Cytoreductive Surgery In Combination Research Articles

Patterns of first-line systemic therapy delivery and adoption of bevacizumab in advanced ovarian cancer in Ontario, Canada.

292 Background: Initial treatment of epithelial ovarian cancer (EOC) consists of combination of cytoreductive surgery (CSR) and/or chemotherapy. Targeted therapies such as bevacizumab have shown to improve outcomes in a subset population with high-risk features. Real-world patterns of systemic therapy delivery in EOC in the modern era are not well understood. Our objective is to evaluate the patterns of first-line systemic treatment of advanced EOC in Ontario, focusing on adoption of bevacizumab, which was approved for use in 2016. Methods: We conducted a retrospective, population cohort study using administrative databases held at the ICES in Ontario, Canada. Patients diagnosed with non-mucinous EOC between 2014 and 2018 were identified from the Ontario Cancer Registry; early-stage disease was excluded. Information on systemic therapy was obtained from Activity Level Reporting and New Drug Funding Program databases. Provider of care (gynecologic oncologist vs medical oncologist) information was obtained from billing codes. Academic cancer centers were identified using validated systemic facility codes from Cancer Care Ontario. Statistical analyses include descriptive statistics, t-tests, and multivariable logistic regression using SAS. Results: Out of 4,680 cases diagnosed with EOC during the study period, 3,632 (77.6%) were considered advanced stage. Median age of cohort was between 65-70, and the majority had Charlson score of 1-2 (97%) and are urban (91.8%). A total of 3,181 (87.6%) patients underwent CRS and 2,722(74.9%) patients underwent chemotherapy. Of those who received chemotherapy, 1,259 (46.2%) received neoadjuvant chemotherapy, 1,012 (37.2%) received upfront CRS, and 451(16.5%) received chemotherapy only. The majority of chemotherapy was delivered by gynecologic oncologists (60.6%) and in academic cancer centres (61.7%). There was no significant difference in use of neoadjuvant chemotherapy between medical oncologists and gynecologic oncologists (p = 0.67). Only 53 chemotherapy patients (1.9%) received bevacizumab containing-regimen in the first-line setting. Medical oncologists were 4 times more likely to administer bevacizumab-containing regimen compared to gynecologic oncologists (OR 4.03, 95% CI.29 – 7.36) after adjusting for age, stage, Charlson score and rurality score on logistic regression. Delivery of bevacizumab is relatively higher in non-academic cancer centres (OR 2.61, 95% CI 2.32- 2.94) while 83% of intraperitoneal chemotherapy is delivered in academic cancer centres. Conclusions: Patterns of care of EOC in Ontario remain heterogenous between care providers and institutions, while uptake of bevacizumab for first-line treatment of EOC remains low. Factors leading to low uptake and real-world outcomes should be explored.

Establishment of a new valid animal model for the evaluation of hyperthermic intraperitoneal chemotherapy (HIPEC) in pediatric rhabdomyosarcoma.

Cytoreductive surgery in combination with hyperthermic intraperitoneal chemotherapy has been established as a novel treatment approach for peritoneal sarcomatosis. Despite promising clinical reports, there is still a lack of knowledge regarding optimal drug usage and local effects. Therefore, we intended to establish a murine animal model for further evaluation. Alveolar rhabdomyosarcoma cells were xenotransplanted into NOD/LtSz-scid IL2Rγnullmice (n=100). The mice received a continuous intraperitoneal lavage with isotonic saline solution as control or with cisplatin (30 or 60mg/m2 ) as treatment group for 60minutes at 37°Cor 42°C (6subgroups, each n=16). Tumor spread was documented by an adapted peritoneal cancer index and MRI (n=4). Tumor and tissue samples, harvested at the end of the perfusion, were evaluated regarding morphology, proliferation, and apoptosis (H&E-, Ki-67-, cleaved caspase 3-staining, TUNEL assay). Extensive peritoneal sarcomatosis in over 91% of the cases was observed. HIPEC was feasible without acute side effects. Ki-67 staining revealed concentration- or temperature-dependent effects of cisplatin-based HIPEC on the tumors. Although cleaved caspase-3 showed only sporadic apoptotic effects. TUNEL assay detected concentration- or temperature-dependent apoptotic effects at the outer tumor surface. MRI scans confirmed the observed tumor dissemination. This is the first animal model for evaluation of HIPEC in pediatric RMS in mice. Cisplatin-based HIPEC had early effects on the proliferation whereas circumscribed apoptotic effects could be detected at the tumor surface. This model allows further insights on the possible efficiency of HIPEC in RMS. Further studies using other drug combinations and treatment will follow.

