperative factors were studied on their relationship to toxicity and mortality. RESULTS: The median hospital stay was 21 days (4-149) with a treatment related toxicity of 54% and a 30 days mortality of 3%. In univariate analysis, toxicity was associated with abdominal tumour load (p<0.01), completeness of cytoreduction (p<0.01), and age (p=0.05). Surgical complications, mainly small bowel perforations/suture leaks, were the main cause of toxicity. A favourable pathology decreased mortality. CONCLUSIONS: Cytoreduction in combination with intraoperative HIPEC in PMP patients is a treatment with a relatively high toxicity, but a considerable long-term survival in selected patients. Toxicity is mainly surgery related. Concentration of cases to acquire sufficient experience and better selection on age, pathology, and extent of disease is essential to reduce treatment related toxicity and mortality.

Pseudomyxoma peritonei usually originates from the appendix: a review of the evidence.

Pseudomyxoma peritonei (PMP) is a rare condition, said to be more common in females during the fourth or fifth decade of life with an incidence believed to be in the region of one per million per year. Although PMP has been reported as originating from many intra-abdominal organs, in the majority of cases an ovarian or appendix cystadenoma or cystadenocarcinoma has been implicated as the primary site. Our experience suggests that most cases arise from the appendix. We have reviewed the clinical and scientific evidence. In the four largest reported series of 393 patients, 181 (46%) were males. Immunohistochemistry techniques in women with both appendical and ovarian tumours favour an appendiceal primary in most cases. The distinction between "benign" adenomucinosis and mucinous adenocarcinoma is important in both treatment and prognosis. Experience suggests that there may well be a spectrum of disease and possibly an "adenoma carcinoma sequence".

Pseudomyxoma peritonei.

Pseudomyxoma peritonei is a rare, slowly progressive disease that produces extensive mucus accumulation within the abdomen and pelvis. It is managed by cytoreductive surgery involving hyperthermic intraoperative intraperitoneal chemotherapy.

Pseudomyxoma peritonei: the 'controversial' disease.

Pseudomyxoma peritonei (PMP) is a rare disease that is characterized by a large amount of mucinous ascites with peritoneal and omental implants. The etiology of the disease remains unclear. Histologically, two main categories have been described: disseminated peritoneal adenomucinosis (DPAM) and peritoneal mucinous carcinomatosis (PMCA). It is commonly diagnosed incidentally at laparotomy. Most investigators agree that radical surgical debulking and appendectomy are the cornerstone of treatment, but the optimal management of the disease remains controversial. The role of intraoperative and intraperitoneal chemotherapy has been evaluated by a number of authors. The clinical outcomes vary widely between the benign and the malignant forms and between the different treatment modalities. We discuss the pathology, origin, clinical presentation, diagnosis, treatment, and prognosis of PMP.

Pseudomyxoma peritonei: a review of current literature.

Pseudomyxoma peritonei is an unusual condition more common in females, in which massive amounts of mucinous ascites in conjunction with mucinous peritoneal and omental implants occur. We performed a MEDLINE search of the English-language literature from 1966 to June 2000, utilizing the key words pseudomyxoma peritonei. All case reports, series and studies regarding this condition were reviewed. Cross-referencing was also performed. The etiology and treatment of this condition are currently controversial. Most investigators agree that surgical debulking and appendectomy are adequate initial therapeutic measures. The role of intraperitoneal chemotherapy, radiotherapy or application of mucolytic therapy remains uncertain. Recent molecular genetic studies suggest the appendix as the organ of primary origin of this disease.