Low-grade Mucinous Carcinoma Peritonei Research Articles

Origin and survival outcomes of Pseudomyxoma peritonei-A retrospective study.

Pseudomyxoma peritonei (PMP) is an unusual clinical condition typically presenting with widespread mucinous neoplastic lesions within the peritoneum resulting in gelatin material-rich ascites. It was first described by Werth in 1884. Ever since, its clinical presentation, definition, site of origin, and prognosis have been a subject of debate. However, many histopathologic, immunohistochemical, and genetic studies have attempted to locate the primary lesion in the appendix in both genders. To analyze the histological origin and survival outcomes of pseudomyxoma peritonei in patients treated at a regional cancer center. Fifteen cases of PMP were diagnosed during the five-year study period. The demographic and clinicopathological details were retrieved; the slides were reviewed and histological parameters reassessed. Descriptive statistics were used to express proportions. Continuous variables were recorded as mean (SD) or median (IQR). Kaplan-Meier (KM) curve was used to estimate overall survival. Mean age for PMP was found to be 47.5 years for low grade Mucinous Carcinoma Peritonei (MCP), 54.2 years for high grade MCP, and 58 years for high grade MCP with signet ring cells. Most common overall presentation was abdominal distension in 53.3% (8/15) of cases, followed by acute appendicitis in 20% (3/15) cases. PMP was detected synchronous with the primary tumor in 9/15 cases (60%). Primary lesion in the appendix was grossly identified in 7/15 cases, while it was not explored in the remaining eight cases. Yet, by combined clinical, radiological, histopathological, and immunohistochemical analysis, we identified that most of the cases (14/15) had an appendiceal origin (93.3%). The overall survival for 12 months was 50% and for 18 months was 37%. The surgeon and radiologist may well bear in mind the most common possibility of an appendiceal origin for PMP and resect the appendix, irrespective of the presence of a grossly or radiologically detectable lesions. We emphasize that immunohistochemistry helped to detect the site of origin even when the primary was occult.

Establishment and characterization of NCC-PMP2-C1: a novel patient-derived cell line of pseudomyxoma peritonei with signet ring cells.

Pseudomyxoma peritonei (PMP) is a rare phenomenon, characterized by accumulation of mucus in the abdominal cavity due to a mucinous neoplasm. Histologically, PMP is divided into three prognostic classes, namely low-grade mucinous carcinoma peritonei (LGMCP), high-grade mucinous carcinoma peritonei (HGMCP), and high-grade mucinous carcinoma peritonei with signet ring cells (HGMCP-S); HGMCP-S exhibits the worst prognosis. Complete cytoreductive surgery and hyperthermic intraperitoneal chemotherapy have been established as the standard therapy for PMP. However, 50% of patients with PMP experience a recurrence, and 30-40% are unable to receive the standard treatment due to invasive diseases. Therefore, novel therapies are required for their treatment. Although patient-derived cell lines are important tools for basic and pre-clinical research, PMP cell lines derived from patients with HGMCP-S have never been reported. Thus, we established a novel PMP cell line NCC-PMP2-C1, using surgically resected tumor tissue from a patient with HGMCP-S. NCC-PMP2-C1 cells were maintained for more than five months and passaged 30 times under culture conditions. NCC-PMP2-C1 cells exhibited multiple deletions and somatic mutations, slow growth, histological features, and dissemination of tumor cells in nude mice. Screening for the anti-proliferative effects of anti-cancer drugs on cells revealed that bortezomib, mubritinib, and romidepsin had a significant response against NCC-PMP2-C1 cells. Thus, the NCC-PMP2-C1 cell line is the first PMP cell line harboring signet ring cells and will be a valuable resource for basic and preclinical studies of HGMCP-S.

Long-term survival following cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in Waikato, Aotearoa New Zealand: a 12-year experience.

Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) have improved survival for selected cases of peritoneal surface malignancy. In 2008, a CRS/HIPEC service was first established in Aotearoa New Zealand (AoNZ) at Waikato and Braemar Hospitals in the Waikato region. This is a retrospective review of a prospectively maintained database of all patients undergoing CRS/HIPEC from 1 January 2008 to 1 November 2020 at Waikato and Braemar Hospitals. We analysed long-term survival and predictors of survival for each tumour type. 240 procedures were performed for 221 patients, including 22 re-do procedures. Cases had a median peritoneal cancer index of 16. Complete cytoreduction (CC0-1) was achieved in 196 cases (81.7%). All complete cytoreduction cases received HIPEC. There were 152 pseudomyxoma peritonei (PMP), 39 colorectal cancers (CRC), 29 appendiceal cancers, eight ovarian cancers, six peritoneal mesotheliomas, and six other cancers. The 5-year overall survival (OS) for PMP with acellular mucin, low-grade mucinous carcinoma peritonei, and high-grade mucinous carcinoma peritonei with or without signet cells were 91.6%, 80.5%, and 72.2%, respectively. 2- and 5-year OS in CRC were 56.7% and 40.4%. The achievement of complete cytoreduction improved the 5-year OS to 87.9% across all PMP and 45.1% in colorectal cancer. Incomplete cytoreduction predicted worse survival in appendiceal PMP. In colorectal cancer, worse survival was predicted in those who had incomplete cytoreduction, liver metastasis, and presentation with obstruction and perforation. Favourable long-term outcomes following CRS/HIPEC for peritoneal surface malignancy have been achieved in AoNZ through the Waikato peritonectomy service.

Correlation between PSOGI pathological classification and survival outcomes of patients with pseudomyxoma peritonei treated using cytoreductive surgery and HIPEC: national referral centre experience and literature review.

The Peritoneal Surface Oncology Group International (PSOGI) consensus subdivided pseudomyxoma peritonei (PMP) into four groups according to histopathological features. The aim of this paper is to report survival outcomes after cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) from a national referral centre and to correlate the PSOGI classification with survival. A retrospective study of a prospectively maintained database was performed. Consecutive patients treated with CRS+HIPEC for PMP of appendiceal origin were included (September-2013 to December-2021). Pathological features of the peritoneal disease were used to classify patients into the four groups proposed by PSOGI. Survival analysis was performed to evaluate the correlation of pathology on overall survival (OS) and disease-free survival (DFS). Overall, 104 patients were identified; 29.6 % were reclassified as acellular mucin (AM), 43.9 % as low-grade mucinous carcinoma peritonei (LGMCP), 22.4 % as high-grade MCP (HGMCP) and 4.1 % as HGMCP with signet ring cells (HGMCP-SRC). Median PCI and rate of optimal cytoreduction were 19 and 82.7 %, respectively. Median OS and DFS were not reached, 5-year OS and DFS were 88.6(SD 0.04) % and 61.6(SD 0.06) %, respectively. Log-Rank test revealed significant differences in terms of OS and DFS across the different histological subgroups (p<0.001 in both cases). However, histology did not retain its significance in the multivariate analysis for OS or DFS (p=0.932 and p=0.872, respectively). Survival outcomes after CRS+HIPEC for PMP are excellent. The PSOGI pathological classification correlates with OS and DFS, but differences were not significant at multivariate analysis when adjusted for other prognostic factors.

600 Acute Appendicitis as an Early Manifestation of Colorectal Cancer for Patients Aged 40 Years and Above

Abstract Aim Presence of underlying colorectal cancer with acute appendicitis is not unfamiliar in medical literature. However, there remains no clear guidance in the follow-up care post-appendicectomy. This study aims to investigate whether acute appendicitis can be an early manifestation of colorectal cancer in older adults and determine the need of routine pre-operative CT imaging and post-operative colonoscopy as a follow-up screen for early detection of colorectal cancer. Method This is a retrospective study comprising 1236 patients, aged 40 years and above, who underwent appendicectomy between January 2006 to September 2021. Results of radiological investigation pre-appendicectomy and colonoscopy post-appendicectomy were reviewed. Patients who were diagnosed immediately and subsequently following appendicectomy were recorded and analysed. Results Of the 1236 patients underwent appendicectomy, 636 (51.5%) were male and 600 (48.5%) were female (Median age 53 years; range 40–96 years). Out of 412 (33.3%) patients who had CT imaging, only one revealed sigmoid tumour which was later confirmed as moderately differentiated adenocarcinoma. 71 (5.7%) patients had colonoscopy post-appendicectomy. Among these, two were diagnosed with caecal cancer. A total of 22 (1.8%) patients were diagnosed with colorectal cancer: 13 adenocarcinoma, 5 carcinoid tumours, 3 low-grade mucinous carcinoma peritonei and 1 lymphoma. 15 (1.2%) were diagnosed at the time of appendicectomy, whereas the remaining 7 (0.6%) were diagnosed between 6 months to 11 years post-appendicectomy. Conclusion Preliminary finding suggests this is an area that warrant further study. Patients aged 40 years and above may benefit from colonoscopy following appendicectomy to exclude the possibility of underlying colorectal cancer.

