Pseudomyxoma Peritonei Syndrome Research Articles

PSEUDOMYXOMA PERITONEI SECONDARY TO A VERY RARE OVARIAN CANCER: PRIMARY INFILTRATIVE INTESTINAL TYPE MUCINOUS ADENOCARCINOMA OF THE OVARY WITH INTESTINAL METASTASIS (A CASE REPORT)

Pseudomyxoma peritonei (PMP) syndrome is a disease that typically occurs from ruptured appendiceal mucocele neoplasms. PMP syndrome may arise from malignant transformation of a primary ovarian cancer. In this case study, we present the evaluation and treatment of a 48-year-old patient diagnosed with a left ovarian mass and significant symptomatic abdominopelvic mucinous ascites. Peritoneal cytology indicated paucicellularmucin. The final diagnosis confirmed the presence of diffuse peritoneal adenomucinosis. The treatment approach involved a cytoreductive surgery and chemotherapy. Our findings contribute to the existing body of literature endorsing the use of this intensive treatment approach, typically reserved for advanced abdominal malignancies. We applied this strategy to a patient presenting with a rare clinical entity, further supporting its efficacy in such cases.

Surgical treatment of pseudomyxoma peritonei-Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy

Pseudomyxoma peritonei syndrome (PMP) is an orphan disease. Surgery is the fundament of treatment. Short review summarizing the state of the art treatment. Cytoreductive surgery (CRS) in combination with hyperthermic intraperitoneal chemotherapy (HIPEC) form the foundations of treatment for PMP. The peritoneal cancer index should be preoperatively determined based on imaging and/or laparoscopy, intraoperatively validated and both should be documented. An extraperitoneal surgical preparation technique leads to effective en bloc resection of the peritoneum and the affected abdominal area. The HIPEC technique should be performed with mitomycinC for 60-90 min. Complete CRS (CC = 0, CC = 1) and the histological subtype are relevant for the prognosis. Structured educational programs and mentoring can optimize the learning curve. The aftercare should be performed at the surgical center. After follow-up imaging at 3 months after CRS, in the first 2 years a control should be carried out every 6months. Thereafter, the intervals can be extended to 1 year. Standardized surgical treatment and HIPEC, optimized specific surgical training and structured follow-up at the center lead to an excellent long-term prognosis for patients with PMP.

Rare occurrence of pseudomyxoma peritonei (PMP) syndrome arising from a malignant transformed ovarian primary mature cystic teratoma treated by cytoreductive surgery and HIPEC: a case report

BackgroundPseudomyxoma peritonei (PMP) syndrome is a disease process that typically occurs from ruptured appendiceal mucocele neoplasms. PMP syndrome arising from malignant transformation of an ovarian primary mature cystic teratoma (MCT) is a pathogenesis rarely encountered.Case PresentationHerein, we report a 28-year-old patient evaluated and treated for a right ovarian mass and large volume symptomatic abdominopelvic mucinous ascites. Molecular profiling and genetic analysis revealed mutations in ATM, GNAS, and KRAS proteins while IHC demonstrated gastrointestinal-specific staining for CK20, CDX2, CK7, and SATB2. Peritoneal cytology showed paucicellular mucin. Diffuse peritoneal adenomucinosis (DPAM) variant of PMP arising from a ruptured ovarian primary MCT after malignant transformation to a low-grade appendiceal-like mucinous neoplasm was ultimately confirmed. Treatment included staged therapeutic tumor debulking and right salpingo-oophorectomy followed by cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC).ConclusionsOur report builds upon the existing literature supporting this aggressive treatment option reserved for advanced abdominal malignancies utilized in this patient with a rare clinical entity.

Clinical treatment progress of pseudomyxoma peritonei syndrome

Pseudomyxoma peritonei syndrome (PMP) is characterized by a gradual expansion of mucoid tumour and fluid at specific sites within abdominopelvic regions as a result of a perforated appendiceal adenoma. The standard therapy for PMP is combining cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy. Maximal tumor debulking surgery (MTD) may be beneficial in patients in whom complete cytoreductive surgery (CCRS) cannot be achieved. It is now recognized that CCRS is one of the strongest predictors of long term survival in patients with PMP. The 5-year survival rate in patients who underwent CCRS was 80.0%-87.4%, however the rate in patients who underwent MTD was only 24.0%-39.2%. This article reviews the pathological classification, diagnosis and treatment of PMP. Key words: Pseudomyxoma peritonei; Cytoreductive surgery; Maximal tumor debulking surgery; Hyperthermic intraperitoneal chemotherapy

An Update on the Diagnosis, Grading, and Staging of Appendiceal Mucinous Neoplasms.

