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2.
Front Immunol ; 15: 1357340, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38504975

RESUMO

In the context of multimodal treatments for abdominal cancer, including procedures such as cytoreductive surgery and intraperitoneal chemotherapy, recurrence rates remain high, and long-term survival benefits are uncertain due to post-operative complications. Notably, treatment-limiting side effects often arise from an uncontrolled activation of the immune system, particularly peritoneally localized macrophages, leading to massive cytokine secretion and phenotype changes. Exploring alternatives, an increasing number of studies investigated the potential of plasma-activated liquids (PAL) for adjuvant peritoneal cancer treatment, aiming to mitigate side effects, preserve healthy tissue, and reduce cytotoxicity towards non-cancer cells. To assess the non-toxicity of PAL, we isolated primary human macrophages from the peritoneum and subjected them to PAL exposure. Employing an extensive methodological spectrum, including flow cytometry, Raman microspectroscopy, and DigiWest protein analysis, we observed a pronounced resistance of macrophages towards PAL. This resistance was characterized by an upregulation of proliferation and anti-oxidative pathways, countering PAL-derived oxidative stress-induced cell death. The observed cellular effects of PAL treatment on human tissue-resident peritoneal macrophages unveil a potential avenue for PAL-derived immunomodulatory effects within the human peritoneal cavity. Our findings contribute to understanding the intricate interplay between PAL and macrophages, shedding light on the promising prospects for PAL in the adjuvant treatment of peritoneal cancer.


Assuntos
Neoplasias Peritoneais , Peritônio , Humanos , Peritônio/metabolismo , Macrófagos Peritoneais , Macrófagos , Cavidade Peritoneal , Neoplasias Peritoneais/metabolismo , Estresse Oxidativo
3.
Cell Death Dis ; 15(3): 218, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38490994

RESUMO

Gastric cancer (GC), notorious for its poor prognosis, often advances to peritoneal dissemination, a crucial determinant of detrimental outcomes. This study intricately explores the role of the TGFß-Smad-LIF axis within the tumor microenvironment in propagating peritoneal metastasis, with a specific emphasis on its molecular mechanism in instigating Neutrophil Extracellular Traps (NETs) formation and encouraging GC cellular functions. Through a blend of bioinformatics analyses, utilizing TCGA and GEO databases, and meticulous in vivo and in vitro experiments, LIF was identified as pivotally associated with GC metastasis, notably, enhancing the NETs formation through neutrophil stimulation. Mechanistically, TGF-ß was substantiated to elevate LIF expression via the activation of the Smad2/3 complex, culminating in NETs formation and consequently, propelling peritoneal metastasis of GC. This revelation uncovers a novel potential therapeutic target, promising a new avenue in managing GC and mitigating its metastatic propensities.


Assuntos
Armadilhas Extracelulares , Neoplasias Peritoneais , Neoplasias Gástricas , Fator de Crescimento Transformador beta , Humanos , Armadilhas Extracelulares/metabolismo , Neutrófilos/metabolismo , Neoplasias Peritoneais/genética , Neoplasias Peritoneais/patologia , Neoplasias Gástricas/patologia , Fator de Crescimento Transformador beta/metabolismo , Microambiente Tumoral , Fator Inibidor de Leucemia/metabolismo , Transdução de Sinais
4.
Cancer Rep (Hoboken) ; 7(3): e2036, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38517451

RESUMO

BACKGROUND: Cancer-related thrombotic microangiopathy (CR-TMA) is a rare type of Coombs-negative hemolytic anemia, which is caused by malignancy and has a poor prognosis. CASE: A 76-year-old female was referred to our hospital due to Coombs-negative hemolytic anemia, which was causing fatigue and dyspnea on exertion, accompanied by schistocytosis. A bone marrow examination demonstrated bone marrow carcinomatosis, and the tumor cells were morphologically suspected to be signet-ring cell carcinoma cells. As we failed to find the primary tumor site before the patient died, she was diagnosed with CR-TMA due to bone marrow carcinomatosis of unknown primary origin. Thrombotic thrombocytopenic purpura (TTP) was rapidly ruled out based on her PLASMIC score. In addition, immunohistochemical staining of a clot section of the bone marrow and tumor marker data were useful for narrowing down the likely primary tumor site. CONCLUSION: Although CR-TMA is an extremely rare phenomenon, clinicians who suspect CR-TMA should quickly rule out TTP and decide whether to provide appropriate chemotherapy or plan for palliative care.


