RARE DISEASE
Pseudomyxoma peritonei
Pseudomyxoma peritonei
Pseudomyxoma peritonei
Synonyms: Adenomucinosis, Gelatinous ascites, PMP
Synonyms: Adenomucinosis, Gelatinous ascites, PMP
Synonyms: Adenomucinosis, Gelatinous ascites, PMP
Drug discovery
3
drugs
With orphan designations
Overview
Pseudomyxoma peritonei (PMP) is a rare, progressive mucinous neoplasm typically arising from appendiceal tumors, causing gelatinous ascites ("jelly belly") and peritoneal implants. It exhibits borderline malignancy, with indolent progression leading to abdominal distension, nutritional compromise, and organ dysfunction. Diagnosis relies on imaging (compartmentalized mucin on CT), tumor markers (CEA, CA19-9), and histology. Gold-standard treatment combines cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) [1][3][8].
Therapies
CRS+HIPEC: Curative intent for resectable disease (5-year survival: 62.5–100% in low-grade vs. 0–65% in high-grade) [1][9].
Systemic chemotherapy: Limited benefit; reserved for unresectable/high-grade cases (e.g., FOLFOX, bevacizumab) [3][13].
Palliative options: Debulking surgery, mucolytics, or pressurized intraperitoneal aerosol chemotherapy (PIPAC) in trials [3][19].
Categories: rare abdominal surgical diseases, rare neoplastic diseases
Research Papers
1,022 drug discovery papers about Pseudomyxoma peritonei, with 4 first-in-class and 3 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
1,022 drug discovery papers about Pseudomyxoma peritonei, with 4 first-in-class and 3 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
categories:
Small molecules
proteins
2026-06-06 | Efficacy and safety of fibrinogen concentrate (BT524) in severe hemorrhage: Phase 3 subcohort analysis of the AdFIrst trial in patients undergoing cytoreductive surgery for pseudomyxoma peritonei.
The AdFIrst phase 3 trial evaluated the efficacy and safety of human fibrinogen concentrate (FC) versus standard of care for major bleeding in complex surgery. This subanalysis evaluated a preemptive hemostatic strategy using FC versus cryoprecipitate (Cryo) to manage severe bleeding patients undergoing major abdominal surgery, specifically cytoreductive surgery (CRS) for pseudomyxoma peritonei (PMP). A single-center UK analysis derived from a randomized, active-controlled, partially blinded, phase 3, non-inferiority trial. Patients undergoing PMP surgery with predicted intraoperative blood loss >2 L were randomized (1:1) to receive either FC (4 g) or two pools of Cryo (10 units) with repeat dosing as required. The primary endpoint was intraoperative blood loss, measured from the decision to treat the patient with trial drug until the end of surgery with a non-inferiority margin of 150 mL (ClinicalTrials.gov: NCT03444324). Between March 2021 and September 2023, 98 patients (48 FC; 50 Cryo) were enrolled, randomized, and evaluated. The primary endpoint was met: Least squares mean intraoperative blood loss was 1517 mL (95% CI, 1331-1703) with FC and 1706 mL (95% CI, 1524-1889) with Cryo, corresponding to a difference of -190 mL (95% CI, -450 to 71; nominal exploratory p = 0.011). The upper bound of the 95% CI was below the prespecified non-inferiority margin, consistent with the non-inferiority observed in the overall trial. Thromboembolic events occurred in fewer patients in the FC group (3 [6.3%]) than in the Cryo group (11 [22%]; nominal exploratory p = 0.041); other safety outcomes were comparable between groups. In patients undergoing CRS for PMP, these results provide supportive evidence for the hemostatic efficacy of FC, consistent with the overall trial and prior studies, with a favorable safety profile. In this single-center PMP subgroup, the findings support a preemptive fibrinogen strategy that may inform practice in other surgical settings and warrants evaluation in future studies.
2026-05-18 | Mucinase from Bacteroides thetaiotaomicron as mucolytic for mucinous cancer pseudomyxoma peritonei.
Mucinous cancers are characterized by tumor gland cells secreting copious amounts of mucus that forms gel-like structures. Pseudomyxoma peritonei (PMP), a rare yet prototypical mucinous malignancy, exemplifies this pathology. Biologically inert mucus coats tumor cells, promoting colonization, immune evasion, and chemoresistance. Pathological mucus accumulation leads to intra-abdominal hypertension, refractory abdominal pain, abdominal adhesions, and intestinal obstruction because of the lack of rapid, efficient, and safe clinical strategies for mucin clearance. Current management relies on extensive cytoreductive surgery to excise tumor masses and adherent mucus. Here, we present an integrated workflow spanning intestinal probiotic protease discovery for the development of mucolytic therapy. By cultivating Bacteroides thetaiotaomicron (B. theta) with PMP-derived mucus as the sole nutrient source, we identified its intrinsic mucolytic capacity. Crucially, transcriptomic analysis revealed that B. theta orchestrates mucus degradation via the PULs gene cluster, with concomitant upregulation of the M60 family metalloproteinases BT4244, BT3015, and BT4272. Functional validation classified these enzymes as "mucinases" responsible for tumor-associated mucin cleavage and mucolysis. Our study provides a foundation for enzyme-targeted PMP therapy, offering a paradigm shift toward minimally invasive, high-efficacy mucolysis. Our findings highlight the translational potential of microbial proteases in addressing clinical challenges posed by mucinous malignancies.
2025-12-18 | The addition of collagenase to BromAc ® for the management of inoperable pseudomyxoma peritonei - in vitro results.
Pseudomyxoma peritonei (PMP) is a rare peritoneal malignancy. BromAc ® is a novel therapeutic agent which has been developed to dissolve and facilitate the drainage of mucin as a palliative treatment for PMP; however, its effect is significantly reduced in patients with hard mucin. This study aimed to assess whether combining collagenase or cysteamine with BromAc ® would be more effective in dissolving hard mucin. This preclinical human in vitro study examined the effect of adding collagenase to BromAc ® on hard mucin samples when incubated at 37 °C over 24 h. The effect of cysteamine alone and in combination with collagenase and BromAc ® was also examined as a supplementary arm of this study. Five experiments were conducted with appropriate controls. Human hard mucin samples were sliced into equal fractions using a sterile surgical scalpel, weighed and noted. The leftover solid mucin was weighed at 0, 1, 3, 5, and 24 h post-treatment. At 24 h post-treatment, all combinations with collagenase demonstrated almost 100 % dissolution of hard mucin. At 3 and 5 h post-treatment, only BromAc ® with collagenase at 250 μg/mL was found to be superior to BromAc ® alone. Combinations with cysteamine were not found to be effective. This study provides promising evidence of the efficacy and synergistic effect of combining BromAc ® with collagenase to dissolve hard mucin. Further preclinical and clinical research should be undertaken to assess its safety and efficacy in the clinical setting.
2025-09-14 | From Theory to Practice: A Comprehensive Review of Pseudomyxoma Peritonei Research and Its Implications for Future Treatment.
Pseudomyxoma peritonei (PMP) is a rare disease characterized by symptoms such as mucinous ascites and omental cake, typically arising from a perforated epithelial tumor of the appendix. Because of its rarity, non-specific histologic characteristics, and slow progression, its pathogenesis and optimal treatment remain subjects of debate. PMP is still a challenging and enigmatic condition. Increasing global attention is being directed toward understanding its pathogenesis and establishing standard treatment approaches. PMP and mucin are inextricably linked. This article highlighted the important role of mucin in the disease's pathogenesis. It also discussed several potential therapeutic strategies for eliminating mucin in PMP. Tumor development and metastasis involve a series of steps that include the interaction between the tumor and the host-derived stromal environment, which promotes angiogenesis and activation of inflammatory cells. Inflammatory cytokines and chemokines play a crucial role in the progression and development of PMP. The microbiome and specific microorganisms may directly influence tumor development, progression, and responses to certain therapies in PMP. Thus, the article summarized the interactions among bacteria, the immune system, and mucin in PMP, focusing on the mechanisms that related to abnormal mucin and tumor growth. This review critically examined the existing literature on the clinical features, pathologic processes, and treatment options in PMP, aiming to guide future research toward identifying novel therapeutic targets and gut-related disease biomarkers.
2025-07-31 | Efficacy and safety of human fibrinogen concentrate (BT524) in patients with major haemorrhage undergoing major orthopaedic or abdominal surgery (AdFIrst): a randomised, active-controlled, multicentre, partially blinded, phase 3 non-inferiority trial.
Major haemorrhage is associated with considerable morbidity and mortality, but the optimal treatment remains disputed. This trial aimed to compare the efficacy and safety of human fibrinogen concentrate (FC) vs. either fresh frozen plasma (FFP) or cryoprecipitate (Cryo) as first-line treatment in patients with major bleeding during major orthopaedic or abdominal surgery, respectively. AdFIrst was a randomised, active-controlled, partially blinded, non-inferiority phase 3 trial conducted at 15 hospitals in Europe. Eligible patients (≥18 years), undergoing major spinal surgery or cytoreductive surgery for pseudomyxoma peritonei, with clinically relevant intraoperative blood loss were randomised by an interactive web response system (1:1) to receive intravenous FC (2-4 g) compared to FFP (15 mL/kg body weight) or Cryo (10 units); doses were repeated as needed. The primary endpoint was intraoperative blood loss from the time of decision to treat until the end of surgery with a non-inferiority margin of 150 mL, assessed in the per-protocol analysis set (PPS). Safety was assessed in all patients who received at least one dose of trial drug. The trial is complete (ClinicalTrials.gov: NCT03444324). Between February 12, 2018, and November 21, 2023, 222 patients (131 [59%] female; 91 [41%] male; 97% white) were enrolled and randomly assigned to receive either FC (n = 110) or FFP/Cryo (n = 112). The PPS included 201 patients (FC: n = 103; FFP/Cryo: n = 98). The primary endpoint was met; the least squares mean (LSM: adjusted mean estimated using ANOVA) intraoperative blood loss was 1381 mL (95% confidence interval [CI] 1187-1574) in the FC group and 1660 mL (95% CI 1461-1860) in the FFP/Cryo group. The LSM difference was -279 mL (95% CI -552 to -6; p < 0·0001), indicating a notable treatment difference beyond non-inferiority. In a post-hoc analysis, FC showed superiority to reduce intraoperative blood loss over FFP/Cryo in the PPS (p = 0·0087). Serious adverse events were reported in 28/110 patients (25%) in the FC and 41/112 patients (37%) in the FFP/Cryo group. Thromboembolic events occurred in 17 patients (FC: 4 (4%) and FFP/Cryo: 13 (12%). There were no treatment-related deaths. In patients undergoing major spinal or cytoreductive surgery for pseudomyxoma peritonei (PMP), FC was non-inferior to FFP/Cryo for the management of clinically relevant intraoperative bleeding. The efficacy and safety advantages observed in this trial support the emerging adoption of first-line use of FC in treatment guidelines. Biotest AG, Germany.
antibodies
2025-06-01 | Clinical features and prognostic analysis of 14 cases of appendiceal mixed neuroendocrine-non-neuroendocrine tumors with peritoneal pseudomyxoma.
