Peritoneal Mucinous Carcinomatosis Research Articles

Breaking the Mucin Barrier: A New Affinity Chromatography-Mass Spectrometry Approach to Unveil Potential Cell Markers and Pathways Altered in Pseudomyxoma Peritonei

BackgroundPseudomyxoma peritonei (PMP) is a rare peritoneal mucinous carcinomatosis with largely unknown underlying molecular mechanisms. Cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy is the only therapeutic option; however, despite its use, recurrence with a fatal outcome is common. The lack of molecular characterisation of PMP and other mucinous tumours is mainly due to the physicochemical properties of mucin.ResultsThis manuscript describes the first protocol capable of breaking the mucin barrier and isolating proteins from mucinous tumours. Briefly, mucinous tumour samples were homogenised and subjected to liquid chromatography using two specific columns to reduce mainly glycoproteins, albumins and immunoglobulin G. The protein fractions were then subjected to mass spectrometry analysis and the proteomic profile obtained was analysed using various bioinformatic tools. Thus, we present here the first proteome analysed in PMP and identified a distinct mucin isoform profile in soft compared to hard mucin tumour tissues as well as key biological processes/pathways altered in mucinous tumours. Importantly, this protocol also allowed us to identify MUC13 as a potential tumour cell marker in PMP.ConclusionsIn sum, our results demonstrate that this protein isolation protocol from mucin will have a high impact, allowing the oncology research community to more rapidly advance in the knowledge of PMP and other mucinous neoplasms, as well as develop new and effective therapeutic strategies.

Clinical and ultrasound features of pseudomyxoma peritonei and its histopathological subtypes among women seen at a Philippine tertiary hospital: A 10-year review

OBJECTIVES: Pseudomyxoma peritonei (PMP) in women arises from an appendiceal or ovarian pathology and presents either of two histological subtypes of differing prognosis, disseminated peritoneal adenomucinosis (DPAM), or peritoneal mucinous carcinomatosis (PMCA). This study aimed to evaluate the demographic, clinical, and sonographic features among affected women and the differences between the two histological subtypes. METHODS: A retrospective study was conducted involving 36 women with histopathological diagnosis of PMP who had preoperative ultrasound and underwent surgery at the department of obstetrics and gynecology in a tertiary hospital. Demographic and clinical data, ultrasound images and reports, and final histopathology were reviewed. To compare the subtypes, one-way analysis of variance for continuous data and Chi-square/Fisher exact test for categorical data were used, with P < 0.05 indicating statistical significance. RESULTS: Patients were mostly >50 years of age, multigravid, and presented with abdominal distention. Ultrasound examinations consistently showed amorphous, mixed echo or echogenic ascites, peritoneal thickening, and omental caking. Adnexal/ovarian masses were detected in 66.7% of cases. Omental caking was significantly more prevalent in PMCA (83.3%; P = 0.0002), whereas larger ovarian tumors (>20 cm) and papillarities were more common in DPAM (both 92.9%; P = 0.0005). Most patients underwent gynecologic surgery (n = 31; 86.1%), and 14 (38.9%) required readmission due to recurrence. The final histopathology revealed largest tumor involvement of the appendix (n = 13; 36.1%), the ovaries (n = 11; 30.5%), or undetermined (n = 12; 33.3%). CONCLUSIONS: Preoperative diagnosis of PMP is possible based on its clinical and ultrasound features. Although the subtypes are similar in most of these features, certain ultrasound findings may aid in distinguishing them.

Efficacy of Systemic Chemotherapy in Patients With Low-grade Mucinous Appendiceal Adenocarcinoma

