Pseudomyxoma Peritonei Research Articles

AB017. SOH22ABS100. Post-treatment surveillance for low-grade appendiceal mucinous neoplasms (LAMN): results from a national surveillance programme

Background: Low-grade appendiceal mucinous neoplasm (LAMN) is an unusual tumour that can progress to pseudomyxoma peritonei (PMP). There is a lack of standardisation of surveillance for LAMN as the progression rate is unclear. The purpose of this study was to evaluate the rate of progression of LAMN to PMP in a national surveillance programme.

High-Grade Appendiceal Mucinous Neoplasm: Clinicopathologic Findings in 35 Cases.

High-grade appendiceal mucinous neoplasm (HAMN) is a relatively recently introduced term describing a rare epithelial neoplasm of the appendix that demonstrates pushing-type invasion but high-grade cytologic atypia. It remains understudied. To describe clinicopathologic features of HAMNs. We identified 35 HAMNs in a multi-institutional retrospective study. Clinical and histologic features were reviewed in all cases, as well as molecular features in 8 cases. Patients were 57 years of age on average and most commonly presented with abdominal/pelvic pain. Histologically, 57% of the tumors showed widespread high-grade features. Architectural patterns in high-grade areas included flat, undulating, or villous growth, and occasionally micropapillary, cribriform, or multilayered growth. Thirteen cases had intact serosa, and the remaining 22 perforated the serosa, including 7 with peritoneal acellular mucin beyond appendiceal serosa and 10 with grade 2 pseudomyxoma peritonei. Molecular abnormalities included KRAS mutations in 7 cases and TP53 mutations in 4. No tumor confined to the appendix recurred. Two patients without pseudomyxoma peritonei at initial presentation developed pseudomyxoma on follow-up. Among 11 patients who presented with pseudomyxoma peritonei, 5 died of disease and 3 were alive with disease at last follow-up. HAMNs have a similar presentation to low-grade appendiceal mucinous neoplasm, and similar stage-based prognosis. When they spread to the peritoneum, they typically produce grade 2 pseudomyxoma peritonei, which may be associated with a worse prognosis than classical grade 1 pseudomyxoma peritonei.

Prognostic value of neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio on low-grade appendiceal mucinous neoplasm: A single tertiary hospital experience.

Low-grade appendiceal mucinous neoplasm (LAMN) is a rare disease, which prognostic factors were difficult to evaluate. Inflammation markers, like neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR), were used as prognosticators for various cancers. This study aimed to investigate the prognostic value of pretreatment NLR and PLR on LAMN. From January 2000 to September 2018, there were 57 patients diagnosed with LAMN in Taipei Veterans General Hospital. Patients diagnosed with mucinous cystadenoma, mucinous tumor with uncertain malignant potential before 2010 were also included based on previous classification. Clinical and pathological data were collected. Patients were separated into high-NLR (NLR-H) and low-NLR (NLR-L) groups according to cutoff value of 3. Similarly, they were separated into high-PLR (PLR-H), and low-PLR (PLR-L) groups with cutoff value of 300. Overall survival (OS) and recurrence-free survival (RFS) were analyzed. Among all patients, the median follow-up time was 42 months. Age, gender, clinical manifestations, type of surgery, and T stage were similar in different NLR and PLR groups. Both NLR-H and PLR-H groups had higher rate of M1 stage of diseases (22.7% vs 9.4%, p = 0.04; 57.1% vs 8.8%, p < 0.01, respectively). PLR-H group had more presence of pseudomyxoma peritonei (PMP) (57.1% vs 15.2%, p = 0.03). In univariate analysis, factors such as age, gender, tumor perforation, and operation did not have impact on OS nor RFS. On the other hand, M1b stage is the only significantly poor prognostic factor on RFS (hazard ratio, 57.96, 95% CI, 5.16-651.23, p < 0.01). Both NLR-H and PLR-H had more M1 stage of diseases, but they were not correlated to OS nor RFS. PLR-H group had higher rate of presence PMP. Nevertheless, patients with LAMN and cellular PMP (M1b stage) had a higher rate of recurrence, and other factors showed no statistical difference in OS nor RFS.