Review of management and treatment of peritoneal metastases from gastric cancer origin.

Gastric cancer (GC) is the third cause of cancer-related deaths in the world, with less than 25% survivors at 5 years. These results are largely related to the high incidence of peritoneal metastases (PM) in these patients. Nowadays, the standard treatment for GC with PM is palliative systemic chemotherapy (SCT) with a survival of 6 months. From the 2000s, the combination of cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) has been gaining popularity for different neoplastic diseases that involve the peritoneal surface. The use of CRS and HIPEC has been studied for GC with PM, with promising results in selected patients, obtaining survival rates never seen before. Moreover, HIPEC and other intraperitoneal chemotherapy techniques have been used to prevent peritoneal recurrences in patients diagnosed on locally advanced GC without macroscopic PM (adjuvant or prophylactic HIPEC). Even, intraperitoneal chemotherapy [laparoscopic HIPEC and neoadjuvant intraperitoneal and systemic chemotherapy (NIPS)] has been used as neoadjuvant treatment to reduce peritoneal disease burden in order to improve the rate of patients in whom complete cytoreduction can be achieved. Finally, patients with high volume peritoneal disease can be treated by palliative intraperitoneal chemotherapy to control the symptoms resulting from malignant ascites, using laparoscopic HIPEC or pressurized intraperitoneal aerosol chemotherapy (PIPAC). This review aims to update the management of PM from GC origin in these different clinical scenarios, based on the literature and the experience of the authors.

Cytoreductive surgery and mitomycin C hyperthermic intraperitoneal chemotherapy with CO2 recirculation (HIPEC-CO2) for colorectal cancer peritoneal metastases: analysis of short-term outcomes.

Peritoneal dissemination from colorectal cancer (CRC) has long been associated with unfavorable prognosis. However, in the last decades, the combination of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) was able to obtain up to 30% 5-year survival rate in selected centers. Despite the wide diffusion of CRS and HIPEC, until now, there are no clear recommendations on the drug of choice for HIPEC nor its technique, and safety and efficacy data of HIPEC regimens and techniques are lacking. We performed a retrospective analysis of a prospectively maintained database of 26 CRS and mitomycin C HIPEC with CO2 recirculation (HIPEC-CO2) for CRC peritoneal metastasis (PM) performed at our center. The main endpoints were morbidity, mortality, the temperature of perfusate during HIPEC and metabolic changes throughout the procedure. Morbidity was assessed by analysis of postoperative adverse events according to the Common Terminology Criteria for Adverse Events (CTCAE version 4.0). Continuous variables of Arterial Blood Gas (ABG) analysis at three time-points were compared by the Student t test. There were no postoperative deaths. The overall grade 3-4 CTCAE complications rate at 30days was 38.4%, with ten severe adverse events occurring to six (23.0%) patients. The temperature within HIPEC perfusion maintained between 41 and 42°C in all cases and we experienced no HIPEC-related intraoperative complications. We observed a significant difference between all baseline and pre-HIPEC ABG parameters evaluated but no statistically significant differences between pre- and post-HIPEC ABG outcomes. This study shows that mitomycin C HIPEC-CO2 is feasible and has a safety profile comparable to that of other HIPEC techniques reported in the literature. Further research is needed to validate prospectively the safety and efficacy of this technique.

Under-Treatment of Older Patients with Newly Diagnosed Epithelial Ovarian Cancer Remains an Issue.

