Aggressive Cytoreductive Surgery Research Articles

Neutrophil Extracellular Traps-Inhibiting and Fouling-Resistant Polysulfoxides Potently Prevent Postoperative Adhesion, Tumor Recurrence, and Metastasis.

Peritoneal metastasis (PM) is considered one of the most dreaded forms of cancer metastases for both patients and physicians. Aggressive cytoreductive surgery (CRS) is the primary treatment for peritoneal metastasis. Unfortunately, this intensive treatment frequently causes clinical complications, such as postoperative recurrence, metastasis, and adhesion formation. Emerging evidence suggests that neutrophil extracellular traps (NETs) released by inflammatory neutrophils contribute to these complications. Effective NET-targeting strategies thus show considerable potential in counteracting these complications but remain challenging. Here, one type of sulfoxide-containing homopolymer, PMeSEA, with potent fouling-resistant and NET-inhibiting capabilities, is synthesized and screened. Hydrating sulfoxide groups endow PMeSEA with superior nonfouling ability, significantly inhibiting protein/cell adhesion. Besides, the polysulfoxides can be selectively oxidized by ClO- which is required to stabilize the NETs rather than H2O2, and ClO- scavenging effectively inhibits NETs formation without disturbing redox homeostasis in tumor cells and quiescent neutrophils. As a result, PMeSEA potently prevents postoperative adhesions, significantly suppresses peritoneal metastasis, and shows synergetic antitumor activity with chemotherapeutic 5-Fluorouracil. Moreover, coupling CRS with PMeSEA potently inhibits CRS-induced tumor metastatic relapse and postoperative adhesions. Notably, PMeSEA exhibits low in vivo acute and subacute toxicities, implying significant potential for clinical postoperative adjuvant treatment.

Clinical perspectives of rare ovarian tumors: clear cell ovarian cancer.

Ovarian clear cell carcinoma (OCCC) is a rare and distinct histological type of epithelial ovarian carcinoma in terms of its histopathological, clinical and genetic features. Patients with OCCC are younger and diagnosed at earlier stages than those with the most common histological type-high-grade serous carcinoma. Endometriosis is considered a direct precursor of OCCC. Based on preclinical data, the most frequent gene alternations in OCCC are mutations of AT-rich interaction domain 1A and phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha. The prognosis of patients with early-stage OCCC is favorable, whereas patients at an advanced stage or who have the recurrent disease have a dismal prognosis due to OCCC's resistance to standard platinum-based chemotherapy. Despite a lower rate of response due to its resistance to standard platinum-based chemotherapy, the treatment strategy for OCCC resembles that of high-grade serous carcinoma, which includes aggressive cytoreductive surgery and adjuvant platinum-based chemotherapy. Alternative treatment strategies, including biological agents based on molecular characteristics specific to OCCC, are urgently needed. Furthermore, due to its rarity, well-designed collaborative international clinical trials are needed to improve oncologic outcomes and the quality of life in patients with OCCC.

Bilateral Thoracic Cytoreductive Surgery for Pseudomyxoma Peritonei of Appendiceal Origin.

Pleural spread occurs in pseudomyxoma peritonei (PMP) in less than 10% of the patients and is treated by thoracic cytoreductive surgery with or without hyperthermic intrathoracic chemotherapy (HITOC). It is performed both for symptom palliation and disease control and includes pleurectomy and decortication and wedge and segmental lung resections. So far, only unilateral spread treated with a thoracic cytoreductive surgery (CRS) has been reported in literature. We report a patient with bilateral thoracic PMP following a complete abdominal CRS and hyperthermic intraperitoneal chemotherapy (HIPEC) who was treated with bilateral staged thoracic CRS and subsequently had a 4th CRS for abdominal disease. The staged procedure was performed as she was symptomatic due to the thoracic disease and there was disease on all pleural surfaces. HITOC was not performed. Both procedures were uneventful with no major morbidity. The patient is currently disease free nearly 84months after the first abdominal CRS and 60months after the second thoracic CRS. Thus, an aggressive CRS in the thorax in patients with PMP can result in a prolongation of survival while preserving the quality of life if the abdominal disease is controlled. A thorough understanding of the disease biology and surgical expertise are both essential for selecting the right patients for these complex procedures and achieving good short- and long-term outcomes.

