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Background Various histological types of gastric carcinomas (GCs) differ in terms of their pathogenesis and their preexisting background, both of which could impact the tumor immune microenvironment (TIME). However, the current understanding of the immune contexture of GC is far from complete. Aim To clarify the tumor-host immune interplay through histopathological features and the tumor immune cycle concept. Methods In total, 50 GC cases were examined (15 cases of diffuse GC, 31 patients with intestinal-type GC and 4 cases of mucinous GC). The immunophenotype of GC was assessed and classified as immune desert (ID), immune excluded (IE) or inflamed (Inf) according to CD8+ cell count and spatial pattern. In addition, CD68+ and CD163+ macrophages and programmed death-ligand 1 (PD-L1) expression were estimated. Results We found that GCs with different histological differentiation demonstrated distinct immune contexture. Most intestinal-type GCs had inflamed TIMEs rich in both CD8+ cells and macrophages. In contrast, more aggressive diffuse-type GC more often possessed ID characteristics with few CD8+ lymphocytes but abundant CD68+ macrophages, while mucinous GC had an IE-TIME with a prevalence of CD68+ macrophages and CD8+ lymphocytes in the peritumor stroma. PD-L1 expression prevailed mostly in intestinal-type Inf-GC, with numerous CD163+ cells observed. Therefore, GCs of different histological patterns have specific mechanisms of immune escape. While intestinal-type GC was more often related to PD-L1 expression, diffuse and mucinous GCs possessing more aggressive behavior demonstrated low immunogenicity and a lack of tumor antigen recognition or immune cell recruitment into the tumor clusters. Conclusion These data help to clarify the links between tumor histogenesis and immunogenicity for a better understanding of GC biology and more tailored patient management.

Background Peritoneal metastasis (PM), arising from gastric cancer (GC), is the most common pattern of synchronous and metachronous dissemination and is generally associated with poor prognosis. New therapeutic modalities are being increasingly employed for such patients. Aim To develop more advanced methods, it becomes necessary to study the results of existing standard treatment methods in patients with PM in order to perform a comparative analysis of the strategies. Methods A retrospective analysis of the efficiency of standard treatment methods (i.e., palliative chemotherapy, palliative gastrectomy, and the best supportive care) was performed on 200 GC patients with synchronous PM. Results The overall survival (OS) rate in 200 GC patients with PM under standard treatment was 5.4 mo. One-year survival occurred in 18.4% of patients. In multivariate analysis, the survival rate was significantly influenced by the following factors: Presence of extraperitoneal metastases, and stage of PM according to both the Japanese Gastric Cancer Association (JGCA) and the peritoneal cancer index (PCI). The median OS and 1-year survival of patients with Р1, P2, and P3 (JGCA) carcinomatosis were 9.8 mo, 6.7 mo, and 4.0 mo, and 47.2%, 18.8%, and 5.1%, respectively. The application of the palliative gastrectomy resulted in an increase in the median OS by up to 17 mo compared to the conservative approach where the value was 8.5 mo (P = 0.05) in patients with Р1 РМ. In patients with Р3, palliative chemotherapy increased the OS by up to 5.6 mo compared to the OS of 3.2 mo (P = 0.0006) for best supportive care. The median OS and 1-year survival of patients with РCI of 1-6, 7-12 and 13+ points were 8.5 mo, 4.2 mo, and 4.1 mo, and 39.8%, 6.7%, and 5.5%, respectively. Palliative gastrectomy increased the median OS to 12.6 mo compared to conservative approach of 8.0 mo (P = 0.03) in patients with РCI of 1-6 points. In patients with РCI 13+ points, only palliative chemotherapy increased the OS to 6.0 mo compared to the OS of 3.4 mo for best supportive care (P = 0.0008). Conclusion GC patients with PM are characterized by extremely poor prognoses. Long-term survivors were found in the group with PCI of 1-6 points, and there was no survival difference in groups with PCI 7-12 vs PCI 13+ points. Palliative gastrectomy could prove effective in treating patients with early stage PM. The three standard treatment methods are equally effective for moderate stages of PM. In cases with advanced peritoneal carcinomatosis, a significant increase in prognosis was registered only after treatment with palliative chemotherapy.

