Treatment Of Pseudomyxoma Peritonei Research Articles

Progress on immuno-microenvironment and immune-related therapies in patients with pseudomyxoma peritonei.

Pseudomyxoma peritonei (PMP) is an indolent malignant syndrome. The standard treatment for PMP is cytoreductive surgery plus intraperitoneal hyperthermic chemotherapy (CRS + HIPEC). However, the high recurrence rate and latent clinical symptoms and signs are major obstacles to further improving clinical outcomes. Moreover, patients in advanced stages receive little benefit from CRS + HIPEC due to widespread intraperitoneal metastases. Another challenge in PMP treatment involves the progressive sclerosis of PMP cell-secreted mucus, which is often increased due to activating mutations in the gene coding for guanine nucleotide-binding protein alpha subunit (GNAS). Consequently, the development of other PMP therapies is urgently needed. Several immune-related therapies have shown promise, including the use of bacterium-derived non-specific immunogenic agents, radio-immunotherapeutic agents, and tumor cell-derived neoantigens, but a well-recognized immunotherapy has not been established. In this review the roles of GNAS mutations in the promotion of mucin secretion and disease development are discussed. In addition, the immunologic features of the PMP microenvironment and immune-associated treatments are discussed to summarize the current understanding of key features of the disease and to facilitate the development of immunotherapies.

Progress in Biological Research and Treatment of Pseudomyxoma Peritonei.

Pseudomyxoma peritonei (PMP) is a rare disease characterized by extensive peritoneal implantation and mass secretion of mucus after primary mucinous tumors of the appendix or other organ ruptures. Cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) is currently the preferred treatment, with excellent efficacy and safety, and is associated with breakthrough progress in long-term disease control and prolonged survival. However, the high recurrence rate of PMP is the key challenge in its treatment, which limits the clinical application of multiple rounds of CRS-HIPEC and does not benefit from conventional systemic chemotherapy. Therefore, the development of alternative therapies for patients with refractory or relapsing PMP is critical. The literature related to PMP research progress and treatment was searched in the Web of Science, PubMed, and Google Scholar databases, and a literature review was conducted. The overview of the biological research, treatment status, potential therapeutic strategies, current research limitations, and future directions associated with PMP are presented, focuses on CRS-HIPEC therapy and alternative or combination therapy strategies, and emphasizes the clinical transformation prospects of potential therapeutic strategies such as mucolytic agents and targeted therapy. It provides a theoretical reference for the treatment of PMP and the main directions for future research.

Efficacy of cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy for pseudomyxoma peritonei

Objective: To evaluate the efficacy and safety of cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) in the treatment of pseudomyxoma peritonei (PMP). Methods: In this descriptive case series study, we retrospective analyzed the records of PMP patients treated with CRS and HIPEC between January 2013 and June 2023 at Affiliated Cancer Hospital and Institute of Guangzhou Medical University. The inclusion criteria were as follows: (1) Aged 18 to 75 years and nonpregnant women. (2) Histologically confirmed diagnosis of pseudomyxoma peritonei. (3) Karnofsky Performance Scale (KPS)>70. (4) The functions of major organs such as the heart, liver, lungs, and kidneys can tolerate major surgery for long periods of time. (5) No evidence of extra-abdominal metastasis. Patients with extensive intra-abdominal adhesions or severe infectious diseases were excluded. The main outcomes were overall survival (OS) and postoperative major complications. The postoperative major complications were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (version 5.0). We used the peritoneal cancer index (PCI) score to quantitatively assess the peritoneal metastases and the completeness of cytoreduction (CCR) score at the end of surgery (CCR-0 and CCR-1 considered to be complete CRS). Results: A total of the 186 PMP patients with a median age of 56 (interquartile range extremes (IQRE), 48-64) years were included, 65 (34.9%) males and 121 (65.1%) females. The median peritoneal cancer index (PCI) score was 28 (20-34). Appendiceal origin accounted for 91.4%. Histological types were low grade in 99 patients (53.2%), high grade in 57 patients (30.6%), and 55 patients (29.6%) received complete cytoreduction (CCR-0/1). The median operative duration was 300 (211-430) minutes for all patients. Treatment-related 30-day mortality was 2.7%; 90-day mortality 4.3%; reoperation 1.6%; and severe morbidity 43.0%. Within the entire series, anemia(27.4%), electrolyte disturbance(11.6%), and hypoalbuminemia(7.5%) were the most frequent major complications (grade 3-4). The incidences of gastrointestinal anastomotic leakage, abdominal bleeding, and abdominal infection were 2.2%, 2.2%, and 4.3%, respectively. After a median follow-up of 38.1 (95%CI:31.2-45.1) months, the 5-year OS was 50.3% (95%CI: 40.7%-59.9%) with a median survival time of 66.1 (95%CI: 43.1-89.1) months. The survival analysis showed that patients with pathological low grade, low PCI, and low CCR score had better survival with statistically significant differences (all P<0.05). Further stratified into complete and incomplete CRS subgroups, the 5-year OS of the CCR-0 and CCR-1 subgroups was 88.9% (95%CI: 68.3%-100.0%) and 77.6% (95%CI: 62.7%-92.5%), respectively; and 42.0% (95%CI: 29.5%-54.5%) in the CCR-2/3 subgroup. Conclusions: CRS and HIPEC may result in a long-term survival benefit for PMP patients with acceptable perioperative morbidity and mortality. This strategy, when complete CRS is possible, could significantly prolong survival for strictly selected patients at experienced centers.

