Background. Adrenocortical carcinoma (ACC) is a rare malignancy characterized by aggressive behavior and poor prognosis. Radical resection remains the only curative treatment, yet locally advanced disease with invasion of adjacent organs and major vessels frequently necessitates combined and multiorgan resections. Evaluating the outcomes and safety of such aggressive surgical approaches is essential to refine treatment strategies and indications. Aim. To evaluate the outcomes and prognostic factors of combined resections in patients with stage III–IV adrenocortical carcinoma, including procedures with vascular and multiorgan involvement. Materials and methods. This retrospective study was conducted at the Blokhin National Medical Research Center of Oncology and included 192 patients with stage III–IV adrenocortical carcinoma who underwent surgery between 1987 and 2022. A detailed analysis was performed for 115 patients who underwent combined resections involving adjacent organs and/or major vessels. For comparison, data from 42 standard adrenalectomies and 13 exploratory interventions were analyzed; an additional group of 20 patients received non-surgical treatment. Survival was assessed using the Kaplan–Meier method, and independent prognostic factors were identified using Cox proportional hazards regression (p 0.05). Results. Among 115 patients who underwent combined resections, postoperative complications occurred in 55.6% versus 16.6% after standard operations (p = 0.0001); postoperative mortality rates were 11.4% and 2.4%, respectively. Radical (R0) resections were associated with significantly better survival: median overall survival reached 84 months versus 4 months after palliative procedures (p 0.01). In stage IV disease, the best outcomes were observed in patients who achieved R0 resection limited to the abdominal cavity (median 41 months), compared to 8 and 11 months after conditionally radical and R2 resections, respectively (p = 0.004). Multivariate analysis confirmed the prognostic significance of resection radicality as prognostic factor. Conclusion. Radical resection remains the key determinant of survival in patients with stage III–IV adrenocortical carcinoma. Our analysis confirms that combined surgical procedures, despite their technical complexity and higher risk of complications, are justified and provide a significant improvement in long-term outcomes for this patient population.

Актуальность. Периоперационная химиотерапия является стандартом лечения пациентов с местно-распространенным резектабельным раком желудка (РЖ). Частота и эффективность периоперационной химиотерапии (ХТ) в зависимости от наличия микросателлитной нестабильности (MSI) у пациентов, получивших преоперационную терапию, остается неясной. Цель. Изучить эффективность периоперационной терапии у больных РЖ с разным уровнем MSI. Материалы и методы. В исследование включены 173 больных местно-распространенным РЖ, получивших периоперационную терапию в ФГБУ «НМИЦ онкологии им. Н.Н. Блохина» Минздрава России. У всех больных проводился тест на микросателлитную нестабильность (MSI-H) с помощью BAT25, BAT26, NR21, NR24, NR27. Оценивалась степень патоморфологического регресса (TRG) по A.M. Mandard, безрецидивная (БРВ) и общая (ОВ) выживаемость. Результаты. В 17 (9,82 %) случаях выявлена MSI-H. Высокая степень TRG выявлена у 15,17 % больных с MSS статусом, 0 из 12 больных — с MSI, получавших FLOT или FOLFIRINOX, и у 3 из 5 больных, получавших химиоиммунотерапию. 6-месячная БРВ у больных с MSS составила 93 % против 58 % у больных MSI-H, получивших ХТ, и 100 % — у больных из группы химиоиммунотерапии (р = 0,034). Выводы. Наши данные показывают, что результаты системной периоперационной ХТ с использованием современных режимов у больных с MSI-H-статусом хуже, чем у больных с MSS-статусом. Добавление ниволумаба к химиотерапии позволили достичь высокой частоты (60 %) полного патоморфологического регресса у группы пациентов с MSI-H статусом.