Simple SummaryCancer treatment and survival in older women is topical and important in an era where the proportion of older adults being treated for cancer in the clinic is rising. As survival outcomes in older women continue to lag behind those of younger and middle-aged women, further investigation is required into current treatment practices to identify target areas to address this deficit. We present treatment patterns, tolerance and outcomes of 280 women aged 65 and above treated for newly diagnosed ovarian cancer at two UK cancer centres between 2009 and 2015. We demonstrate that older women continue to receive lower rates of standard care first line therapy. When adjusted for stage at diagnosis, surgical outcome and chemotherapy given, age was not an independent risk factor for poorer overall survival.Older women with ovarian cancer have disproportionately poorer survival outcomes than their younger counterparts and receive less treatment. In order to understand where the gaps lie in the treatment of older patients, studies incorporating more detailed assessment of baseline characteristics and treatment delivery beyond the scope of most cancer registries are required. We aimed to assess the proportion of women over the age of 65 who are offered and receive standard of care for first-line ovarian cancer at two UK NHS Cancer Centres over a 5-year period (December 2009 to August 2015). Standard of care treatment was defined as a combination of cytoreductive surgery and if indicated platinum-based chemotherapy (combination or single-agent). Sixty-five percent of patients aged 65 and above received standard of care treatment. Increasing age was associated with lower rates of receiving standard of care (35% > 80 years old versus 78% of 65–69-year-olds, p = 0.000). Older women were less likely to complete the planned chemotherapy course (p = 0.034). The oldest women continue to receive lower rates of standard care compared to younger women. Once adjusted for Federation of Gynaecology and Obstetrics (FIGO) stage, Eastern Cooperative Oncology Group (ECOG) performance status and first-line treatment received, age was no longer an independent risk factor for poorer overall survival. Optimisation of vulnerable patients utilising a comprehensive geriatric assessment and directed interventions to facilitate the delivery of standard of care treatment could help narrow the survival discrepancy between the oldest patients and their younger counterparts.

How to win the ovarian cancer stem cell battle: destroying the roots.

Ovarian cancer has the highest mortality rate among gynecologic malignancies. The combination of cytoreductive surgery and chemotherapy is the standard regimen for the treatment of ovarian cancer. The initial treatment is usually effective, but many patients with ovarian cancer experience recurrence, and treatment options for recurrent disease remain challenging. Cancer stem cells (CSCs) are suggested to play an essential role in cancer recurrence after initial chemotherapy. Furthermore, they are of great interest as CSCs may also be involved in chemotherapy susceptibility. Thus, understanding the characteristics and mechanisms by which CSCs display resistance to therapeutic agents is important to design effective cancer treatments. In this review, we describe and discuss current therapeutic regimens for ovarian cancer, as well as the various CSC markers, association between CSCs and disease progression, correlation of CSCs with poor prognosis, enrichment of CSCs in tumor tissues following repeated chemotherapy cycles, activation of major signaling pathways following chemotherapy, and potential inhibitors that suppress these signaling cascades. In addition, clinical trials evaluating novel targeted therapies to overcome chemotherapy resistance will be reviewed. The combination of traditional chemotherapy and CSC-targeted therapy could be an effective and promising anticancer treatment for ovarian cancer. Understanding the biological properties of CSCs and the mechanism of chemotherapy resistance are critical to design and develop new therapeutic strategies to overcome CSC-associated chemotherapy resistance.

THE EFFECT OF CYTOREDUCTIVE SURGERY AND INTRAPERITONEAL HYPERTHERMIC CHEMOPERFUSION (HIPEC) ON THE CLINICAL OUTCOME OF TREATMENT OF PATIENTS WITH ADVANCED GASTRIC CANCER

Introduction. For gastric cancer (GC), metastatic peritoneal carcinomatosis (PC) is a typical process. PC and its consequences usually lead to the death of 20-40 % of patients with GC. For carefully selected patients, intraperitoneal hyperthermic chemoperfusion may be considered. The aim of the study was to investigate the effect of cytoreductive surgery in combination with HIPEC on the clinical course of the postoperative period, the frequency of postoperative complications and side effects of chemotherapeutic drugs in the treatment of advanced GC. Materials and methods. The results of treatment of 34 patients with advanced GC were considered. The patients were divided into two groups: IA group — 24 patients with advanced GC, who first underwent complete primary cytoreductive surgery (CRS) with adjuvant chemotherapy (ACT) according to the FLOT scheme and IB group — 10 patients with advanced GC treated by CRS + ACT + HIPEC. Results. Comparing the number of patients with postoperative complications in groups IA (CRS + ACT) and IB (CRS + HIPEC + ACT) using the exact bilateral Fisher’s test p> 0. 05. Comparing the frequency of side effects of chemotherapeutic treatment in the FLOT mode in groups IA (CRS + ACT) and IB (CRS + HIPEC + ACT), the values ??of χ2 = 20. 750, χ2Cr = 28. 568 (p = 0. 0622) were obtained. Conclusions. The usage of HIPEC in combination with complete CRS and ACT is a promising method of treatment of this group of patients. As a result of this study, it was proved that there is no statistically significant effect on the clinical course of the postoperative period due to the increase in the frequency of postoperative complications or side effects of chemotherapeutic drugs.