Bland–Altman agreement analysis between CT predicted and surgical peritoneal cancer index in pseudomyxoma peritonei of appendiceal origin

Peritoneal cancer index (PCI) is the surgical variable most commonly used to quantify the extent of peritoneal metastases for pseudomyxoma peritonei (PMP) patients. The present study aimed to investigate the agreement between CT predicted and surgical PCI by the Bland–Altman method for PMP of appendiceal origin. A total of 167 PMP patients of appendiceal origin were included between 2016 and 2021. Bland–Altman analysis was performed for both total PCI and selected PCI (regions 2 + 9–12). After the Bland–Altman plot was drawn, the mean bias and its 95% limit of agreements (LoAs) was quantified. Besides, the correlation coefficients between CT-PCI and surgical PCI were also been calculated. The Bland–Altman plot showed the mean bias ± SD between total CT-PCI and surgical PCI as 0.431 ± 3.005, with the LoAs from − 5.459 to 6.321. There were nine points of difference in total PCI exceeded the 95% LoAs, with the rate of 5.39% (9/167). As for selected CT-PCI, Bland–Altman plot showed the mean bias ± SD between selected CT-PCI and surgical PCI as − 0.287 ± 1.955, with the LoAs from − 4.118 to 3.544. There were ten points of difference in selected PCI exceeded the 95% LoAs, with the rate of 5.99% (10/167). The Spearman's rank correlation coefficient between total CT-PCI and surgical PCI was 0.911, P < 0.001, as for selected CT-PCI and surgical PCI, the coefficient was 0.909, P < 0.001. Although there was a strong correlation for both total and selected CT-PCI with surgical PCI, however, the agreement is still not good in Bland–Altman analysis, which suggested that CT-PCI cannot predict surgical PCI accurately even in professional PMP treatment centers. In brief explanation, CT makes it difficult to distinguish the borderline between tumor tissue and mucus and to detect tumor lesions in the small intestine regions, which caused overestimation or underestimation by CT-PCI. In the future, a multiple linear regression model based on CT-PCI might accurately predict surgical PCI preoperatively.

Whole-Exome Sequencing Identifies Mutation Profile and Mutation Signature-Based Clustering Associated with Prognosis in Appendiceal Pseudomyxoma Peritonei.

This work describes exhaustive mutation profile of PMP based on WES data and derives ten mutation signatures, which divides patients into two clusters and serve as an independent prognostic factor associated with 3-year survival.

Oral administration of bromelain and acetylcysteine in pseudomyxoma peritonei (PMP) caused by low-grade appendiceal mucinous neoplasm (LAMN): a case report

BackgroundPseudomyxoma Peritonei (PMP) is a severe neoplastic clinical syndrome characterised by secretion of mucin from tumors often originating in the appendix. The standard treatment includes cytoreductive surgery (CRS) combined with heated intraperitoneal chemotherapy (HIPEC). A new perspective in PMP treatment aims at the mucins themselves as a therapeutic target.Case presentationHere we report the first case of PMP with peritoneal dissemination of mucinous implants caused by low-grade appendiceal mucinous neoplasm (LAMN) in a 58-year-old white male exclusively treated by appendectomy and oral administration of bromelain and acetylcysteine in the context of a medical self-experimentation (by co-author T.R.). Observation so far covers a period of 48 months including regular magnetic resonance imaging (MRI) with stable findings.ConclusionsOral administration of bromelain and acetylcysteine can be used in the treatment of PMP caused by LAMN without relevant clinical side effects.