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

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

Which classification system defines best prognosis of mucinous neoplasms of the appendix with peritoneal dissemination: TNM vs PSOGI?

AimsSeveral classification systems are used for pseudomyxoma peritonei. The four-tiered classification system proposed by Peritoneal Surface Oncology Group International (PSOGI) and the two-tiered proposed by the eighth edition of the...

Ki67 does not predict recurrence for low-grade appendiceal mucinous neoplasms with peritoneal dissemination after cytoreductive surgery and HIPEC

Low-grade appendiceal mucinous neoplasms (LAMN) can disseminate to become low-grade mucinous carcinoma peritonei (LGMCP), which is optimally treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC). Approximately half of the patients with LGMCP recur despite complete cytoreduction, and risk factors for recurrence are poorly understood. We sought to evaluate if Ki67 predicts progression of LGMCP after CRS/HIPEC. A retrospective review of a prospectively maintained database was performed to identify patients treated with complete CRS/HIPEC for LGMCP from 2008 to 2019 with Ki67 assessed. Patient characteristics, histologic data, average and focally high "hotspot") Ki67 index, progression-free survival (PFS), and overall survival (OS) were analyzed. Ki-67 immunostain was performed on the histologic section with the highest cellularity and architectural complexity. Forty-four patients with LGMCP (55% male, median age 61) were identified. The median Ki67 score and hotspot Ki67 score was 15% (1-70) and 50% (1-90), respectively. On univariate analysis, average Ki67 and hotspot Ki67 were not predictive of PFS when analyzed as continuous normalized values (HR 1.0, p=0.79 and HR 1.1, p=0.38, respectively) or as categorical values when stratified by the median (HR 0.9, p=0.67 and HR 1.0, p=0.93). This remained true on multivariate analysis when stratified for peritoneal cancer index, CEA, and completeness of cytoreduction score for both normalized Ki67 and hotspot Ki67 (HR 0.9 [95% CI 0.8-1.3], p=0.94 and HR 1.04 [95% CI 0.8-1.3], p=0.73, respectively). Ki67 failed to predict disease recurrence for patients with LGMCP in this cohort.

New insights in the pathology of peritoneal surface malignancy.

Pathology is central to the management of peritoneal surface malignancy. This article highlights some recent advances that have had an impact on patient management or could do so in the near future. Malignant peritoneal mesothelioma, particularly the epithelioid subtype, is amenable to radical therapy in selected cases, and factors such as ki67 proliferation index, expression of BAP1 and mutation in CDKN2A show promise as prognostic indicators. Our understanding of multicystic mesothelioma has improved in recent years; it is a true neoplasm for which surgery may be indicated. Serous carcinomas involving the peritoneum are now known to originate from tubal epithelium. They are of two distinct types, high grade and low grade, which are now recognized as different neoplasms with distinctive features, oncogenesis and behavior. Pseudomyxoma peritonei (PMP) is an unusual condition that usually arises from an appendiceal mucinous neoplasm. Recent consensus in the classification and nomenclature of these lesions is discussed, including the distinction between low grade and high grade appendiceal mucinous neoplasms (HAMN), and the diagnostic criteria for appendiceal adenocarcinoma. PMP is divided into four prognostic groups: acellular mucin, low grade mucinous carcinoma peritonei, high grade mucinous carcinoma peritonei, and high grade mucinous carcinoma peritonei with signet ring cells. The pseudomyxoma microbiome is a promising area for clinical intervention but has been the subject of little research activity. Goblet cell adenocarcinoma (previously known as 'goblet cell carcinoid') is a distinctive type of appendiceal adenocarcinoma. Its behavior correlates with histologic features, but no general consensus for classification has been reached.