Assuntos
Anemia Hemolítica , Carcinoma , Coagulação Intravascular Disseminada , Neoplasias Primárias Desconhecidas , Neoplasias Peritoneais , Púrpura Trombocitopênica Trombótica , Microangiopatias Trombóticas , Feminino , Humanos , Idoso , Coagulação Intravascular Disseminada/etiologia , Coagulação Intravascular Disseminada/complicações , Púrpura Trombocitopênica Trombótica/complicações , Púrpura Trombocitopênica Trombótica/diagnóstico , Medula Óssea , Neoplasias Primárias Desconhecidas/complicações , Neoplasias Primárias Desconhecidas/diagnóstico , Microangiopatias Trombóticas/etiologia , Microangiopatias Trombóticas/complicações , Anemia Hemolítica/complicações
5.
BMC Med ; 22(1): 119, 2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38481209

RESUMO

BACKGROUND: Intravenous leiomyomatosis (IVL), pulmonary benign metastatic leiomyomatosis (PBML), and leiomyomatosis peritonealis disseminata (LPD) are leiomyomas with special growth patterns and high postoperative recurrence rates. We report the safety and efficacy of a pilot study of sirolimus in the treatment of recurrent IVL, PBML, and recurrent LPD. METHODS: This was a pilot study to evaluate the safety and efficacy of sirolimus in the treatment of leiomyomatosis (ClinicalTrials.gov identifier NCT03500367) conducted in China. Patients received oral sirolimus 2 mg once a day for a maximum of 60 months or until disease progression, intolerable toxicity, withdrawal of consent, or investigator decision to stop. The primary end point of this study was the objective response rate. Secondary end points included safety and tolerability, disease control rate, and progression-free survival. RESULTS: A total of 15 patients with leiomyomatosis were included in the study, including five with recurrent IVL, eight with PBML and two with recurrent LPD. The median follow-up time was 15 months (range 6-54 months), nine patients (60%) had treatment-related adverse events (including all levels), and two patients had treatment-related grade 3 or 4 adverse events. The objective response rate was 20.0% (95% CI, 7.1-45.2%), and the disease control rate was 86.7% (95% CI, 62.1-96.3%). Partial response was achieved in three patients. The median response time in the three partial response patients was 33 months (range 29-36 months), and the sustained remission time of these three patients reached 0, 18, and 25 months, respectively. CONCLUSIONS: Sirolimus was safe and effective in the treatment of recurrent IVL, PBML, and recurrent LPD. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT03500367. Registered on 18 April 2018.


Assuntos
Leiomiomatose , Neoplasias Peritoneais , Humanos , Progressão da Doença , Leiomiomatose/tratamento farmacológico , Leiomiomatose/complicações , Leiomiomatose/patologia , Neoplasias Peritoneais/complicações , Neoplasias Peritoneais/patologia , Neoplasias Peritoneais/cirurgia , Projetos Piloto , Sirolimo/efeitos adversos
6.
JCO Precis Oncol ; 8: e2300546, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38513167