A case study on jelly belly: Pseudomyxoma peritonei

Pseudomyxoma peritonei (PMP) is a rare malignant growth characterised by the progressive accumulation of mucus-secreting (mucinous) tumour cells within the abdomen and pelvis. The common manifestations in patients are abdominal distension and appendicitis-like symptoms. Computed tomography scan with contrast of the chest, abdomen and pelvis is currently the imaging modality of choice for the diagnosis of PMP. As per the current guideline, the curative treatment for PMP is complete cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy. The purpose of this article is to highlight the rarity of the disease and the typical presenting symptoms, the trends in diagnosis and treatment, the role of nurses and the challenges faced in taking care of patients with rare malignancies receiving treatment.

Enteral nutrition provides favorable postoperative outcomes for patients with pseudomyxoma peritonei: a retrospective study.

Pseudomyxoma peritonei (PMP) is a rare malignancy, and many uncertainties regarding its treatment and prognosis still remain. The main treatment for PMP is cytoreductive surgery (CRS) combined with heated intraperitoneal chemotherapy (HIPEC), which can lead to intra-abdominal trauma and systemic reactions. Enteral nutrition (EN) is an important and beneficial perioperative option for major complicated abdominal surgery compared with total parenteral nutrition (TPN). However, the role of EN in PMP after surgery is still unknown. The purpose of this study was to analyze the effects of EN on postoperative outcomes in PMP patients. The perioperative clinical data of PMP patients from Xiangya Hospital of Central South University who accepted CRS plus HIPEC from January 2011 to December 2018 were collected and analyzed. The effects of EN on the nutritional status, postoperative complications, and hospital stay time of patients with PMP were studied. We further analyzed the risk factors affecting hospital stay and complications in PMP patients after surgery. A total of 51 PMP patients accepted CRS and were enrolled in this study, including 25 cases in the EN group and 26 patients in the TPN group. The baseline demographic characteristics and preoperative nutritional status were not significantly different between the two groups. The postoperative absolute lymphocyte count (P<0.001), hemoglobin (P=0.016), and albumin (P<0.001) levels of the EN group were higher than those of the TPN group, but the postoperative hospital stay time (P=0.008) and the complication rate (P=0.03) in the EN group were less than those in the TPN group. Logistic regression analysis showed that age (P=0.031), American Society of Anesthesiologists (ASA) score (P=0.008), and EN (P=0.024) were independent risk factors for postoperative hospital stay in PMP patients. ASA score (P=0.006), number of prior operations (P=0.021), and EN (P=0.035) were independent risk factors for postoperative complications in PMP patients. EN support results in better outcomes and is an independent protective factor for the postoperative hospital stay time and complications of PMP patients.

Peritoneal surface malignancy spread reoperations after cytoreductive surgery + HIPEC.

Peritoneal malignancies (PM) are observed in about 1030% of patients suffering from gastrointestinal malignant diseases, both in connection with the primary surgical management or as metachronous metastases due to cancer recurrence. In the 1980s a new method of cytoreductive surgery (CRS) + HIPEC (hyperthermic intraperitoneal chemotherapy) was introduced. Today, we consider this method to be the gold standard for treatment of pseudomyxoma peritonei and peritoneal mesothelioma. The method increases overall survival (OS) of patients diagnosed with colorectal cancer, primary peritoneal and ovarian cancers. However, the disease recurs after this demanding treatment in the certain group of patients, approximately in 2544% of patients treated for pseudomyxoma peritonei, and in 40% and up to 82% of those treated for mesothelioma and colorectal cancer, respectively. Based on literary data (PubMed-Medline, last 5 years) and our own experience we present the basic factors associated with tumor recurrence, possibility of treatment using repeated CRS + HIPEC, data regarding second-look operations, and as applicable, prophylactic HIPEC. The method CRS + HIPEC provides an effective treatment of peritoneal carcinomatosis even in cases of recurrence. The second-look operations and prophylactic HIPEC may favorably affect the prognosis after primary R0 resections.