Patients undergoing cytoreductive surgery for peritoneal malignancy of appendiceal origin should be consented for umbilical excision as 30% have umbilical infiltration

Cytoreductive surgery (CRS) for peritoneal malignancy has traditionally included umbilical excision with no published evidence on the incidence of umbilical involvement. The primary aim of this work was to determine the incidence of umbilical involvement in patients undergoing CRS for peritoneal malignancy of appendiceal origin. The secondary aim was to investigate the relationship of umbilical involvement with prior surgery affecting the umbilicus, such as diagnostic laparoscopy and midline laparotomy. This study is from a national referral centre in the United Kingdom for appendiceal tumours and peritoneal malignancy. It is a retrospective analysis from a dedicated prospective database. We evaluated the most recent 200 consecutive patients who underwent CRS for peritoneal malignancy of appendiceal origin where all pathology specimens were reported by a recognized expert pathologist in appendiceal tumours and peritoneal malignancy. From June 2016 to September 2019, 200 consecutive patients had CRS and 178 had umbilical excision. Of these 54/178 (30.3%) had disease involving the umbilicus. The pathological findings in the 178 patients were low-grade mucinous carcinoma peritonei in 90/178 (50.6%), high-grade mucinous carcinoma peritonei in 31/178 (17.4%), metastatic appendiceal adenocarcinoma in 29/178 (16.4%) and diffuse acellular mucin in 28/178 (15.7%). Umbilical involvement was found in 25/90 (27.8%) with low-grade, 11/31 (35.5%) with high-grade, 8/29 (27.6%) with adenocarcinoma and 10/28 (35.7%) of patients with acellular mucin. In the 54 patients with umbilical disease, 30/54 (55.6%) had previous diagnostic surgery affecting the umbilicus. In the 124 patients without umbilical disease, 76/124 (61.2%) had prior surgery involving the umbilicus. The difference between the groups was not significant (p=0.24). In patients with peritoneal malignancy of appendiceal origin, approximately 30% have umbilical involvement, irrespective of the primary appendiceal pathology. Umbilical involvement was not associated with prior surgery involving the umbilicus. This is the first report to document the incidence of umbilical pathology and supports consideration of routine umbilical excision in CRS for peritoneal malignancy.

S2097 Pseudomyxoma Peritonei Presenting with Extrinsic Compression on Esophagogastroduodenoscopy and Colonoscopy

INTRODUCTION: Pseudomyxoma peritonei (PMP) is a rare disease characterized by mucinous ascites, classically originating from a ruptured low-grade appendiceal mucocele. We present a case of PMP identified because of signs of extrinsic compression on esophagogastroduodenoscopy (EGD) and colonoscopy. CASE DESCRIPTION/METHODS: A 66-year-old male presented for screening colonoscopy and EGD. His medical history was significant for renal calculi and recurrent acid reflux resistant to medical therapy. He denied weight gain or abdominal distension. A colonoscopy performed six years prior identified a single 3 mm tubular adenoma, diverticulosis, and internal hemorrhoids. Colonoscopy revealed sigmoid diverticulosis, a benign stricture in the recto-sigmoid colon, and a large, extrinsic-appearing mass in the descending colon (Figure 1). EGD revealed LA Grade C reflux esophagitis, a hiatal hernia, gastritis, one large non-bleeding duodenal ulcer with a clean ulcer base, and possible extrinsic compression in the gastric body (Figure 2). A CT Abdomen/Pelvis with contrast was obtained to further characterize this apparent extrinsic compression, which revealed diffuse low-density masses and ascites distending the peritoneal cavity with scalloped appearance of the liver and spleen. He was referred to surgical oncology and underwent a diagnostic laparoscopy with peritoneal biopsies that revealed extensive mucin and fibrin deposits, consistent with PMP. He underwent cytoreduction, right hemicolectomy, and hyperthermic intraperitoneal chemotherapy (HIPEC). Surgical pathology showed low grade mucinous carcinoma peritonei and the appendix showed a low-grade mucinous neoplasm. Repeat CT Abdomen/Pelvis with contrast revealed significantly improved peritoneal carcinomatosis and multiloculated, multiseptated, low attenuation masses throughout the abdomen. CEA was 58.3 at five months post-operative from 159.6 preoperatively. Seven months post-operatively the patient was doing well without findings concerning for recurrent disease. DISCUSSION: The incidence of PMP is estimated to be 1-3 per million per year. The growth of appendiceal mucinous tumors is indolent, and they are frequently diagnosed incidentally during evaluation for other conditions. They are classically identified on colonoscopy as an abnormal appearing appendiceal orifice (“volcano sign”) atop a “mound” of normal-appearing mucosa. This case highlights the importance of considering extraluminal etiologies for unexpected findings on endoscopy.Figure 1.: Extrinsic-appearing mass in the descending colon.Figure 2.: Possible gastric mass or extrinsic compression in the gastric body.Figure 3.: CT Abdomen/Pelvis with oral and IV contrast showing diffuse low-density masses and ascites, distending the peritoneal cavity with scalloped appearance of the liver.