Survival of patients with stage IV high-grade serous ovarian cancer treated with intraperitoneal versus intravenous platinumbased chemotherapy (501)

Survival of patients with stage IV high-grade serous ovarian cancer treated with intraperitoneal versus intravenous platinumbased chemotherapy (501)

CHOOSING THE STAGE OF TREATMENT IN PATIENTS WITH ADVANCED FORMS OF OVARIAN CANCER

Ovarian cancer ranks third among the tumors of the reproductive system in women. This disease has no screening.It is characterized by a latent course and, as a result, is diagnosed at the advanced stages of the tumor process. There are two methods of treatment for this disease: aggressive cytoreductive surgery and anticancer drug therapy. However, the phasing of approaches causes controversy among oncologists. This article will consider approaches to choosing the stage of treatment for patients with advanced ovarian cancer based on the analysis of international studies.

Peritoneal metastases after laparoscopic ovarian cystectomy for ovarian teratoma with unexpected somatic-type malignancy

Laparoscopic ovarian cystectomy has been an accepted treatment for benign ovarian teratoma. We report a 10-year-old girl who developed peritoneal metastases after laparoscopic ovarian cystectomy for benign-looking ovarian teratoma that contained an unexpected somatic-type primitive neuroectodermal tumor. She underwent aggressive cytoreductive surgery, chemotherapy, autologous stem cell transplantation and radiotherapy, and achieved remission. We should consider avoiding the laparoscopic approach for ovarian cystectomy in children and adolescents with suspected ovarian teratoma.

Clear cell carcinoma of the ovary: Epidemiology, pathological and biological features, treatment options and clinical outcomes

Clear cell carcinoma of the ovary is a rare and distinct histotype of epithelial ovarian carcinomas. Women diagnosed with clear cell carcinomas are usually younger and diagnosed at earlier stages than those with the most common high-grade serous histology. Endometriosis is considered a main risk factor for the development of clear cell carcinoma of the ovary, and it can be considered a precursor of of this tumor, as it is identified in more than 50% of patients with clear cell carcinoma.Different molecular pathways and alterations heve been identified in ovarian clear cell carcinoma, including the most common mutations of AT-rich interaction domain 1A [ARID1A] and phosphatidylinositol-4,5-bisphosphate 3-kinase [PIK3] catalytic subunit alpha [PIK3CA].The prognosis of patients at early stage is favorable, while patients with advanced or recurrent disease experience a poor oncologic outcomes.Despite a lower rate of responses due to an intrinsic chemoresistance, the treatment strategy for advanced disease resembles the treatment of high-grade serous carcinoma, which includes aggressive cytoreductive surgery and platinum-based chemotherapy. For this reason, the role of adjuvant chemotherapy in patients with stage I disease undergoing complete surgical staging is still under debate.Alternative treatments, including biological agents that target different pathways constitute the most promising treatment strategies, and well-designed, collaborative international trials should be designed in order to improve the oncologic outcomes and the quality of life of patients with this aggressive disease.

Desmoplastic Small Round Cell Tumor: A Review of Main Molecular Abnormalities and Emerging Therapy.

Simple SummaryDesmoplastic small round cell tumor is a rare neoplasm with extremely aggressive behavior. Despite the multimodal treatment for newly diagnosed patients with chemotherapy, cytoreductive surgery and radiation, the cure rate is still low. For relapsed or progressive disease, there is limited data regarding second and third-line therapies. Novel agents have shown only modest activity. Recent molecular changes have been identified in this disease and this opens opportunities to be explored in future clinical trials.Desmoplastic small round cell tumor (DSRCT) is an extremely rare, aggressive sarcoma affecting adolescents and young adults with male predominance. Generally, it originates from the serosal surface of the abdominal cavity. The hallmark characteristic of DSRCT is the EWSR1–WT1 gene fusion. This translocation up-regulates the expression of PDGFRα, VEGF and other proteins related to tumor and vascular cell proliferation. Current management of DSRCT includes a combination of chemotherapy, radiation and aggressive cytoreductive surgery plus intra-peritoneal hyperthermic chemotherapy (HIPEC). Despite advances in multimodal therapy, outcomes remain poor since the majority of patients present disease recurrence and die within three years. The dismal survival makes DSRCT an orphan disease with an urgent need for new drugs. The treatment of advanced and recurrent disease with tyrosine kinase inhibitors, such as pazopanib, sunitinib, and mTOR inhibitors was evaluated by small trials. Recent studies using comprehensive molecular profiling of DSRCT identified potential therapeutic targets. In this review, we aim to describe the current studies conducted to better understand DSRCT biology and to explore the new therapeutic strategies under investigation in preclinical models and in early phase clinical trials.