Comprehensive Understanding and Evolutional Therapeutic Schemes for Pseudomyxoma Peritonei: A Literature Review.

Pseudomyxoma peritonei is an infrequent solid tumor in clinical practice. The low morbidity and deficient understanding of this mucus-secreting malignant disease increase the risks of delayed identification or uncontrollable deterioration. In quite a lot cases, patients go through complete cytoreduction surgery and hyperthermic intraperitoneal chemotherapy could receive a long time survival over 5 years. But the recurrence rate is also hard to overlook. Unlike other types of cancer, the standard treatment for this considerable groups has not been confirmed yet. With the advanced medical progression, studies have been carrying out based on pathogenesis, biological characters, and mutated gene location. All but a few get statistical survival benefits, let alone the breaking progress on research or therapeutic practice in the field. We try to give a comprehensive exposition of pseudomyxoma peritonei around the epidemiology, radiologic features, clinical manifestation, present treatment and promising schemes, hoping to arise much attention and reflection on the feasible solutions, especially for the recrudescent part.

Enhanced computed tomography imaging features predict tumor grade in pseudomyxoma peritonei

Because few studies have focused on the correlation between computed tomography (CT) signs and tumor grade in pseudomyxoma peritonei (PMP), we evaluated predictive value of abdominal enhanced CT in identifying high- vs. low-grade cases. In all, 75 patients diagnosed with PMP after surgery were consecutively recruited. The preoperative enhanced CT images were retrospectively analyzed for ascites, hepatic scalloping, omental and peritoneal lesion appearance, intralesional calcification and septa, and peripheral organ involvement. Logistic regression models were applied to analyze the relationship of CT signs with PMP grade. Receiver operating characteristic curves were generated to evaluate the potential utility of CT signs in detecting high-grade PMP. Massive ascites (P=0.017) and peritoneal solid nodules (P<0.001) were more common in high-grade cases. Multivariate logistic regression identified massive ascites [odds ratio (OR) =4.389, 95% confidence interval (CI): 1.210-15.921; P=0.025] and peritoneal solid nodules (OR =19.932, 95% CI: 3.560-111.596; P<0.001) as independent predictors of high-grade PMP. For the 55 patients with hepatic scalloping, the maximum thickness of mucin deposition at the hepatic scalloping wave in high-grade PMP was thinner than that in low-grade PMP (P=0.021). Thickness of mucin deposition at the hepatic scalloping wave (OR =0.346, 95% CI: 0.148-0.809; P=0.014) was an independent predictor of high-grade PMP, with a cutoff value of 18.6 mm. Cancer antigen 125 (CA125) combined with CT signs was significantly better at diagnosing high-grade PMP than was CA125 alone in both the overall patients [area under the ROC curve (AUC): 0.812 vs. 0.656; P=0.020] and those with hepatic scalloping (AUC: 0.859 vs. 0.600; P=0.007). The CT signs of high-grade PMP significantly differ from those of low-grade PMP, and thus combining CT signs with CA125 may be highly valuable for classifying PMP.

Validating the PSOGI classification of peritoneal disease from non-carcinoid epithelial appendiceal neoplasms in the curative and palliative setting: an observational retrospective study.