Clinicopathological Characteristics of Pseudomyxoma Peritonei Originated from Ovaries.

ObjectiveThis study aims to demonstrate clinicopathological characteristics and immunohistopathological phenotypes of pseudomyxoma peritonei (PMP) originated from ovaries.MethodsThe primary origin of PMP was explored by reviewing H&E sections retrospectively and performing a series of immunohistochemical staining on CK7, CK20, CDX2, CEA, Villin, SATB2, CA125, ER, PR, and MUC.ResultsAmong 310 PMP patients, a few originated from extra-appendix, whereas eight cases were of ovarian origin (2.6%), including three teratoma-associated ovarian mucinous tumors and five primary ovarian mucinous tumors with spontaneous or iatrogenic rupture, respectively. Most peritoneal metastases were acellular mucin or low-grade mucinous carcinoma peritonei (6/8, 75%), while the rest were high-grade mucinous carcinoma peritonei (2/8, 25%). Tumors were positive for CK20, CDX2, CEA, and Villin. SATB2 was specifically diffuse positive in teratoma-associated ovarian mucinous tumors, and negative in primary ovarian mucinous tumors. Differential expression of MUC was observed in these tumors.ConclusionPMP of ovarian origin is extremely rare. The precise diagnosis requires serial sections of the appendix or suspicious tissue to exclude appendiceal mucinous neoplasms, as well as comprehensive analysis of clinical features, surgical findings, histopathological characteristics, and immunohistochemistry on specific biomarkers.

Defining "Complete Cytoreduction" After Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy (CRS/HIPEC) for the Histopathologic Spectrum of Appendiceal Carcinomatosis.

The completeness of cytoreduction (CC) score, which quantifies residual tumor, is a major prognostic factor when treating appendiceal carcinomatosis with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC). Both CC-0 and CC-1 are considered complete cytoreductions (CC-0/1) and associated with the best outcomes. We analyzed if the CC-0/1 definition is reliable across appendiceal histopathologic subtypes. A prospective database of CRS/HIPEC patients with appendiceal carcinomatosis from 1998 to 2019 was reviewed to identify patients with CC-0/1. Kaplan-Meier overall survival (OS) and progression-free survival (PFS) by CC-score for each histopathology were calculated. Overall, 297 patients had CC-0/1. Mean age was 54 ± 12years with 67% females. Histopathologic subtypes were 45% low-grade mucinous carcinoma peritonei (LGMCP), 27% high-grade MCP (HGMCP), 20% HGMCP with signet ring cells (HGMCP-S), and 8% goblet cell adenocarcinoma (GCAC). CC-0 and CC-1 occurred in 57% and 43% of LGMCP, 65% and 35% of HGMCP, 68% and 32% of HGMCP-S, and 79% and 21% of GCAC, respectively. OS and PFS were statistically longer for CC-0 versus CC-1 in HGMCP-S (p = 0.001 and p = 0.005, respectively) and GCAC (p < 0.001 and p < 0.001), but not in LGMCP (p = 0.098 and p = 0.398) or HGMCP (p = 0.167 and p = 0.356). Survival outcomes for CC-0 and CC-1 after CRS/HIPEC are different for HGMCP-S and GCAC but not for LGMCP and HGMCP. In HGCMP-S and GCAC, only CC-0 should be considered a complete cytoreduction and analyzed separately from CC-1. This distinction is key to understand disease behavior, accurately address patient prognosis, and explore new treatment strategies.