Background . microsatellite instability (MSI) is a prognostic marker of survival in many malignant diseases and show resistance to chemotherapy at early stages of colorectal cancer and show no benefits from chemotherapy at early stages of colorectal cancer. However, the role of MSI in resectable gastric cancer (GC) remains unknown. Aim. To study the results of treatment of resectable gastric cancer with microsatellite instability. Materials and methods . The study included 286 patients with resectable gC who received treatment at the N. N. Blokhin national medical Research Center of Oncology. All patients underwent PCR testing for MSI-H in 5 markers (BAT25, BAT26, NR21, NR24, NR27). Tumor regression grades (TRG) were evaluated according to the mandard tumour regression score, including disease-free survival and overall survival. Results. MSI indicated in 27 cases (9.44 %) out of 286 resectable gastric cancer. In group patients who received only surgical treatment, 2-year disease-free survival in patients with MSI-H was 77.80 % versus 88.29 % in MSS patients (hazard ratio (HR) 1.82, 95 % confidence interval (CI) 0.37–8.82, p = 0.45), 2-year overall survival in patients with MSI-H was 88.90 % versus 95.36 % in MSS patients (HR 2.03, 95 % CI 0.20–19.8, p = 0.54). In patients who received perioperative chemotherapy, 28.57 % (4 / 14) had progression in MSI-H tumor versus 3.61 % (6 / 166) in MSS tumor (p <0.001). In group patients who received treatment combined with chemotherapy, 2-year disease-free survival in patients with MSI-H was 59.60 % versus 67.36 % (HR 1.96, CI 95 % 0.88–4.35, p = 0.09), 2-year overall survival in patients with MSI-H was 67.30 % versus 85.86 % in MSS patients (HR 1.86, 95 % CI 0.64–5.41, p = 0.25) Conclusion. MSI-H is not a favorable prognosis factor in patients with resectable GC who are treated surgically combined with chemotherapy. The prevalence of progression in patients with MSI-H-status is higher than MSS-status with perioperative chemotherapy (FLOT / FOLFIRINOX).

Background. Peripheral nerve sheath malignancies (PNSM) are a rare and aggressive group of sarcomas that can occur sporadically, after radiation therapy, or related to neurofibromatosis type 1. Loss of function of NF1, TP53, and CDKN2A genes is thought to contribute to the progression of benign neurofibroma to PNSM and is a poor prognostic sign. The optimal management of patients with this disease is currently unresolved, and specific prognostic factors have not been established. Aim. To analyze the results of surgical treatment in patients with PNSM and establish prognostic factors of overall and recurrence-free survival rate. Materials and methods. The retrospective and prospective studies enrolled adult patients with histologically confirmed PNSM treated between 1998 and 2021 at the N.N. Blokhin National Medical Research Center for Oncology. Surgical intervention was performed on 61 patients, 38 (62%) females and 23 (38%) males. The most common PNSM localization was paravertebral (22 [36%] patients), followed by retroperitoneal (14 [23%] patients), and upper and lower extremities (13 [21%] and 12 [20%] patients, respectively). Results. For PNSM patients with a history of surgery, the median overall survival (OS) was 46 months (95% confidence interval 26.165.9). The 3-year and 5-year OS was 46% and 31%, respectively. The median recurrence-free survival (RFS) was 27 months (8.745.3), and 3-year and 5-year RFS was 26% and 13%, respectively. Median OS for grade 1 malignancies was not achieved, while grade 2 and grade 3 malignancy was 53 and 33 months, respectively (p=0.033). The median RFS for grade 1, 2, and 3 tumors was 119, 43, and 15 months, respectively (p=0.078). Patients who underwent radical (R0) surgery had higher RFS (p=0.006) and OS (p0.0001). After radical (R0) surgery, the median OS was not achieved; after nonradical (R1/R2) surgery, the median was 34 months. The median RFS was 124 months after R0-resection and 48 months after R1/R2. Conclusion. The most significant prognostic factors in PNSM patients are the radicality of the surgery performed and the malignancy grade. In our study, tumor size and localization did not affect the long-term treatment results.

Abstract Background According to TCGA (The Cancer Genome Atlas) and ACRG (Asian Cancer Research Group) classifications, tumors with high microsatellite instability (MSI-H) are classified as a specific group. Currently, perioperative chemotherapy is a standard of care in patients with locally advanced resectable gastric cancer (LARGC) in Western countries. Immune checkpoint inhibitors (ICIs) have shown efficacy in the treatment of metastatic gastric cancer, but their role in the neoadjuvant setting has not been studied. It is still unknown whether MSI-H tumors can benefit from perioperative therapy. Methods We analyzed patients with LARGC who had perioperative therapy from September 2019 to March 2023 at N.N.Blokhin National Medical Research Center of Oncology (Russia Federation). All patients were analyzed for MSI using PCR. Clinico-pathological factors, tumor regression grade (according to Mandard classification), disease-free (DFS), and overall survival (OS) were calculated and correlated with MSI status. Patients with MSI-H after December 2021 received perioperative chemoimmunotherapy (FOLFOX + nivolumab). Results The MSI-H phenotype was indicated in 29 (10.35%) out of 280 analyzed tumors. In 272 patients who received perioperative chemotherapy, the 2-year DFS was 51.40% in MSI-H tumors vs. 68.35% in MSS tumors (HR = 2.22, 95% CI 1.08–4.54, p = 0.028). The 2-year OS was 62.1% in MSI-H tumors vs. 83.27% in MSS tumors (HR = 2.71, 95% CI 1.12–6.53, p = 0.026). 3 (37.5%) patients out of 8 with MSI-H status who received perioperative chemoimmunotherapy had a complete pathologic response (TRG-1). Conclusion Our study shows diminished survival in patients with MSI-H gastric cancer undergoing perioperative chemotherapy. Then introduction of immunotherapy into perioperative treatment in patients with MSI-H gastric cancer demonstrates encouraging activity.