Few studies on long-term survival have been published since the new updated pseudomyxoma peritonei (PMP) classification was published in 2016. The aim was to investigate long-term survival according to the Peritoneal Surface Oncology Group International (PSOGI) classification and compare prognostic factors. From Uppsala University Hospital, consecutive patients referred for cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) from 2004 to 2017 with peritoneal disease from non-carcinoid mucinous epithelial appendiceal neoplasms were included in the study. The peritoneal disease was divided into four groups: mucin only, low-grade mucinous carcinoma peritonei (MCP-1), high-grade (MCP-2), and high-grade with signet ring cells (MCP-3). Survival curves were rendered, and prognostic factors were compared. The study included 223 patients: 36 with mucin only, 112 with MCP-1, 70 with MCP-2, and 5 with MCP-3. Thirty-eight patients had a palliative debulking or open/close procedure. The 5- and 10-year overall survival was 97% and 97% for mucin only, 83% and 70% for MCP-1, 69% and 49% for MCP-2, with no patients still under follow-up after 5 years in the MCP-3 group. In a multivariable analysis, completeness of cytoreduction (CC) score 2-3 and PSOGI class MCP-3 were significantly associated with lower survival. The 5-year overall survival in the palliative setting was 40% vs. 44% (MCP-1 vs. MCP-2, P>0.05) with median survival 51 vs. 53 months, respectively. The PSOGI classification of PMP provides a solid differentiation of prognostic groups after CRS/HIPEC treatment, but not in the palliative setting.

Radiomics analysis based on CT\u2019s greater omental caking for predicting pathological grading of pseudomyxoma peritonei

The objective of this study was to predict the preoperative pathological grading and survival period of Pseudomyxoma peritonei (PMP) by establishing models, including a radiomics model with greater omental caking as the imaging observation index, a clinical model including clinical indexes, and a combined model of these two. A total of 88 PMP patients were selected. Clinical data of patients, including age, sex, preoperative serum tumor markers [CEA, CA125, and CA199], survival time, and preoperative computed tomography (CT) images were analyzed. Three models (clinical model, radiomics model and combined model) were used to predict PMP pathological grading. The models’ diagnostic efficiency was compared and analyzed by building the receiver operating characteristic (ROC) curve. Simultaneously, the impact of PMP’s different pathological grades was evaluated. The results showed that the radiomics model based on the CT’s greater omental caking, an area under the ROC curve ([AUC] = 0.878), and the combined model (AUC = 0.899) had diagnostic power for determining PMP pathological grading. The imaging radiomics model based on CT greater omental caking can be used to predict PMP pathological grading, which is important in the treatment selection method and prognosis assessment.

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.

Recurrence of initially localized appendiceal mucinous neoplasms after radical resection: survey analysis and literature review.

Appendiceal mucinous neoplasm (AMN) is a rare tumor that may be successfully treated by appendectomy. However, some patients develop recurrence as pseudomyxoma peritonei. The present study investigated the recurrence rate after radial resection for AMN. A survey on AMN was sent to 171 institutions, and 286 cases were analyzed. The risk of recurrence was assessed according to clinical parameters. Recurrence rates were compared with data from the literature. There were 250 cases in the low-grade group and 36 in the high-grade group, with perforation being detected in 50 cases. After a median follow-up period of 30months, recurrence was detected in 17 cases, including 12 with high-grade histology and 10 with perforation. Two patients with low-grade histology and no perforation developed recurrence. Independent prognostic factors for recurrence were high-grade histology (p = 0.0001, RR = 8.56) and perforation (p = 0.0168, RR = 3.45). Four groups were classified by histology and perforation: group A: high-grade, perforation ( +), group B: high-grade, perforation (-), group C: low-grade, perforation ( +), group D: low-grade, perforation (-). Five-year recurrence rates in groups A, B, C, and D were 46.7, 25.9, 13.3, and 1.5%, respectively. All cases of recurrence were detected within 3years, except for two in group B. Recurrence in cases with low-grade histology and no perforation was rare; however, a postoperative survey for at least 3years is required. In contrast, cases with high-grade histology or perforation need to be monitored using a similar approach to colon cancer. Prophylactic CRS + HIPEC may be considered.

Current Opinion and Practice on Peritoneal Carcinomatosis Management: The North African Perspective.