Narrative review on serous primary peritoneal carcinoma of unknown primary site: four questions to be answered.

Serous peritoneal papillary carcinoma (SPPC) represents a particular cancer of unknown primary (CUP) entity that arises in the peritoneal surface lining the abdomen and pelvis without a discriminative primary tumor site. In this review, we discuss the validity of SPPC as a distinct entity. Clinically, patients with SPPC are older, have higher parity and later menarche, are more often obese and probably have poorer survival compared to those with primary ovarian cancer. Pathologically, SPPC is more anaplastic and multifocal, unlike primary ovarian cancer which is commonly unifocal. Biologically, it presents a higher expression of proliferative signals and similar cell cycle and DNA repair protein expression. These differences hint towards SPPC and primary ovarian cancer being as a spectrum of disease. Patients with SPPC are traditionally managed similarly to stage III–IV ovarian cancer. The recommended approach integrates aggressive cytoreductive surgery, hyperthermic intraperitoneal chemotherapy, and systemic chemotherapy to remove the macroscopic tumor, eradicate the microscopic residual disease, and control the microscopic metastasis. However, the available evidence lacks proper randomized or prospective studies on SPPC and is limited to retrospective series. The diligent identification of SPPC is warranted to design specific clinical trials that eventually evaluate the impact of the new therapeutics on this distinct entity.

Aggressive surgery could overcome the extent of initial peritoneal dissemination for advanced ovarian, fallopian tube, and peritoneal carcinoma

We examined whether the extent of initial peritoneal dissemination affected the prognosis of patients with advanced ovarian, fallopian tube, and peritoneal carcinoma when initially disseminated lesions > 1 cm in diameter were removed, regardless of the timing of aggressive cytoreductive surgery. The extent of peritoneal dissemination was assessed by the peritoneal cancer index (PCI) at initial laparotomy in 186 consecutive patients with stage IIIC/IV. Sixty patients underwent primary debulking surgery and 109 patients underwent neoadjuvant chemotherapy followed by interval debulking surgery. Seventeen patients could not undergo debulking surgery because of disease progression during neoadjuvant chemotherapy. The median initial PCI were 17. Upper abdominal surgery and bowel resection were performed in 149 (80%) and 171 patients (92%), respectively. Residual disease ≤ 1 cm after surgery was achieved in 164 patients (89%). The initial PCI was not significantly associated with progression-free survival (PFS; p = 0.13) and overall survival (OS; p = 0.09). No residual disease and a high-complexity surgery significantly prolonged PFS (p < 0.01 and p = 0.02, respectively) and OS (p < 0.01 and p ≤ 0.01, respectively). The extent of initial peritoneal dissemination did not affect the prognosis when initially disseminated lesions > 1 cm were resected.

Impact of Neoadjuvant Chemotherapy on the Outcomes of Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Colorectal Peritoneal Metastases: A Multi-Institutional Retrospective Review.