Gastrointestinal stromal tumors (GIST) are the most common type of mesenchymal malignancies of the gastrointestinal (GI) tract. Almost 10% of them are originated outside of the GI tract (extra-GIST), while GIST of the greater omentum constitutes about 1% among stromal tumors. More than 80% of GIST have mutations in c-KIT and PDGFRA genes. Herein we demonstrate the case of successful treatment of patient with giant omental GIST with c-KIT exon 11 mutation. 64-years-old woman, was admitted to the Department of abdominal oncology with complaints of shortness of breath and abdominal enlargement in volume. CT-scan revealed a large tumor in the abdominal cavity with tumor size of 543422 cm. The patient underwent left thoraco-abdominal approach. It was found that the tumor was originated from the greater omentum with several metastases located on the peritoneum of the left lateral channel. Resection of the large omentum, splenectomy, liver resection and was done. Postoperative immunohistochemical study showed the expression of CD117, CD34 in tumor cells. Ki-67 index was 1215%. Genetic study revealed c-KIT exon 11 mutation. Treatment with imatinib 400 mg per day was started. Patient has been treated with imatinib for 12 years. On control examination we have found a metastasis in the anterior abdominal wall 3,532,5 cm in diameter. Afterwards we performed resection of anterior abdominal wall with metastasis on 9 November 2017. Immunohistochemical study confirmed metastasis of GIST. The index of tumor proliferation activity (Ki-67) was 45%. Patient prolonged imatinib treatment at the dose of 400 mg per day after operation. No signs of progression have been revealed on control examination 72 months after the operation. 12-year progression-free survival during imatinib treatment is unique in our practice. Moreover, in the case of further progression, we have second and third-line targeted therapy (sunitinib and regorafenib) and surgery treatment in local progression.

Relevance. Leiomyosarcomas is highly aggressive tumors with poor prognosis. Surgical resection is a standard treatment approach. However, data of long-term results of surgical treatment are lacking due to rarity of retroperitoneal form of leiomyosarcoma. Prognostic significance of tumor size, grade and recurrence type remains unclear as well. Aim. To analyze results of surgical treatment of patients with retroperitoneal leiomyosarcoma and to define prognostic factors which are associated with disease-free and overall survival. Materials and methods. The study included patients with primary retroperitoneal leiomyosarcomas who have received surgical or combined treatment between January 2003 and April 2019 at Blokhin National Medical Research Centre of Oncology. Short- and long-term clinical outcomes of surgical and combined treatment as well as recurrence rate, pattern of recurrence and morphological features were analyzed in order to define prognostic factors of disease-free and overall survival. Results. The study included 64 patients with primary retroperitoneal leiomyosarcomas 12 men (18%) and 52 women (82%). Median tumor size was 10.55.0 cm. Most of the operations (93.3%) were done by open approach. Combined resections were performed in 62.5% of cases (n=40), vascular resections in 17.2% cases (n=11). Radical (R0) resections were performed in 54 cases (85.9%). Postoperative morbidity and mortality rate were 39% and 0% respectively. Adjuvant chemotherapy or radiotherapy received 21 (35%) patients and 1 (1.7%) patient respectively. 46 (71.9%) patients had a disease recurrence. Recurrence type (local recurrence/distant metastases) did not influence overall survival (р=0.655). Median disease-free survival was 27 months (95% CI 1043.9). 3-year and 5-year disease-free survival was 43% and 21% respectively. Median overall survival was 79 months (95% CI 49108.9). 3-year and 5-year overall survival was 73% and 59% respectively. Among patients grade 2 and grade 3 tumors median disease-free survival was 49 vs. 18 months (р=0.271), median overall survival 146 vs. 58 months (р=0.018). There were no statistically significant differences in rate of radical resections among patients with different tumor location (р=0.804) or its size (р=0,520). Patients, who have undergone radical (R0) resection, had better overall (р=0.028) and disease-free survival (р0.001). Adjuvant chemotherapy was not associated lower risk of disease recurrence (p=0.976), type of recurrence (р=0.981) and lower overall survival (р=0.284). Conclusion. Tumor grade and radical resection are the most important prognostic factors in patients with retroperitoneal leiomyosarcoma. In our study, tumor size was not correlated with long-term results and possibility of radical resection.