BackgroundThe status of peritoneal surface malignancy (PSM) management in North Africa is undetermined. The aim of this study was to assess and compare current practice and knowledge regarding PSM and examine satisfaction with available treatment options and need for alternative therapies in North Africa.MethodsThis is a qualitative study involving specialists participating in PSM management in North Africa. The survey analyzed demographic characteristics and current knowledge and opinions regarding PSM management in different institutions. We also looked at goals and priorities, satisfaction with treatment modalities and heated intraperitoneal chemotherapy (HIPEC) usefulness according to specialty, country, years of experience, and activity sector.ResultsOne-hundred and three participants responded to the survey (response rate of 57%), including oncologists and surgeons. 59.2% of respondents had more than 10 years experience and 45.6% treated 20–50 PSM cases annually. Participants satisfaction with PSM treatment modalities was mild for gastric cancer (3/10 [IQR 2–3]) and moderate for colorectal (5/10 [IQR 3–5]), ovarian (5/10 [IQR 3–5]), and pseudomyxoma peritonei (5/10 [IQR 3–5]) type of malignancies. Good quality of life and symptom relief were rated as main priorities for treatment and the need for new treatment modalities was rated 9/10 [IQR 8–9]. The perceived usefulness of systemic chemotherapy in first intention was described as high by 42.7 and 39.8% of respondents for PSM of colorectal and gastric origins, while HIPEC was described as highly useful for ovarian (49.5%) and PMP (73.8) malignancies.ConclusionsThe management of PSM in the North African region has distinct differences in knowledge, treatments availability and priorities. Disparities are also noted according to specialty, country, years of expertise, and activity sector. The creation of referral structures and PSM networks could be a step forward to standardized PSM management in the region.

Genetic diagnosis of pseudomyxoma peritonei originating from mucinous borderline tumor inside an ovarian teratoma

BackgroundPseudomyxoma peritonei is a rare disease condition mainly caused by primary mucinous tumors from the appendix and rarely from the ovary, such as when mucinous ovarian tumors arise from within a teratoma. Molecular analyses of pseudomyxoma from the appendix showed that KRAS and GNAS pathogenic variants are common genetic features of pseudomyxoma peritonei. However, the origin of the tumors is difficult to be identified via genetic variants alone. This study presents a case of pseudomyxoma peritonei of ovarian origin, which was diagnosed by comprehensive genomic profiling with ploidy analysis in a series of primary, recurrent, and autopsy tumor specimens.Case presentationA 40-year-old woman was diagnosed with Stage IC2 mucinous ovarian tumor of borderline malignancy with mature cystic teratoma, upon clinical pathology. Immunohistochemical analysis suggested that the mucinous tumor was derived from the intestinal component of an ovarian teratoma. Three years later, intraperitoneal recurrence was detected, which subsequently progressed to pseudomyxoma peritonei. Genomic analysis detected KRAS (G12D), GNAS (R201C), and FBXW7 (R367*) variants in the primary tumor. In addition, the tumor showed aneuploidy with loss of heterozygosity (LOH) in all its chromosomes, which suggested that the primary ovarian tumor was derived from germ cells. Existence of one Barr body suggested the existence of uniparental disomy of the tumors throughout the genome, instead of a haploid genotype. All three pathogenic variants remained positive in the initial recurrent tumor, as well as in the paired DNA from the whole blood in pseudomyxoma peritonei. The pathogenic variant of KRAS (G12D) was also identified in the autopsy specimen of the appendix by droplet digital polymerase chain reaction.ConclusionsThis study pathologically and genetically confirmed that the primary ovarian borderline tumor was derived from the intestinal component of an ovarian teratoma, and that the subsequent pseudomyxoma peritonei progressed from the primary ovarian tumor. Integrative genomic analysis was useful to identify cellular origin of tumors, as well as to precisely interpret the process of disease progression.