Investigating the utility of extended mutation analysis in gastrointestinal peritoneal metastasis

Outcomes for gastrointestinal peritoneal metastases (GI-PM) are worse compared to systemic metastases, with a paucity of data exploring extended mutation profiling. An exploratory mutation analysis in GI-PMs was performed as a "proof of concept" of potential predictive values of profiling in GI-PM and rates of actionable mutations. The study included 40 GI-PM patients: 14 low-grade mucinous carcinoma peritonei and 26 HG-PM (12 colons, 10 appendix, 4 small bowels). Demographics, histologies, peritoneal cancer indexes, cytoreduction scores, and survival data were collected. NGS 50-gene mutation profiling was performed on 38 specimens. The association of mutations with survival was evaluated in high-grade PM. KRAS, TP53, and SMAD4 mutations were observed in 61%, 29%, and 8% of cases across all tumor histologies. In 66% cases >1 mutations occurred, associated with decreased survival in HG-PM: 32 vs 73 months, P = .03. TP53 or SMAD4 mutations were associated with decreased survival in HG-PM: 22 vs 48 months, P = .02. Actionable mutations were detected in 70%. Actionable mutations were detected at high rates. GI-PMs have similar mutational profiles and TP53, SMAD4, and/or >1 mutation were associate with decreased survival in HG-PM. This data supports the concept of the extended mutation profiling utility in GI-PM warranting further investigation.

Clinical evaluation of tumor-stroma ratio in pseudomyxoma peritonei from the appendix

To evaluate the effect of tumor-stroma ratio (TSR) on disease progression and prognosis of pseudomyxoma peritonei (PMP) from the appendix. The study included 30 PMP patients with complete individual patient data, who underwent cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) in Beijing Shijitan Hospital. Image-Pro Plus was used to quantitatively analyze the proportion of tumor and stromal areas in hematoxylin-eosin staining pathological images, from which TSR was derived. Correlation studies were conducted to evaluate the relationships between TSR and clinicopathological features, immunohistochemical characteristics, and prognosis of PMP. Among 30 PMP patients, there were 16 males (53.3%) and 14 females (46.7%), with the mean age of (54.9±2.3) years. There were 15 cases (50.0%) of low-grade mucinous carcinoma peritonei (LMCP) and high-grade mucinous carcinoma peritonei (HMCP), respectively, with vascular tumor emboli occurring in 4 cases (13.3%), nerve invasion occurring in 3 cases (10.0%), and lymphatic metastasis occurring in 4 cases (13.3%). The median peritoneal cancer index (PCI) score was 36 (range: 3-39). The median TSR was 8% (range: 2%-24%), with TSR≤10% in 19 cases (63.3%) and TSR>10% in 11 cases (36.7%). Immunohistochemistry showed that 16 cases (53.3%) had Ki67 label index ≤ 50% and 14 cases (46.7%) > 50%. The mutation rate of p53 was 56.7% and the loss rate of MMR protein was 11.8%. In addition, the expression rates of MUC2, MUC5AC, CDX2, CK7, and CK20 were 66.7%, 100.0%, 82.6%, 56.0%, and 92.3%, respectively. There were significant correlations between TSR and histopathological types, nerve invasion, Ki67 label index, and p53 mutation (P<0.05 for all). At the end of the last follow-up, 21 patients (70.0%) died and 9 patients (30.0%) survived, including 6 patients survived with tumor. The median overall survival (OS) was 12.7 months (95%CI: 10.4-11.5 months), and the 1-, 2-, and 3-year survival rates were 60.5%, 32.3%, and 27.7%, respectively. The median OS was 19.4 months (95%CI: 3.0-35.9 months) in the TSR≤10% group, versus 12.6 months (95%CI: 0.7-24.5 months) in the TSR>10% group (χ2=3.996, P=0.046). TSR is correlated with histopathological types, tumor proliferation, invasion behaviors and prognosis of PMP, thus could be a new prognostic indicator for PMP.