Appendiceal mixed neuroendocrine-non-neuroendocrine neoplasms (a-MiNENs) combined with peritoneal pseudomyxoma (PMP) represent an exceptionally rare and clinically challenging entity. This study aims to elucidate the clinical characteristics of this unique tumor subtype and identify critical prognostic factors, thereby providing insights into the management and outcomes of affected patients. We conducted a retrospective analysis of 14 patients diagnosed with a-MiNEN and PMP at the Department of Myxoma, Aerospace Center Hospital, between January 2014 and September 2022. Data included demographics, symptoms, tumor grading, treatments, and outcomes. Pathological evaluation revealed a diverse spectrum of tumor grades and PMP subtypes: 5 cases were classified as G1 neuroendocrine tumors (NET), 4 as G2 NET, and 5 as G3 neuroendocrine carcinoma (NEC). Regarding PMP subtypes, 5 cases had disseminated peritoneal adenomucinosis (DPAM), 4 had peritoneal mucinous carcinomatosis (PMCA), and 5 had peritoneal mucinous carcinomatosis with signet ring cell carcinoma (PMCA-S). The median postoperative survival time was 28.55 months, with 1-year and 2-year survival rates of 80.0% and 66.7%, respectively. Patients aged < 60 years, male sex, absence of right hemicolectomy, postoperative peritoneal cancer index (PCI) ≥ 25, and perineural invasion demonstrated significantly lower 1-year and 2-year survival rates compared to their counterparts, with distinct separation observed in the Kaplan-Meier curves. These factors likely reflect biological differences in disease progression, inadequate surgical debulking, and aggressive tumor behavior. a-MiNEN with PMP progresses rapidly. Young patients, male patients, those with absence of right hemicolectomy, postoperative PCI ≥ 25 and perineural invasion may face poorer outcomes. This study, one of the few to analyze this rare condition, underscores the need for targeted treatments and further validation in larger cohorts.
2024-11-15 | Comparison of functional characterization of cancer stem cells in different tumor tissues of pseudomyxoma peritonei.
Pseudomyxoma peritonei (PMP) is a rare malignant peritoneal tumor that readily recurs and metastasizes. Studies have shown that cancer stem cells (CSCs) play an important role in tumor recurrence, metastasis, and prognosis. In this study, our aim was to isolate CSCs from various tissues of PMP patients and compare their proliferation, migration, and anti-inflammatory abilities. We identified CSCs subsets with markers CD133+, CD166+, and CD133+/CD166+ at the gene level using single-cell mRNA sequencing (scRNA-seq). Appendiceal CSCs (AC), peritoneal CSCs (PC), and mucous CSCs (MC) were obtained using MACSQuant Tyto sorting technology and FlowSight imaging flow cytometry. The cells were cultured and markers were identified. Finally, the functional phenotypes of the three cell types were compared. CSCs content was highest in the appendiceal tumor tissue and lowest in the mucous tissue. The cell viability rate of the sorted CSCs was above 98%, and the positive rate of CD133+ and CD166+ was 70-80%, and CD133+/CD166+ was about 30%. Among the three types of CSCs, MC had the highest proliferation ability, and TNF-α has the greatest inhibitory effect on AC migration. AC in patients was more inert and anti-inflammatory, whereas abdominal cavity MC and PC were more active. This study revealed the biological characteristics of CSCs in different tumor tissues of patients with PMP, providing a reference for future targeted CSCs therapy.
2024-09-23 | Pseudomyxoma Peritonei Arising From a Mucinous Ovarian Borderline Tumor Treated With Paclitaxel, Cisplatin, and Bevacizumab: A Case Report.
Pseudomyxoma peritonei (PMP) is a rare disease caused by primary mucinous neoplasms. Here, we describe a case where a large ovarian tumor was initially removed laparoscopically, followed by an appendectomy. The patient was diagnosed with PMP arising from an ovarian mucinous borderline tumor with a KRAS mutation. Treatment included bevacizumab-containing chemotherapy, resulting in complete remission.
2023-07-20 | A2AR Expression and Immunosuppressive Environment Independent of KRAS and GNAS Mutations in Pseudomyxoma Peritonei
In pseudomyxoma peritonei (PMP), KRAS and GNAS mutations are frequent. We hypothesized that these mutations may contribute to the suppression of antitumor immunity: KRAS may induce GMCSF expression, while GNAS may enhance the expression of cyclic adenosine monophosphate and A2AR signaling. This study aimed to explore possible mechanisms facilitated by KRAS and GNAS mutations for escaping immune surveillance. Additionally, we looked for new potential therapeutic and prognostic targets in this rare disease which is poorly characterized at the molecular level. GM-CSF, A2AR, CD73, CD39, and PD-L1 expression was investigated by immunohistochemistry in 40 PMPs characterized for GNAS and KRAS mutational status. Immune cell populations were studied by immunohistochemistry and nanostring nCounter®. Following the criteria of a prognostic nomogram reported for PMP, we stratified the patients into two different risk groups, with 28 "low-risk" and 12 "high-risk" patients. We observed the expression of GM-CSF (74%); CD39 (37%); CD73 (53%); A2AR (74%); and PD-L1 (16%) which was unrelated to GNAS or KRAS status. The tumor microenvironment showed the presence of CD4+ T cells (86%); CD8+ T cells (27%); CD20+ B (67%); CD15+ cells (86%); and CD163+ M2 macrophages (67%), while CD56+ NK cells were absent. CD163 expression (27%) in PMP tumor cells was associated with poor prognosis. GNAS mutation and A2AR expression were not associated with a specific immune transcriptional signature. However, the expression assay revealed 21 genes associated with prognosis. The "high-risk" patients exhibited worse progression-free survival (HR = 2.3, CI 95%: 1.1-5.1, p = 0.034) and significant downregulation of MET, IL8, PPARG, DTX4, HMGA1, ZIC2, WNT5B, and CCRL2. In conclusion, we documented the presence of immunosuppressive factors such as GM-CSF, A2AR, and PD-L1 in PMP. These factors were not associated with GNAS and KRAS status and could be explored as therapeutic molecular targets. Additionally, a set of potential prognostic biomarkers, including CD163 expression in tumor cells, deserve further investigation.
2023-01-03 | Rare Mucinous Adenocarcinoma of the Appendix Undergoing Multiple Recurrent Surgical Interventions
Primary appendiceal carcinomas are rare and often found incidentally when the appendix is surgically removed. Adenocarcinoma predominates the histological types of malignancies, with mucinous adenocarcinoma being the most prevalent of the various subtypes. Pseudomyxoma peritonei (PMP), a complication seen in mucinous adenocarcinoma of the appendix (MAA), is the collection of mucinous ascites in the intra-abdominal cavity and the thickening of the surrounding viscera by mucin-producing tumor cells. PMP initially presents with increased abdominal discomfort and girth and, in later stages, presents with obstructive abdomen symptoms. These symptoms are nonspecific and can be a challenge to pinpoint. Such was the case for our patient, in this case report, who initially presented with dyspepsia and later demonstrated compressive symptoms and weight loss, raising concern for malignancy. An appendiceal pathology was of concern when his right lower quadrant pain acutely worsened during an abdominal ultrasound, and imaging and biopsy confirmed MAA with PMP. The aim of this report is to shed light on the management of recurrent MAA. Our patient's recurrent MAA was managed with debulking procedures and three rounds of hyperthermic intraperitoneal chemotherapy (HIPEC) and was managed postoperatively with folinic acid, fluorouracil, and irinotecan (FOLFIRI) and bevacizumab, which in its totality helped achieve a progression-free survival of more than two years. We believe that cytoreduction and intraoperative chemotherapy prolong survival in patients with recurrent disease, as was the case with our patients. Our patient also demonstrated benefit as his disease stabilized after starting bevacizumab; however, more studies need to be performed at a larger scale to show a consistent relationship.
small molecules
2026-09-28 | Long-term survival after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for appendiceal neoplasms: A Brazilian cancer center experience.
Appendiceal neoplasms represent less than 1% of all gastrointestinal cancers. Epithelial mucinous neoplasms of the appendix are classified as low grade, high grade, or adenocarcinoma. Pseudomyxoma peritonei, the peritoneal dissemination of these tumors, is a common clinical presentation. The management of peritoneal carcinomatosis is complex and involves cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy, a modality associated with significant surgical morbidity and resource demands. Nevertheless, cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy remains the standard of care. To evaluate overall survival and disease-free survival following cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy for appendiceal tumors in a Latin American cancer center. We conducted a retrospective observational cohort study including patients aged 18-75 years who underwent cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy between 2001 and 2021. Survival analysis was performed using Kaplan-Meier estimates and the log-rank test to compare overall survival and disease-free survival up to 10 years or until last follow-up or death. Cox proportional hazards models were applied to identify risk factors associated with recurrence and mortality. A total of 139 patients were included; 45.3% were male, with a mean age of 49.8 years. Fifty-four patients had mucinous neoplasms, and 85 patients had adenocarcinomas. The mean peritoneal cancer index was 14.9, and complete cytoreductive surgery was achieved in 133 patients (95.6%). The most commonly used chemotherapy agents were mitomycin (74.8%) and oxaliplatin (25.2%). At 10 years, overall survival and disease-free survival were 64.8% and 55.2%, respectively. Histology was significantly associated with prognosis (P = .04 for overall survival and P = .02 for disease-free survival at 10 years). In multivariable Cox regression, the use of oxaliplatin was associated with an increased risk of recurrence (hazard ratio, 2.71; 95% confidence interval, 1.26-5.53). Poorly differentiated or signet-ring cell histology was associated with a 3.5-fold increased risk of recurrence (hazard ratio, 3.54; 95% confidence interval, 1.44-8.68) and a 3-fold increased risk of death (hazard ratio, 2.9; 95% confidence interval, 1.14-7.26). Cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy is a complex but effective treatment for appendiceal neoplasms, providing favorable long-term survival rates with acceptable mortality when performed at experienced referral centers. Our study suggests that both the hyperthermic intraperitoneal chemotherapy drug and histological subtype influenced disease-free survival. These findings underscore the importance of careful patient selection and specialized multidisciplinary care to optimize outcomes.