Актуальность . Лейомиосаркомы – высокоагрессивные опухоли и характеризуются неблагоприятным прогнозом. Хирургический метод является основным методом лечения. С учетом редкости забрюшинных лейомиосарком литературные данные об отдаленных результатах хирургического лечения немногочисленны, также остается неясной прогностическая значимость таких факторов, как размеры опухоли, степень злокачественности и характер прогрессирования заболевания, что определяет актуальность проведения данного исследования. Цель . Проанализировать результаты хирургического лечения больных забрюшинной лейомиосаркомой и выявить факторы, влияющие на безрецидивную и общую выживаемость. Материалы и методы . Был проведен ретроспективный и проспективный анализ результатов лечения пациентов с забрюшинными неорганными лейомиосаркомами, которым выполнялось хирургическое или комбинированное лечение в ФГБУ «НМИЦ онкологии им. Н.Н. Блохина» в период с 2003 по 2019 г. Изучены и проанализированы демографические и клинические показатели, непосредственные и отдаленные результаты хирургического лечения, характер возникающего рецидива заболевания, оценено влияние клинико-морфологических факторов на безрецидивную и отдаленную выживаемость. Результаты . Всего в исследование были включены 64 больных первичной забрюшинной лейомиосаркомой, среди которых было 12 (18%) мужчин и 52 (82%) женщины. Средний размер опухоли составил 105±50 мм. В большинстве случаев (93,3%) операции были выполнены открытым доступом. Комбинированные операции выполнены в 62,5% случаев (n=40), резекция магистральных сосудов – в 17,2% случаев (n=11). Радикальная операция (R0) была выполнена в 54 (85,9%) случаях. Частота послеоперационных осложнений составила 39%, послеоперационная летальность – 0%. Адъювантная химиотерапия или лучевая терапия была проведена в 35% случаев (n=21) и 1,7% случаев (n=1) соответственно. Рецидив заболевания возник у 46 (71,9%) больных. Тип прогрессирования заболевания (местный рецидив/появление отдаленных метастазов) не влиял значимо на показатели общей выживаемости ( р =0,655). Медиана безрецидивной выживаемости в общей популяции больных составила 27 мес (95% доверительный интервал – ДИ 10–43,9 мес). Трехлетняя и 5-летняя безрецидивная выживаемость составила 43 и 21% соответственно. Медиана общей выживаемости – 79 мес (95% ДИ 49–108,9 мес). Трехлетняя и 5-летняя общая выживаемость составила 73 и 59% соответственно. Медиана безрецидивной выживаемости при опухолях 2 и 3-й степени злокачественности составила 49 и 18 мес соответственно ( р =0,271), медиана общей выживаемости – 146 и 58 мес соответственно ( р =0,018). Не было выявлено статистически значимых различий в частоте радикальных операций в зависимости от локализации опухоли ( р =0,804) или ее размеров ( р =0,520). У пациентов, перенесших радикальную (R0) операцию, были получены более высокие показатели общей ( р =0,028) и безрецидивной выживаемости ( р <0,001). Проведение адъювантной терапии не влияло значимо на риск развития рецидива заболевания ( p =0,976), тип прогрессирования заболевания ( р =0,981) и общую выживаемость ( р =0,284). Выводы . Наиболее значимыми факторами прогноза у больных забрюшинной лейомиосаркомой являются степень злокачественности опухоли и радикальность выполненной операции. Размер опухоли в нашем исследовании не влиял на отдаленные результаты лечения и возможность выполнения радикальной операции.