Background and objectives. During the two past decades, a new therapeutic approach to ovarian cancer (OC) has been developed. This combines cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). However, almost no data exist regarding the utility of biomarkers of morphological heterogeneity as prognostic factors in such patients. Methods. A retrospective study of the effectiveness of CRS and HIPEC was carried out in 59 patients with ovarian cancer. Biomarkers of morphological heterogeneity of OC were studied as prognostic factors: OC pathogenic types (based on the identification of р53 mutated gene protein expression) and homologous recombination deficit (basing on the identification of BRCA 1 gene expression status). Results. The survival of patients reliably differed with the division into two pathogenetic OC types established by immunohistochemistry: the median disease-free survival of type I OC patients was 14±1.7 months, type ІІ – 8±1.6 months (р = 0.007); the median overall survival of type I OC patients was 23.5±6.7 months, type ІІ – 12±1.9 months (р = 0.017). The median overall survival of patients with the somatic mutation of BRCA 1 gene and complete cytoreduction was 22±4.8 months, and without the somatic mutation of BRCA 1 gene – 12±3.3 months (р = 0.047). Conclusions. These data demonstrate that identification of the pathogenetic type of OC and BRCA 1 status may be useful for the personalized therapy of ovarian cancer patients treated with CRS/HIPEC.

Treatment of late stages of the tumor process requires the implementation of increasingly high-tech and complex interventions, aimed at improving the overall and disease-free survival, improving the quality of life of patients. HIPEC technique is a point of growth at which progress in oncology and all medical science can be demonstrated. Among the specialists involved in the implementation of this type of specialized care, there is still no consensus on what traits the malignant process of the peritoneum should be able to use this technique. Intraperitoneal hyperthermic perfusion (HIPEC) is gaining popularity as a method of palliative treatment of patients with common tumors of the abdominal cavity. Using the popular medical virtual search engine PubMed identified 2140 cited publications on the search query "hipec, peritoneal" and 752 cited publications "hipec, peritoneal, CRS", finally the phrase "hipec, cancer, randomized trial" with the clarifying characteristic "Clinical Trial" (excludes review articles) – 30 scientific publications, 10 of them in the last 5 years. All this demonstrates the growing interest to HIPEC around the world. The technique is used mainly for ovarian cancer, mesothelioma, pseudomyxoma of the peritoneum, colorectal cancer, and gastric cancer. It is possible as a combination of surgically performed PE and HIPEC, and HIPEC in mono-mode, in the absence of macroscopically detected carcinoma of the abdominal cavity, but positive washings from the peritoneum in verified cancer. It is performed both during the cytoreductive operation and as the second stage as a component of the Second look procedure, as well as in the adjuvant mode in the absence of carcinomatosis, but of high potential danger of peritoneal dissemination (for example, if the tumor has infiltrated the entire wall of the organ). HIPEC has never become a standard treatment, and multicenter randomized trials are regularly conducted on this topic.

Ovarian cancer (OC) represents the most lethal malignancy in gynaecologic oncology practice and shows a high recurrence rate due to its early chemoresistance to first-line chemotherapy. Yet, timely selection of the correct treatment strategy is likely to prolong a patient’s survival. MicroRNAs (miRNAs) are a class of short non-coding RNAs responsible for the expression of 30%–60% of human genes. In numerous studies, miRNAs have been used to provide the overall prognosis for patients and analyse the process’s prevalence and responses to chemotherapy. In particular, miRNAs as markers for predicting the sensitivity of OC to platinum- and taxane-based chemotherapeutics can significantly improve the treatment efficacy. This article highlights two families of miRNAs: miR-200 and let-7, which are promising for further research on OC and its chemosensitivity.