2026-09-23 | A 6.3 kg uterine tumor resembling an ovarian sex cord-stromal tumor (UTROSCT): A case report.
Uterine tumor resembling ovarian sex cord-stromal tumor (UTROSCT) is a rare uterine neoplasm characterized by sex cord-like differentiation. Although typically indolent and confined to the uterus, UTROSCT can occasionally exhibit atypical clinical and pathological behavior, complicating preoperative diagnosis. A 52-year-old postmenopausal woman (G3P3A0) with no significant medical history presented with a painless umbilical swelling persisting for eight months. Physical and radiological assessment revealed a paraumbilical hernia and she was scheduled for elective laparoscopic repair. Intraoperatively, a large amount of viscous gelatinous material was unexpectedly discovered in the peritoneal cavity, with no visible peritoneal or visceral mass. Peritoneal biopsies and cytology suggested a low-grade neoplasm of uncertain origin, initially raising suspicion of pseudomyxoma peritonei (PMP). Computed tomography showed a large soft-tissue lesion occupying the lower abdomen and pelvic cavity, extending to the umbilicus and supplied by a branch of the uterine artery. Multidisciplinary tumor board discussion favored a uterine source, and cytoreductive surgery with total hysterectomy and peritonectomy was performed. A 40 cm encapsulated gelatinous uterine mass weighing 6.3 kg was excised. Histopathology and immunohistochemistry confirmed UTROSCT with positivity for sex cord markers and hormone receptors. Margins were negative and there was no lymphovascular invasion. The postoperative course was uneventful. The patient received adjuvant tamoxifen therapy and remained disease-free during 48 months of follow-up. This case illustrates an exceedingly rare presentation of UTROSCT, with much large tumor size than previously reported.
2026-09-06 | Ten-year recurrence-free survival in stage IV perforated appendiceal mucinous adenocarcinoma with high-risk features: a case report.
Appendiceal mucinous adenocarcinoma (MAC) associated with pseudomyxoma peritonei (PMP) has a poor prognosis in advanced stages. Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) is generally regarded as the standard treatment for PMP, but its management may require individualization based on tumor burden, histopathological risk, the patient's condition, and available treatment options. A 71-year-old man was initially managed conservatively for suspected acute appendicitis and was later referred to our department because of persistent appendiceal enlargement. Before the planned outpatient evaluation, he developed perforated appendicitis and underwent emergency laparoscopic appendectomy. Pathological examination showed MAC with high-risk features and a positive surgical margin. After multidisciplinary discussion, additional surgery aimed at macroscopic disease reduction was performed without CRS/HIPEC, including right hemicolectomy, lymph node dissection, and resection of visible peritoneal nodules and a paracaval lymph node. Postoperative FDG-PET/CT suggested residual pelvic disease, and systemic chemotherapy with capecitabine, oxaliplatin, and bevacizumab was administered. A clinical complete response was achieved, and the patient has remained recurrence-free for 10 years. This case suggests that long-term recurrence-free survival may be possible when the biologically active tumor burden is limited, timely surgery achieves substantial macroscopic disease reduction, and effective systemic chemotherapy controls residual disease, even if CRS/HIPEC is not performed. Long-term RFS may be achievable in carefully selected patients with stage IV appendiceal MAC and PMP, even without CRS/HIPEC. This case does not challenge CRS/HIPEC as the standard strategy for PMP but supports individualized multidisciplinary decision-making when CRS/HIPEC is not feasible or not selected.
2026-08-25 | SPONTANEOUSLY RUPTURED APPENDICEAL MUCOCELE DIAGNOSED ON CROSS-SECTIONAL IMAGING: A CASE REPORT
Appendiceal mucocele is a rare condition characterized by mucinous distension of the appendix. Spontaneous rupture is a serious complication that can lead to pseudomyxoma peritonei, a gelatinous disease of the peritoneum requiring aggressive management. We present the case of a 54-year-old man without prior surgical history who presented with acute right lower quadrant pain. Initial ultrasonography revealed localized fluid in the right iliac fossa. CT and MRI confirmed the diagnosis of spontaneously ruptured appendiceal mucocele. The patient underwent complete cytoreduction with appendicectomy and hyperthermic intra-peritoneal chemotherapy (CHIP). Histological findings were consistent with a low-grade mucinous neoplasm with pseudomyxoma peritonei. The patient had no postoperative complications. This case demonstrates that ultrasonography can detect early signs of rupture, while CT and MRI enable definitive diagnosis. Systematic evaluation for extraluminal mucin is essential when mucocele is suspected. CHIP represents an innovative therapeutic approach for pseudomyxoma peritonei.
2026-07-31 | Clinicopathological features and outcomes in 132 patients with perforated high grade appendiceal mucinous neoplasm treated with cytoreductive surgery and HIPEC - A single institution experience.
Non infiltrative mucinous appendiceal neoplasms are categorized into low grade appendiceal mucinous neoplasms (LAMN) and high grade appendiceal mucinous neoplasms (HAMN). The incidence of lymph node involvement in patients with a HAMN, the need for right hemicolectomy and its impact on prognosis after cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) has not been widely studied, nor reported. This was a single institution retrospective analysis of prospectively collected data of patients who underwent CRS and HIPEC for a HAMN between January 2015 and December 2023. Clinicopathological variables such as Peritoneal Cancer Index (PCI), completeness of cytoreduction (CC), histological subtype, lymph node status and survival were analysed. Between 2015 and 2023, 1615 patients underwent CRS and HIPEC for perforated appendiceal tumours. HAMNs were histologically confirmed in 132/1615 (8.2%). CRS and HIPEC was performed for a HAMN diagnosed after appendicectomy in 54/132 (40.9%) and 78 presented with the appendix tumour in situ, proceeding straight to surgery. The peritoneal disease in patients with HAMN was high grade mucinous carcinoma peritonei (MCP) in the majority (58.3%), with the remainder having low grade MCP (15.1%), acellular mucin (12.9%) or no peritoneal disease (13.6%). Overall, 96/132 (72.7%) underwent a right hemicolectomy as part of cytoreduction. Eight patients (8/96, 8.3%) had lymph node involvement in the colectomy specimens. The median PCI for those with nodal metastases (N = 8) was 29 with high grade MCP in all 8. Overall, 37/132 developed recurrence during the study period. All had peritoneal recurrence and 9/37 also had thoracic disease. In the 54 patients who had a HAMN at previous appendicectomy, 20/54 (37%) had no detectable disease on pre-operative imaging. However, histologically confirmed peritoneal disease was detected in the cytoreductive surgery specimen in 7/20 (35%). Less than 10% of patients with a perforated HAMN had involved nodes. Positive lymph node status appeared to be associated with high volume and high grade peritoneal disease. Overall, 35% of patients with a HAMN at appendicectomy had histologically proven peritoneal disease despite normal imaging. CRS and HIPEC is advocated for selected patients with a HAMN, predominantly for peritoneal disease cure and control.
cell therapies
2026-08-01 | TPW 8.06 Intestinal Transplantation for End-Stage Recurrent Pseudomyxoma Peritonei: The Impact of Nutritional and Functional Status on Outcomes Following Intestinal Transplantation
Abstract Aim To evaluate how anthropometrics affect post-transplant outcomes in patients with PMP. Intestinal transplantation can extend survival in patients with advanced, recurrent PMP not amenable to cytoreduction. Patient selection is challenging as patients may survive many years with advanced disease, but delaying referral can preclude transplant. Traditional anthropometrics, such as BMI, may be inaccurate due to tumour mass. Methods PMP referrals over a ten-year period were used to obtain anthropometric, demographic and survival data. Skeletal muscle area was measured using pre-transplant L3 CT-scans and adjusted for height to derive the skeletal muscle index (SMI). SMI was categorised as Normal, Class I or Class II depletion (n within 1SD, 2SD>n>1SD, n>2SD respectively) based on sex-adjusted values in a healthy population. Mid-Arm Muscle Circumference (MAMC), Grip Strength and Triceps Skin Fold Thickness (TSF) were also measured. Results Forty-nine referrals were reviewed. 17/49 patients (35%) were transplanted, 22% were listed but not transplanted (usually due to deterioration or debulking surgery), and 43% were never listed (unsuitable). Post-referral survival was significantly longer in transplanted patients compared with non-listed patients (median=4.01 and 0.76 years respectively). SMI, but not BMI, was significantly increased in the transplant group, and patients with normal SMI were more likely to be transplanted (χ2 df=2, p<0.05). SMI Class, MAMC, and TSF were not significantly associated with survival, or hospital/ICU length-of-stay. Conclusions Intestinal transplant for PMP can significantly extend survival. Nutritional status, particularly SMI, influences the decision for transplantation although there is limited evidence to support an association with improved post-transplant outcomes.