RESUMO

PURPOSE: Gastric cancers commonly spread to the peritoneum. Its presence significantly alters patient prognosis and treatment-intent; however, current methods of peritoneal staging are inaccurate. Peritoneal tumor DNA (ptDNA) is tumor-derived DNA detectable in peritoneal lavage fluid. ptDNA positivity may indicate peritoneal micrometastasis and may be more sensitive than cytology in staging the peritoneum. In this meta-analysis, we evaluated the prognostic potential of ptDNA in gastric cancer. METHODS: PubMed, Embase, Scopus, and Web of Science databases were searched using PRISMA guidelines. Studies published between January 1, 1990, and April 30, 2023, containing quantitative data relating to ptDNA in gastric cancer were meta-analyzed. RESULTS: Six studies were analyzed. Of the total 757 patients with gastric adenocarcinoma, 318 (42.0%) were stage I, 311 (41.0%) were stage II/III, 116 (15.3%) were stage IV, and 22 (2.9%) were undetermined. Overall, ptDNA detected cytology-positive cases with a sensitivity and specificity of 85.2% (95% CI, 66.5 to 100.0) and 91.5% (95% CI, 86.5 to 96.6), respectively. Additionally, ptDNA was detected in 54 (8.5%) of 634 cytology-negative patients. The presence of ptDNA negatively correlated with pathological stage I (relative risk [RR], 0.29 [95% CI, 0.13 to 0.66]) and positively correlated with pathological stage IV (RR, 8.61 [95% CI, 1.86 to 39.89]) disease. Importantly, ptDNA positivity predicted an increased risk of peritoneal-specific metastasis (RR, 13.81 [95% CI, 8.11 to 23.53]) and reduced 3-year progression-free (RR, 5.37 [95% CI, 1.39 to 20.74]) and overall (hazard ratio, 4.13 [95% CI, 1.51 to 11.32]) survival. CONCLUSION: ptDNA carries valuable prognostic information and can detect peritoneal micrometastases in patients with gastric cancer. Its clinical utility in peritoneal staging for gastric cancer deserves further investigation.


Assuntos
Neoplasias Peritoneais , Neoplasias Gástricas , Humanos , Peritônio , Neoplasias Peritoneais/diagnóstico , Neoplasias Peritoneais/genética , Prognóstico , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/genética , Estadiamento de Neoplasias , DNA , Biomarcadores
7.
Cancer Med ; 13(6): e7101, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38506243

RESUMO

BACKGROUND: Pseudomyxoma peritonei (PMP) is a rare clinical malignant syndrome, and its rarity causes a lack of pathology research. This study aims to quantitatively analyze HE-stained pathological images (PIs), and develop a new predictive model integrating digital pathological parameters with clinical information. METHODS: Ninety-two PMP patients with complete clinic-pathological information, were included. QuPath was used for PIs quantitative feature analysis at tissue-, cell-, and nucleus-level. The correlations between overall survival (OS) and general clinicopathological characteristics, and PIs features were analyzed. A nomogram was established based on independent prognostic factors and evaluated. RESULTS: Among the 92 PMP patients, there were 34 (37.0%) females and 58 (63.0%) males, with a median age of 57 (range: 31-76). A total of 449 HE stained images were obtained for QuPath analysis, which extracted 40 pathological parameters at three levels. Kaplan-Meier survival analysis revealed eight clinicopathological characteristics and 20 PIs features significantly associated with OS (p < 0.05). Partial least squares regression was used to screen the multicollinearity features and synthesize four new features. Multivariate survival analysis identified the following five independent prognostic factors: preoperative CA199, completeness of cytoreduction, histopathological type, component one at tissue-level, and tumor nuclei circularity variance. A nomogram was established with internal validation C-index 0.795 and calibration plots indicating improved prediction performance. CONCLUSIONS: The quantitative analysis of HE-stained PIs could extract the new prognostic information on PMP. A nomogram established by five independent prognosticators is the first model integrating digital pathological information with clinical data for improved clinical outcome prediction.


Assuntos
Neoplasias Peritoneais , Pseudomixoma Peritoneal , Masculino , Feminino , Humanos , Pseudomixoma Peritoneal/patologia , Prognóstico , Nomogramas , Análise de Sobrevida , Estudos Retrospectivos
8.
Gan To Kagaku Ryoho ; 51(2): 199-201, 2024 Feb.
Artigo em Japonês | MEDLINE | ID: mdl-38449412

RESUMO

A 72-year-old man underwent right hemicolectomy for transverse colon cancer(pT4aN1aM0, Stage ⅢB), after which he received adjuvant chemotherapy(capecitabine plus oxaliplatin[CAPOX])for 6 months. Three years after the first surgery, FDG-PET/CT revealed a tumor in the abdomen. He underwent a tumorectomy and adjuvant chemotherapy(CAPOX plus bevacizumab[BV])performed for 6 months. Two years after a tumorectomy, the CEA level rose again. He was diagnosed peritoneal metastasis again. A central venous(CV)port was implanted for access to the right internal jugular vein, and he received systemic chemotherapy(fluorouracil, Leucovorin, and irinotecan[FOLFIRI]plus BV)as an outpatient. One year after this recurrence, no peritoneal dissemination was detected by CT. Thereafter, total 49 courses of FOLFIRI plus BV were introduced, but chemotherapy was discontinued due to CV port-related infection. Three months later, low back pain appeared and became a diagnosis of spondylodiscitis. He had surgery, but follow-up CT performed 8 years after the first surgery detected multiple liver metastasis. It was considered necessary to take infection control measures during long-term chemotherapy.