Despite advances in our understanding of appendiceal mucinous neoplasms and their relationship to the pseudomyxoma peritonei syndrome, the classification of mucinous tumors of the appendix is still confusing. This review will provide an update on the various classification systems that have been recently proposed for appendiceal mucinous neoplasia, with a particular emphasis on how to handle and report the histologic findings for these tumors using the newly published Peritoneal Surface Oncology Group International (PSOGI) and American Joint Committee on Cancer (AJCC) eighth edition guidelines. A simplified approach to diagnostic reporting of appendiceal mucinous neoplasms based on the 3-tier AJCC grading scheme is detailed and specific criteria for assessing grade in appendiceal mucinous neoplasia will be outlined. In addition, histologic mimics of appendiceal mucinous neoplasia and how to distinguish these mimics from mucinous neoplasia will be discussed. Finally, despite improvements in diagnostic terminology, significant challenges in classifying appendiceal mucinous neoplasia persist and diagnostic strategies will be detailed to assist practicing pathologists in these challenging scenarios.

A proposal of Brazilian Society of Surgical Oncology (BSSO/SBCO) for standardizing cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) procedures in Brazil: pseudomixoma peritonei, appendiceal tumors and malignant peritoneal mesothelioma

Cytoreductive surgery plus hypertermic intraperitoneal chemotherapy has emerged as a major comprehensive treatment of peritoneal malignancies and is currently the standard of care for appendiceal epithelial neoplasms and pseudomyxoma peritonei syndrome as well as malignant peritoneal mesothelioma. Unfortunately, there are some worldwide variations of the cytoreductive surgery and hypertermic intraperitoneal chemotherapy techniques since no single technique has so far demonstrated its superiority over the others. Therefore, standardization of practices might enhance better comparisons between outcomes. In these settings, the Brazilian Society of Surgical Oncology considered it important to present a proposal for standardizing cytoreductive surgery plus hypertermic intraperitoneal chemotherapy procedures in Brazil, with a special focus on producing homogeneous data for the developing Brazilian register for peritoneal surface malignancies.

Management of Pseudomyxoma Peritonei Syndrome during Pregnancy

Objectives: To improve skill in making a diagnosis and management of pseudomyxoma peritoneum originating borderline mucinous ovarian tumor during pregnancy. Methods: Case report. Conclusion: Diagnosis of pseudomyxoma peritoneum during pregnancy is difficult before surgery. Management is based on grade of malignancy and gestational age of pregnancy. [Indones J Obstet Gynecol 2013; 1-3: 161-5] Keywords: mucinous tumor, pregnancy, pseudomyxoma peritoneum

Regional Therapies for Advanced Cancer

potentiating factor for responses to ILI versus limb perfusions, but measurement of the degree of hypoxia is poorly reported. By using optical spectroscopy, tumor hypoxia was measured as being more profound than in the normal skin of patients undergoing ILI. This technique could help noninvasively examine the tissue microenvironment and provide clues to the effectiveness of therapies. Lohani et al. 3 present their research examining the microenvironment regarding patients with the pseudomyxoma peritonei syndrome; their work examines cytokines in the serum and ascites. They also attempt to correlate these levels with the stroma and tumor cells. While C-reactive protein is elevated in patients with pseudomyxoma peritonei, traditional inflammatory markers such as IL-1 were not elevated. This work supports a complex model of inflammation and neoplasia demonstrating the peritoneal synthesis of cytokines and serum elevations of IL-8 and MIP-1b. While understanding that tumor‐host microenvironments are important in advancing the field, the direct impact of these interactions is seen in patients who undergo regional therapies. The next articles demonstrate the delicate balance between aggressiveness of disease, genetics, and histology in predicting response to therapy. Magge et al. 4 tackle a difficult problem in evaluating the role of cytoreductive surgery and HIPEC in the management of patients with gastric cancer and peritoneal carcinomatosis. Close on the heels of a recently published randomized trial, this study demonstrates the survival benefit in selected patients with gastric cancer in a Western population. 5 Despite aggressive surgical techniques and careful selection of patients with minimal peritoneal disease [median peritoneal carcinomatosis index (PCI) = 10], the 3-year survival in this cohort was a humbling 18 %. The group identified characteristics such as male gender, signet ring histology, incomplete cytoreduction, and multivisceral surgery as factors predicting either worse survival or progression of disease.

The influence of tumor cell entrapment phenomenon on the natural history of Pseudomyxoma peritonei syndrome.