Implementation of the enhanced recovery after surgery protocol for patients with peritoneal carcinomatosis undergoing cytoreductive surgery and hyperthermic intraperitoneal chemoperfusion.

Aim of the studyTo investigate the feasibility of enhanced recovery after surgery (ERAS) protocol for patients with primary peritoneal carcinomatosis (PC) undergoing cytoreductive surgery with hyperthermic intraperitoneal chemoperfusion (HIPEC) based on the length of hospital stay (LOS), return of bowel function, the incidence of postoperative complications, and quality of life (QLQ) analysis.Material and methodsThe study included a total of 37 patients with primary PC of different origin, who underwent cytoreductive surgery plus HIPEC. Patients were divided into 2 groups: Group I (nonERAS) – 20 patients and Group II (ERAS) – 17 patients.ResultsThe median LOS in Group I (nonERAS) (12.35 ± 3.9) was longer than in Group II (ERAS) (6.8 ± 1.9) (p < 0.01). The use of the ERAS protocol significantly contributed to the faster return of bowel function (peristalsis and stool) in the postoperative period (p < 0.01). There was no statistically significant difference in the incidence of postoperative complications between the ERAS and nonERAS groups, which supports its clinical safety. Improved QLQ according to the obtained data has also been achieved due to the introduction of the principles of the ERAS protocol.ConclusionsThe obtained results prove the expediency and feasibility of the implementation of the ERAS protocol among patients undergoing cytoreductive surgery in combination with HIPEC.

Canadian guidelines on the management of colorectal peritoneal metastases.

Modern management of colorectal cancer (crc) with peritoneal metastasis (pm) is based on a combination of cytoreductive surgery (crs), systemic chemotherapy, and hyperthermic intraperitoneal chemotherapy (hipec). Although the role of hipec has recently been questioned with respect to results from the prodige 7 trial, the role and benefit of a complete crs were confirmed, as observed with a 41-month gain in median survival in that study, and 15% of patients remaining disease-free at 5 years. Still, crc with pm is associated with a poor prognosis, and good patient selection is essential. Many questions about the optimal management approach for such patients remain, but all patients with pm from crc should be referred to, or discussed with, a pm surgical oncologist, because cure is possible. The objective of the present guideline is to offer a practical approach to the management of pm from crc and to reflect on the new practice standards set by recent publications on the topic.

Hyperthermic intraoperative intrapleural chemotherapy and surgical cytoreduction as part of multimodal treatment of malignant pleural mesothelioma – case report

Malignant pleural mesothelioma is one of the most aggressive malignancies with a very poor prognosis. Multimodal treatment consisting of three modalities – chemotherapy, radiotherapy and cytoreductive surgery is optimal. The use of new therapeutic modalities, such as hyperthermic intraoperative intrapleural chemotherapy or photodynamic therapy can improve the current results of mesothelioma treatment. Combined hyperthermic intraoperative chemotherapy and cytoreductive surgery as part of multimodal therapy of malignant mesothelioma has been used since 2017 at the 1st Department of Surgery of University Hospital Olomouc. The authors report the case of a 47-year-old man with malignant epithelioid mesothelioma of the left pleural cavity. Following neoadjuvant chemotherapy, this patient underwent extrapleural pneumonectomy with intraoperative intracavitary hyperthermic chemotherapy. The postoperative period was complicated by circulatory instability and later by tension fluidothorax with signs of heart failure. Currently, 8 months have elapsed from the surgery and the patient remains without any signs of recurrence.