Assuntos
Neoplasias Peritoneais , Masculino , Humanos , Idoso , Neoplasias Peritoneais/tratamento farmacológico , Neoplasias Peritoneais/cirurgia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Peritônio , Quimioterapia Adjuvante , Irinotecano
9.
Gan To Kagaku Ryoho ; 51(2): 214-216, 2024 Feb.
Artigo em Japonês | MEDLINE | ID: mdl-38449417

RESUMO

A 52-year-old woman was presented with abdominal distension. Chest-abdominal CT showed some tumors in the left breast, enlarged axillary lymph nodes, ovary metastasis peritoneal thickening, a large amount of ascites. The diagnosis of needle biopsy in the breast mass was invasive ductal carcinoma, Luminal A type. The large amount of ascites decreased after the start of administration of fulvestrant and CDK4/6 inhibitor(PAL). Also chest and abdominal CT showed reduction of all lesions. We found the high expression of cyclin D1 protein and the negative of p16 protein in tissues of the needle biopsy. Fifty months later, she continues to do good ADL and PR status. We experienced a case of metastatic breast cancer with massive ascites and peritoneal metastasis that was successfully treated with a CDK4/6 inhibitor(PAL)and achieved long- term survival.


Assuntos
Neoplasias da Mama , Neoplasias Ovarianas , Neoplasias Peritoneais , Piperazinas , Piridinas , Feminino , Humanos , Pessoa de Meia-Idade , Ascite , Neoplasias da Mama/tratamento farmacológico , Neoplasias Peritoneais/tratamento farmacológico , Quinase 4 Dependente de Ciclina
10.
PLoS One ; 19(3): e0294018, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38437211

RESUMO

Standard treatment for patient with peritoneal metastases from colorectal cancer is cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). In recent years, the efficacy of oxaliplatin-based HIPEC has been challenged. An intensified HIPEC (oxaliplatin+irinotecan) in combination with early postoperative intraperitoneal chemotherapy (EPIC) has shown increased recurrence-free survival in retrospective studies. The aim of this trial is to develop a new HIPEC/EPIC regimen and evaluate its effect on morbidity, oncological outcome, and quality-of-life (QoL). This study is designed as a combined phase I/III multicenter randomized trial (RCT) of patients with peritoneal metastases from colorectal cancer eligible for CRS-HIPEC. An initial phase I dose escalation study, designed as a 3+3 stepwise escalation, will determine the maximum tolerable dose of 5-Fluorouracil (5-FU) as 1-day EPIC, enrolling a total of 15-30 patients in 5 dose levels. In the phase III efficacy study, patients are randomly assigned intraoperatively to either the standard treatment with oxaliplatin HIPEC (control arm) or oxaliplatin/irinotecan-HIPEC in combination with single dose of 1-day 5-FU EPIC (experimental arm). 5-FU is administered intraoperatively after CRS-HIPEC and closure of the abdomen. The primary endpoint is 12-month recurrence-free survival. Secondary endpoints include 5-year overall survival, 5-year recurrence-free survival (registry based), postoperative complications, and QoL up to 3 years after study treatment. This phase I/III trial aims to identify a more effective treatment of colorectal peritoneal metastases by combination of HIPEC and EPIC.