Pathological prognostic factors of pseudomyxoma peritonei: comprehensive clinicopathological analysis of 155 cases

Pseudomyxoma peritonei (PMP) is an extremely rare malignancy, characterized by extensive peritoneal implantation and colloidal ascites. This study was to explore the pathological prognostic factors of PMP. Specimens from 155 PMP patients were analyzed by H&E and immunohistochemistry. Parameters included primary tumor location, histological grade, lymph node metastasis, tumor emboli in the blood and lymph vessels, perineural invasion, Ki67 labeling index, p53, mismatch repair (MMR) gene mutations, MUC1, MUC2, MUC5AC, and MUC6. Clinicopathological and follow-up data were subjected to univariate and multivariate analyses. The patients included 63.2% (n = 98) low-grade mucinous carcinoma peritonei, 31.6% (n = 49) high-grade mucinous carcinoma peritonei and 5.2% (n = 8) high-grade mucinous carcinoma peritonei with signet ring cells. There were 9.7% (n = 15) with lymph node metastasis; 11.6% (n = 18) with angiolymphatic invasion; 6.3% (n = 8) with defective MMR (dMMR); 35.5% (n = 55) with Ki67 labeling index ≥ 50%; 36.1% (n = 56) with p53 mutation. For PMP from appendiceal origin (n = 140), univariate analysis identified 10 potential prognostic factors. But Multivariate analysis identified only histologic grade was the independent prognostic factor for OS. Mortality risk of high-grade peritoneal mucinous carcinoma or high-grade peritoneal mucinous carcinoma with signet ring cells was 7.056 times (P < .0001, 95% CI: 2.701-18.435) or 27.224 times (P < .0001, 95% CI: 6.207-119.408), respectively, higher than low-grade. For PMP from the appendiceal origin, histological grade could be the only independent prognostic factor.

Pseudomyxoma Peritonei Arising From a Low-Grade Mucinous Neoplasm of the Urachus

Abstract Urachal mucinous tumors range from low-grade lesions traditionally called cystadenomas to frankly invasive mucinous adenocarcinomas. Occasionally, they can lead to the syndrome of pseudomyxoma peritonei (PMP). We report a patient who presented with abdominal distension and had raised tumor markers. A computed tomography scan revealed a calcified cystic lesion of the bladder dome together with features of PMP. These findings were confirmed at laparotomy, and cytoreductive surgery with hyperthermic intraperitoneal chemotherapy was performed. Histologically, the urachal lesion was a low-grade urachal mucinous tumor (mucinous cystic tumor of low malignant potential). The peritoneal disease was associated with ovarian involvement and omental cake and was designated low-grade mucinous carcinoma peritonei on histology. The immunoprofile was typical for lesions of this type, featuring expression of CK20, CEA, and CDX2, but no expression of CK7. We review the literature of PMP arising from urachal primary neoplasms and identify 58 cases reported previously. Based on the limited data available, it appears that urachal lesions account for about 1 in 200 cases of PMP. Owing to the clinical and pathological similarities between urachal and appendiceal mucinous tumors, we recommend a simple classification based on the principles applied to appendiceal lesions and argue this is more appropriate than a classification based on ovarian nomenclature.

Selection and Characteristics of Patients with Peritoneal Dissemination from Appendiceal Cancer with Exceptional/Poor Survival After CRS/HIPEC.