2026-07-01 | 1446 Intestinal Transplantation for End-Stage Recurrent Pseudomyxoma Peritonei: The Impact of Nutritional and Functional Status on Outcomes Following Intestinal Transplantation
Abstract Aim To evaluate how anthropometrics affect post-transplant outcomes in patients with PMP. Intestinal transplantation can extend survival in patients with advanced, recurrent PMP not amenable to cytoreduction. Patient selection is challenging as patients may survive many years with advanced disease, but delaying referral can preclude transplant. Traditional anthropometrics, such as BMI, may be inaccurate due to tumour mass. Method PMP referrals over a ten-year period were used to obtain anthropometric, demographic and survival data. Skeletal muscle area was measured using pre-transplant L3 CT-scans and adjusted for height to derive the skeletal muscle index (SMI). SMI was categorised as Normal, Class I or Class II depletion (n within 1SD, 2SD>n>1SD, n>2SD respectively) based on sex-adjusted values in a healthy population. Mid-Arm Muscle Circumference (MAMC), Grip Strength and Triceps Skin Fold Thickness (TSF) were also measured. Results Forty-nine referrals were reviewed. 17/49 patients (35%) were transplanted, 22% were listed but not transplanted (usually due to deterioration or debulking surgery), and 43% were never listed (unsuitable). Post-referral survival was significantly increased in the transplanted group compared to the non-listed group (median=4.01 and 0.76 years respectively). SMI, but not BMI, was significantly increased in the transplant group, and patients with normal SMI were more likely to be transplanted (χ2 df=2, p<0.05). SMI Class, MAMC, and TSF were not significantly associated with survival, or hospital/ICU length-of-stay. Conclusions Intestinal transplant for PMP can significantly extend survival. Nutritional status, particularly SMI, is linked to the decision for transplantation although there is limited evidence to support an association with improved post-transplant outcomes.
2026-06-26 | Appendiceal Mucinous Neoplasms and Pseudomyxoma Peritonei: Current Classification and the Role of Intraperitoneal Chemotherapy.
Appendiceal mucinous neoplasms (AMNs) are a rare but clinically significant category of gastrointestinal tumors, ranging from low-grade appendiceal mucinous neoplasm (LAMN), the main precursor of pseudomyxoma peritonei (PMP), to high-grade appendiceal mucinous neoplasm (HAMN), poorly differentiated and signet-ring-cell adenocarcinomas, and goblet cell adenocarcinoma. Although current WHO and PSOGI classifications provide well established diagnostic criteria, controversies persist regarding the biological behavior and prognostic significance of the most aggressive subtypes and the relationship between HAMN and mucinous adenocarcinoma. While appendectomy is sufficient for localized LAMN, cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) is the treatment of choice for peritoneal dissemination This review integrates the histopathological and molecular classification of AMN and PMP with the evolution of intraperitoneal chemotherapy. Key findings indicate that KRAS and GNAS mutations are central drivers of mucin overproduction and peritoneal spread, that tumor grade and mucin cellularity remain the strongest prognostic determinants, and that the evidence supporting HIPEC and PIPAC derives largely from observational rather than randomized data. As a novel insight, we highlight the emerging role of patient-derived organoids as translational models for functional drug testing. Progress will depend on integrating molecular characterization, critical appraisal of intraperitoneal therapies, and organoid-based testing to advance individualized treatment for peritoneal surface malignancies.
2026-06-24 | High-grade Peritoneal Pseudomyxoma of Primary Ovarian Origin Revealed by a Borderline Mucinous Tumor in a 26-year-old Woman: A Case Report and Literature Review
Pseudomyxoma peritonei (PMP) is a rare condition predominantly originating from appendiceal neoplasms, making true primary ovarian PMP an exceptional and widely debated clinical entity. Establishing a primary Müllerian origin requires exhaustive histological and immunohistochemical evaluation to exclude an occult appendiceal tumor. A highly unusual clinical scenario involves a 26-year-old nulliparous woman presenting with a large borderline mucinous ovarian tumor paradoxically associated with high-grade peritoneal implants. Comprehensive pathological workup (CK7+, PAX8+, CK20−, CDX2−) and completely normal appendiceal serial sections definitively confirmed the primary ovarian origin. Standard-of-care management relies on complete cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC). Successful CC0 cytoreduction and HIPEC were achieved, integrated with proactive ovarian cortex cryopreservation. This unusual presentation highlights the striking biological discordance that can exist between a primary tumor and its peritoneal dissemination, emphasizing the critical role of specialized multidisciplinary management, rigorous pathology, and early oncofertility integration for young patients.
2026-06-06 | Quality of life in patients with pseudomyxoma peritonei treated with cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy and implications for ERAS-informed rehabilitation.
Cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy (CRS + HIPEC) is the standard of care for pseudomyxoma peritonei (PMP) but is associated with substantial perioperative burden and prolonged recovery. Contemporary data on health-related quality of life (HRQoL) trajectories after CRS + HIPEC remain limited, as does their integration into perioperative and rehabilitation planning. We aimed to characterize short- and mid-term HRQoL changes after CRS + HIPEC in PMP and to identify ERAS-informed rehabilitation priorities based on postoperative symptom and function trajectories. We screened 273 patients from our institutional PMP CRS + HIPEC database and included 111 adults who had adequate EORTC QLQ-C30 data for longitudinal analysis. HRQoL was assessed using the EORTC QLQ-C30 at baseline and 1 week, 1, 3, 6, 9 and 12 months postoperatively. Longitudinal changes were summarized descriptively, and mean differences versus baseline were interpreted using established minimally important difference thresholds (≥10 points). At 1 week postoperatively, physical, role, emotional, cognitive and social functioning and global QoL declined by 22.9, 41.6, 13.3, 19.7, 20.5 and 28.4 points, respectively, all exceeding the threshold for clinically meaningful deterioration. Fatigue, pain, dyspnoea, insomnia, appetite loss and financial difficulties showed peak or near-peak worsening at 1 week, whereas constipation and diarrhea peaked at 3 months. Overall QoL was worst around 1 month postoperatively and then improved steadily; by 12 months, most functional scales and symptoms had returned to or approached baseline (e.g. global QoL -1.1 points vs. preoperative), although mild residual cognitive and bowel disturbances persisted in some patients. CRS + HIPEC for PMP imposes a pronounced but largely transient HRQoL burden, characterized by a sharp early decline, mid-term recovery and near-restoration of baseline QoL within 6-12 months. Our findings support an ERAS-informed rehabilitation framework that prioritizes pain control, respiratory recovery, nutrition, sleep, and psychological support. These elements should be interpreted as clinically informed rehabilitation priorities rather than as a validated intervention package directly derived from this observational dataset. These findings inform preoperative counseling and the timing of follow-up after CRS + HIPEC.
other
2024-08-05 | Genome-Wide Analysis of DNA Methylation in Pseudomyxoma Peritonei Originated from Appendiceal Neoplasms.
Pseudomyxoma peritonei (PMP) is a disease characterized by progressive accumulation of intraperitoneal mucinous ascites produced by neoplasms in the abdominal cavity. Since the prognosis of patients with PMP remains unsatisfactory, the development of effective therapeutic drug(s) is a matter of pressing concern. Genetic analyses of PMP have clarified the frequent activation of GNAS and/or KRAS. However, the involvement of global epigenetic alterations in PMPs has not been reported. To clarify the genetic background of the 15 PMP tumors, we performed genetic analysis using AmpliSeq Cancer HotSpot Panel v2. We further investigated global DNA methylation in the 15 tumors and eight noncancerous colonic epithelial tissues using MethylationEPIC array BeadChip (Infinium 850k) containing a total of 865,918 probes. This is the first report of comprehensive DNA methylation profiles of PMPs in the world. We clarified that the 15 PMPs could be classified into at least two epigenotypes, unique methylation epigenotype (UME) and normal-like methylation epigenotype (NLME), and that genes associated with neuronal development and synaptic signaling may be involved in the development of PMPs. In addition, we identified a set of hypermethylation marker genes such as HOXD1 and TSPYL5 in the 15 PMPs. These findings may help the understanding of the molecular mechanism(s) of PMP and contribute to the development of therapeutic strategies for this life-threatening disease.
2024-01-15 | Efficacy of Different Oncolytic Vaccinia Virus Strains for the Treatment of Murine Peritoneal Mesothelioma
Effective treatment options for peritoneal surface malignancies (PSMs) are scarce. Oncolytic virotherapy with recombinant vaccinia viruses might constitute a novel treatment option for PSM. We aimed to identify the most effective oncolytic vaccinia virus strain in two murine mesothelioma cell lines and the oncolytic potential in a murine model of peritoneal mesothelioma. Cell lines AB12 and AC29 were infected in vitro with vaccinia virus strains Lister (GLV-1h254), Western Reserve (GLV-0b347), and Copenhagen (GLV-4h463). The virus strain GLV-0b347 was shown most effective in vitro and was further investigated by intraperitoneal (i.p.) application to AB12 and AC29 mesothelioma-bearing mice. Feasibility, safety, and effectiveness of virotherapy were assessed by evaluating the peritoneal cancer index (PCI), virus detection in tumor tissues and ascites, virus growth curves, and comparison of overall survival. After i.p. injection of GLV-0b347, virus was detected in both tumor cells and ascites. In comparison to mock-treated mice, overall survival was significantly prolonged, ascites was less frequent and PCI values declined. However, effective treatment was only observed in animals with limited tumor burden at the time point of virus application. Nonetheless, intraperitoneal virotherapy with GLV-0b347 might constitute a novel therapeutic option for the treatment of peritoneal mesothelioma. Additional treatment modifications and combinational regimes will be investigated to further enhance treatment efficacy.
2022-12-06 | A New Molecular (P)Layer in Pseudomyxoma Peritonei: The Splicing Machinery is Dysregulated and Linked to Low Survival
Abstract Purpose : Pseudomyxoma peritonei (PMP) is a rare cancer that causes chronic and uncontrollable mucus accumulation, gradually leading to intraperitoneal organ adhesion, bowel obstruction, malnutrition, and eventually cachexia and death. Aggressive cytoreductive surgery and hyperthermic intraperitoneal chemotherapy offer the best results; but the probability of relapse remains high. The study of the distinct molecular layers underlying PMP is essential to understand its genesis and progression. Alternative splicing is emerging as a new player in all cancers, but its role in PMP is unknown. The aim of this work was to assess the splicing machinery status in PMP and determine its potential contribution to disease prognosis. Methods : A set of 62 splicing-related genes were evaluated in a cohort of 29 patients using a microfluidic array, and their levels were compared between tumor and non-tumor tissue and correlated to relevant clinical parameters. Selected components were validated by immunohistochemistry and subsequently studied in detail by enrichment analyses. Results : Results revealed a profound dysregulation of the splicing machinery at RNA/protein level, which allowed to distinguish between tumor and control tissues. Particularly, the splicing factors HNRNPK , MBNL1 , PTBP1 and RAVER1 were associated with poor prognosis and their expression was linked to TP53 regulation and inflammation processes. Conclusions : These findings provide the first evidence for the dysregulation of the splicing machinery in PMP, suggesting that it could be functionally altered and play a role in this rare malignant disease. Therefore, its detailed understanding could help to identify novel prognostic biomarkers and therapeutic targets in PMP.
proteins
2026-06-06 | Efficacy and safety of fibrinogen concentrate (BT524) in severe hemorrhage: Phase 3 subcohort analysis of the AdFIrst trial in patients undergoing cytoreductive surgery for pseudomyxoma peritonei.