Assuntos
Neoplasias Colorretais , Neoplasias Peritoneais , Humanos , Ensaios Clínicos Fase I como Assunto , Neoplasias Colorretais/tratamento farmacológico , Fluoruracila/uso terapêutico , Quimioterapia Intraperitoneal Hipertérmica , Irinotecano , Estudos Multicêntricos como Assunto , Oxaliplatina/uso terapêutico , Neoplasias Peritoneais/tratamento farmacológico , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Sistema de Registros , Estudos Retrospectivos , Ensaios Clínicos Fase III como Assunto
11.
Int J Biol Sci ; 20(4): 1314-1331, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38385088

RESUMO

Peritoneal metastasis (PM) continues to limit the clinical efficacy of gastric cancer (GC). Early growth response 1 (EGR1) plays an important role in tumor cell proliferation, angiogenesis and invasion. However, the role of EGR1 derived from the tumor microenvironment in reshaping the phenotypes of GC cells and its specific molecular mechanisms in increasing the potential for PM are still unclear. In this study, we reported that EGR1 was significantly up-regulated in mesothelial cells from GC peritoneal metastases, leading to enhanced epithelial-mesenchymal transformation (EMT) and stemness phenotypes of GC cells under co-culture conditions. These phenotypes were achieved through the transcription and secretion of TGF-ß1 by EGR1 in mesothelial cells, which could regulate the expression and internalization of CD44s. After being internalized into the cytoplasm, CD44s interacted with STAT3 to promote STAT3 phosphorylation and activation, and induced EMT and stemness gene transcription, thus positively regulating the metastasis of GC cells. Moreover, TGF-ß1 secretion in the PM microenvironment was significantly increased compared with the matched primary tumor. The blocking effect of SHR-1701 on TGF-ß1 was verified by inhibiting peritoneal metastases in xenografts. Collectively, the interplay of EGR1/TGF-ß1/CD44s/STAT3 signaling between mesothelial cells and GC cells induces EMT and stemness phenotypes, offering potential as a therapeutic target for PM of GC.


Assuntos
Proteína 1 de Resposta de Crescimento Precoce , Neoplasias Peritoneais , Neoplasias Gástricas , Humanos , Linhagem Celular Tumoral , Movimento Celular , Proteína 1 de Resposta de Crescimento Precoce/genética , Proteína 1 de Resposta de Crescimento Precoce/metabolismo , Transição Epitelial-Mesenquimal/fisiologia , Receptores de Hialuronatos/genética , Receptores de Hialuronatos/metabolismo , Peritônio/patologia , Transdução de Sinais/genética , Fator de Transcrição STAT3/genética , Fator de Transcrição STAT3/metabolismo , Neoplasias Gástricas/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Microambiente Tumoral/genética , Animais
12.
ACS Nano ; 18(8): 6130-6146, 2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38349890

RESUMO

Gastric cancer is one of the most prevalent digestive malignancies. The lack of effective in vitro peritoneal models has hindered the exploration of the potential mechanisms behind gastric cancer's peritoneal metastasis. An accumulating body of research indicates that small extracellular vesicles (sEVs) play an indispensable role in peritoneal metastasis of gastric cancer cells. In this study, a biomimetic peritoneum was constructed. The biomimetic model is similar to real peritoneum in internal microstructure, composition, and primary function, and it enables the recurrence of peritoneal metastasis process in vitro. Based on this model, the association between the mechanical properties of sEVs and the invasiveness of gastric cancer was identified. By performing nanomechanical analysis on sEVs, we found that the Young's modulus of sEVs can be utilized to differentiate between malignant clinical samples (ascites) and nonmalignant clinical samples (peritoneal lavage). Furthermore, patients' ascites-derived sEVs were verified to stimulate the mesothelial-to-mesenchymal transition, thereby promoting peritoneal metastasis. In summary, nanomechanical analysis of living sEVs could be utilized for the noninvasive diagnosis of malignant degree and peritoneal metastasis of gastric cancer. This finding is expected to contribute future treatments.


Assuntos
Vesículas Extracelulares , Neoplasias Peritoneais , Neoplasias Gástricas , Humanos , Peritônio/patologia , Neoplasias Gástricas/diagnóstico , Neoplasias Peritoneais/diagnóstico , Ascite/patologia , Biomimética , Vesículas Extracelulares/patologia
13.
Anticancer Res ; 44(2): 731-741, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38307555