Appendiceal adenocarcinoma is a rare tumor, and given the inherent difficulties in performing prospective trials in such a rare disease, there are currently minimal high-quality data to guide treatment decisions, highlighting the need for more preclinical and clinical investigation for this disease. To prospectively evaluate the effectiveness of fluoropyrimidine-based systemic chemotherapy in patients with inoperable low-grade mucinous appendiceal adenocarcinoma. This open-label randomized crossover trial recruited patients at a single tertiary care comprehensive cancer center from September 2013 to January 2021. The data collection cutoff was May 2022. Enrollment of up to 30 patients was planned. Eligible patients had histological evidence of a metastatic low-grade mucinous appendiceal adenocarcinoma, with radiographic imaging demonstrating the presence of mucinous peritoneal carcinomatosis and were not considered candidates for complete cytoreductive surgery. Key exclusion criteria were concurrent or recent investigational therapy, evidence of bowel obstruction, and use of total parenteral nutrition. Data were analyzed from November 2021 to May 2022. Patients were randomized to either 6 months observation followed by 6 months of chemotherapy, or initial chemotherapy followed by observation. The primary end point was the percentage difference in tumor growth in treatment and observation groups. Key secondary end points included patient-reported outcomes in the chemotherapy and observation periods, objective response rate, rate of bowel complications, and differences in overall survival (OS). A total of 24 patients were enrolled, with median (range) age of 63 (38 to 82) years, and equal proportion of men and women (eg, 12 men [50%]); all patients had ECOG performance status of 0 or 1. A total of 11 patients were randomized to receive chemotherapy first, and 13 patients were randomized to receive observation first. Most patients (15 patients [63%]) were treated with either fluorouracil or capecitabine as single agent; 3 patients (13%) received doublet chemotherapy (leucovorin calcium [folinic acid], fluorouracil, and oxaliplatin or folinic acid, fluorouracil, and irinotecan hydrochloride), and bevacizumab was added to cytotoxic chemotherapy for 5 patients (21%). Fifteen patients were available to evaluate the primary end point of difference in tumor growth during treatment and observation periods. Tumor growth while receiving chemotherapy increased 8.4% (95% CI, 1.5% to 15.3%) from baseline but was not significantly different than tumor growth during observation (4.0%; 95% CI, -0.1% to 8.0%; P = .26). Of 18 patients who received any chemotherapy, none had an objective response (14 patients [77.8%] had stable disease; 4 patients [22.2%] had progressive disease). Median (range) OS was 53.2 (8.1 to 95.5) months, and there was no significant difference in OS between the observation-first group (76.0 [8.6 to 95.5] months) and the treatment-first group (53.2 [8.1 to 64.1] months; hazard ratio, 0.64; 95% CI, 0.16-2.55; P = .48). Patient-reported quality-of-life metrics identified that during treatment, patients experienced significantly worse fatigue (mean [SD] score, 18.5 [18.6] vs 28.9 [21.3]; P = .02), peripheral neuropathy (mean [SD] score, 6.67 [12.28] vs 38.89 [34.88]; P = .01), and financial difficulty (mean [SD] score, 8.9 [15.2] vs 28.9 [33.0]; P = .001) compared with during observation. In this prospective randomized crossover trial of systemic chemotherapy in patients with low-grade mucinous appendiceal adenocarcinoma, patients did not derive clinical benefit from fluorouracil-based chemotherapy, given there were no objective responses, no difference in OS when treatment was delayed 6 months, and no difference in the rate of tumor growth while receiving chemotherapy. ClinicalTrials.gov Identifier: NCT01946854.

Durable Response after Repeat Cytoreductive Surgery (CRS) and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) in a Patient with Extensive Mucinous Adenocarcinoma of the Appendix

Mucinous adenocarcinoma of the appendix is a rare form of lower gastrointestinal (GI) tract cancer. These cancers have a high tendency to progress towards peritoneal metastasis and their response to systemic treatment is typically low. Together, cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) have become an established form of therapy used to prolong the survival of patients with this disease. Repeat CRS and HIPEC have been shown to be feasible in selected patients with GI peritoneal carcinomatosis (PC), among which those with appendix cancer receive the greatest benefit. The peritoneal cancer index (PCI) and completeness of cytoreduction have been shown to be important predictors of outcomes. However, repeat cytoreduction in patients with a high-volume peritoneal tumor burden (peritoneal cancer index (PCI) > 30) is not typically performed due to concerns regarding morbidity and mortality. Herein, we describe a case of repeat CRS and HIPEC for extensive appendiceal mucinous peritoneal carcinomatosis after initial incomplete cytoreduction and durable remission of 28 months without adjuvant chemotherapy. In appendiceal mucinous cancers, repeat CRS can achieve a durable response despite an initial failed CRS and high-volume disease.

A case of pancreaticoduodenectomy and partial hepatic resection as repeat cytoreductive surgery for recurrent pseudomyxoma peritonei