Background. Leiomyosarcoma is one of the most common types of soft tissue sarcomas. Radical surgical resection with subsequent adjuvant chemotherapy remain the most effective treatment approach. Immunotherapy based on inhibition of PD-L1 (programmed death ligand 1) or its receptor PD1 (programmed death 1) is considered a promising treatment option. Level of PD-L1 expression in tumor cells and presence of microsatellite instability (МSI) could be considered prognostic and predictive markers of disease progression and effectiveness of immunotherapy.The study objective is to determine PD-L1 expression level and МSI status in patients with retroperitoneal leiomyosarcomas and evaluate their effect on overall and recurrence-free survival.Materials and methods. The study included 57 patients with retroperitoneal leiomyosarcomas who underwent surgical or combination treatment. Analysis of clinical and morphological characteristics was performed; results of surgical treatment were researched. Evaluation of PD-L1 expression and MSI status was performed using immunohistochemical and molecular genetic analysis.Results. PD-L1 expression and MSI status were evaluated in 41 patients of 57. In 10 (24 %) of 41 cases, positive PD-L1 expression was observed (expression level 3–50 %). In 1 (2.4 %) patient, the primary tumor and metastatic lesion had low MSI level (MSI-low, MSI-L). Median follow-up was 31 months. In patients with positive PD-L1 expression, higher Ki-67 proliferative index was observed compared to patients with PD-L1 negative tumors (58.8 and 47.8 % respectively; р = 0.02), as well as significantly lower median overall survival for grade II tumors (30 and 105 months; p = 0.043). In grade III leiomyosarcomas, a trend towards lower median overall survival in patients with PD-L1‑negative tumors (31.0 months) compared to patients with PD-L1 expression (61.2 months) (р = 0.11) was observed.Conclusion. Among patients with retroperitoneal leiomyosarcomas, positive expression of PD-L1 was observed in 24 % (10 / 41) of cases and MSI-low status was found in 2.4 % (1 / 41) of cases. In patients with grade 2 tumors, positive PD-L1 expression is associated with significantly lower overall survival. PD-L1 expression in patients with retroperitoneal leiomyosarcomas could be considered a prognostic marker and a potential therapeutic target.

Schwannomas are rare tumors that arise from well-differentiated schwannoma cells of peripheral nerve sheaths. Schwannomas are usually benign tumors. However, malignant form of schwannomas may occur, which is associated with high recurrence rate and unfavorable long-term prognosis. Retroperitoneal localization of schwannomas is rare. With a little data available it is difficult to develop a unified approach for preoperative evaluation, surgical treatment and follow-up of patients with retroperitoneal schwannomas. Assessment of malignant potential of tumor before resection is challenging while immunohistochemical analysis of resected specimen allows to clearly define histological type and malignant grade of tumor. Complete resection of retroperitoneal schwannoma is the only treatment option that may provide acceptable long-term results. As most of the retroperitoneal schwannomas are localized in an anatomical complex area there is high risk of combined resection and massive intraoperative blood loss. Choice of optimal operative approach, necessity of sacral and nerve resection depending on the degree of disease extent remains the matter of debates. Benign retroperitoneal schwannomas have favourable prognosis for long-term survival while malignant tumors are associated with high recurrence rate.

Адренокортикальный рак (АКР) имеет высокий злокачественный потенциал в преобладающем большинстве случаев, однако у некоторых больных АКР характеризуется вялым, неагрессивным течением, когда пациенты с доказанными отдаленными метастазами или рецидивом могут жить без прогрессирования достаточно продолжительное время. Индолентный курс АКР определен как отсутствие роста доказанных злокачественных опухолевых узлов за период 12 мес. и более. Проведен сравнительный анализ клинико-морфологических характеристик 7 больных с индолентным АКР в сравнении с контрольной группой, состоящей из 157 больных, оперированных по поводу АКР. Изучены клинические характеристики, гистологические критерии Вейса, индекс пролиферативной активности Ki67, экспрессия белка р53, b-катенина. У 7 пациентов, оперированных многократно (до 5 раз), отмечено индолентное течение рецидивного или метастатического АКР. Максимальный срок наблюдения, когда отсутствовал рост опухоли, составил более 37 мес. Клинические характеристики больных обеих групп достоверно не отличались. Гистологические критерии Вейса, индекс Ki67, экспрессия белка р53 также достоверно не отличались. Экспрессия b-катенина, как ядерная, так и цитоплазматическая, отсутствовала в клетках АКР с индолентным течением, различия по сравнению с контрольной группой достоверны. Индолентное течение обусловлено биологическими особенностями опухоли, не отражается в клинических показателях, характеризующих первичную опухоль. Возможно, одним из механизмов, приводящих к подобному течению заболевания, является инактивация сигнального пути Wnt/b-катенин. Феномен индолентного течения АКР, характеризующегося, как правило, высоким злокачественным потенциалом, требует дальнейших исследований.