RESUMO

BACKGROUND/AIM: The aim of this study was to describe and evaluate the patterns, perioperative outcomes, and survival rates of patients subjected to hepatic resections for ovarian-derived liver metastasis as part of cytoreductive surgery with or without hyperthermic intraperitoneal chemotherapy (HIPEC). Furthermore, we investigated two subgroups of tumor patterns: hematogenous liver metastasis and infiltrative liver metastatic spread. PATIENTS AND METHODS: A retrospective study was conducted. Patients from a University Tertiary Hepatic and Peritoneal Surface Malignancy Center with primary or recurrent ovarian cancer, who underwent liver resection as part of cytoreductive surgery between January 1992 and December 2022, were included. RESULTS: Data from 35 patients were analyzed. Both median overall survival (OS) and disease-specific survival (DSS) were 24.97 months. In a multivariate setting, the combined effect of age, peritoneal carcinomatosis index, body mass index, hematogenous liver metastasis vs. infiltrative spread types, and HIPEC (HR=0.2372; 95%CI=0.0719-0.7823; p=0.0181) over OS was tested. Survival analysis revealed no differences between the two metastatic spread types (OS: p=0.9720; DSS: p=0.9610). Younger age (p=0.0301), splenectomy (p=0.0320), lesser omentectomy (p=0.0178), and right upper quadrant peritonectomy (p=0.0373) were more characteristic for those patients with infiltrative liver metastatic spread. CONCLUSION: Complete cytoreductive surgery, including hepatic resection is a feasible approach with or without additional HIPEC, which may provide survival benefit for patients with advanced and/or recurrent ovarian cancer. If metastatic and infiltrative liver involvement is suspected, liver-specific imaging is recommended.


Assuntos
Hipertermia Induzida , Neoplasias Hepáticas , Neoplasias Ovarianas , Neoplasias Peritoneais , Humanos , Feminino , Neoplasias Peritoneais/secundário , Estudos Retrospectivos , Hipertermia Induzida/métodos , Recidiva Local de Neoplasia/tratamento farmacológico , Neoplasias Ovarianas/patologia , Carcinoma Epitelial do Ovário/cirurgia , Carcinoma Epitelial do Ovário/tratamento farmacológico , Procedimentos Cirúrgicos de Citorredução/métodos , Resultado do Tratamento , Neoplasias Hepáticas/tratamento farmacológico , Taxa de Sobrevida , Terapia Combinada , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
14.
Anticancer Res ; 44(2): 613-619, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38307557

RESUMO

BACKGROUND/AIM: Cell-free and concentrated ascites reinfusion therapy (CART) was established for refractory ascites and renovated CART (Keisuke Matsusaki (KM) -CART) has been recently developed especially for malignant ascites; however, the actual clinical efficacy of KM-CART has been rarely reported. PATIENTS AND METHODS: We performed 226 KM-CART procedures in 104 patients with malignant ascites in three hospitals from August 2013 to September 2018. Medical records were retrospectively reviewed for ascites data, related complications, symptoms before and after each CART and prognosis after the first CART. The modified Glasgow Prognostic Score (mGPS) was reviewed before every procedure, as an indicator of nutritional status. RESULTS: Pancreatic cancer was the most common indication for the KM-CART procedure, followed by gastric cancer, hepatocellular carcinoma, ovarian cancer, and cholangiocarcinoma (five major diseases). The 50% survival times of these five major diseases after the first procedure were 25, 39, 31, 49, and 33 days, respectively. The mean survival time for all patients was 73.5 days, and 75.6 days for those with the five major diseases. All patients experienced symptomatic relief, and complications were rare. Repeated KM-CART was performed in 47.1% of the patients, most often in those with ovarian cancer (66.7%). Regarding the mGPS at the first CART procedure, 89% of patients were in the group with the poorest nutritional status. Patients who underwent KM-CART three or more times had longer survival than those who were treated once or twice. CONCLUSION: Repeated KM-CART provides a survival benefit for patients with malignant ascites, even in cases of poor nutritional status.