BackgroundFor recurrent pseudomyxoma peritonei (PMP), repeat cytoreductive surgery (CRS) with or without hyperthermic intraperitoneal chemotherapy (HIPEC) can provide survival benefits if patients are carefully selected. We describe a case of pancreaticoduodenectomy and partial liver resection (HPD) as the repeat CRS for a recurrent tumor that infiltrated the pancreatic head around the hepatic hilum. This is the first report of HPD for recurrent PMP.Case presentationThe patient was a 58-year-old male without comorbidities. In 2001, he was diagnosed with PMP at the time of laparoscopic cholecystectomy. In 2004, CRS, including total peritoneal resection, pyloric gastrectomy, splenectomy, and right hemicolectomy with HIPEC was performed (peritoneal cancer index (PCI) = 28). In 2008, the first repeat CRS with HIPEC was performed (PCI = 14). In 2016, fourth repeat CRS, including partial hepatectomy with HIPEC for recurrence of the round ligament of the liver, was performed. In 2017, a tumor of 5 cm in size was observed from the hepatic hilum to the pancreatic head, which infiltrated the main pancreatic duct. Other tumors 2 cm in size were observed (PCI = 7). We performed the fifth repeat CRS, including HPD. The adhesions of the small intestine from around the liver to the lower abdomen were detached for the reconstruction of pancreatojejunostomy and cholangiojejunostomy. The uncinate approach was applied for the pancreatic head resection because it was difficult to identify the cranial part of the pancreas due to adhesions in the hepatoduodenal ligament and the omental bursa. We approached to the origin of the extrahepatic Glissonean pedicle by resecting a part of the liver around the hepatic hilum using transhepatic hilar approach. A complete cytoreduction was achieved. The postoperative pathological diagnosis was a recurrence of PMP, which is equivalent to peritoneal mucinous carcinomatosis. He was discharged on the 22nd postoperative day without major postoperative complications. The patient survived without recurrence four years after HPD.ConclusionsEven for recurrence around the hepatic hilum and the pancreatic head, repeat CRS can be safely performed by applying the techniques of hepatobiliary pancreatic surgery.

Appendiceal Neoplasm

Appendiceal neoplasms are rare and are typically found in the setting of metastatic disease or, less commonly, as an incidental finding in an appendectomy specimen in cases of appendicitis or an unrelated condition. The World Health Organization classifies appendiceal neoplasms as benign or malignant. The management of the mucinous variety of appendiceal neoplasms is influenced by the presence of peritoneal involvement. Selected patients with metastatic appendiceal neoplasms are treated with surgical cytoreduction and intraperitoneal chemotherapy and/or systemic chemotherapy. Nonmetastatic appendiceal adenocarcinoma is typically managed with staging right colectomy and adjuvant fluorouracil-based chemotherapy based on colon cancer guidelines. Neuroendocrine tumors (NETs) constitute 50 to 77% of all appendiceal neoplasms and 19% of all gastrointestinal NETs. Right hemicolectomy is indicated if the size of the NET is more than 2 cm, the base of the appendix is involved, it is a high-grade tumor, or the depth of invasion of the mesoappendix is more than 3 mm. This review contains 7 figures, 9 tables and 37 references Key Words: appendiceal adenocarcinoma, appendiceal adenoma, appendiceal neoplasm, diffuse peritoneal adenomucinosis, Goblet cell carcinoid of appendix, low-grade appendiceal mucinous neoplasm, mucocele of appendix, neuroendocrine tumor of appendix, peritoneal mucinous carcinomatosis (PMCA), pseudomyxoma peritonei

Appendiceal Neoplasm

Appendiceal neoplasms are rare and are typically found in the setting of metastatic disease or, less commonly, as an incidental finding in an appendectomy specimen in cases of appendicitis or an unrelated condition. The World Health Organization classifies appendiceal neoplasms as benign or malignant. The management of the mucinous variety of appendiceal neoplasms is influenced by the presence of peritoneal involvement. Selected patients with metastatic appendiceal neoplasms are treated with surgical cytoreduction and intraperitoneal chemotherapy and/or systemic chemotherapy. Nonmetastatic appendiceal adenocarcinoma is typically managed with staging right colectomy and adjuvant fluorouracil-based chemotherapy based on colon cancer guidelines. Neuroendocrine tumors (NETs) constitute 50 to 77% of all appendiceal neoplasms and 19% of all gastrointestinal NETs. Right hemicolectomy is indicated if the size of the NET is more than 2 cm, the base of the appendix is involved, it is a high-grade tumor, or the depth of invasion of the mesoappendix is more than 3 mm. This review contains 7 figures, 9 tables and 36 references Key Words: appendiceal adenocarcinoma, appendiceal adenoma, appendiceal neoplasm, diffuse peritoneal adenomucinosis, Goblet cell carcinoid of appendix, low-grade appendiceal mucinous neoplasm, mucocele of appendix, neuroendocrine tumor of appendix, peritoneal mucinous carcinomatosis (PMCA), pseudomyxoma peritonei

Establishment of patient derived xenograft model of high-grade mucinous carcinoma peritonei accompanied with signet ring cells and identification of biological characteristics