MANEJO DE LA CARCINOMATOSIS PERITONEAL DE ORIGEN COLORRECTAL Y REALIDAD EN PANAMÁ

RESUMEN &#x0D; Antecedentes &#x0D; El término carcinomatosis peritoneal fue utilizado por primera vez por Sampson en 1931 para describir la diseminación peritoneal de una neoplasia avanzada de ovario. Hoy el término carcinomatosis peritoneal incluye toda diseminación tumoral, local o masiva, que compromete la serosa peritoneal y las estructuras anatómicas vecinas. Un 30% a 40% de pacientes con carcinoma colorrectal van a desarrollar en algún momento metástasis, es decir 90 pacientes, de hecho la carcinomatosis peritoneal es la segunda presentación más común de la metástasis a distancia del cáncer de colon.&#x0D; Objetivo: Presentar la evidencia publicada sobre el abordaje y tratamiento quirúrgico de la carcinomatosis peritoneal de cáncer colorrectal en otras latitudes e impulsar el estudio, manejo y difusión de los conocimientos de la metástasis peritoneal principalmente a nivel nacional.&#x0D; Diseño: Se utilizaron artículos científicos indexados entre 2010 y 2020, que fueron seleccionados por su relevancia, validez y calidad de contenido, como aquellos disponibles en National Center for Biotechnology Information, Surgical Oncology Clinics of North America, Annals of Surgical Oncology, World Journal of Surgical Oncology obtenidas a través de diversas bibliotecas virtuales.&#x0D; Conclusión: La cirugía citorreductora en combinación con quimioterapia intraperitoneal hipertérmica ha mejorado la sobrevida global a los 5 años de 40 a 51% dando resultados prometedores en pacientes con carcinomatosis peritoneal de origen colorrectal altamente seleccionados e incluso se considera el único tratamiento potencialmente curativo.&#x0D; Palabras claves: carcinomatosis peritoneal, cáncer colorrectal, Cirugía citorreductora (CRS), quimioterapia intraperitoneal hipertérmica (HIPEC).

Biodegradable Implants Combined with Immunogenic Chemotherapy and Immune Checkpoint Therapy for Peritoneal Metastatic Carcinoma Postoperative Treatment.

Peritoneal seeding represents one of the most frequent sites of metastasis for late-stage gastrointestinal and gynecological cancer. At present, the major treatment method for peritoneal metastatic carcinoma (PMC) is the combination of cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC). Nevertheless, the 5 year survival rate of patients after these treatments is still far from satisfactory. Here, we report a biodegradable implant co-loaded with doxorubicin (DOX) and anti-PD-1 monoclonal antibody (aPD-1) (BI@DOX+aPD-1) for a combination of immunogenic chemotherapy and immune checkpoint therapy for PMC postoperative treatment. The bio-implant is fabricated with oxidized dextran (ODEX) and 4-arm poly(ethylene glycol) amine (4-arm PEG-NH2) by Schiff's base reaction at mild conditions, with DOX and aPD-1 loaded inside during and after the fabrication process, respectively. In vitro studies confirmed the slow and sustained release of DOX and aPD-1 from the bio-implants. In vivo studies showed that the bio-implants could be gradually degraded and maintain relatively high concentrations of therapeutic agents in the mouse abdomen. In a murine CT26 PMC model, the BI@DOX+aPD-1 resulted in a 89.7% tumor-suppression rate after peritoneal implantation. Importantly, the combination therapy of DOX and aPD-1 in the bio-implant showed an excellent synergistic effect with a Q value of 2.35. This easy-fabricated bio-implant combined with DOX and aPD-1 should be promising for clinical PMC postoperative treatment.

PKPD Modeling and Dosing Considerations in Advanced Ovarian Cancer Patients Treated with Cisplatin-Based Intraoperative Intraperitoneal Chemotherapy