Assuntos
Neoplasias dos Ductos Biliares , Neoplasias Hepáticas , Neoplasias Ovarianas , Neoplasias Peritoneais , Feminino , Humanos , Ascite/etiologia , Ascite/terapia , Ascite/patologia , Estudos Retrospectivos , Neoplasias Peritoneais/complicações , Neoplasias Ovarianas/complicações , Neoplasias Hepáticas/complicações , Neoplasias dos Ductos Biliares/complicações , Ductos Biliares Intra-Hepáticos/patologia
15.
Anticancer Res ; 44(2): 533-542, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38307583

RESUMO

BACKGROUND/AIM: Malignant ascites is a common condition in patients with terminal cancer. Treatments, such as diuretics, percutaneous drainage of ascites, and abdominal vein shunting have been advocated. However, these treatments have not achieved sufficient palliative effects. Therefore, the development of innovative therapies is mandated, especially for new therapies that require the creation of a fluid simulation of malignant ascites. However, there have been no previous studies on the physical properties of malignant ascites, including viscosity, which are necessary for the development of such a fluid. Therefore, we prospectively investigated the physical properties of malignant ascites. PATIENTS AND METHODS: This single-center, prospective, observational study included 30 patients between November 2021 and January 2023. The primary endpoint was the viscosity of the malignant ascites, and the secondary endpoints included other viscosity studies, biochemical tests, and the presence of malignant cells in the ascites. RESULTS: The median viscosity was 1.105 mPa*S. The viscosity of malignant ascites tended to decrease with increasing temperature, which is common for liquids. Malignant ascites fluid containing malignant cells tended to be more viscous than ascites fluid without malignant cells; furthermore, albumin levels tended to be higher in the former than in the latter. CONCLUSION: Malignant ascites' median viscosity was 1.105 mPa*S. Correlation between viscosity and temperature showed a decreasing trend. These findings contribute valuable insights for future malignant ascites management and device development.


Assuntos
Ascite , Neoplasias Peritoneais , Humanos , Ascite/etiologia , Estudos Prospectivos , Viscosidade , Líquido Ascítico
16.
JCO Glob Oncol ; 10: e2300432, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38330272

RESUMO

PURPOSE: Cytoreductive surgery/hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) programs are often limited to centers in developed countries because of extensive requirements. We aimed to analyze efficacy and challenges of CRS/HIPEC centers in lower-middle-income settings in the Ukraine example. METHODS: A multicenter descriptive study was conducted using data sets (2008-2022) from Kyiv, Lviv, and Odesa centers. Patients with appendiceal neoplasm (AN); colorectal cancer (CRC); malignant peritoneal mesothelioma (MPM); and epithelial ovarian, fallopian tube, and primary peritoneal cancer (EOC) treated with CRS ± HIPEC were included. Overall survival (OS) was analyzed for N ≥ 20 cohorts using the Kaplan-Meier method. RESULTS: We included 596 patients. At Kyiv and Lviv centers, 37 and 28 patients with AN had completeness of cytoreduction (CC-0/1) rates of 84% and 71%, respectively. Thirty-day major morbidity stood at 24% and 18%, respectively. Median OS was not reached (NR) at both centers. Nineteen patients with CRC from Kyiv, 11 from Lviv, and 156 from Odesa had CC-0/1 rates of 84%, 91%, and 86%, respectively. Thirty-day major complications occurred in 16%, 18%, and 8%, respectively. Median OS in the Odesa cohort was 35 (95% CI, 32 to 38) months. Among 15 Kyiv, five Lviv, and six Odesa patients with MPM, CC-0/1 rates were 67%, 80%, and 100%, respectively, while major complications occurred in 13%, 0%, and 17%, respectively. OS was not analyzed because of small MPM cohorts. At Kyiv, Lviv, and Odesa centers, 91, 40, and 89 patients, respectively, had primary EOC. CC-0/1 rates were 79%, 100%, and 80%, and 30-day major morbidity rates were 23%, 5%, and 6%, respectively. Median OS was NR, 71 (95% CI, 32 to 110), and 67 (95% CI, 61 to 73) months, respectively. CONCLUSION: CRS/HIPEC programs in lower-middle-income environment can achieve safety and survival that meet global standards. Our discussion highlights common obstacles in such settings and proposes effective overcoming strategies.