Objective: To establish the patient derived xenograft (PDX) model of pseudomyxoma peritonei (PMP), and identify the key characteristics of tumor biology of this model, in order to provide a reliable model for studying the pathological mechanisms and new therapeutic strategies of PMP. Methods: PMP tumor tissue was obtained from surgery and cut into pieces after washing. Then tumor pieces were implanted subcutaneously in BAL B/c-nu mice for 6 stable passages. In the 7th passage, tumor tissue was implanted orthotopically into abdomen. Subcutaneous tumor and orthotopic tumor were then homogenized to make tumor cell suspension, implanted into abdomen of 10 BAL B/c-nu mice through midline laparotomy, 100 μl for each. The key experimental parameters including body weight changes in the observation period, experimental peritoneal cancer index (ePCI) score at the autopsy, histopathological and immunohistochemical characteristics, and gene expression profiles by high-throughput whole-genome exon sequencing were detected and recorded. Results: The successful rate of established orthotopic PDX model of human PMP was 100% (10/10). The animals showed smooth body weight increases after tumor inoculation until day 27, then the body weight began to decrease steadily. Widespread tumor dissemination of PMP tumor through the whole abdomen was found by autopsy, including the diaphragm, liver, spleen, stomach, kidney, parietal peritoneum, bowel and mesenterium. Gelatinous ascites was also observed in abdominopelvic cavity. The ePCI score ranged from 5 to 9, with a 8 of median ePCI. Histopathological studies showed peritoneal mucinous carcinomatosis accompanied with signet ring cells (PMCA-S), obvious tumor cell atypia and parenchymal invasion.Immunohistochemistry showed the expressions of MUC1, MUC2, MUC5AC, CEA, CA199, CK20, CDX-2 and Ki-67 were positive, MUC6, CK7 and p53 were negative. Whole-exome sequencing identified that the most significant genetic alteration is the exon10 missense mutation c. 1621A>C of KIT gene, the mutation abundance was 89.7%. Conclusion: PDX model of PMCA-S is successfully established, which displays the characters of high-degree malignancy, high proliferation and strong aggressiveness.

Establishment of patient-derived xenograft model of peritoneal mucinous carcinomatosis with signet ring cells and in vivo study on the efficacy and toxicity of intraperitoneal injection of 5-fluorouracil.

BackgroundPseudomyxoma peritonei (PMP) is an indolent malignancy and insensitive to systemic chemotherapy. The authors established patient‐derived xenograft (PDX) model of PMP, and evaluated the efficacy and toxicity of intraperitoneal (i.p.) administration of 5‐fluorouracil (5‐FU) in this model.MethodsHuman PMP sample was collected to establish subcutaneous (s.c.) and i.p. model. In vivo study of i.p. injection of 5‐FU was performed in i.p. model, with experimental peritoneal cancer index (ePCI) score and pathological examinations for evaluating the efficacy and toxicity.ResultsBoth s.c. and i.p. models were constructed. The average passage interval of s.c. model was 44.2 ± 5.2 days, and the i.p. model was characterized by disseminated solid tumor nodules in abdominal‐pelvic cavity. Both models were diagnosed as peritoneal mucinous carcinomatosis with signet ring cells (PMCA‐S). Immunohistochemical characteristics was similar to human. GNAS mutation was detected in both model and patient. In the in vivo study, average ePCI of treatment group was lower than control and vehicle group (P = .004). Histopathology revealed obvious tumor necrosis in treatment group, and decreased Ki67 positive rate (P = .010). In toxicity study, 5‐FU significantly influenced body weight (P = .010) and 1 animal from treatment group died on day 14. Congestive splenomegaly was observed (88.9%). Hepatotoxicity presented as acidophilic body (55.6%), cholestasis (100%), bile canaliculus hyperplasia and obstruction (22.2%), and lymphocyte accumulation (77.8%).ConclusionsPDX model of PMCA‐S was established successfully, and i.p. 5‐FU could inhibit tumor proliferation and progression, with decreased Ki67 positive rate and ePCI score. Hepatotoxicity was the main side effect.

Pathological prognostic factors of pseudomyxoma peritonei

Objective: To analyze the pathological features of pseudomyxoma peritonei (PMP) in correlation with the survival status and independent prognostic factors. Methods: One-hundred and fifty-five PMP specimens were collected at Beijing Shijitan Hospital, Capital Medical University, from 2012 to 2018. Conventional histopathological evaluation was performed to document the primary tumor site, histopathological type, lymph nodes metastasis, tumor emboli in the blood and lymph vessels, nerve invasion and cellular density. The immunohistochemical parameters including Ki-67, p53, MMR-related protein, MUC2 and MUC5AC were analyzed. Clinical follow-up data were reviewed to correlate with pathological prognostic factors using Kaplan-Meier estimator and Cox proportional hazards regression model for univariate and multivariate analysis. Results: Among 155 PMP patients, there were 77 males and 78 females. There were 98 cases (63.2%) of low-grade peritoneal mucinous carcinomatosis, 49 cases (31.6%) of high-grade peritoneal mucinous carcinomatosis, 8 cases (5.2%) of high-grade mucinous carcinoma peritonei with signet ring cells; only 15 cases (9.7%) with lymph node metastasis; 18 cases (11.6%) with tumor emboli in the blood and lymph vessels; 8/126 (6.3%) were positive dMMR; 100 cases (64.5%) had Ki-67 label index <50%, and 56 cases(36.1%) presented with mutant type p53. Univariate analysis revealed 11 survival-related pathological parameters including gender, age, primary tumor site, histopathological type, lymph node metastasis, tumor emboli in the blood and lymph vessels, nerve invasion, cellular density, Ki-67 label index rate, p53 and dMMR. Multivariate analysis identified 4 independent prognostic factors including the histopathological type (HR 59.78, P<0.01), lymph node metastasis (HR 3.74, P=0.028), nerve invasion (HR 7.81, P=0.007) and dMMR (HR 9.82, P<0.01). Conclusions: Histopathological type is the most important prognostic factor of PMP with dMMR as an independent molecular prognostic indicator.

