A core microbiome associated with the peritoneal tumors of pseudomyxoma peritonei

Pseudomyxoma peritonei (PMP) is a malignancy characterized by dissemination of mucus-secreting cells throughout the peritoneum. This disease is associated with significant morbidity and mortality and despite effective treatment options for early-stage disease, patients with PMP often relapse. Thus, there is a need for additional treatment options to reduce relapse rate and increase long-term survival. A previous study identified the presence of both typed and non-culturable bacteria associated with PMP tissue and determined that increased bacterial density was associated with more severe disease. These findings highlighted the possible role for bacteria in PMP disease. To more clearly define the bacterial communities associated with PMP disease, we employed a sequenced-based analysis to profile the bacterial populations found in PMP tumor and mucin tissue in 11 patients. Sequencing data were confirmed by in situ hybridization at multiple taxonomic depths and by culturing. A pilot clinical study was initiated to determine whether the addition of antibiotic therapy affected PMP patient outcome. We determined that the types of bacteria present are highly conserved in all PMP patients; the dominant phyla are the Proteobacteria, Actinobacteria, Firmicutes and Bacteroidetes. A core set of taxon-specific sequences were found in all 11 patients; many of these sequences were classified into taxonomic groups that also contain known human pathogens. In situ hybridization directly confirmed the presence of bacteria in PMP at multiple taxonomic depths and supported our sequence-based analysis. Furthermore, culturing of PMP tissue samples allowed us to isolate 11 different bacterial strains from eight independent patients, and in vitro analysis of subset of these isolates suggests that at least some of these strains may interact with the PMP-associated mucin MUC2. Finally, we provide evidence suggesting that targeting these bacteria with antibiotic treatment may increase the survival of PMP patients. Using 16S amplicon-based sequencing, direct in situ hybridization analysis and culturing methods, we have identified numerous bacterial taxa that are consistently present in all PMP patients tested. Combined with data from a pilot clinical study, these data support the hypothesis that adding antimicrobials to the standard PMP treatment could improve PMP patient survival.https://doi.org/10.1186/1750-1172-8-10

Comparison of Survival in Patients with Isolated Peritoneal Carcinomatosis from Colorectal Cancer Treated with Cytoreduction and Melphalan or Mitomycin-C as Hyperthermic Intraperitoneal Chemotherapy Agent

Background. The role of hyperthermic intraperitoneal chemotherapy (HIPEC) for peritoneal carcinomatosis (PC) from colorectal cancer (CRC) is debated. Melphalan as a perfusion agent has also demonstrated survival benefit in other recurrent and chemoresistant malignancies. Thus, we hypothesize that melphalan as a HIPEC agent may improve overall survival (OS) and progression-free survival (PFS) in patients with PC from CRC. Methods. A retrospective review of a prospective database of 48 patients who underwent optimal CRS (CC-0/1) and HIPEC from 2001-2016 was performed. Nineteen had CRS/HIPEC with melphalan (group I) and 29 with mitomycin-C (group II). Survival was estimated using the Kaplan-Meier method. Cox regression was used for multivariate analysis. Perioperative variables were compared. Results. Mean age at CRS/HIPEC was 53±10 years. Median peritoneal cancer index (PCI) was 17 vs 13 in groups I and II, respectively (p=0.86). PCI≥20 occurred in 9 (47%) and 13 (45%) patients in groups I and II, respectively. Positive lymph nodes were identified in 8/19 (42%) vs 12/29 (41%) in groups I and II, respectively (p=0.73). Multivariate analysis identified PCI≥20 as a predictive factor of survival (HR: 7.5). Median OS in groups I and II was 36 and 28 months, respectively (p=0.54). Median PFS in groups I and II was 10 and 20 months, respectively (p=0.05). Conclusions. CRS/HIPEC with MMC had longer median PFS in PC from CRC. PCI≥20 was the only independent predictive factor for survival. Until longer follow-up is available, we recommend using MMC in CRS/HIPEC for PC from CRC. Further prospective randomized studies are necessary