Pseudomyxoma peritonei syndrome (PMP) may be associated with slow "benign" or malignant process. However, the natural history of this disease is slow progression to death. Its treatment is variable and controversial. In this current study we have compared the patients with Pseudomyxoma peritonei syndrome with recurrences due to the cell entrapment hypothesis. Data were derived from a database of patients with PMP treated at our hospitals from 2004 to 2009. All patients had undergone various surgical operations prior to referral to our institutions for definitive treatment. All patients had recurrences in special sites due to entrapment of malignant cells. There are 6 patients, four men and two women. The initial clinical presentation of the disease was hernia in one, appendicitis in three and ovarian mass in one. The mean time from the initial operation to be definitive management was 23.5 months with an average of 1.83 operations per patient. After cytoreduction and hyperthermic intraperitoneal chemotherapy (HIPEC) the mean survival was 31 months with minimal recurrences and only 0.3 operations per patient. Our data suggest that the patients should be referred to a center with a peritoneal surface malignancy program after the PMP diagnosis as soon as possible. Incomplete debulking procedures and minimal invasive operations promote uncontrollable intraabdominal tumor growth due to tumor cell entrapment and the tendency of PMP to grow at wound sites.

Operative Findings, Early Complications, and Long-Term Survival in 456 Patients With Pseudomyxoma Peritonei Syndrome of Appendiceal Origin

Pseudomyxoma peritonei syndrome is a clinical entity characterized by mucinous ascites usually originating from a perforated mucinous appendiceal tumor. Currently optimal therapy is considered complete macroscopic tumor removal (complete cytoreduction) combined with heated intraperitoneal chemotherapy. When complete cytoreduction is not achievable, major tumor debulking is undertaken. The long-term follow-up of patients undergoing surgery for perforated appendiceal tumors in a national pseudomyxoma center is reported. Between March 1994 and July 2009, 456 patients with pseudomyxoma peritonei syndrome from perforated appendiceal tumors underwent surgery. The treatment strategy involved a combination of cytoreductve surgery aiming for macroscopic tumor removal, combined with hyperthermic intraperitoneal chemotherapy with mitomycin C. Where complete tumor removal was not possible, maximal tumor debulking was performed. Perioperative outcomes and predicted 5- and 10-year survival are reported. Overall 15 of 456 (3%) tumors were not resectable at laparotomy. Of the 441 patients who had resection, 289 (66%) had complete cytoreduction and 152 (34%) had major tumor debulking. Postoperative in-hospital mortality was 1.6% and grade 3/4 morbidity was 7%. The Kaplan-Meier method predicted 5- and 10-year overall survival of 69% and 57%, respectively. Five- and 10-year predicted survival was 87% and 74% for the 289 patients who had complete cytoreduction compared with 34% and 23% for the 152 who had major tumor debulking. Complete tumor removal was achieved in 289 of 441 (66%) patients with peritoneal dissemination from perforated appendiceal tumors with good long-term survival and probable cure in more than two-thirds.

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.

Analysis of Loss of Heterozygosity for Tumor-Suppressor Genes Can Accurately Classify and Predict the Clinical Behavior of Mucinous Tumors Arising From the Appendix

Pseudomyxoma peritonei is a rare heterogenous clinical syndrome with a variable clinical course. On the basis of the hypothesis that cumulative mutational damage can predict biological aggressiveness, we evaluated the utility of integrated histopathology and molecular analysis for patients with pseudomyxoma peritonei syndrome. Tissue specimens from 23 mucinous appendiceal tumors were analyzed. DNA samples from multiple sites were analyzed for loss of heterozygosity by using a panel of 15 allelic loss microsatellite markers and K-ras-2 point mutational damage. The fractional mutational rate (FMR), determined as the number of mutated markers divided by the total number of informative markers, was calculated by using the six most informative markers and the K-ras-2 gene. Kappa statistics were calculated to test the association between FMR and the histopathologic classification. Our study included 6 female and 17 male patients with a mean age of 53.6 years and a mean survival of 43.9 months. We found an association between tumor loss of heterozygosity markers and histopathologic classification (P < .05). In addition, there was also an association between the FMR and pathological classification as well as between the FMR and survival (P < .05). An FMR less than .25 indicated low-grade disease, an FMR of .25 to .50 indicated intermediate grade, and an FMR greater than .5 indicated a high-grade tumor. Mutational profiling of accumulated allelic loss and point mutational damage correlated strongly with histopathologic definitions of pseudomyxoma peritonei disease and helped to predict the prognosis of these patients. FMR, along with histopathology, offers a comprehensive classification of these rare tumors.