Cytoreductive surgery (CRS) with or without hyperthermic intraperitoneal chemotherapy (HIPEC) is associated with improved survival for patients with colorectal peritoneal metastases (CR-PM). However, the role of neoadjuvant chemotherapy (NAC) prior to CRS-HIPEC is poorly understood. A retrospective review of adult patients with CR-PM who underwent CRS+/-HIPEC from 2000–2017 was performed. Among 298 patients who underwent CRS+/-HIPEC, 196 (65.8%) received NAC while 102 (34.2%) underwent surgery first (SF). Patients who received NAC had lower peritoneal cancer index score (12.1 + 7.9 vs. 14.3 + 8.5, p = 0.034). There was no significant difference in grade III/IV complications (22.4% vs. 16.7%, p = 0.650), readmission (32.3% vs. 23.5%, p = 0.114), or 30-day mortality (1.5% vs. 2.9%, p = 0.411) between groups. NAC patients experienced longer overall survival (OS) (median 32.7 vs. 22.0 months, p = 0.044) but similar recurrence-free survival (RFS) (median 13.8 vs. 13.0 months, p = 0.456). After controlling for confounding factors, NAC was not independently associated with improved OS (OR 0.80) or RFS (OR 1.04). Among patients who underwent CRS+/-HIPEC for CR-PM, the use of NAC was associated with improved OS that did not persist on multivariable analysis. However, NAC prior to CRS+/-HIPEC was a safe and feasible strategy for CR-PM, which may aid in the appropriate selection of patients for aggressive cytoreductive surgery.

Therapy and Prophylaxis of Peritoneal Metastases from Colorectal Cancer.

Stage IV colorectal cancer is associated with high mortality, and the prognosis is significantly worse for patients have peritoneal metastases. Peritoneal carcinomatosis from colorectal cancer was considered incurable with an infaust prognosis. Median survival of untreated patients is about 6 months and palliative systemic chemotherapy can prolonge this time up to 20 months. Patients with this disease were previously only surgically treated if they had severe clinical symptoms or complications. This view has changed dramatically over the past 15 years. Aggressive cytoreductive surgery in combination with intraperitoneal chemotherapy may prolong median survival for more than 40 months in selected patients. The Peritoneal Surface Oncology Group International (PSOGI), the international authority on the treatment of peritoneal tumors, recommends cytoreduction with intraperitoneal chemotherapy as the standard of care for selected patients with moderate-to-small volume peritoneal metastases secondary to colorectal cancer. Macroscopic cytoreduction appears to be essential; however, the role of hyperthermic intraperitoneal chemotherapy and the optimal chemotherapeutic agent for intraperitoneal lavage to treat peritoneal metastases from colorectal cancer remain unclear. The results of ongoing and future clinical trials are eagerly awaited.

Right sided colon cancer and peritoneal carcinomatosis

Peritoneal carcinomatosis is a late manifestation of colon cancer. Patients with right sided colon cancer have increased incidence of peritoneal carcinomatosis compared to those with left sided colon cancers. Conventional intravenous chemotherapy has traditionally been less effective in management of colorectal cancer with peritoneal carcinomatosis. Mucinous histology of the primary colon cancer, more commonly seen with right sided colon cancers, is resistant to chemotherapy and showed more favorable response with aggressive cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemoperfusion (HIPEC). With appropriate preoperative planning, patients that can be treated with complete tumor debulking with CRS have the most favorable outcomes. Development of CRS along with HIPEC in recent years yielded another potential therapy in addition to systemic chemotherapy for management of this disease. Potentially, metastatic peritoneal carcinomatosis can now be treated with CRS and HIPEC in order to achieve long-term survival in carefully selected individuals.

Morbidity and mortality in women with advanced ovarian cancer who underwent primary cytoreductive surgery compared to cytoreductive surgery for recurrent disease: a meta-analysis.