Peptide vaccine targeting mutated GNAS: a potential novel treatment for pseudomyxoma peritonei

BackgroundPseudomyxoma peritonei (PMP) is a rare, slow-growing abdominal cancer with no efficacious treatment options in non-resectable and recurrent cases. Otherwise, rare activating mutations in the GNAS oncogene are remarkably frequent...

The Biological Synthesis and the Function of Mucin 2 in Pseudomyxoma Peritonei.

Excessive mucus secretion is the most prominent feature of pseudomyxoma peritonei (PMP), which often leads to significant increase in abdominal circumference, intractable abdominal pain, progressive intestinal obstruction, abdominal organ adhesions, and cachexia. Excessive mucus secretion is also the main cause of death. Cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) is the recommended treatment for PMP. However, recurrence is frequently observed even after CRS and HIPEC, presenting similar clinical manifestations. Mucin 2 (MUC2) is the main type of mucin in PMP and plays a key role in the progressive sclerosis of mucus. To comprehensively demonstrate the biosynthetic process and molecular features of MUC2 and to provide new directions for the development of PMP mucolytic strategies, this review systematically summarizes the molecular biology of MUC2, including MUC2 gene structure, transcription, translation, post-translational modification, tertiary structure, and factors regulating mucus viscoelasticity. The results show that MUC2 is a highly glycosylated protein, with glycan accounts for 80% to 90% of the dry weight. The assembly pattern of MUC2 is highly complicated, presenting a bead-like filament. Salt concentration, pH, mucin concentration and trefoil factor family may contribute to the increase in mucus viscoelasticity and sclerosis, which could be used to develop drugs to soften or even dissolve mucus in the future.

Pseudomyxoma Peritonei: A Case Report

Pseudomyxoma peritonei (PMP) is a rare condition, consisting of mucinous ascites and multifocal mucinous epithelial implants. This disease mainly affects women. It may remain asymptomatic, discovered during laparotomy. The most frequent symptom is abdominal distension associated with diffuse abdominal pain. Mucinous tumours of the appendix are the most frequent cause of pseudomyxoma peritoneum, accounting for 90% of cases, and ovarian origin remains very rare. There are essentially two types of treatment for PMP: firstly multiple surgical debulking and secondly cytoreduction surgery with peri-operative intraperitoneal chemotherapy consisting of hyperthermic intraperitoneal chemotherapy with or without immediate post-operative intraperitoneal chemotherapy. We report a case of peritoneal pseudomyxoma secondary to a mucinous tumour of the right ovary.

Two-step cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for pseudomyxoma peritonei with high peritoneal carcinomatosis index

BackgroundComplete cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) is the only curative treatment for pseudomyxoma peritonei (PMP) arising from the appendix. High peritoneal carcinomatosis index (PCI) is associated with an increased risk of surgical complications. The objective of this study was to present the results of a planned two-step surgical strategy to decrease postoperative morbidity and improve resectability of patients with very high PCI.MethodsAll consecutive patients who underwent a planned two-step surgical approach for PMP between January 2012 and March 2020 were retrospectively included. This approach was offered for patients with low-grade PMP with PCI > 28 for which feasibility of a complete CRS in one operation was uncertain. The first surgery included a complete CRS of the inframesocolic compartment and omentectomy. HIPEC was delivered at the second surgery, after complete CRS of the supramesocolic compartment. Postoperative morbidity was assessed using the Clavien-Dindo classification and survival results were also collected.ResultsEight patients underwent the two-step approach. The median PCI was 33 (29–39) and the median time between the two procedures was 111 days (90–212 days). One patient was deemed unresectable at the second surgery. The rate of major morbidity was 0% for the first step and 25% for the second step, with no mortality. Median follow-up was 53.8 months (3–73 months).ConclusionA two-step surgical management for low-grade PMP patients with very high PCI is safe and feasible, with acceptable postoperative morbidity and no compromise on oncological outcomes.