Multiple intestinal hemangioma concurrent with low-grade appendiceal mucinous neoplasm presenting as intussusception\u2014a case report and literature review

BackgroundCases with intussusception caused by either intestinal hemangiomas or appendiceal mucinous neoplasms are extremely rare.Case presentationIn this study, we reported a 47-year-old male presented with paroxysmal abdominal pain and postprandial bloating for 3 days. CT results indicated a high possibility of secondary intussusception in ascending colon. Histopathology indicated a mixed type of cavernous and capillary hemangioma, combined with low-grade appendiceal mucinous neoplasms (LAMNs) and intestinal obstruction. The patient underwent laparotomy and right hemicolectomy. Finally, the patient was followed up for 4 months with no disease progression.ConclusionsRare studies reported the intestine hemangiomas coincided with appendix low-grade mucinous tumor. Its manifestations are not specific, which is a challenge in the preoperative diagnosis. For cases with intussusception that was not observed in time, it may lead to intestinal necrosis and diffuse peritonitis. Additionally, the ruptured mucinous tumor in the appendix may lead to pathogenesis of pseudomyxoma peritonei. Therefore, accurate diagnosis and appropriate surgery-based treatment contribute to the improvement of prognosis and severe outcomes among these patients.

Low grade appendiceal mucinous neoplasm

Low grade appendiceal mucinous neoplasm (LAMN) is a rare tumour which lacks usual form of destructive invasion but has ability to spread to peritoneum and ovaries which frequently progresses to pseudomyxoma peritonei and often result in death of patient despite the bland histology of the mucinous epithelium. There are lot of controversies about its classification, clinical significance of pseudomyxoma peritonei, whether ovarian mucinous tumours in this setting are separate primaries or are the metastasis from the appendiceal tumours which are to be solved. We reported two cases of LAMN in which first case was with pseudomyxoma peritonei with secondary involvement of left ovary while other was simple LAMN without any involvement. Whenever we diagnosed LAMN it is necessary to look for ovarian involvement and pseudomyxoma peritonei.It is necessary to rule out ovarian involvement and pseudomyxoma peritonie whenever we diagnosed LAMN. The unified approach of grading pseudomyxoma peritonei is required for more standardized and prognostically valuable diagnostic reporting.

Cytoreductive surgery and concomitant hyperthermic thoracoabdominal chemotherapy for pseudomyxoma peritonei with abdominal and pleural involvement.

Cytoreductive surgery and concomitant hyperthermic thoracoabdominal chemotherapy for pseudomyxoma peritonei with abdominal and pleural involvement.

Establishment and Characterization of NCC-PMP1-C1: A Novel Patient-Derived Cell Line of Metastatic Pseudomyxoma Peritonei.

Pseudomyxoma peritonei (PMP) is the intraperitoneal accumulation of mucus due to a mucinous tumor. PMP predominantly occurs in low-grade carcinomas. The incidence rate of PMP is one to two cases per million people per year. The standard therapy of PMP comprises complete cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. PMP recurs in about 50% of patients, and 30–40% are unable to receive the standard treatment because of its invasiveness. Therefore, novel therapies are of the utmost necessity. For basic and pre-clinical research, patient-derived cell lines are essential resources. However, only two PMP cell lines have been reported. Thus, we established a novel PMP cell line from resected metastatic PMP tissue. The cell line, named NCC-PMP1-C1, was maintained for more than 5 months and was passaged 25 times. NCC-PMP1-C1 cells demonstrated multiple deletions, slow growth, tumorigenic ability, and dissemination of tumor cells in nude mice. We also used NCC-PMP1-C1 cells to screen drugs, which demonstrated a significant response to daunorubicin HCl, homoharringtonine, mitomycin C, and ponatinib. The NCC-PMP1-C1 cell line is the first PMP cell line derived from metastasized tissue and will be a potential resource for basic and pre-clinical research of metastasized PMP.