BackgroundThe primary treatment for advanced ovarian cancer is aggressive cytoreductive surgery (CRS), which is associated with considerable morbidity. The aim of this meta-analysis is to compare morbidity associated with primary CRS and secondary CRS for recurrent disease.MethodsA literature search was performed using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines for publications reporting morbidity and mortality in patients undergoing CRS in primary and recurrent ovarian malignancy. Embase, Medline, Pubmed, Pubmed Central, clinicaltrials. gov and Cochrane databases were searched. Two independent reviewers applied inclusion and exclusion criteria to select included papers. A total of 215 citations were reviewed; 6 studies comprising 641 patients were selected for the analysis.ResultsResults were reported as mean differences or pooled odds ratios (OR) with 95 % confidence intervals (95 % CI). The overall morbidity rate was 38.4 %, and this did not differ between the two groups (p=0.97). This did not change when only Clavien-Dindo grade 3 and 4 morbidities were accounted for (14 % primary CRS, 15 % recurrent, p=0.83). Compared to primary CRS, secondary CRS was associated with a similar operative time (mean 400 min, I2=79 %, p=0.45), rate of bowel resection (I2=75 %, p=0.37) and transfusion requirements (MD – 0.7 L, I2=76 %, p=0.45). The mortality rate in both groups was too low to allow for meaningful meta-analysis, with four deaths in the group undergoing primary cytoreductive surgery (1.0 %) and two deaths in the group with recurrent disease (0.9 %).ConclusionsIn conclusion, secondary CRS for recurrent ovarian cancer is a safe and feasible option in carefully pre-selected patients with comparable morbidity to primary CRS.

Isolated carcinomatosis of the abdominal cavity in women: the features of immunophenotypes and morphometric parameters.

Patients with isolated abdominal carcinomatosis are traditionally treated similarly to patients with ovarian cancer stage III/IV. Despite histological, molecular and clinical similarities, this approach leaves no room for studying the individual biology of this phenotype of cancer of unknown primary localization. In addition, some metastases of gastrointestinal, pancreatic-biliary or endometrial adenocarcinomas simulate the histological and/or immunohistochemical (IHC) characteristics of primary ovarian adenocarcinomas. Over the past three decades, understanding the biology and pathways of intra-abdominal dissemination of tumors, taking into account the protective function of the peritoneal barrier against further tumor spreading, has led many researchers to consider the concept of peritoneal carcinomatosis as a locoregional disease. In the absence of other systemic metastases, new multimodal approaches combining aggressive cytoreductive surgery, intraperitoneal hyperthermia chemotherapy, and systemic chemotherapy are considered promising for improving disease control and increasing survival. Materials and methods. A retrospective analysis of clinical data, histological and IHC characteristics of biopsy material of 24 women with isolated abdominal carcinomatosis at the age of 28 to 81 years (mean 56.29±14.68, median 58.5) and 46 cases of primary ovarian tumors of women at the age of 27 to 76 years (mean 52.17±12.72, median 53.5), was performed to determine differential diagnostic criteria. IHC profile of primary ovarian tumors determined the most specific markers of cytokeratin C7 and CA125 (mucin 16), which in 43 out of 46 (93.48%) and 37 of 46 (80.43%) were respectively positive at least partially. It should be noted that 1 undifferentiated carcinoma was negative for both markers, only for SC7-2 mucinous adenocarcinomas and 1 low-grade, but only for CA125-2 endometrioid, 2 light-celled, 1 undifferentiated carcinoma and 4 low-grade adenocarcinomas (the latter were regarded as primary in exclusion of other localizations on the basis of a complete survey). Receptors to estrogens were determined in 14 of 46 (30.43%) of observations, which indicates their prognostic, and not diagnostic significance. In the group of women with isolated carcinomatosis of the abdominal cavity, SK7 was identified in 21 of 24 (87.5%) observations, CA125 in 16 of 24 (66.67%), all of whom had SC7 immunoreactivity, but only 9 of them demonstrated the presence of estrogen receptors, and 6 – serous phenotype (WT-1+), and 1 – mesothelioma (CK7 +, calretinin +). It should be noted that CA125-partially positive tumor patterns were often mixed with undifferentiated and nopapillary tumor deposits. These women were older than of the entire subgroup (mean 61.4 ± 10.08, median 61), but without significant difference (p>0.05). Conclusions. Only 2/3 of the investigated cases of carcinomatosis without primary localization in women after IHC research can be convincingly attributed to ovarian metastases for the application of appropriate therapy. Other 33.33% percent in our study were divided into 1 - neuroendocrine cancer (Chromogranin +, Synaptophysin +), 3 - colorectal (CK20 + CDX2 +), 2 - moderately and 1 - low-grade carcinomas with doubtful immunophenotypes (CK20+/-CDX2-/+CK7-/+Vimentin -/+), as well as 1 mesothelioma.