Pseudomyxoma Peritonei (PMP) and Peritoneal Mesothelioma (PM) are both rare peritoneal malignancies. Currently, affected patients may be treated with Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy offering long-term survival or even cure in selected patients. However, many issues regarding the optimal treatment strategy are currently under debate. To aid physicians involved in the treatment of these patients in clinical decision making, the PSOGI executive committee proposed to create a consensus statement on PMP and PM. This manuscript describes the methodology of the consensus process. The Delphi technique is a reliable method for attaining consensus on a topic that lacks scientific evidence through multiple voting rounds which feeds back responses to the participants in between rounds. The GRADE system provides a structured framework for presenting and grading the available evidence. Separate questionnaires were created for PMP and PM and sent during two voting rounds to 80 and 38 experts, respectively. A consensus threshold of 51.0% was chosen. After the second round, consensus was reached on 92.9%-100.0% of the questions. The results were presented and discussed in the plenary session at the PSOGI 2018 international meeting in Paris. A third round for the remaining issues is currently in progress. In conclusion, using the Delphi technique and GRADE methodology, consensus was reached in many issues regarding the treatment of PM and PMP amongst an international panel of experts. The main results will be published in the near future.

Виконання поєднання гастректомії (ГЕ), перитонеоектомії (ПЕ) і внутрішньочеревної гіпертермічної хіміоперфузії (ВЧГТХП) при раку шлунка (РШ) є частиною специфічної медичної ідеології, яку впровадила група ентузіастів, об’єднаних під егідою PSOGI ​​(Peritoneal Surface Oncology Group International – Всесвітня медична спільнота з вивчення перитонеального канцероматозу). Очікується, що з часом ГЕ/ПЕ/ВЧГТХП стане стандартом комбінованого лікування хворих на канцероматоз при РШ. У статті представлено досвід Одеського центру реконструктивної та пластичної медицини і Одеського національного медичного університету щодо використання методики внутрішньочеревної гіпертермічної хіміоперфузії (ВЧГТХП або процедури HIPEC), у т.ч. в лікуванні хворих на перитонеально-дисемінований рак шлунка. Коротко представлено огляд деяких етапів розвитку хірургії раку шлунка. Мета дослідження – вивчити і дослідити виживання хворих на канцероматоз при використанні стандартної внутрішньовенної хіміотерапії і процедури HIPEC. Матеріали і методи. У дослідження включено 47 осіб, яких прооперовано з приводу канцероматозу очеревини в період 2015–2017 рр. У клініці реконструктивної та пластичної медицини Одеського національного медичного університету. Досліджували тільки радикально або умовно-радикально прооперованих хворих. Середній вік – 54,9 року, чоловіків – 14, жінок – 33. В усіх випадках діагноз було верифіковано гістологічно. Для порівняння виживання хворих після ПЕ/ВЧГТХП було набрано ретроспективну групу порівняння, в яку включили 22 хворих на канцероматоз черевної порожнини, для лікування яких застосовували тільки внутрішньовенну системну хіміотерапію (СХ). Результати досліджень та їх обговорення. Проведене власне спостереження, засноване на аналізі історій хвороби 47 хворих, яким провели ВЧГТХП при раку шлунка, раку яєчників, колоректальному раку і деяких інших видах злоякісної патології черевної порожнини. Порівнювали виживання хворих після процедури HIPEC і пацієнтів із канцероматозом черевної порожнини, яким виконали тільки внутрішньовенну системну хіміотерапію (СХ). Виживання хворих після виконання циторедуктивних операцій (у статті використано Міжнародну абревіатуру CRS – cytoreductive surgery), в т.ч. з приводу раку шлунка, була незначно гірше, ніж після СХ. Інтерес представляє можлівість індивідуалізації схеми ВЧГТХП з точки зору призначення певного хіміопрепарату. У зв’язку з цим оформлено патент UA 121792 U від 11.12.2017. Машуков А. О., Максімовський В. Є., Четвериков С. Г., Лук’янчук О. В., Осадчий Д. М., Заволока С. О., Роша Л. Г., Пирогов В. В. Спосіб лікування раку шлунка, ускладненого канцероматозом черевної порожнини. При цьому застосовано індівідуальний підхід процедури HIPEC до виконання залежно від експресії того чи іншого маркера в пухлинній тканині. Перед процедурою виконують лапароскопію із забором достатньої кількості матеріалу з пухлинної тканини, з подальшим його імуногістохімічним дослідженням на основні маркера чутливості терапії: TOP2A, ERCC1, TS. Висновки. З огляду на міжнародні дані й дані деяких вітчизняних онкологічних центрів (Львівський онкологічний регіональний лікувально-діагностичний центр), необхідний більш ретельний відбір хворих, ґрунтуючись на значенні перитонеального індексу канцероматозу (PCI – peritoneal carcinomatosis index) і рівні планованої циторедукції.