Pseudomyxoma peritonei arising from colonic polyps

Aims Pseudomyxoma peritonei may have as its primary site a mucinous gastrointestinal adenoma or carcinoma that gains access to the peritoneal cavity. This manuscript describes this disease arising from a benign or malignant colonic polyp. Methods From a database of over 1000 pseudomyxoma peritonei patients and colorectal carcinomatosis patients, three cases were identified in which the primary tumor site was a colonic polyp. The clinical history and course of these patients were studied. Results In a review of the clinical management of these patients, all three had an event whereby neoplastic cells from the surface of the colonic polyp could have gained access to the free peritoneal cavity. The patients developed the characteristic pseudomyxoma peritonei syndrome. All three patients were treated with cytoreductive surgery plus perioperative hyperthermic intraperitoneal chemotherapy. Conclusions Colonic polyps can serve as a source of dysplastic cells whereby pseudomyxoma peritonei can result. Caution to prevent seeding to the free peritoneal cavity during surgery for colonic polyps should be observed. If pseudomyxoma peritonei develops, cytoreductive surgery and perioperative intraperitoneal chemotherapy should be considered for treatment.

Appendiceal Mucinous Tumors and Pseudomyxoma Peritonei

Pseudomyxoma peritonei is an overused and underspecified condition that has garnered much attention in the historic literature. In recent years, this condition has been convincingly linked to appendiceal mucinous neoplasms, yet there has been insufficient attention to the histologic characteristics, classification, and differential diagnostic considerations of these neoplasms when encountered by the surgical pathologist. This review provides a coherent approach to the diagnosis and classification of appendiceal mucinous tumors and the peritoneal implants associated with the pseudomyxoma peritonei syndrome with emphasis on differential diagnostic considerations and recommendations for the final pathology report.

Recurrence of Pseudomyxoma Peritonei within the Inguinal Canal

Tumor appearing in an inguinal hernia sac indicates widespread carcinomatosis with ascites. A new onset hernia is a common clinical presentation of pseudomyxoma peritonei syndrome arising in an appendiceal mucinous tumor. Recurrence of pseudomyxoma peritonei within the inguinal region was previously reported in only a single patient. We present five patients with a recurrence of pseudomyxoma peritonei tumor nodules in the inguinal region following cytoreductive surgery and attempt to understand the etiology of this treatment failure. From a database of 910 patients with mucinous appendiceal tumors with peritoneal dissemination who had definitive treatment, five patients who had disease recurrence within the inguinal region were identified. The clinical histories were studied and presented in order to make future recommendations regarding the management of these patients. Five patients with ages ranging 39 to 67 years had a mucinous tumor in the inguinal region as a recurrence after a previous cytoreductive surgery combined with perioperative intraperitoneal chemotherapy. One of them had separate recurrence in both right and left inguinal regions. All these patients were made disease-free by the reoperative surgery with a sacrifice of the testicle in four. None have evidence of a recurrence of an inguinal hernia despite the lack of formal repair. At the time of initial cytoreductive surgery the surgeon should be aware of the inguinal region as a possible site of relapse. This may be more problematic in patients who have had prior surgery with mucoid fluid in a hernia as the presenting sign of pseudomyxoma peritonei. Inguinal recurrences should be removed with clear margins even if orchiectomy is required.

Cytoreductive surgery and perioperative intraperitoneal chemotherapy: a new standard of care for appendiceal mucinous tumors with peritoneal dissemination.

In the past, mucinous appendiceal tumors and the pseudomyxoma peritonei syndrome were treated with serial debulking procedures. Some benefit was achieved, but no long-term survivals were seen. A new standard of care that involves the complete removal of all visible disease using peritonectomy procedures combined with intraperitoneal chemotherapy washing has developed. This new approach is jeopardized when extensive prior surgical procedures have violated the peritoneum as a first line of defense of the host against carcinomatosis. In patients who have a complete cytoreduction, a 5-year survival of 80% is expected. In patients who have an incomplete cytoreduction, no 10-year survivors are seen. These studies suggest a new standard of care for appendiceal mucinous tumors with peritoneal dissemination.

Clinically aggressive pseudomyxoma peritonei: a variant of a histologically indolent process.