Prognostic value of the volume time index (VTI) ratio for patients with appendiceal cancer with peritoneal carcinomatosis treated by cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC).

e15704 Background: Completeness of cytoreduction score (CC-score) and tumour volume (as expressed by the peritoneal cancer index (PCI)) have been demonstrated as important post-operative prognostic factors in those patients with appendix cancer with peritoneal metastases undergoing CRS/HIPEC. A previous analysis included a pre-operative factor and demonstrated the tumour marker to volume index (CA19-9/PCI) in patients who had low grade appendiceal cancer with peritoneal metastases was an independent prognostic factor for overall survival (OS). This analysis aims to evaluate VTI as a prognostic factor in low- and high-grade appendix neoplasms with peritoneal dissemination managed with CRS/HIPEC. Methods: A retrospective cohort study of all patients diagnosed with appendiceal cancer with peritoneal dissemination managed with CRS/IPC from 1996 to 2017 was performed by analysing the survival effect of the ratio of tumour volume to the time between initial tumour resection and CRS/HIPEC. VTI was stratified into low versus high groups, and tumour grade was divided into low grade: diffuse peritoneal adenomucinosis (DPAM); and high grade: peritoneal mucinous carcinomatosis (PMCA). Results: Two hundred and sixty-four patients were included. For both DPAM and PMCA, there was no statistically significant difference in overall survival between patients with a low versus high VTI. For both low and high VTI in DPAM, the median survival was not reached, p= 0.586. For PMCA, those with a low VTI had an overall survival of 63 months (95%CI 48-NR), versus those with a high VTI 69 months (95%CI 45-NR), p= 0.97. There was no statistically significant difference in the median recurrence free survival (RFS) between low and high VTI for both DPAM and PMCA. Conclusions: The volume to time ratio for appendix cancer with peritoneal dissemination was not an independent prognostic indicator for overall survival in patients undergoing CRS/HIPEC, suggesting that this index is not a valuable pre-operative planning tool.

Analysis of feasibility and survival in repeated cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) in appendiceal cancer with peritoneal dissemination.

e15702 Background: CRS/HIPEC has been established as the method of choice for the management of peritoneal dissemination from appendiceal cancer. With recurrence rates after first surgery as high as 44%, re-do CRS/HIPEC is evolving as an effective recurrent treatment regime. This analysis examines the feasibility of repeated CRS/HIPEC for patients with appendiceal cancer with peritoneal dissemination and evaluates the survival outcomes. Methods: A retrospective cohort study of 1074 patients who had CRS/HIPEC procedures and had a recorded tumour grade from 1996 to 2017 was performed. Morbidity and mortality as well as the survival effect was analysed. Tumour grade was divided into low grade: diffuse peritoneal adenomucinosis (DPAM); and high grade: peritoneal mucinous carcinomatosis (PMCA). Results: Initial CRS/HIPEC comprised of 991 patients, with 148 of those undergoing repeated CRS/HIPEC for appendiceal cancer with peritoneal dissemination. The overall survival for patients with DPAM who had only one CRS/HIPEC was 248 months with a five-year survival of 80%, compared to an overall survival of 75 months and five-year survival of 54% in those who had repeated CRS/HIPEC. For patients with PMCA, the overall survival of those who only had one CRS/HIPEC was 63 months with a five-year survival of 47%, compared to an overall survival of 52 months and five-year survival of 44% in those who had repeated CRS/HIPEC. There was no statistically significant difference in the morbidity and mortality for patients who had repeated CRS/HIPEC for management of appendiceal cancer with peritoneal metastases when compared to those who only had one. Conclusions: This study suggests that re-do CRS/HIPEC is a feasible and effective treatment regime in the management of tumour recurrence in appendiceal cancer with peritoneal dissemination, with no difference in the morbidity and mortality of patients who had repeated CRS/HIPEC compared to only one procedure.

Factors influencing long-term survival after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for pseudomyxoma peritonei originating from appendiceal neoplasms.