Survival in peritoneal dissemination from appendiceal cancer after complete cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) varies within each histopathologic subtype. Analyzing patients with unique responses may uncover the mechanisms behind their extreme outcomes. We proposed a method to identify retrospectively and to characterize patients who responded exceptionally well or very poorly within each histopathologic subtype. Retrospective review of patients with low-grade mucinous carcinoma peritonei (LGMCP), high-grade MCP (HGMCP), and HGMCP with signet ring cells (HGMCP-S) with complete CRS/HIPEC (CC-0/1) was performed. Patients were divided by recurrence status. Median follow-up was calculated for each. Exceptional responders (ExR) were defined as alive without recurrence after median follow-up of the nonrecurrent group. Poor responders (PoR) were defined as disease recurrence before median follow-up of the recurrent group. Perioperative characteristics were analyzed. LGMCP, HGMCP, and HGMCP-S had 48 (41%), 19 (23%), and 7 (14%) ExR and 11 (10%), 20 (24%), and 20 (39%) PoR, respectively. All ExR had lower median PCI (26 vs. 36 [p = 0.004]; 13 vs. 33.5 [p < 0.001]; 3 vs. 29.5 [p = 0.001]). Fewer LGMCP and HGMCP ExR had abnormal tumor markers (36% vs. 90% [p = 0.003]; 22% vs. 74% [p = 0.003]). More HGMCP and HGMCP-S ExR had CC-0 (vs. CC-1) cytoreductions (84% vs. 50%, p = 0.041; 100% vs. 40%, p = 0.008). Stratifying patients by recurrence status and follow-up time successfully selects ExR and PoR within each histopathologic subtype. Perioperative characteristics of ExR versus PoR differ across histopathologic subtypes, except for disease burden. Genetic analysis may further elucidate differences and aid in the development of novel targeted therapies.

Can low grade PMP be divided into prognostically distinct subgroups based on histological features? A retrospective study and the importance of using the appropriate classification

IntroductionThe pathological classification of PMP of appendiceal origin has prognostic and treatment implications. Our goals were to• Classify low grade mucinous carcinoma peritonei (LGMCP) into prognostically distinct subgroups based on histological features.• Compare the reproducibility of the WHO and the PSOGI classifications for both PMP and the appendiceal primary tumor. Patients and methodsA retrospective analysis of patients undergoing CRS and HIPEC or debulking surgery was done. All the tumors were re-classified according to the PSOGI classification. LGMCP was further classified into three histological subgroups and the impact on survival was evaluated. ResultsFrom Jun 2011 to June 2016, 101 patients underwent CRS with HIPEC (n = 89) or debulking surgery (n=12). The median PCI was 28 (3–39) and 74.1% patients had CC-0/1 resections. Of the 76.2% patients who had LGMCP, 4 patients (5.1%) were classified as group 1, 54 (70.1%) as group 2 and 19 patients (24.6%) as group 3. At a median follow up of 21 months, the disease free survival was not reached, 30 months and 14 months for groups 1, 2 and 3 respectively (p = 0.09). There was no difference in overall survival. Using the WHO classification, there was a discordance in the grade of the primary tumor and the peritoneal lesions in 19.8% and conflicting terminology was used in 62% of patients. ConclusionsThe subgroups of LGMCP described here are prognostically different though this needs further prospective evaluation in larger series. The PSOGI classification is more uniformly reproducible and should be preferred to the WHO classification.

Preserving fertility in pseudomyxoma peritonei, a novel approach.

Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) is the gold standard treatment for patients with pseudomyxoma peritonei (PMP) but involves routine bilateral salpingo-oophorectomy. Young women wishing to maintain fertility may be reluctant to pursue this. An alternative strategy in women with low-grade PMP has been explored in the form of laparoscopic evacuation of pelvic and ovarian mucin with resection of the appendiceal tumour. Between January 2012 and January 2015, four young women (aged 28-35 years) with PMP seeking to maintain fertility underwent laparoscopy, appendicectomy and pelvic mucinous evacuation and washout. Data regarding intra-operative and histopathological findings were collected. Endpoints were fertility-related outcomes and oncological follow-up. Infertility was a presenting symptom in three of the four women. All four had significant pelvic mucinous disease on radiological imaging and were offered CRS and HIPEC as definitive treatment, but chose laparoscopy with appendicectomy and copious irrigation and washout of the pelvis with stripping of mucinous disease off the ovarian surfaces. Postoperative histology demonstrated a low-grade appendiceal mucinous neoplasm (LAMN) in all patients with acellular mucin or low-grade mucinous carcinoma peritonei in the peritoneal cavity. All patients successfully conceived subsequently and gave birth to healthy babies. After 12-29 months follow-up, all women are well with no radiological or laparoscopic evidence of disease recurrence. In patients with low-grade PMP, initial therapeutic laparoscopy can restore fertility, whilst providing short- to medium-term disease control. This modality in young women wishing to have children appears to be a feasible alternative to immediate CRS and HIPEC.