Abstract 3670: Treatment of epithelial ovarian cancer with folate receptor (α/β) targeted chemotherapy is enhanced by CTLA-4 blockade: Learning from animal models

Abstract Epithelial ovarian cancer (EOC) remains to be the most lethal form of gynecologic malignancies despite aggressive cytoreductive surgery (i.e. debulking) followed by standard chemotherapy. The alpha folate receptor (FRα) has long been recognized as a tumor target for EOC due to its frequently intense overexpression (&amp;gt;80%) in the most common serous histotype. Recently, the beta folate receptor (FRβ) has been discovered on tumor-associated macrophages (TAMs) which are present at various densities in solid tumors but are also found abundant in malignant ascites of EOC patients. The ascites TAMs are strongly immunosuppressive, and high TAM frequency is correlated with poor patient prognosis and treatment resistance. Respectively, tumor- and TAM-associated FRα and FRβ are both functionally active which allows for folate-targeted delivery of small-molecule drug payloads via receptor-mediated endocytosis. Using flow cytometry, we characterized total ascites cells harvested from human IGROV1 xenograft (hFRα) and murine ID8-CL15 syngeneic (mFRα) models at the time of euthanasia. Approximately 70% of IGROV1 and 25% of ID8-Cl15 ascites TAMs (F4/80+ CD11b+) were found to express a functional mFRβ. While ascites fluids from both models caused a dramatic reduction of FRα functionality on tumor cells in-vivo and ex-vivo, FRβ expression and functionality on ascites TAMs were largely unaffected. Interestingly, in the ID8-CL15 model, the ratio of ascites CD8+ T cells to CD4+ T cells decreased as total FR functionality on TAMs increased. Two small-molecule folate-drug conjugates with different mechanisms of action showed activity in extending the survival of tumor-bearing animals. While CTLA-4 blockage alone was completely inactive in the ID8-CL15 model, a combination regimen significantly enhanced the activity of a folate conjugate carrying a potent DNA cross-linking agent. Our data suggest that EOC treatment may require a multi-pronged approach by targeting both FRα-expressing tumor cells and FRβ-expressing TAMs. In addition, immune checkpoint inhibitors may further enhance the FR-targeted therapeutics by modulating the ascites tumor microenvironment. Citation Format: Yingjuan Lu, Theresa P. Johnson, Leroy W. Wheeler, Alex M. Lloyd, Vicky A. Cross, Elaine M. Westrick, Nikki L. Parker, Christopher P. Leamon. Treatment of epithelial ovarian cancer with folate receptor (α/β) targeted chemotherapy is enhanced by CTLA-4 blockade: Learning from animal models [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3670. doi:10.1158/1538-7445.AM2017-3670

Patient-derived xenograft mouse models of pseudomyxoma peritonei recapitulate the human inflammatory tumor microenvironment.

Pseudomyxoma peritonei (PMP) is a neoplastic syndrome characterized by peritoneal tumor implants with copious mucinous ascites. The standard of care for PMP patients is aggressive cytoreductive surgery performed in conjunction with heated intraperitoneal chemotherapy. Not all patients are candidates for these procedures and a majority of the patients will have recurrent disease. In addition to secreted mucin, inflammation and fibrosis are central to PMP pathogenesis but the molecular processes that regulate tumor‐stromal interactions within the peritoneal tumor microenvironment remain largely unknown. This knowledge is critical not only to elucidate PMP pathobiology but also to identify novel targets for therapy. Here, we report the generation of patient‐derived xenograft (PDX) mouse models for PMP and assess the ability of these models to replicate the inflammatory peritoneal microenvironment of human PMP patients. PDX mouse models of low‐ and high‐grade PMP were generated and were of a similar histopathology as human PMP. Cytokines previously shown to be elevated in human PMP were also elevated in PDX ascites. Significant differences in IL‐6 and IL‐8/KC/MIP2 were seen between human and PDX ascites. Interestingly, these cytokines were mostly secreted by mouse‐derived, tumor‐associated stromal cells rather than by human‐derived PMP tumor cells. Our data suggest that the PMP PDX mouse models are especially suited to the study of tumor‐stromal interactions that regulate the peritoneal inflammatory environment in PMP as the tumor and stromal cells in these mouse models are of human and murine origins, respectively. These mouse models are therefore, likely to be useful in vivo surrogates for testing and developing novel therapeutic treatment interventions for PMP.