Early postoperative intraperitoneal chemotherapy (EPIC) following cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in 632 patients with pseudomyxoma peritonei of appendiceal origin: A single institution experience

BackgroundThere is ongoing controversy concerning the indications and benefits of early postoperative intraperitoneal chemotherapy (EPIC) following cytoreductive surgery (CRS) and hyperthermic intra-peritoneal chemotherapy (HIPEC) in patients with pseudomyxoma peritonei. The main contra-indications preventing wide-spread use of EPIC are reports of an increased postoperative morbidity with no clear evidence of oncological benefit. This paper reports a single high volume institution experience with EPIC over a 25-year period. MethodsThis is a retrospective analysis of a single institution prospective database of patients undergoing CRS and HIPEC for appendiceal neoplasms from March 1994 to December 2019. Sub group analysis of patients who received EPIC with 5FU 15mg/m2 is reported and compared with patients who did not receive EPIC. ResultsOverall, 632/1564 (40%) received EPIC. Patients who received EPIC were younger (median age 55 (IQR 45–63) vs 59 (IQR 50–68)) with similar extent of disease to those who did not have EPIC. EPIC was more likely to be given after complete cytoreduction. The use of EPIC has reduced over the last 25 years from 78% of patients initially to 16% most recently. Length of stay in critical care and total hospital stay were longer in patients who received EPIC but surprisingly major morbidity (Clavien Dindo Grade >3) was lower (p = 0.001). ConclusionEPIC can be administered safely following CRS and HIPEC for PMP of appendix origin when used in carefully selected patients in a high-volume centre. Randomised trials are needed to establish impact on disease free and overall survival to optimize selection criteria.

Mucinous appendiceal neoplasms and pseudomyxoma peritonei: Morphological and clinical findings, differential diagnosis, and prognosis.

Low-grade appendiceal mucinous neoplasms (LAMN) of the appendix have bland cytological features and well-differentiated morphology. Despite this, they may cause a pseudomyxoma peritonei (PMP) disease characterized by mucinous deposits in the peritoneal cavity and may exhibit malignant behavior. In this study, we evaluated the clinical course and histopathological findings of LAMN. The rate of progression to PMP, factors affecting its development, and the clinical course of cases with PMP were investigated. Twelve thousand and forty-seven cases who underwent appendectomy were reviewed, and 71 mucinous lesions cases whose slides are in our archive were included in the study. Histopathological findings were re-evaluated. Morphological findings that guide the differential diagnosis, the clinical course of the patients, and factors affecting PMP development were determined. The cases were divided into group 1 non-neoplastic (9.9%), group 2 benign (18.3%), group 3 LAMN (60.6), and group 4 malignant neoplasms (11.3%). Age, gender, appendix diameter, gross appearance, epithelial characteristics, and presence of microcalcification were significantly different between the patient groups. The presence of mucin in the ileocecal region was found to be significant in the development of PMP. It was observed that the additional procedure performed after the appendectomy did not prevent a recurrence. LAMNs are lesions with characteristic findings and different behaviors. The only method to distinguish from the lesions included in the differential diagnosis is to interpret the histopathological findings correctly. Additional operations after appendectomy do not contribute to preventing recurrence.

A proposal for modification of PSOGI classification according to Ki-67 proliferation index in pseudomyxoma peritonei.

Background: Pseudomyxoma peritonei (PMP) is a rare malignancy, classified according to PSOGI, whose response to treatment remains highly heterogeneous within the high-grade (HG) category. Molecular profiling of PMP cases might help to better categorize patients and predict treatment responses.v

Overall survival is more closely associated with peritoneal than primary appendiceal pathological grade in pseudomyxoma peritonei with discordant pathology

Background: The WHO classification of mucinous appendix neoplasms and pseudomyxoma peritonei (PMP) describes low- and high-grade histology and is of prognostic importance. The grade of the metastatic peritoneal disease can occasionally be different from the primary appendix tumour. This analysis aimed to report outcomes from a high-volume centre in patients with pathological discordance.

The impact of Sarcopenia on Short and Long Term Outcomes after Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy

Background: Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) is a potentially curative treatment for peritoneal metastases (PM) from colorectal cancer (CRC) or pseudomyxoma peritonei (PMP). The aim of this study was to assess the impact of sarcopenia on outcomes after CRS-HIPEC.