The AdFIrst phase 3 trial evaluated the efficacy and safety of human fibrinogen concentrate (FC) versus standard of care for major bleeding in complex surgery. This subanalysis evaluated a preemptive hemostatic strategy using FC versus cryoprecipitate (Cryo) to manage severe bleeding patients undergoing major abdominal surgery, specifically cytoreductive surgery (CRS) for pseudomyxoma peritonei (PMP). A single-center UK analysis derived from a randomized, active-controlled, partially blinded, phase 3, non-inferiority trial. Patients undergoing PMP surgery with predicted intraoperative blood loss >2 L were randomized (1:1) to receive either FC (4 g) or two pools of Cryo (10 units) with repeat dosing as required. The primary endpoint was intraoperative blood loss, measured from the decision to treat the patient with trial drug until the end of surgery with a non-inferiority margin of 150 mL (ClinicalTrials.gov: NCT03444324). Between March 2021 and September 2023, 98 patients (48 FC; 50 Cryo) were enrolled, randomized, and evaluated. The primary endpoint was met: Least squares mean intraoperative blood loss was 1517 mL (95% CI, 1331-1703) with FC and 1706 mL (95% CI, 1524-1889) with Cryo, corresponding to a difference of -190 mL (95% CI, -450 to 71; nominal exploratory p = 0.011). The upper bound of the 95% CI was below the prespecified non-inferiority margin, consistent with the non-inferiority observed in the overall trial. Thromboembolic events occurred in fewer patients in the FC group (3 [6.3%]) than in the Cryo group (11 [22%]; nominal exploratory p = 0.041); other safety outcomes were comparable between groups. In patients undergoing CRS for PMP, these results provide supportive evidence for the hemostatic efficacy of FC, consistent with the overall trial and prior studies, with a favorable safety profile. In this single-center PMP subgroup, the findings support a preemptive fibrinogen strategy that may inform practice in other surgical settings and warrants evaluation in future studies.
2026-05-18 | Mucinase from Bacteroides thetaiotaomicron as mucolytic for mucinous cancer pseudomyxoma peritonei.
Mucinous cancers are characterized by tumor gland cells secreting copious amounts of mucus that forms gel-like structures. Pseudomyxoma peritonei (PMP), a rare yet prototypical mucinous malignancy, exemplifies this pathology. Biologically inert mucus coats tumor cells, promoting colonization, immune evasion, and chemoresistance. Pathological mucus accumulation leads to intra-abdominal hypertension, refractory abdominal pain, abdominal adhesions, and intestinal obstruction because of the lack of rapid, efficient, and safe clinical strategies for mucin clearance. Current management relies on extensive cytoreductive surgery to excise tumor masses and adherent mucus. Here, we present an integrated workflow spanning intestinal probiotic protease discovery for the development of mucolytic therapy. By cultivating Bacteroides thetaiotaomicron (B. theta) with PMP-derived mucus as the sole nutrient source, we identified its intrinsic mucolytic capacity. Crucially, transcriptomic analysis revealed that B. theta orchestrates mucus degradation via the PULs gene cluster, with concomitant upregulation of the M60 family metalloproteinases BT4244, BT3015, and BT4272. Functional validation classified these enzymes as "mucinases" responsible for tumor-associated mucin cleavage and mucolysis. Our study provides a foundation for enzyme-targeted PMP therapy, offering a paradigm shift toward minimally invasive, high-efficacy mucolysis. Our findings highlight the translational potential of microbial proteases in addressing clinical challenges posed by mucinous malignancies.
2025-12-18 | The addition of collagenase to BromAc ® for the management of inoperable pseudomyxoma peritonei - in vitro results.
Pseudomyxoma peritonei (PMP) is a rare peritoneal malignancy. BromAc ® is a novel therapeutic agent which has been developed to dissolve and facilitate the drainage of mucin as a palliative treatment for PMP; however, its effect is significantly reduced in patients with hard mucin. This study aimed to assess whether combining collagenase or cysteamine with BromAc ® would be more effective in dissolving hard mucin. This preclinical human in vitro study examined the effect of adding collagenase to BromAc ® on hard mucin samples when incubated at 37 °C over 24 h. The effect of cysteamine alone and in combination with collagenase and BromAc ® was also examined as a supplementary arm of this study. Five experiments were conducted with appropriate controls. Human hard mucin samples were sliced into equal fractions using a sterile surgical scalpel, weighed and noted. The leftover solid mucin was weighed at 0, 1, 3, 5, and 24 h post-treatment. At 24 h post-treatment, all combinations with collagenase demonstrated almost 100 % dissolution of hard mucin. At 3 and 5 h post-treatment, only BromAc ® with collagenase at 250 μg/mL was found to be superior to BromAc ® alone. Combinations with cysteamine were not found to be effective. This study provides promising evidence of the efficacy and synergistic effect of combining BromAc ® with collagenase to dissolve hard mucin. Further preclinical and clinical research should be undertaken to assess its safety and efficacy in the clinical setting.
2025-09-14 | From Theory to Practice: A Comprehensive Review of Pseudomyxoma Peritonei Research and Its Implications for Future Treatment.
Pseudomyxoma peritonei (PMP) is a rare disease characterized by symptoms such as mucinous ascites and omental cake, typically arising from a perforated epithelial tumor of the appendix. Because of its rarity, non-specific histologic characteristics, and slow progression, its pathogenesis and optimal treatment remain subjects of debate. PMP is still a challenging and enigmatic condition. Increasing global attention is being directed toward understanding its pathogenesis and establishing standard treatment approaches. PMP and mucin are inextricably linked. This article highlighted the important role of mucin in the disease's pathogenesis. It also discussed several potential therapeutic strategies for eliminating mucin in PMP. Tumor development and metastasis involve a series of steps that include the interaction between the tumor and the host-derived stromal environment, which promotes angiogenesis and activation of inflammatory cells. Inflammatory cytokines and chemokines play a crucial role in the progression and development of PMP. The microbiome and specific microorganisms may directly influence tumor development, progression, and responses to certain therapies in PMP. Thus, the article summarized the interactions among bacteria, the immune system, and mucin in PMP, focusing on the mechanisms that related to abnormal mucin and tumor growth. This review critically examined the existing literature on the clinical features, pathologic processes, and treatment options in PMP, aiming to guide future research toward identifying novel therapeutic targets and gut-related disease biomarkers.
2025-07-31 | Efficacy and safety of human fibrinogen concentrate (BT524) in patients with major haemorrhage undergoing major orthopaedic or abdominal surgery (AdFIrst): a randomised, active-controlled, multicentre, partially blinded, phase 3 non-inferiority trial.
Major haemorrhage is associated with considerable morbidity and mortality, but the optimal treatment remains disputed. This trial aimed to compare the efficacy and safety of human fibrinogen concentrate (FC) vs. either fresh frozen plasma (FFP) or cryoprecipitate (Cryo) as first-line treatment in patients with major bleeding during major orthopaedic or abdominal surgery, respectively. AdFIrst was a randomised, active-controlled, partially blinded, non-inferiority phase 3 trial conducted at 15 hospitals in Europe. Eligible patients (≥18 years), undergoing major spinal surgery or cytoreductive surgery for pseudomyxoma peritonei, with clinically relevant intraoperative blood loss were randomised by an interactive web response system (1:1) to receive intravenous FC (2-4 g) compared to FFP (15 mL/kg body weight) or Cryo (10 units); doses were repeated as needed. The primary endpoint was intraoperative blood loss from the time of decision to treat until the end of surgery with a non-inferiority margin of 150 mL, assessed in the per-protocol analysis set (PPS). Safety was assessed in all patients who received at least one dose of trial drug. The trial is complete (ClinicalTrials.gov: NCT03444324). Between February 12, 2018, and November 21, 2023, 222 patients (131 [59%] female; 91 [41%] male; 97% white) were enrolled and randomly assigned to receive either FC (n = 110) or FFP/Cryo (n = 112). The PPS included 201 patients (FC: n = 103; FFP/Cryo: n = 98). The primary endpoint was met; the least squares mean (LSM: adjusted mean estimated using ANOVA) intraoperative blood loss was 1381 mL (95% confidence interval [CI] 1187-1574) in the FC group and 1660 mL (95% CI 1461-1860) in the FFP/Cryo group. The LSM difference was -279 mL (95% CI -552 to -6; p < 0·0001), indicating a notable treatment difference beyond non-inferiority. In a post-hoc analysis, FC showed superiority to reduce intraoperative blood loss over FFP/Cryo in the PPS (p = 0·0087). Serious adverse events were reported in 28/110 patients (25%) in the FC and 41/112 patients (37%) in the FFP/Cryo group. Thromboembolic events occurred in 17 patients (FC: 4 (4%) and FFP/Cryo: 13 (12%). There were no treatment-related deaths. In patients undergoing major spinal or cytoreductive surgery for pseudomyxoma peritonei (PMP), FC was non-inferior to FFP/Cryo for the management of clinically relevant intraoperative bleeding. The efficacy and safety advantages observed in this trial support the emerging adoption of first-line use of FC in treatment guidelines. Biotest AG, Germany.
antibodies
2025-06-01 | Clinical features and prognostic analysis of 14 cases of appendiceal mixed neuroendocrine-non-neuroendocrine tumors with peritoneal pseudomyxoma.