Three distinct morphologic types of pseudomyxoma peritonei syndrome have been defined: disseminated peritoneal adenomucinosis (DPAM), peritoneal mucinous carcinoma (PMCA), and a hybrid morphologic type. Prognosis is best in patients with DPAM; unfortunately, some patients with DPAM succumb to a rapidly progressive disease process. We identified a subset of 11 patients with a histopathology of DPAM but a clinical course showing an invasive disease process. As a comparison group, from a database of 501 patients with pseudomyxoma peritonei, we selected 22 age- and sex-matched controls with a DPAM histology who are alive with no evidence of disease. Clinical factors were identified for comparison of case and control groups. Expression of mucin antigens, mucin (MUC)1 and MUC2, were evaluated using immunohistochemistry. The study group consisted of 11 patients (five men and six women), with a median survival of 52.2 months (SD 7.46) and a 31% 5-year survival. All 22 matched control cases (10 men and 12 women) are alive and disease-free. Clinical data on the study and control groups including co-morbidity were similar. No significant difference in the expression of MUC1 (P = 0.74, Fisher's exact test) or MUC2 (P = 0.34, Fisher's exact test) was demonstrated between groups. Further investigation of pseudomyxoma peritonei at a molecular and genetic level may help to formulate a more comprehensive classification.

Chronic perineal fistula as a late failure manifestation of pseudomyxoma peritonei syndrome

Pseudomyxoma peritonei syndrome (PMP) is a rare but fascinating entity in surgical oncology. It consists of the accumulation of mucus in the peritoneal cavity, sometimes in huge amounts, in most of the cases after rupture of an appendiceal tumor. The diagnosis and management of PMP has changed significantly in the past 15 years, with the institution of an aggressive therapeutic combination: cytoreductive surgery and intraperitoneal perioperative chemotherapy. Few reports deal with the late manifestations and complications at endstage of the disease. The cases presented here are unique in that they illustrate a late 'failure' in the perianal area in three patients with long-term PMP.

Clinical presentation of the Pseudomyxoma peritonei syndrome.

Pseudomyxoma peritonei syndrome is characterized by a gradual expansion of mucoid tumour and fluid at specific sites within abdominopelvic regions as a result of a perforated appendiceal adenoma. The aim was to analyse the presenting symptoms and signs of patients with this condition. Of 410 patients with appendiceal tumours 217 had the diagnosis of pseudomyxoma peritonei syndrome with histological confirmation. A retrospective review of the clinical characteristics that determine presentation was performed. Overall, suspected acute appendicitis was the most common presentation (27 per cent). For women the diagnosis was most commonly made while being evaluated for an ovarian mass (39 per cent). Increasing abdominal girth was the second most common presentation overall (23 per cent). Thirty patients (14 per cent) presented with new-onset hernia, of which the majority (26) were inguinal hernias. Consideration of appendicitis, increased abdominal girth, ovarian mass and new-onset hernia as caused by this syndrome may facilitate diagnosis and definitive treatment.

Cytoreduction including total gastrectomy for pseudomyxoma peritonei

AbstractBackgroundCytoreductive surgery supplemented by perioperative intraperitoneal chemotherapy is a therapeutic option for selected patients with pseudomyxoma peritonei syndrome. In some patients, the stomach and/or its vascular supply are so covered by mucinous tumour that total gastrectomy is required for complete resection.MethodsForty-five patients underwent total gastrectomy with a temporary diverting jejunostomy as part of the surgical treatment of pseudomyxoma peritonei syndrome of appendiceal origin. Heated intraoperative intraperitoneal chemotherapy with mitomycin was used in all patients, and 36 had early postoperative intraperitoneal 5-fluorouracil. To date, 39 patients have had second-look surgery and stoma closure; 37 had additional perioperative intraperitoneal chemotherapy. A prospective database was maintained on all patients.ResultsThe median age was 47 (range 33–66) years. Median interval from diagnosis of pseudomyxoma peritonei to definitive cytoreductive surgery was 23 (range 0–140) months. Six patients presented with intestinal obstruction. The need for gastrectomy was predicted before operation by abdominal computed tomography. Mean operative time was 13 (range 9–17) h. Mean intraoperative requirement for packed red blood cells was 3·0 units, and that for fresh frozen plasma was 9·9 units. Six peritonectomy procedures, including total gastrectomy, were required for complete cytoreduction. All except seven patients were maintained on parenteral nutrition before second-look surgery for jejunostomy closure. All but two patients have resumed oral nutrition with discontinuation of parenteral feeding. There was one postoperative death and one late death. Thirty-seven patients are alive and disease-free, 0–56 months after initiation of treatment.ConclusionTotal gastrectomy with a temporary diverting jejunostomy may be used to facilitate complete cytoreduction in patients with advanced pseudomyxoma peritonei syndrome.