Locally advanced gastric cancer with a high risk of intraperitoneal progression is characterized by poor prognosis. After radical surgery, most patients die during the first two years post-operation as a result of disease progression. The prevailing type of progression and the leading cause of death in patients with gastric cancer is implantation metastasis. The main risk factors for peritoneal carcinomatosis in such patients include: gastric tumor invasion into serosa, the presence of tumor cells in peritoneal washings, the largeness of the tumor as accompanied by extensive serous lesions, infiltrative type of tumor growth, histological variants of gastric cancer prone to implantation metastasis and metastatic lesions in regional lymph nodes. Systemic chemotherapy does not provide effective eradication of subclinical peritoneal carcinomatosis in patients with locally advanced gastric cancer. The vast majority of patients who suffer from locally advanced gastric cancer and run a high risk of implantation metastasis are characterized by subclinical peritoneal dissemination at primary diagnosis, which means a rapidly fatal prognosis for such patients. In recent years, however, the paradigm of treatment of locally advanced gastric cancer has changed: a combination of surgery and adjuvant hyperthermic intraperitoneal chemotherapy is used increasingly, and presents an alternative to the previously accepted surgery only approach. It is also likely to increase the survival rate.

The treatment of peritoneal surface malignancies ranges from palliative care to full cytoreductive surgery (CRS) and Heated Intraperitoneal Chemotherapy HIPEC. Ongoing monitoring of patient recruitment and volume is usually carried out through dedicated registries. With multiple registries available worldwide, we sought to investigate the nature, extent and value of existing worldwide CRS and HIPEC registries.METHODS: A questionnaire was sent out to all known major treatment centres. The questionnaire covers: general purpose of the registry; inclusion criteria in the registry; the date the registry was first established; volume of patients in the registry and description of the data fields in the registries. Finally, the population size of the catchment area of the registry was collected.RESULTS: 27 questionnaires where returned. National databases are established in northwest European countries. There are five international general databases. Most database collect data on patients who have undergone an attempt to CRS and HIPEC. Two registries collect data on all patients with peritoneal carcinomatosis regardless the treatment. Most registries are primarily used for tracking outcomes and complications. When correlating the number of cases of CRS and HIPEC that are performed to the catchment area of the various registry, a large variation in the number of performed procedures related to the overall population was noted, ranging from 1.3 to 57 patients/million year with an average of 15 patients/1 million year.CONCLUSION: CRS and HIPEC is a well-established treatment for peritoneal surface malignancies worldwide. However, the coverage as well as the registration of treatment procedures differs widely. The most striking difference is the proportion of HIPEC procedures per capita which ranges from 1.3 to 57 patients per million. This suggests either a difference in patient selection, lack of access to HIPEC centres or lack of appropriate data collection.

Introduction Peritoneal metastasis (PM) of hepatocellular carcinoma (HCC) without distant spread are rare. The related prognosis is poor without standard treatment available. The role of cytoreduction surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is poorly documented. Methods An international multicentric cohort was constituted by retrospective analysis of 21 patients undergoing CRS/HIPEC for PM of HCC between 1992 and 2016 from 10 reference centers of PSOGI. Data on clinical features, treatment strategies, and survival outcomes were analyzed. Results The median time interval from the diagnosis of PM to the procedure was 4.5 months. The median peritoneal cancer index was 14. Sixteen patients had complete cytoreduction (CCR0-1). Ten patients had grades 3 to 4 complications. The median duration of follow-up was 52.2 months. The median OS was 46.7 months. The projected 3y-OS and 5y-OS were 88.9 and 49.4% respectively. The median OS for patients with CCR0-1 resection was not reached whereas it was 5.9 months for those with CCR2-3 resection after CRS (p = 0.0005). The median RFS was 26.3 months and projected RFS at 3 years of 36.5 months Three prognostic factors were associated with improved RFS in the univariate analysis: preoperative chemotherapy (p = 0.0156), PCI >15 (p = 0.009), Number of chemotherapy agents used for HIPEC (p = 0.005). Conclusion CRS/HIPEC is a safe and effective approach in selected patients with PM of HCC. CRS/HIPEC gives the patient a chance for a good relapse free and overall survival and should be considered as an option.