BackgroundPseudomyxoma peritonei (PMP) is a rare disease, most commonly of appendiceal origin. Treatment consists of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS–HIPEC). The aim of this study was to identify prognostic factors for recurrence and survival.MethodsThis was an observational study using a prospectively designed database containing consecutive patients with PMP originating from the appendix, undergoing CRS–HIPEC at a tertiary referral centre between 1996 and 2015. Histopathological slides were reassessed. Cox regression was used for multivariable analyses.ResultsOf 225 patients identified, 36 (16·0 per cent) were diagnosed with acellular mucin, 149 (66·2 per cent) had disseminated peritoneal adenomucinosis (DPAM) and 40 (17·8 per cent) had peritoneal mucinous carcinomatosis (PMCA). The 5‐year overall survival (OS) rates were 93, 69·8 and 55 per cent respectively. Recurrence was observed in 120 patients (53·3 per cent), 39 of whom (17·3 per cent) were treated with a second CRS–HIPEC procedure. Factors independently associated with poor disease‐free survival were six or seven affected regions (hazard ratio (HR) 6·01, 95 per cent c.i. 2·04 to 17·73), incomplete cytoreduction (R2a resection: HR 1·67, 1·05 to 2·65; R2b resection: HR 2·00, 1·07 to 3·73), and more than threefold raised carcinoembryonic antigen (CEA) and/or carbohydrate antigen (CA) 19‐9 level (HR 2·31, 1·30 to 4·11). Factors independently associated with poorer OS were male sex (HR 1·74, 1·09 to 2·77), incomplete cytoreduction (R2a resection: HR 1·87, 1·14 to 3·08; R2b resection: HR 2·28, 1·19 to 4·34), and more than threefold raised CEA and/or CA19‐9 level (HR 2·89, 1·36 to 6·16).ConclusionCEA and CA19‐9 levels raised more than threefold above the upper limit identify patients with PMP of appendiceal origin and poorer survival.

Long term survival analysis after hyperthermic intraperitoneal chemotherapy with oxaliplatin as a treatment for appendiceal peritoneal carcinomatosis

Background and objectivesComplete cytoreductive surgery (CRS) followed by hyperthermic intraperitoneal chemotherapy (HIPEC) have been proven to lengthen survival in appendiceal peritoneal carcinomatosis (PC-A). The aim of this study was to analyze survival results of this therapy in our institution over the last 10 years. MethodsData was retrospectively reviewed and analyzed. Treatment consisted of CRS plus HIPEC with oxaliplatin. Ronnett's histologic classification was used (peritoneal mucinous carcinomatosis (PMCA), PMCA with intermediate features (PMCA-I) and disseminated peritoneal adenomucinosis (DPAM)). Overall survival (OS) and disease-free survival (DFS) estimates were calculated using Kaplan–Meier survival curves. Results109 patients with PC-A underwent laparotomy with curative intent. Of those, 92 underwent CRS plus HIPEC. Median follow-up was 42 months. The 5 and 10-year OS rates for the HIPEC group were 82.2% and 76.5%. The 5 and 10-year OS estimates for DPAM and PMCA-I subgroups were 100% and 100%, 78.1% and 72.9%, respectively. For the PMCA subgroup, the 3 and 5-year OS were 61.4% and 40.1%, respectively. The 5 and 10-year DFS estimates were 71.9% and 42.7%. ConclusionCRS plus HIPEC with oxaliplatin represent an effective therapeutic approach for PC-A. Long term OS estimates for patients treated at our institution are encouraging.

Pseudomyxoma peritonei treated with cytoreductive surgery and hyperthermic chemotherapy: a 7-year single-center experience.

Pseudomyxoma peritonei (PMP) is a rare clinical entity characterized by diffuse intraabdominal gelatinous collections with mucinous implants on the peritoneal surfaces and omentum. This condition should be considered a borderline malignancy with disease progression over time. Encouraging treatment results have been recently reported with the combination of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). . From December 2003 to December 2010, 18 patients with PMP were referred to our institution. All patients underwent peritonectomy and CRS combined with HIPEC in accordance with Sugarbaker's procedure. The mean Peritoneal Cancer Index score was 27.6 (range, 5-39). Twelve (67%) patients had disseminated peritoneal adenomucinosis and 6 (33%) peritoneal mucinous carcinomatosis. Optimal cytoreduction with no visible residual disease or residual disease ≤2.5 mm in diameter was achieved in all patients. The mean duration of the surgical procedure including HIPEC was 9 hours and 30 minutes (range, 5-13 hours); major morbidity occurred in 30% of patients and the mortality was 11%. The mean follow-up was 27 months (range, 1-72) and the 5-year overall survival 66%. In line with the existing literature, our experience suggests that patients with PMP could benefit from CRS + HIPEC in terms of survival and locoregional disease control.