Pseudomyxoma peritonei: two case study and literatures review

Pseudomyxoma peritonei (PMP) is a rare neoplastic illness with unique clinical and pathologic patterns. This disease characterized by being chronic, indolent, and relapsing. It is diagnostically challenging and very vague disease. It characterized by huge amounts of thick mucinous ascites with multiple omental and peritoneal implants that is gradually fill the abdominal and pelvic cavities. The most common clinical features are progressive abdominal distention with increase in the abdominal girth. Diagnosis of Pseudomyxoma peritonei (PMP) is usually difficult due to its vague symptoms especially in the early stages. Ultrasound examination is very useful and generally has pictures similar to that of CT scan images. Treatment of Pseudomyxoma peritonei (PMP) is cytoreductive (debulking) surgery to remove the mucin and the tumor implants in the peritoneal cavity. This is followed by intraoperative hyperthermic peritoneal chemotherapy (HIPEC). Recurrence of pseudomyxoma peritonei (PMP) patients is quite common as particularly when the disease is diagnosed and treated in the late stage.

Complete pathologic response after two-stage cytoreductive surgery with HIPEC for bulky pseudomyxoma peritonei: proof of concept

Introduction Pseudomyxoma peritonei (PMP) is a rare disease characterized by the progressive accumulation of mucinous ascites and peritoneal implants. The optimal treatment for PMP includes the association of complete cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC). For patients with a large burdensome disease, the completeness of cytoreduction sometimes requires maximal effort surgery. The aim of this article is to provide proof of concept for two stage cytoreductive surgery (CRS) in this category of patients. Methods and materials A two stage CRS and HIPEC with oxaliplatin was proposed for patients with bulky PMP including important involvement of the serosal surfaces of the bowel or colon who had an impaired nutritional status. The residual disease at the end of the first stage was less than 5 mm of thickness on several implants. Clinical, surgical and histopathological variables were analyzed. Results All eight patients completed the two-stage strategy. Mortality was nil. One Clavien Dindo grade 3 event occurred in each stage. After a median follow up of 29.5 months, all patients were alive and free of recurrence. All of the patients had histopathological complete response on the specimens obtained from the residual sites during the second stage surgery. Conclusions Two-stage surgical strategy is feasible for bulky PMP patients and it is associated with little high-grade morbidity and enhanced visceral sparing.

Laparoscopic Cytoreductive Surgery with Hyperthermic Intraperitoneal Chemotherapy (L-CRS/HIPEC) for Perforated Low-Grade Appendiceal Mucinous Neoplasm (LAMN II)

IntroductionCytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) is an established treatment for pseudomyxoma peritonei resulting from a perforated low-grade appendiceal mucinous neoplasm (LAMN II). In patients with localized disease, a laparoscopic procedure (L-CRS/HIPEC) can be undertaken.MethodsThis video demonstrates L-CRS/HIPEC in a 66-year-old male who had previously undergone an appendicectomy for an LAMN II lesion. The preoperative computed tomography (CT) scan suggested disease localized to the right iliac fossa. However, laparoscopic assessment unexpectedly revealed disease in the pelvis and on the right hemidiaphragm and liver surface.ResultsA technique for treating the thin film of mucin in the pelvis and on the right hemidiaphragm is demonstrated. The liver is mobilized to facilitate ablation of mucin on the serosal surface of the right lobe. Tips and tricks for starting the omentectomy, dealing with the vascular pedicle, and completing the dissection in the left upper quadrant are shown. The Peritoneal Cancer Index (PCI) score was 5 (3 for the right upper quadrant, 1 for the pelvis, 1 for the small bowel), and the cytoreduction score was CC-1. The operative duration was 8.5 h, and length of hospital stay was 5 days. The patient returned to work after 6 weeks.DiscussionL-CRS/HIPEC can be performed when patients are unexpectedly found to have disease, provided the appendiceal pathology is low grade and the PCI score is low. There are potential benefits to this approach, with a shorter length of hospital stay and faster functional recovery when compared with traditional open surgery.

Orphan designation: Acetylcysteine, Treatment of pseudomyxoma peritonei

Orphan designation: Acetylcysteine, Treatment of pseudomyxoma peritonei

Orphan designation: Bromelain, Treatment of pseudomyxoma peritonei

Orphan designation: Bromelain, Treatment of pseudomyxoma peritonei

Orphan designation: Acetylcysteine, Treatment of pseudomyxoma peritonei

Orphan designation: Acetylcysteine, Treatment of pseudomyxoma peritonei

Orphan designation: Bromelain, Treatment of pseudomyxoma peritonei

Orphan designation: Bromelain, Treatment of pseudomyxoma peritonei