Appendiceal mixed neuroendocrine-non-neuroendocrine neoplasms (a-MiNENs) combined with peritoneal pseudomyxoma (PMP) represent an exceptionally rare and clinically challenging entity. This study aims to elucidate the clinical characteristics of this unique tumor subtype and identify critical prognostic factors, thereby providing insights into the management and outcomes of affected patients. We conducted a retrospective analysis of 14 patients diagnosed with a-MiNEN and PMP at the Department of Myxoma, Aerospace Center Hospital, between January 2014 and September 2022. Data included demographics, symptoms, tumor grading, treatments, and outcomes. Pathological evaluation revealed a diverse spectrum of tumor grades and PMP subtypes: 5 cases were classified as G1 neuroendocrine tumors (NET), 4 as G2 NET, and 5 as G3 neuroendocrine carcinoma (NEC). Regarding PMP subtypes, 5 cases had disseminated peritoneal adenomucinosis (DPAM), 4 had peritoneal mucinous carcinomatosis (PMCA), and 5 had peritoneal mucinous carcinomatosis with signet ring cell carcinoma (PMCA-S). The median postoperative survival time was 28.55 months, with 1-year and 2-year survival rates of 80.0% and 66.7%, respectively. Patients aged < 60 years, male sex, absence of right hemicolectomy, postoperative peritoneal cancer index (PCI) ≥ 25, and perineural invasion demonstrated significantly lower 1-year and 2-year survival rates compared to their counterparts, with distinct separation observed in the Kaplan-Meier curves. These factors likely reflect biological differences in disease progression, inadequate surgical debulking, and aggressive tumor behavior. a-MiNEN with PMP progresses rapidly. Young patients, male patients, those with absence of right hemicolectomy, postoperative PCI ≥ 25 and perineural invasion may face poorer outcomes. This study, one of the few to analyze this rare condition, underscores the need for targeted treatments and further validation in larger cohorts.
2024-11-15 | Comparison of functional characterization of cancer stem cells in different tumor tissues of pseudomyxoma peritonei.
Pseudomyxoma peritonei (PMP) is a rare malignant peritoneal tumor that readily recurs and metastasizes. Studies have shown that cancer stem cells (CSCs) play an important role in tumor recurrence, metastasis, and prognosis. In this study, our aim was to isolate CSCs from various tissues of PMP patients and compare their proliferation, migration, and anti-inflammatory abilities. We identified CSCs subsets with markers CD133+, CD166+, and CD133+/CD166+ at the gene level using single-cell mRNA sequencing (scRNA-seq). Appendiceal CSCs (AC), peritoneal CSCs (PC), and mucous CSCs (MC) were obtained using MACSQuant Tyto sorting technology and FlowSight imaging flow cytometry. The cells were cultured and markers were identified. Finally, the functional phenotypes of the three cell types were compared. CSCs content was highest in the appendiceal tumor tissue and lowest in the mucous tissue. The cell viability rate of the sorted CSCs was above 98%, and the positive rate of CD133+ and CD166+ was 70-80%, and CD133+/CD166+ was about 30%. Among the three types of CSCs, MC had the highest proliferation ability, and TNF-α has the greatest inhibitory effect on AC migration. AC in patients was more inert and anti-inflammatory, whereas abdominal cavity MC and PC were more active. This study revealed the biological characteristics of CSCs in different tumor tissues of patients with PMP, providing a reference for future targeted CSCs therapy.
2024-09-23 | Pseudomyxoma Peritonei Arising From a Mucinous Ovarian Borderline Tumor Treated With Paclitaxel, Cisplatin, and Bevacizumab: A Case Report.
Pseudomyxoma peritonei (PMP) is a rare disease caused by primary mucinous neoplasms. Here, we describe a case where a large ovarian tumor was initially removed laparoscopically, followed by an appendectomy. The patient was diagnosed with PMP arising from an ovarian mucinous borderline tumor with a KRAS mutation. Treatment included bevacizumab-containing chemotherapy, resulting in complete remission.
2023-07-20 | A2AR Expression and Immunosuppressive Environment Independent of KRAS and GNAS Mutations in Pseudomyxoma Peritonei
In pseudomyxoma peritonei (PMP), KRAS and GNAS mutations are frequent. We hypothesized that these mutations may contribute to the suppression of antitumor immunity: KRAS may induce GMCSF expression, while GNAS may enhance the expression of cyclic adenosine monophosphate and A2AR signaling. This study aimed to explore possible mechanisms facilitated by KRAS and GNAS mutations for escaping immune surveillance. Additionally, we looked for new potential therapeutic and prognostic targets in this rare disease which is poorly characterized at the molecular level. GM-CSF, A2AR, CD73, CD39, and PD-L1 expression was investigated by immunohistochemistry in 40 PMPs characterized for GNAS and KRAS mutational status. Immune cell populations were studied by immunohistochemistry and nanostring nCounter®. Following the criteria of a prognostic nomogram reported for PMP, we stratified the patients into two different risk groups, with 28 "low-risk" and 12 "high-risk" patients. We observed the expression of GM-CSF (74%); CD39 (37%); CD73 (53%); A2AR (74%); and PD-L1 (16%) which was unrelated to GNAS or KRAS status. The tumor microenvironment showed the presence of CD4+ T cells (86%); CD8+ T cells (27%); CD20+ B (67%); CD15+ cells (86%); and CD163+ M2 macrophages (67%), while CD56+ NK cells were absent. CD163 expression (27%) in PMP tumor cells was associated with poor prognosis. GNAS mutation and A2AR expression were not associated with a specific immune transcriptional signature. However, the expression assay revealed 21 genes associated with prognosis. The "high-risk" patients exhibited worse progression-free survival (HR = 2.3, CI 95%: 1.1-5.1, p = 0.034) and significant downregulation of MET, IL8, PPARG, DTX4, HMGA1, ZIC2, WNT5B, and CCRL2. In conclusion, we documented the presence of immunosuppressive factors such as GM-CSF, A2AR, and PD-L1 in PMP. These factors were not associated with GNAS and KRAS status and could be explored as therapeutic molecular targets. Additionally, a set of potential prognostic biomarkers, including CD163 expression in tumor cells, deserve further investigation.
2023-01-03 | Rare Mucinous Adenocarcinoma of the Appendix Undergoing Multiple Recurrent Surgical Interventions
Primary appendiceal carcinomas are rare and often found incidentally when the appendix is surgically removed. Adenocarcinoma predominates the histological types of malignancies, with mucinous adenocarcinoma being the most prevalent of the various subtypes. Pseudomyxoma peritonei (PMP), a complication seen in mucinous adenocarcinoma of the appendix (MAA), is the collection of mucinous ascites in the intra-abdominal cavity and the thickening of the surrounding viscera by mucin-producing tumor cells. PMP initially presents with increased abdominal discomfort and girth and, in later stages, presents with obstructive abdomen symptoms. These symptoms are nonspecific and can be a challenge to pinpoint. Such was the case for our patient, in this case report, who initially presented with dyspepsia and later demonstrated compressive symptoms and weight loss, raising concern for malignancy. An appendiceal pathology was of concern when his right lower quadrant pain acutely worsened during an abdominal ultrasound, and imaging and biopsy confirmed MAA with PMP. The aim of this report is to shed light on the management of recurrent MAA. Our patient's recurrent MAA was managed with debulking procedures and three rounds of hyperthermic intraperitoneal chemotherapy (HIPEC) and was managed postoperatively with folinic acid, fluorouracil, and irinotecan (FOLFIRI) and bevacizumab, which in its totality helped achieve a progression-free survival of more than two years. We believe that cytoreduction and intraoperative chemotherapy prolong survival in patients with recurrent disease, as was the case with our patients. Our patient also demonstrated benefit as his disease stabilized after starting bevacizumab; however, more studies need to be performed at a larger scale to show a consistent relationship.
small molecules
2026-09-28 | Long-term survival after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for appendiceal neoplasms: A Brazilian cancer center experience.
Appendiceal neoplasms represent less than 1% of all gastrointestinal cancers. Epithelial mucinous neoplasms of the appendix are classified as low grade, high grade, or adenocarcinoma. Pseudomyxoma peritonei, the peritoneal dissemination of these tumors, is a common clinical presentation. The management of peritoneal carcinomatosis is complex and involves cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy, a modality associated with significant surgical morbidity and resource demands. Nevertheless, cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy remains the standard of care. To evaluate overall survival and disease-free survival following cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy for appendiceal tumors in a Latin American cancer center. We conducted a retrospective observational cohort study including patients aged 18-75 years who underwent cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy between 2001 and 2021. Survival analysis was performed using Kaplan-Meier estimates and the log-rank test to compare overall survival and disease-free survival up to 10 years or until last follow-up or death. Cox proportional hazards models were applied to identify risk factors associated with recurrence and mortality. A total of 139 patients were included; 45.3% were male, with a mean age of 49.8 years. Fifty-four patients had mucinous neoplasms, and 85 patients had adenocarcinomas. The mean peritoneal cancer index was 14.9, and complete cytoreductive surgery was achieved in 133 patients (95.6%). The most commonly used chemotherapy agents were mitomycin (74.8%) and oxaliplatin (25.2%). At 10 years, overall survival and disease-free survival were 64.8% and 55.2%, respectively. Histology was significantly associated with prognosis (P = .04 for overall survival and P = .02 for disease-free survival at 10 years). In multivariable Cox regression, the use of oxaliplatin was associated with an increased risk of recurrence (hazard ratio, 2.71; 95% confidence interval, 1.26-5.53). Poorly differentiated or signet-ring cell histology was associated with a 3.5-fold increased risk of recurrence (hazard ratio, 3.54; 95% confidence interval, 1.44-8.68) and a 3-fold increased risk of death (hazard ratio, 2.9; 95% confidence interval, 1.14-7.26). Cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy is a complex but effective treatment for appendiceal neoplasms, providing favorable long-term survival rates with acceptable mortality when performed at experienced referral centers. Our study suggests that both the hyperthermic intraperitoneal chemotherapy drug and histological subtype influenced disease-free survival. These findings underscore the importance of careful patient selection and specialized multidisciplinary care to optimize outcomes.
2026-09-23 | A 6.3 kg uterine tumor resembling an ovarian sex cord-stromal tumor (UTROSCT): A case report.