CYTOREDUCTIVE SURGICAL TREATMENT WITH INTRAOPERATIVE PHOTODYNAMIC THERAPY IN PATIENTS WITH MUCINOUS PERITONEAL CARCINOMATOSIS

Clinical observation of a patient with an orphan disease (mucinous peritoneal carcinomatosis) after 2 courses of intraoperative photodynamic therapy with photogem photosensitizer is presented. During the first course of photodynamic therapy, photogem was administered at a dose of 2.5 mg/kg, the energy density of the laser radiation was 10 J/cm2. The duration of stabilization after the first course of treatment was 2 years, after which the progression of the disease was registered. The second course of photodynamic therapy was carried out in the same way. The duration of stabilization after the first course of treatment was 2.5 years. The patient died as a result of an accident unrelated to the disease.

Long-term outcomes with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in peritoneal carcinomatosis from appendiceal cancer: An 18-year experience.

4098 Background: Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) have become standard of care for patients with peritoneal carcinomatosis (PC) from appendiceal cancer (AC). We reviewed our experience and outcomes. Methods: A retrospective review of 614 CRS/HIPEC procedures from 1998-2016 was performed. Patient characteristics, surgical variables, and postoperative outcomes of first CRS/HIPEC were analyzed. Results: Two hundred ninety patients with PC from AC underwent 334 CRS/HIPEC’s. Median age at diagnosis and surgery was 52 (22-79) and 53 (23-81) years, respectively; 65% (187) were female. Prior surgical score was 0, 1, 2, and 3 in 20%, 38%, 37%, and 5%, respectively. Prior systemic chemotherapy was reported in 30% of patients. Median time from diagnosis to CRS/HIPEC was 4 months (0-182). Pre-operative tumor markers (CEA, CA-125, CA-19-9) were positive in 48% with one, two, and three positive markers in 21%, 15%, and 13% patients, respectively. Median Peritoneal Cancer Index was 29. Mitomycin-C was the HIPEC agent of choice. Mean operative time was 10 hours (R: 4-19) and median length of stay was 10 days (R: 4-93). Histology included 59% (171) peritoneal mucinous carcinomatosis (PMCA), 41% (119) disseminated peritoneal adenomucinosis (DPAM). Lymph nodes were positive in 47% PMCA. Complete cytoreduction rate was 87% (84% PMCA, 92% DPAM [p = 0.048]). Grade III-V complications occurred in 21%, with one 30-day mortality (0.3%). Overall, median progression-free survival (PFS) was 84 months with 5-year PFS of 56%. Median PFS was 43 months in PMCA and not reached in DPAM. Five year PFS was 40% PMCA and 82% DPAM (p &lt; 0.001). Median overall survival (MOS) was 139 months with 61% 5-year OS. MOS was 53 months in PMCA and not reached in DPAM. Five year OS was 47% PMCA and 85% DPAM (p &lt; 0.001). At 42-month median follow-up, 68% were alive (92 PMCA/103 DPAM) with 84% disease free (72 PMCA/92 DPAM), 28% died of disease (73 PMCA/7 DPAM). Conclusions: CRS/HIPEC is an effective treatment for patients with PC from AC providing meaningful long term survival in low and high grade tumors and should be considered the standard of care.

Early Data Of Patients With Pseudomyxoma Peritonei From Appendiceal Origin Treated By A Strategy Of Cytoreductive Surgery And Hyperthermic Intraperitoneal Chemotherapy

Background. Appendiceal peritoneal pseudomyxoma (PMP) is very rare disease and its longterm prognosis is poor. The aim of this study was to evaluate the results of an aggressive treatment approach used in our institution for the last 4 years. Methods. We selected all patients with PMP from appendiceal origin who were treated by cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) at the Klaipeda University Hospital between January 2012 and January 2016. Data from all patients with PMP arising from the appendix were retrospectively collected and analyzed. Treatment consisted of complete surgical cytoreduction , followed by hyperthermic intraperitoneal chemotherapy with mitomycin at 42°C over 90 minutes. Ronnett’s hystologic classification was used for tumor grading. Results. A total of 6 patients underwent cytoreduction and peritonectomy plus HIPEC. Median age at diagnosis was 57 years (range, 39-67). All our patients were female. The previous surgery score at the moment of admission was PSS-2 for three patients, PSS-3 for 3 patients. Four patients were diagnosed as diffuse peritoneal adenomucinosis (DRAM) and two as peritoneal mucinous carcinomatosis( PMCA). In all of the patients, optimal cytoreduction CC-0 (5 patients) and CC-1 (one patient) was achieved. The median peritoneal cancer index (PCI) was 17 (range, 14-25) as an indicator of disease extension.The median number of visceral resections performed per patient was 3 (range, 1-5). The median duration of CRS/HIPEC was 8 hours and 10 minutes (range, 7 hours and10 min. to 9 hours 20 min). Mean postoperative stay was 13 days (range, 8-18). The 30 days postoperative and in-hospital mortality were zero . One patient experienced temporary haemorhagic cystitis. The mean follow-up period was 28 months ( range, 8-45). At the time of analysis all patients are alive and without recurrence. Conclusions PMP from appendiceal origin can be treated with curative intent in a large percentage of cases by cytoreductive surgery associated with HIPEC. This new approach could be performed safely with acceptable morbidity and mortality in selected patients treated in specialized centers.