BACKGROUND AND OBJECTIVES Clinical experience suggests that cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) play an important role in the management of ovarian cancer. In order to improve patient selection, the peritoneal surface disease severity score (PSDSS) was previously introduced for use in colorectal cancer patients. However, almost no data exist regarding the utility of the PSDSS index in ovarian cancer patients. METHODS A retrospective study of the effectiveness of CRS and HIPEC was carried out in 59 patients with ovarian cancer. The PSDSS was based on three criteria: symptoms, extent of peritoneal dissemination, and primary tumor structure as assessed by histology and biomarker expression. RESULTS The overall survival time for patients with ovarian cancer in PSDSS Stage I was 48 ± 25.3 months. For PSDSS Stage II, the survival time was 26.5 ± 4.7 months. For PSDSS Stage III, it was 15.5 ± 4 months, and for PSDSS Stage IV, it was 6 ± 4.3 months. A multivariate analysis showed that the PSDSS stage was the only independent survival predictor. CONCLUSIONS These data demonstrate that a PSDSS based on two pathogenetic types may be useful for predicting survival outcomes in ovarian cancer patients treated with CRS/HIPEC.

Poster: "ECR 2017 / C-3086 / The efficiency of CT at pre-operative evaluation stage of PCI in patients with recurrent ovarian cancer " by: " O. Hural , Y. Mylyan, M. Fetsych, R. Yarema; Lviv/UA"

Patients with locally advanced gastric cancer (GC) and/or peritoneal metastases have a poor prognosis despite systemic chemotherapy or palliative surgery. The aim of this retrospective comparative non-randomised study was to evaluate aggressive cytoreduction in combination with hyperthermic intraperitoneal chemoperfusion (HIPEC) as a novel treatment strategy for patients with intraperitoneal disseminated and locally advanced GC.Forty-nine GC patients with serosal invasion (n = 19), limited peritoneal metastases (n = 20), or disseminated peritoneal metastases and tense ascites (n = 10) underwent combination therapy with HIPEC. Three matched control groups undergoing standard therapies were retrospectively identified.Combination therapy for serosa-invasive GC reduced the level of metachronous peritoneal carcinomatosis and increased median survival from 12 months to 22.5 months (p = 0.001). The median and 1-year survival rates for intraperitoneal disseminated GC patients undergoing therapy with the use of HIPEC were 12 months and 68.8% compared with 8 months and 25%, respectively (p = 0.004) for control subgroup patients (palliative chemotherapy). The symptomatic use of HIPEC allows effective elimination of recurrent ascites in GC patients.HIPEC is a well-tolerated and effective method of adjuvant therapy for gastric cancer with high risk of intraperitoneal progression. Cytoreduction followed by HIPEC improves survival in patients with limited peritoneal carcinomatosis of gastric origin.

The amount of lymph node dissection (LD) required during surgical treatment of gastric cancer surgery has been quite controversial. In the 1970s and 1980s, Japanese surgeons developed a doctrine of aggressive preventive gastric cancer surgery that was based on extended (D2) LD volumes. The West has relatively lower incidence rates of gastric cancer, and in Europe and the United States the most common LD volume was D0-1. This eventually caused a scientific conflict between the Eastern and Western schools of surgical thought: Japanese surgeons determinedly used D2 LD in surgical practice, whereas European surgeons insisted on repetitive clinical trials in the European patient population. Today, however, one can observe the results of this complex evolution of views. The D2 LD is regarded as an unambiguous standard of gastric cancer surgical treatment in specialized European centers. Such a consensus of the Eastern and Western surgical schools became possible due to the longstanding scientific and practical search for methods that would help improve the results of gastric cancer surgeries using evidence-based medicine. Today, we can claim that D2 LD could improve the prognosis in European populations of patients with gastric cancer, but only when the surgical quality of LD execution is adequate.