Oncologic Risk Stratification Following Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Appendiceal Carcinomatosis.

Patients with peritoneal carcinomatosis (PC) of appendiceal origin demonstrate variable oncologic outcomes, despite aggressive cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC). We sought to devise a prognostic risk stratification system for oncologic outcomes following CRS-HIPEC. A total of 197 patients undergoing CRS-HIPEC for the treatment of appendiceal PC were reviewed from a prospective database. Kaplan-Meier survival curves and multivariate Cox regression models were used to identify prognostic factors affecting oncologic outcomes. Clinicopathologic variables affecting overall survival (OS) were utilized to develop a prognostic staging system and nomograms. Univariate and multivariate Cox regression analysis indicated that high-grade tumor histology, lymph node metastasis, and incomplete cytoreduction were high-risk features, adversely affecting OS. Patients were stratified on the presence of high-risk features as follows: low-risk patients had no risk factors (n=102); intermediate-risk patients had one risk factor (n=49); and high-risk patients had more than one risk factor (n=46). Median OS for low-risk patients was not reached, and was 43 and 22months for intermediate-risk and high-risk patients, respectively. Five-year OS was 72, 43, and 13% for low-, intermediate- and high-risk patients, respectively (p<0.0003 for low vs. intermediate risk, and p=0.06 for intermediate vs. high risk). We propose a three-tier staging system for appendiceal PC following CRS-HIPEC, based on histologic grade, lymph node involvement, and completeness of cytoreduction. The presence of any one or more of these high-risk features significantly decreased survival in our single-institution database and provided the basis for a prognostic staging system and corresponding nomograms.

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in gastric cancer.

Gastric cancer associated peritoneal carcinomatosis (GCPC) has a poor prognosis with a median survival of less than one year. Systemic chemotherapy including targeted agents has not been found to significantly increase the survival in GCPC. Since recurrent gastric cancer remains confined to the abdominal cavity in many patients, regional therapies like aggressive cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) have been investigated for GCPC. HIPEC has been used for three indications in GC- as an adjuvant therapy after a curative surgery, HIPEC has been shown to improve survival and reduce peritoneal recurrences in many randomised trials in Asian countries; as a definitive treatment in established PC, HIPEC along with CRS is the only therapeutic modality that has resulted in long-term survival in select groups of patients; as a palliative treatment in advanced PC with intractable ascites, HIPEC has been shown to control ascites and reduce the need for frequent paracentesis. While the results of randomised trials of adjuvant HIPEC from western centres are awaited, the role of HIPEC in the treatment of GCPC is still evolving and needs larger studies before it is accepted as a standard of care.

Pseudo-pseudomyxoma peritonei from peritoneal sarcomatosis

Background: Pseudomyxoma peritonei (PMP) is a rare clinical entity of mucinous ascites, most commonly associated with appendiceal mucinous neoplasms. Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) remains the current standard of care for PMP. Peritoneal sarcomatosis (PS) is an exceptionally rare disease with a poor prognosis. PMP associated with PS has not been previously described. The role of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for PS with or without PMP is not well-defined. PS manifesting like PMP has not been previously described. Case presentation: A 74-year-old patient with several weeks history of vague abdominal pain and increased abdominal girth was referred to our facility after incidental finding of PMP during laparoscopic inguinal hernia repair. After complete work-up, he was advised to undergo CRS/HIPEC. Intra-operatively, he was noted to have extensive mucinous ascites and underwent aggressive CRS and HIPEC Result: Final pathology revealed myxoid liposarcoma with associated intraperitoneal mucin dissemination, which was confirmed with cytogenetic analysis. Conclusion: We describe a rare case of pseudomyxoma peritonei originating from an intra-abdominal sarcoma. We propose the term of “pseudo-pseudomyxoma peritonei” to appropriately describe this unusual clinical event.