Uterine tumor resembling ovarian sex cord-stromal tumor (UTROSCT) is a rare uterine neoplasm characterized by sex cord-like differentiation. Although typically indolent and confined to the uterus, UTROSCT can occasionally exhibit atypical clinical and pathological behavior, complicating preoperative diagnosis. A 52-year-old postmenopausal woman (G3P3A0) with no significant medical history presented with a painless umbilical swelling persisting for eight months. Physical and radiological assessment revealed a paraumbilical hernia and she was scheduled for elective laparoscopic repair. Intraoperatively, a large amount of viscous gelatinous material was unexpectedly discovered in the peritoneal cavity, with no visible peritoneal or visceral mass. Peritoneal biopsies and cytology suggested a low-grade neoplasm of uncertain origin, initially raising suspicion of pseudomyxoma peritonei (PMP). Computed tomography showed a large soft-tissue lesion occupying the lower abdomen and pelvic cavity, extending to the umbilicus and supplied by a branch of the uterine artery. Multidisciplinary tumor board discussion favored a uterine source, and cytoreductive surgery with total hysterectomy and peritonectomy was performed. A 40 cm encapsulated gelatinous uterine mass weighing 6.3 kg was excised. Histopathology and immunohistochemistry confirmed UTROSCT with positivity for sex cord markers and hormone receptors. Margins were negative and there was no lymphovascular invasion. The postoperative course was uneventful. The patient received adjuvant tamoxifen therapy and remained disease-free during 48 months of follow-up. This case illustrates an exceedingly rare presentation of UTROSCT, with much large tumor size than previously reported.
2026-09-06 | Ten-year recurrence-free survival in stage IV perforated appendiceal mucinous adenocarcinoma with high-risk features: a case report.
Appendiceal mucinous adenocarcinoma (MAC) associated with pseudomyxoma peritonei (PMP) has a poor prognosis in advanced stages. Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) is generally regarded as the standard treatment for PMP, but its management may require individualization based on tumor burden, histopathological risk, the patient's condition, and available treatment options. A 71-year-old man was initially managed conservatively for suspected acute appendicitis and was later referred to our department because of persistent appendiceal enlargement. Before the planned outpatient evaluation, he developed perforated appendicitis and underwent emergency laparoscopic appendectomy. Pathological examination showed MAC with high-risk features and a positive surgical margin. After multidisciplinary discussion, additional surgery aimed at macroscopic disease reduction was performed without CRS/HIPEC, including right hemicolectomy, lymph node dissection, and resection of visible peritoneal nodules and a paracaval lymph node. Postoperative FDG-PET/CT suggested residual pelvic disease, and systemic chemotherapy with capecitabine, oxaliplatin, and bevacizumab was administered. A clinical complete response was achieved, and the patient has remained recurrence-free for 10 years. This case suggests that long-term recurrence-free survival may be possible when the biologically active tumor burden is limited, timely surgery achieves substantial macroscopic disease reduction, and effective systemic chemotherapy controls residual disease, even if CRS/HIPEC is not performed. Long-term RFS may be achievable in carefully selected patients with stage IV appendiceal MAC and PMP, even without CRS/HIPEC. This case does not challenge CRS/HIPEC as the standard strategy for PMP but supports individualized multidisciplinary decision-making when CRS/HIPEC is not feasible or not selected.
2026-08-25 | SPONTANEOUSLY RUPTURED APPENDICEAL MUCOCELE DIAGNOSED ON CROSS-SECTIONAL IMAGING: A CASE REPORT
Appendiceal mucocele is a rare condition characterized by mucinous distension of the appendix. Spontaneous rupture is a serious complication that can lead to pseudomyxoma peritonei, a gelatinous disease of the peritoneum requiring aggressive management. We present the case of a 54-year-old man without prior surgical history who presented with acute right lower quadrant pain. Initial ultrasonography revealed localized fluid in the right iliac fossa. CT and MRI confirmed the diagnosis of spontaneously ruptured appendiceal mucocele. The patient underwent complete cytoreduction with appendicectomy and hyperthermic intra-peritoneal chemotherapy (CHIP). Histological findings were consistent with a low-grade mucinous neoplasm with pseudomyxoma peritonei. The patient had no postoperative complications. This case demonstrates that ultrasonography can detect early signs of rupture, while CT and MRI enable definitive diagnosis. Systematic evaluation for extraluminal mucin is essential when mucocele is suspected. CHIP represents an innovative therapeutic approach for pseudomyxoma peritonei.
2026-07-31 | Clinicopathological features and outcomes in 132 patients with perforated high grade appendiceal mucinous neoplasm treated with cytoreductive surgery and HIPEC - A single institution experience.
Non infiltrative mucinous appendiceal neoplasms are categorized into low grade appendiceal mucinous neoplasms (LAMN) and high grade appendiceal mucinous neoplasms (HAMN). The incidence of lymph node involvement in patients with a HAMN, the need for right hemicolectomy and its impact on prognosis after cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) has not been widely studied, nor reported. This was a single institution retrospective analysis of prospectively collected data of patients who underwent CRS and HIPEC for a HAMN between January 2015 and December 2023. Clinicopathological variables such as Peritoneal Cancer Index (PCI), completeness of cytoreduction (CC), histological subtype, lymph node status and survival were analysed. Between 2015 and 2023, 1615 patients underwent CRS and HIPEC for perforated appendiceal tumours. HAMNs were histologically confirmed in 132/1615 (8.2%). CRS and HIPEC was performed for a HAMN diagnosed after appendicectomy in 54/132 (40.9%) and 78 presented with the appendix tumour in situ, proceeding straight to surgery. The peritoneal disease in patients with HAMN was high grade mucinous carcinoma peritonei (MCP) in the majority (58.3%), with the remainder having low grade MCP (15.1%), acellular mucin (12.9%) or no peritoneal disease (13.6%). Overall, 96/132 (72.7%) underwent a right hemicolectomy as part of cytoreduction. Eight patients (8/96, 8.3%) had lymph node involvement in the colectomy specimens. The median PCI for those with nodal metastases (N = 8) was 29 with high grade MCP in all 8. Overall, 37/132 developed recurrence during the study period. All had peritoneal recurrence and 9/37 also had thoracic disease. In the 54 patients who had a HAMN at previous appendicectomy, 20/54 (37%) had no detectable disease on pre-operative imaging. However, histologically confirmed peritoneal disease was detected in the cytoreductive surgery specimen in 7/20 (35%). Less than 10% of patients with a perforated HAMN had involved nodes. Positive lymph node status appeared to be associated with high volume and high grade peritoneal disease. Overall, 35% of patients with a HAMN at appendicectomy had histologically proven peritoneal disease despite normal imaging. CRS and HIPEC is advocated for selected patients with a HAMN, predominantly for peritoneal disease cure and control.
cell therapies
2026-08-01 | TPW 8.06 Intestinal Transplantation for End-Stage Recurrent Pseudomyxoma Peritonei: The Impact of Nutritional and Functional Status on Outcomes Following Intestinal Transplantation
Abstract Aim To evaluate how anthropometrics affect post-transplant outcomes in patients with PMP. Intestinal transplantation can extend survival in patients with advanced, recurrent PMP not amenable to cytoreduction. Patient selection is challenging as patients may survive many years with advanced disease, but delaying referral can preclude transplant. Traditional anthropometrics, such as BMI, may be inaccurate due to tumour mass. Methods PMP referrals over a ten-year period were used to obtain anthropometric, demographic and survival data. Skeletal muscle area was measured using pre-transplant L3 CT-scans and adjusted for height to derive the skeletal muscle index (SMI). SMI was categorised as Normal, Class I or Class II depletion (n within 1SD, 2SD>n>1SD, n>2SD respectively) based on sex-adjusted values in a healthy population. Mid-Arm Muscle Circumference (MAMC), Grip Strength and Triceps Skin Fold Thickness (TSF) were also measured. Results Forty-nine referrals were reviewed. 17/49 patients (35%) were transplanted, 22% were listed but not transplanted (usually due to deterioration or debulking surgery), and 43% were never listed (unsuitable). Post-referral survival was significantly longer in transplanted patients compared with non-listed patients (median=4.01 and 0.76 years respectively). SMI, but not BMI, was significantly increased in the transplant group, and patients with normal SMI were more likely to be transplanted (χ2 df=2, p<0.05). SMI Class, MAMC, and TSF were not significantly associated with survival, or hospital/ICU length-of-stay. Conclusions Intestinal transplant for PMP can significantly extend survival. Nutritional status, particularly SMI, influences the decision for transplantation although there is limited evidence to support an association with improved post-transplant outcomes.
2026-07-01 | 1446 Intestinal Transplantation for End-Stage Recurrent Pseudomyxoma Peritonei: The Impact of Nutritional and Functional Status on Outcomes Following Intestinal Transplantation
Abstract Aim To evaluate how anthropometrics affect post-transplant outcomes in patients with PMP. Intestinal transplantation can extend survival in patients with advanced, recurrent PMP not amenable to cytoreduction. Patient selection is challenging as patients may survive many years with advanced disease, but delaying referral can preclude transplant. Traditional anthropometrics, such as BMI, may be inaccurate due to tumour mass. Method PMP referrals over a ten-year period were used to obtain anthropometric, demographic and survival data. Skeletal muscle area was measured using pre-transplant L3 CT-scans and adjusted for height to derive the skeletal muscle index (SMI). SMI was categorised as Normal, Class I or Class II depletion (n within 1SD, 2SD>n>1SD, n>2SD respectively) based on sex-adjusted values in a healthy population. Mid-Arm Muscle Circumference (MAMC), Grip Strength and Triceps Skin Fold Thickness (TSF) were also measured. Results Forty-nine referrals were reviewed. 17/49 patients (35%) were transplanted, 22% were listed but not transplanted (usually due to deterioration or debulking surgery), and 43% were never listed (unsuitable). Post-referral survival was significantly increased in the transplanted group compared to the non-listed group (median=4.01 and 0.76 years respectively). SMI, but not BMI, was significantly increased in the transplant group, and patients with normal SMI were more likely to be transplanted (χ2 df=2, p<0.05). SMI Class, MAMC, and TSF were not significantly associated with survival, or hospital/ICU length-of-stay. Conclusions Intestinal transplant for PMP can significantly extend survival. Nutritional status, particularly SMI, is linked to the decision for transplantation although there is limited evidence to support an association with improved post-transplant outcomes.