The Role of Microorganisms in Appendiceal Pseudomyxoma Peritonei: A Review

Pseudomyxoma peritonei (PMP) is a rare clinical syndrome. It originates from neoplasms of the appendix and leads to the formation of peritoneal implants and the accumulation of mucinous ascites. PMP represents a spectrum of low to high-grade disease. Despite aggressive management, many PMP patients recur, leading to debilitating symptoms and few treatment options. Therefore, scientists have continued to look for ways to improve treatment and further understand disease pathogenesis. Microorganisms were previously hypothesized to play a role in PMP progression and development. Hence, antibacterial treatment was suggested by some authors, but the data were limited. In this paper, we review the current data on the role of bacteria in PMP, discuss the significance, and suggest possible solutions to the inherent challenges in these studies. Given the limitations of the discussed studies, we remain skeptical about introducing novel antibacterial treatment into clinical practice at this time; however, the available data are valuable and indicate that more research into the molecular mechanisms of PMP is needed

Peritoneal metastases from rare ovarian cancer treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC)

There are limited treatment options and no consensus on the management of advanced rare ovarian malignancies. Rare ovarian malignancies can present with peritoneal metastases (PM), featuring a similar presentation to more common ovarian subtypes. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) is an effective treatment for PM of non-gynecologic origin and, recently, epithelial ovarian cancer. We evaluated the feasibility of CRS/HIPEC in the management of PM from rare ovarian malignancies and report postoperative outcomes on these patients

Critical Analysis of Stage IV Epithelial Ovarian Cancer Patients after Treatment with Neoadjuvant Chemotherapy followed by Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy (CRS/HIPEC)

Background. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) after neoadjuvant chemotherapy (NACT) showed promise as initial treatment for stage IIIC (SIII) epithelial ovarian cancer (EOC); however, stage IV (SIV) outcomes are rarely reported. We assessed our experience and outcomes treating newly diagnosed SIV EOC with NACT plus CRS/HIPEC compared to SIII patients. Methods. Advanced EOC from 2015–2018 managed with NACT (carboplatin/paclitaxel) due to unresectable disease or poor performance status followed by interval CRS/HIPEC were reviewed. Perioperative factors were assessed. Overall survival (OS) and progression-free survival (PFS) were analyzed by stage. Results. Twenty-seven FIGO stage IIIC (n = 12) and IV (n = 15) patients were reviewed. Median NACT cycles were 3 and 4, respectively. Post-NACT omental caking, ascites, and pleural effusions decreased/resolved in 91%, 91%, and 100% of SIII and 85%, 92%, and 71% of SIV. SIII/SIV median PCI was 21 and 20 obtaining 92% and 100% complete cytoreduction (≤0.25 cm), respectively. Median organ resections were 6 and 7, respectively. Grade III/IV surgical complications were 0% SIII and 23% SIV, without hospital mortality. Median time to adjuvant chemotherapy was 53 and 74 days, respectively (p=0.007). SIII OS at 1 and 2 years was 100% and 83% and 87% and 76% in SIV (p=0.269). SIII 1-year PFS was 54%; median PFS: 12 months. SIV 1- and 2- year PFS was 47% and 23%; median PFS: 12 months (p=0.944). Conclusion. Outcomes in select initially diagnosed and unresectable SIV EOC are similar to SIII after NACT plus CRS/HIPEC. SIV EOC may benefit from CRS/HIPEC, and further studies should explore this treatment approach

Radioimmunoguided surgery in recurrent colorectal cancer: the role of carcinoembryonic antigen, computerized tomography, and physical examination

From January 1986 to December 1987, 32 patients with recurrent colorectal cancer had second-look radioimmunoguided surgery (RIGS system). All patients had pathologic confirmation of recurrence. The RIGS system identified 81% of recurrences, and in six patients recurrent tumor was identified only by RIGS. All patients had physical examination, Carcinoembryonic antigen (CEA) assay, and computerized tomography of the abdomen and pelvis. Detection of recurrence was based on symptoms in six, elevated CEA value in 25, and physical examination in one. The CEA was elevated preoperatively in 30 patients; two false-negative results occurred in symptomatic patients who had pelvic recurrence. The median CEA value in those with liver recurrence was 30 ng/ml (range 5.2 to 298) and for pelvic recurrence 13 ng/ml (range 1.9 to 31) (P < .05). The overall sensitivity of CT was 41% (abdomen other than liver 37%, liver 56%, and pelvis 22%). The combination of elevated CEA, symptoms, and physical findings identified 100% of recurrences. We conclude that a rising CEA remains the most accurate indicator of recurrence. CT should not be done routinely to detect recurrent colorectal cancer unless CEA is elevated or the patient is symptomatic. In our study the intraoperative use of the RIGS system aided the surgeon in identifying occult tumors