Intraperitoneal chemoperfusion (IPEC) of cisplatin is a popular treatment for advanced ovarian cancer, typically under hyperthermia (HIPEC). The use of cisplatin under (H)IPEC is off-label, and the role of hyperthermia is unknown. The aim of this study was to characterize the pharmacokinetic/pharmacodynamic (PKPD) properties of cisplatin under (H)IPEC and to predict the optimal treatment regimen. Using a randomized design, data on intact cisplatin perfusate and plasma concentrations, leukocyte counts-a hematotoxicity marker-and serum creatinine-a nephrotoxicity marker-were collected from 50 patients treated with a combination of cytoreductive surgery (CRS) and either normothermic or hyperthermic IPEC of cisplatin dosed at 75, 100, and 120mg/m2. The non-linear mixed effects modeling technique was used to construct the PKPD models. The PK of intact cisplatin was characterized by a two-compartment model. A semi-physiological myelosuppression model for the leukopenia was modified to account for the CRS-induced leukocytosis and the residual myelosuppression effect of neoadjuvant chemotherapy. The incidence and severity of nephrotoxicity were described by a discrete-time Markov model. Hyperthermia increased the absorption rate of cisplatin by 16.3% but did not show a clinically relevant impact on the investigated toxicities compared with normothermia. Leukopenia was not severe, but nephrotoxicity can become severe or life-threatening and was affected by the dose and IPEC duration. The model predicted that nephrotoxicity is minimal at a cisplatin dose of 75mg/m2 with an IPEC duration of 1-2h and an 1-h duration is favored for doses between 100 and 120mg/m2. Graphical abstract.

Weekly Dose-Dense Paclitaxel and Triweekly Low-Dose Cisplatin: A Well-Tolerated and Effective Chemotherapeutic Regimen for First-Line Treatment of Advanced Ovarian, Fallopian Tube, and Primary Peritoneal Cancer.

A combination of cytoreductive surgery, either primary (PCS) or interval (ICS), and chemotherapy with a platinum-paclitaxel regimen is the well-accepted treatment for advanced-stage epithelial ovarian cancer (EOC), fallopian tube cancer (FTC), and primary peritoneal serous carcinoma (PPSC), but it is still uncertain whether a combination of dose-dense weekly paclitaxel and low-dose triweekly cisplatin is useful in the management of these patients. Therefore, we retrospectively evaluated the outcomes of women with advanced-stage EOC, FTC, and PPSC treated with PCS and subsequent dose-dense weekly paclitaxel (80 mg/m2) and low-dose triweekly cisplatin (20 mg/m2). Between January 2011 and December 2017, 32 women with International Federation of Gynecology and Obstetrics (FIGO) stage IIIC–IV EOC, FTC, or PPSC were enrolled. Optimal PCS was achieved in 63.5% of patients. The mean and median progression-free survival was 36.5 and 27.0 months, respectively (95% confidence interval (CI): 26.8–46.2 and 11.3–42.7 months, respectively). The mean overall survival was 56.0 months (95% CI: 43.9–68.1 months), and the median overall survival could not be obtained. The most common all-grade adverse events (AEs) were anemia (96.9%), neutropenia (50%), peripheral neuropathy (28.1%), nausea and vomiting (34.4%), and thrombocytopenia (15.6%). These AEs were predominantly grade 1/2, and only a few patients were complicated by grade 3/4 neutropenia (21.9%) and anemia (6.3%). A multivariate analysis indicated that only suboptimal PCS was significantly correlated with a worse prognosis, resulting in an 11.6-fold increase in the odds of disease progression. In conclusion, our data suggest that dose-dense weekly paclitaxel (80 mg/m2) combined with low-dose triweekly cisplatin (20 mg/m2) is a potentially effective and highly tolerable front-line treatment in advanced EOC, FTC, and PPSC. Randomized trials comparing the outcome of this regimen to other standard therapies for FIGO stage IIIC–IV EOC, FTC, and PPSC are warranted.

Malignant Peritoneal Tumors - Introduction.

This article provides an introduction to peritoneal tumors, which are the subject of a series of review papers published in Issue 5 (2019) of Klinicka onkologie. Many malignant peritoneal tumors are characterized by production of mucinous and gelatinous masses, multiple peritoneal disability, so-called peritoneal carcinomatosis, and various grades of malignancy depending on their origin, staging, and histological type. Malignant peritoneal tumors are rare and their clinical symptomatology is nonspecific and varies according to the extent of disability. Diagnosis, particularly in the initial asymptomatic stages, is very complicated and often impossible, and tumors are often diagnosed by chance during other operations. Malignant peritoneal tumors were regarded as incurable and lethal for a long time; however, this view has changed over the past three decades. The Sugarbaker method, a combination of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy, was introduced in the 1990s. Postoperative cytostatic lavage is usually performed in specific cases. Classifications for the extent of disease and completeness of cytoreduction were established. Studies repeatedly confirmed the efficacy of this treatment for peritoneal malignancy. The combination of an aggressive surgical approach and intraperitoneal chemotherapy not only enhances quality of life, but also prolongs progression-free survival and overall survival in selected patients. Specialized centers for treatment of peritoneal malignancy were established based on results from the Czech Republic and around the world. These centers provide complex care, including specific surgical interventions and follow-up, for selected patients with primary and secondary peritoneal malignancy.