2026-06-26 | Appendiceal Mucinous Neoplasms and Pseudomyxoma Peritonei: Current Classification and the Role of Intraperitoneal Chemotherapy.
Appendiceal mucinous neoplasms (AMNs) are a rare but clinically significant category of gastrointestinal tumors, ranging from low-grade appendiceal mucinous neoplasm (LAMN), the main precursor of pseudomyxoma peritonei (PMP), to high-grade appendiceal mucinous neoplasm (HAMN), poorly differentiated and signet-ring-cell adenocarcinomas, and goblet cell adenocarcinoma. Although current WHO and PSOGI classifications provide well established diagnostic criteria, controversies persist regarding the biological behavior and prognostic significance of the most aggressive subtypes and the relationship between HAMN and mucinous adenocarcinoma. While appendectomy is sufficient for localized LAMN, cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) is the treatment of choice for peritoneal dissemination This review integrates the histopathological and molecular classification of AMN and PMP with the evolution of intraperitoneal chemotherapy. Key findings indicate that KRAS and GNAS mutations are central drivers of mucin overproduction and peritoneal spread, that tumor grade and mucin cellularity remain the strongest prognostic determinants, and that the evidence supporting HIPEC and PIPAC derives largely from observational rather than randomized data. As a novel insight, we highlight the emerging role of patient-derived organoids as translational models for functional drug testing. Progress will depend on integrating molecular characterization, critical appraisal of intraperitoneal therapies, and organoid-based testing to advance individualized treatment for peritoneal surface malignancies.
2026-06-24 | High-grade Peritoneal Pseudomyxoma of Primary Ovarian Origin Revealed by a Borderline Mucinous Tumor in a 26-year-old Woman: A Case Report and Literature Review
Pseudomyxoma peritonei (PMP) is a rare condition predominantly originating from appendiceal neoplasms, making true primary ovarian PMP an exceptional and widely debated clinical entity. Establishing a primary Müllerian origin requires exhaustive histological and immunohistochemical evaluation to exclude an occult appendiceal tumor. A highly unusual clinical scenario involves a 26-year-old nulliparous woman presenting with a large borderline mucinous ovarian tumor paradoxically associated with high-grade peritoneal implants. Comprehensive pathological workup (CK7+, PAX8+, CK20−, CDX2−) and completely normal appendiceal serial sections definitively confirmed the primary ovarian origin. Standard-of-care management relies on complete cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC). Successful CC0 cytoreduction and HIPEC were achieved, integrated with proactive ovarian cortex cryopreservation. This unusual presentation highlights the striking biological discordance that can exist between a primary tumor and its peritoneal dissemination, emphasizing the critical role of specialized multidisciplinary management, rigorous pathology, and early oncofertility integration for young patients.
2026-06-06 | Quality of life in patients with pseudomyxoma peritonei treated with cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy and implications for ERAS-informed rehabilitation.
Cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy (CRS + HIPEC) is the standard of care for pseudomyxoma peritonei (PMP) but is associated with substantial perioperative burden and prolonged recovery. Contemporary data on health-related quality of life (HRQoL) trajectories after CRS + HIPEC remain limited, as does their integration into perioperative and rehabilitation planning. We aimed to characterize short- and mid-term HRQoL changes after CRS + HIPEC in PMP and to identify ERAS-informed rehabilitation priorities based on postoperative symptom and function trajectories. We screened 273 patients from our institutional PMP CRS + HIPEC database and included 111 adults who had adequate EORTC QLQ-C30 data for longitudinal analysis. HRQoL was assessed using the EORTC QLQ-C30 at baseline and 1 week, 1, 3, 6, 9 and 12 months postoperatively. Longitudinal changes were summarized descriptively, and mean differences versus baseline were interpreted using established minimally important difference thresholds (≥10 points). At 1 week postoperatively, physical, role, emotional, cognitive and social functioning and global QoL declined by 22.9, 41.6, 13.3, 19.7, 20.5 and 28.4 points, respectively, all exceeding the threshold for clinically meaningful deterioration. Fatigue, pain, dyspnoea, insomnia, appetite loss and financial difficulties showed peak or near-peak worsening at 1 week, whereas constipation and diarrhea peaked at 3 months. Overall QoL was worst around 1 month postoperatively and then improved steadily; by 12 months, most functional scales and symptoms had returned to or approached baseline (e.g. global QoL -1.1 points vs. preoperative), although mild residual cognitive and bowel disturbances persisted in some patients. CRS + HIPEC for PMP imposes a pronounced but largely transient HRQoL burden, characterized by a sharp early decline, mid-term recovery and near-restoration of baseline QoL within 6-12 months. Our findings support an ERAS-informed rehabilitation framework that prioritizes pain control, respiratory recovery, nutrition, sleep, and psychological support. These elements should be interpreted as clinically informed rehabilitation priorities rather than as a validated intervention package directly derived from this observational dataset. These findings inform preoperative counseling and the timing of follow-up after CRS + HIPEC.
other
2024-08-05 | Genome-Wide Analysis of DNA Methylation in Pseudomyxoma Peritonei Originated from Appendiceal Neoplasms.
Pseudomyxoma peritonei (PMP) is a disease characterized by progressive accumulation of intraperitoneal mucinous ascites produced by neoplasms in the abdominal cavity. Since the prognosis of patients with PMP remains unsatisfactory, the development of effective therapeutic drug(s) is a matter of pressing concern. Genetic analyses of PMP have clarified the frequent activation of GNAS and/or KRAS. However, the involvement of global epigenetic alterations in PMPs has not been reported. To clarify the genetic background of the 15 PMP tumors, we performed genetic analysis using AmpliSeq Cancer HotSpot Panel v2. We further investigated global DNA methylation in the 15 tumors and eight noncancerous colonic epithelial tissues using MethylationEPIC array BeadChip (Infinium 850k) containing a total of 865,918 probes. This is the first report of comprehensive DNA methylation profiles of PMPs in the world. We clarified that the 15 PMPs could be classified into at least two epigenotypes, unique methylation epigenotype (UME) and normal-like methylation epigenotype (NLME), and that genes associated with neuronal development and synaptic signaling may be involved in the development of PMPs. In addition, we identified a set of hypermethylation marker genes such as HOXD1 and TSPYL5 in the 15 PMPs. These findings may help the understanding of the molecular mechanism(s) of PMP and contribute to the development of therapeutic strategies for this life-threatening disease.
2024-01-15 | Efficacy of Different Oncolytic Vaccinia Virus Strains for the Treatment of Murine Peritoneal Mesothelioma
Effective treatment options for peritoneal surface malignancies (PSMs) are scarce. Oncolytic virotherapy with recombinant vaccinia viruses might constitute a novel treatment option for PSM. We aimed to identify the most effective oncolytic vaccinia virus strain in two murine mesothelioma cell lines and the oncolytic potential in a murine model of peritoneal mesothelioma. Cell lines AB12 and AC29 were infected in vitro with vaccinia virus strains Lister (GLV-1h254), Western Reserve (GLV-0b347), and Copenhagen (GLV-4h463). The virus strain GLV-0b347 was shown most effective in vitro and was further investigated by intraperitoneal (i.p.) application to AB12 and AC29 mesothelioma-bearing mice. Feasibility, safety, and effectiveness of virotherapy were assessed by evaluating the peritoneal cancer index (PCI), virus detection in tumor tissues and ascites, virus growth curves, and comparison of overall survival. After i.p. injection of GLV-0b347, virus was detected in both tumor cells and ascites. In comparison to mock-treated mice, overall survival was significantly prolonged, ascites was less frequent and PCI values declined. However, effective treatment was only observed in animals with limited tumor burden at the time point of virus application. Nonetheless, intraperitoneal virotherapy with GLV-0b347 might constitute a novel therapeutic option for the treatment of peritoneal mesothelioma. Additional treatment modifications and combinational regimes will be investigated to further enhance treatment efficacy.
2022-12-06 | A New Molecular (P)Layer in Pseudomyxoma Peritonei: The Splicing Machinery is Dysregulated and Linked to Low Survival
Abstract Purpose : Pseudomyxoma peritonei (PMP) is a rare cancer that causes chronic and uncontrollable mucus accumulation, gradually leading to intraperitoneal organ adhesion, bowel obstruction, malnutrition, and eventually cachexia and death. Aggressive cytoreductive surgery and hyperthermic intraperitoneal chemotherapy offer the best results; but the probability of relapse remains high. The study of the distinct molecular layers underlying PMP is essential to understand its genesis and progression. Alternative splicing is emerging as a new player in all cancers, but its role in PMP is unknown. The aim of this work was to assess the splicing machinery status in PMP and determine its potential contribution to disease prognosis. Methods : A set of 62 splicing-related genes were evaluated in a cohort of 29 patients using a microfluidic array, and their levels were compared between tumor and non-tumor tissue and correlated to relevant clinical parameters. Selected components were validated by immunohistochemistry and subsequently studied in detail by enrichment analyses. Results : Results revealed a profound dysregulation of the splicing machinery at RNA/protein level, which allowed to distinguish between tumor and control tissues. Particularly, the splicing factors HNRNPK , MBNL1 , PTBP1 and RAVER1 were associated with poor prognosis and their expression was linked to TP53 regulation and inflammation processes. Conclusions : These findings provide the first evidence for the dysregulation of the splicing machinery in PMP, suggesting that it could be functionally altered and play a role in this rare malignant disease. Therefore, its detailed understanding could help to identify novel prognostic biomarkers and therapeutic targets in PMP.
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Drug Discovery Landscape
3 orphan drug designations for Pseudomyxoma peritonei.
3 orphan drug designations for Pseudomyxoma peritonei.
Drug | Therapy type | Orphan designation | Clinical trial status | Sponsor |
|---|---|---|---|---|
bromelain + acetylcysteine | small molecules | FDA | MUCPharm Pty Ltd. | |
Bromelain | proteins | EMA | Mucpharm Europe Limited | |
Acetylcysteine | small molecules | EMA | Mucpharm Europe Limited |
“Terminated” – programs with discontinued clinical trials, or with no updates reported for 5 years after completion or 12 years after the last trial started.
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