Significance of epithelial cell clusters in pseudomyxoma peritonei.

Pseudomyxoma peritonei (PMP) is a rare clinical syndrome characterised by distension of the peritoneum by jelly-like ascites. Cytological evaluation of peritoneal fluid is often an initial diagnostic test for possible ovarian and/or appendiceal primary tumours. The present work was conducted to study the usefulness of peritoneal fluid cytomorphology in the early diagnosis of PMP and to evaluate the significance of the presence of epithelial cell (EC) clusters and their prognostic implications. We evaluated the detailed cytological features of 21 cases of PMP retrospectively. Both conventional and liquid-based cytology smears of peritoneal fluid were reviewed, cytological features were compared with histological findings and cases were classified into disseminated peritoneal adenomucinosis (DPAM) and peritoneal mucinous carcinomatosis (PMCA). In our study, the common causes of PMP were primary gastrointestinal malignancies (appendix and colorectal, 57.14%), followed by primary ovarian mucinous neoplasms (28.57%) and synchronous ovarian and appendicular tumours (14.28%). Thick mucinous material was present in all cases (100%). ECs were present in 18 of 21 (85.17%) patients, with mild nuclear atypia in the majority of cases. Histiocytes, mesothelial cells and fibroblast-like, spindle-shaped cells with entrapped mucin were also noted in the background. The cases of PMCA showed greater numbers of EC clusters in cytology smears and these patients had recurrent episodes of PMP. On cytomorphology, high-grade tumours were more cellular and frequently showed EC clusters with moderate to severe atypia, prominent nucleoli and mitosis, and were more prone to PMCA.

The role of cytoreductive surgery and heated intraperitoneal chemotherapy (CRS/HIPEC) in patients with peritoneal carcinomatosis (PC) of appendiceal origin (AO).

707 Background: Peritoneal carcinomatosis of mucinous appendiceal tumor origin is a rare condition which has poor prognosis if treated with limited surgery or systemic chemotherapy. Several publications show that CRS/HIPEC gives a significant survival benefit for patients with PC of AO. However, many patients do not get appropriate treatment. We show data from our 17-year experience using CRS/HIPEC in PC of AO. Methods: Retrospective analysis of a prospective database of 251 patients with PC of AO was performed. Peritoneal cancer index (PCI), completeness of cytoreduction (CC), lymph node (LN) status, and histopathology data was collected. The impact of each variable evaluated by Hazard ratio analysis. Overall survival (OS) estimated by Kaplan-Meier curves. Results: Mean age 53 years (range 23-81). 251 patients underwent 290 CRS/HIPEC procedures. 31 patients had 2, and 4 patients had 3 CRS/HIPEC. A total of 149 patients (59%) had peritoneal mucinous carcinomatosis (PMCA) and 102 (41%) had disseminated peritoneal adenomucinosis (DPAM) (Ronnett classification). Mean follow-up 4.8 years with a median of 4.7 years. Complete cytoreduction was achieved in 84% (89% DPAM, 80% PMCA; p = 0.047). Mean length of surgery 11.3 hours, mean hospital stay 14 days. No in-hospital or 30-day mortality. 73% had PCI &gt; 20 (78% DPAM; 68% PMCA). LN metastasis in 42% with PMCA. OS from date of HIPEC was 93%, 86%, 81% in DPAM and 90%, 60%, 44% in PMCA for 1, 3, and 5 years, respectively. With CC, the 5-year OS was 84% in DPAM and 49% in PMCA. All PMCA patients with incomplete cytoreduction (n = 30) had PCI ≥ 20 (p &lt; 0.001). Hazard ratios were 2.5 (95% confidence interval [95% CI] 1.3-4.5), 3.1 (95% CI 2.0-4.9), 3.6 (95% CI 2.1-6.2), for PCI &lt; 20, complete cytoreduction, and histopathology (DPAM vs. PMCA), respectively. Hazard ratio (for LN status in patients with PMCA was 3.0 (95% CI 1.8-5.1). Conclusions: Meaningful survival could be achieved in PC of AO even with extensive peritoneal disease (PCI &gt; 20). We consider CRS/HIPEC a standard of care for these patients. CRS/HIPEC should be provided in specialized centers by trained surgeons where complete cytoreduction could be frequently accomplished.