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.

Treatment of Malignant Peritoneal Mesothelioma.

Malignant mesothelioma is a highly malignant disease that most often occurs in the pleura of the thoracic cavity, followed by the peritoneum, pericardium, or tinea vaginalis testis. Malignant peritoneal mesothelioma (MPM) accounts for 10-15% of all mesotheliomas. The most significant risk factor for MPM is exposure to asbestos. There is no specific symptomatology, and imaging (computed tomography) and histopathology are crucial for diagnosis. There are no generally accepted guidelines for radical treatment of MPM. Previously, the prognosis of MPM patients was poor, with survival of up to 1 year. However, median survival of patients who are suitable candidates for radical therapy is currently 3-5 years. A combination of cytoreductive surgery (CRS) and hyperthermic perioperative chemotherapy (HIPEC) is recommended in selected patients, while chemotherapy alone has insufficient efficacy. Systemic chemotherapy remains the only treatment option for patients who are unsuitable for CRS and HIPEC. In selected patients scheduled for or currently undergoing CRS and HIPEC, surgery may be performed in combination with systemic chemotherapy in the neoadjuvant or adjuvant setting; however, the benefit is unclear. There are no recommendations for follow-up of MPM patients after radical surgery. Existing guidelines for the pleural form (e.g., those issued by the European Society for Medical Oncology) do not specify the frequency or method of investigation. In the absence of specific serum markers, only CA 125 and mesothelin are generally available. Imaging methods include ultrasonography, computed tomography, and magnetic resonance imaging.

Clinical Factors Associated with Longer Hospital Stay Following Ovarian Cancer Surgery.

Background: Ovarian cancer (OC) is the leading cause of death from gynecologic malignancy and is treated with a combination of cytoreductive surgery and platinum-based chemotherapy. Extended length of stay (LOS) after surgery can affect patient morbidity, overall costs, and hospital resource utilization. The primary objective of this study was to identify factors contributing to prolonged LOS for women undergoing surgery for ovarian cancer. Methods: The American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database was queried to identify women from 2012–2016 who underwent hysterectomy for ovarian, fallopian tube and peritoneal cancer. The primary outcome was LOS >50th percentile. Preoperative and intraoperative variables were examined to determine which were associated with prolonged LOS. Results: From 2012–2016, 1771 women underwent elective abdominal surgery for OC and were entered in the ACS-NSQIP database. The mean and median LOS was 4.6 and 4.0 days (IQR 0–38), respectively. On multivariate analysis, factors associated with prolonged LOS included: American Society of Anesthesiologists (ASA) Classification III (aOR 1.71, 95% CI 1.38–2.13) or IV (aOR 1.88, 95% CI 1.44–2.46), presence of ascites (aOR 1.88, 95% CI 1.44–2.46), older age (aOR 1.23, 95% CI 1.13–1.35), platelet count >400,000/mm3 (aOR 1.74, 95% CI 1.29–2.35), preoperative blood transfusion (aOR 11.00, 95% CI 1.28–94.77), disseminated cancer (aOR 1.28, 95% CI 1.03–1.60), increased length of operation (121–180 min, aOR 1.47, 95% CI 1.13-1.91; >180 min, aOR 2.78, 95% CI 2.13–3.64), and postoperative blood transfusion within 72 h of incision (aOR 2.04, 95% CI 1.59–2.62) (p < 0.05 for all). Conclusions: Longer length of hospital stay following surgery for OC is associated with many patient, disease, and treatment-related factors. The extent of surgery, as evidenced by perioperative blood transfusion and length of surgical procedure, is a factor that can potentially be modified to shorten LOS, improve patient outcomes, and reduce hospital costs.

CHALLENGES IN CHOICE OF THE TREATMENT STRATEGY FOR PATIENTS WITH RECURRENT PSEUDOMYXOMA PERITONEI

Pseudomixoma peritonei is a rare type of peritoneal carcinomatosis accompanied by accumulation of mucus and high recurrence rate and in some cases complicated with intestinal obstruction. In the last 10–15 years, there has been observed a significant improvement in overall survival of patients with recurrent pseudomyxoma, who underwent cytoreductive surgery in combination with intraperitoneal chemotherapy. However, the frequency of recurrences of peritoneal pseudomyxoma after optimal cytoreduction can reach 80–90 % in the first 2 years.The purpose of the study was to analyze the results of combined therapy (cytoreductive surgery and hypothermic intraperitoneal chemoperfusion) in patients with recurrent pseudomyxoma peritonei, who previously underwent cytoreductive surgery.Material and Methods. The study included 43 patients previously undergoing cytoreductive surgery for pseudomyxoma peritonei in the Thoracic Oncology Department of the N.N. Blokhin National Medical Research Center of Oncology.Results. Re-operations were performed in 11 of the 43 patients with recurrent pseudomixoma peritonei after previously performed cytoreductive surgery. Repeated intraperitoneal chemoperfusion with hyperthermia was performed in 6 patients. Of the 11 reoperated patients, 7 had a complete cytoreduction (CC-0), recurrence was detected within 22 to 47 months; 2 patients had CC-1 and recurrence was observed within 12 and 15 months. Optimal cytoreduction (CC0-1) was achieved in 7 of the 11 patients. The maximum follow-up period was 44 months. Recurrence was noted in 9 patients, while the majority of patients had a satisfactory quality of life. Two patients showed signs of partial intestinal obstruction. None of the patients died during the follow-up period. In two patients with optimal (CC-0) cytoreduction, there were no signs of disease progression 9 and 15 months after re-surgery. One-year disease-free survival rate was 51 %.Conclusion. Repeated surgeries for recurrent pseudomyxoma present a great challenge for surgeons due to the difficulty in achieving optimal cytoreduction. Optimal cytoreduction in initial surgery should be considered as the main condition for repeated surgery. Moreover, additional criterion for a favorable prognosis is the time to progression of disease.

THE ROLE OF SURGICAL STAGE IN COMBINATION THERAPY FOR PATIENTS WITH LOCALLY ADVANCED CERVICAL CANCER

Objective: to justify the expediency of the surgical stage as a part of the combination treatment for stage IIA-IIIB cervical cancer. Materials and methods. The study included 343 women with stage IIA-IIIB cervical cancer treated from 2013 to 2016 with mandatory follow-up for at least 2 years. Patients were divided into 2 groups. The first group included 214 patients who received a combination treatment. At the first stage, neoadjuvant chemoradiation therapy was performed (remote radiation therapy 5 days a week with radio modification with Cisplatin once a week at a dose of 40 mg/m2). After evaluating the effect, patients were subjected to surgical treatment or continued chemoradiotherapy. The second group (n = 129) received standard combined radiation therapy. Various schemes of combination and complex treatment and standard combined radiation therapy were evaluated using the indices of general and relapse-free survival. Results. The proposed scheme for the combination therapy for patients with locally advanced cervical cancer showed significantly higher survival rates at all the analyzed stages. For the combined treatment group with complete cytoreduction, the two-year overall and relapse-free survival with stage IIA is 94.1% vs. 82.4%, with IIB 90.8% vs. 80.3%, with IIB 87.5% vs. 75%, with IIB with metastatic lesion of regional lymph nodes 85% vs. 70%. For the second group, two-year overall and relapse-free survival with stage IIA 75% vs. 50%, with IIB 70.9% vs. 56.3%, with IIB 59.1% vs. 40.9%, with IIB with metastatic lesion of regional lymph nodes 62.2% and 40.5%. The advantages of this approach are most clearly seen within patients with metastatic lesions of regional lymph nodes (85% vs. 62% accordingly). Conclusion. Cytoreductive surgery in combination with the combination therapy allows to achieve a significant increase in overall and relapse-free survival for patients with locally advanced cervical cancer compared with standard treatment programs.