Assuntos
Neoplasias Peritoneais , Feminino , Humanos , Neoplasias Peritoneais/terapia , Neoplasias Peritoneais/patologia , Ucrânia/epidemiologia
17.
Cancer Res Commun ; 4(2): 475-486, 2024 02 20.
Artigo em Inglês | MEDLINE | ID: mdl-38329392

RESUMO

Peritoneal metastases (PM) are common in metastatic colorectal cancer (mCRC). We aimed to characterize patients with mCRC and PM from a clinical and molecular perspective using the American Association of Cancer Research Genomics Evidence Neoplasia Information Exchange (GENIE) Biopharma Collaborative (BPC) registry. Patients' tumor samples underwent targeted next-generation sequencing. Clinical characteristics and treatment outcomes were collected retrospectively. Overall survival (OS) from advanced disease and progression-free survival (PFS) from start of cancer-directed drug regimen were estimated and adjusted for the left truncation bias. A total of 1,281 patients were analyzed, 244 (19%) had PM at time of advanced disease. PM were associated with female sex [OR: 1.67; 95% confidence interval (CI): 1.11-2.54; P = 0.014] and higher histologic grade (OR: 1.72; 95% CI: 1.08-2.71; P = 0.022), while rectal primary tumors were less frequent in patients with PM (OR: 0.51; 95% CI: 0.29-0.88; P < 0.001). APC occurred less frequently in patients with PM (N = 151, 64% vs. N = 788, 79%) while MED12 alterations occurred more frequently in patients with PM (N = 20, 10% vs. N = 32, 4%); differences in MED12 were not significant when restricting to oncogenic and likely oncogenic variants according to OncoKB. Patients with PM had worse OS (HR: 1.45; 95% CI: 1.16-1.81) after adjustment for independently significant clinical and genomic predictors. PFS from initiation of first-line treatment did not differ by presence of PM. In conclusion, PM were more frequent in females and right-sided primary tumors. Differences in frequencies of MED12 and APC alterations were identified between patients with and without PM. PM were associated with shorter OS but not with PFS from first-line treatment. SIGNIFICANCE: Utilizing the GENIE BPC registry, this study found that PM in patients with colorectal cancer occur more frequently in females and right-sided primary tumors and are associated with worse OS. In addition, we found a lower frequency of APC alterations and a higher frequency in MED12 alterations in patients with PM.


Assuntos
Antineoplásicos , Neoplasias do Colo , Neoplasias Colorretais , Neoplasias Peritoneais , Neoplasias Retais , Humanos , Feminino , Neoplasias Colorretais/genética , Neoplasias Peritoneais/genética , Estudos Retrospectivos , Antineoplásicos/uso terapêutico , Neoplasias do Colo/tratamento farmacológico , Neoplasias Retais/tratamento farmacológico , Genômica , Sistema de Registros
18.
Front Immunol ; 15: 1347900, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38384469

RESUMO

Background: The presence of peritoneal metastases (PMs) in patients with colorectal cancer (CRC) confers a poor prognosis and only a minority of patients will benefit from the available treatment options. In primary CRC tumors, it is well established that a high infiltration of CD8+ effector T cells correlates to a favorable patient outcome. In contrast, the immune response induced in PMs from CRC and how it relates to patient survival is still unknown. In this study, we characterized the immune infiltrates and the distribution of immune checkpoint receptors on T cells from PMs from CRC, in order to evaluate the potential benefit of checkpoint blockade immunotherapy for this patient group. Methods: Surgically resected PM tissue from CRC patients (n=22) and synchronous primary tumors (n=8) were processed fresh to single cell suspensions using enzymatic digestion. Surface markers and cytokine production were analyzed using flow cytometry. Results: T cells dominated the leukocyte infiltrate in the PM specimens analyzed, followed by monocytes and B cells. Comparing two different PMs from the same patient usually showed a similar distribution of immune cells in both samples. The T cell infiltrate was characterized by an activated phenotype and markers of exhaustion were enriched compared with matched circulating T cells, in particular the checkpoint receptors PD-1 and TIGIT. In functional assays most cytotoxic and helper T cells produced INF-γ and TNF following polyclonal stimulation, while few produced IL-17, indicating a dominance of Th1-type responses in the microenvironment of PMs. Conclusion: Immune cells were present in all PMs from CRC examined. Although infiltrating T cells express markers of exhaustion, they produce Th1-type cytokines when stimulated. These results indicate the possibility to augment tumor-specific immune responses within PMs using checkpoint blockade inhibitors.


Assuntos
Antineoplásicos , Neoplasias Colorretais , Neoplasias Peritoneais , Humanos , Linfócitos do Interstício Tumoral , Neoplasias Peritoneais/metabolismo , Citocinas/metabolismo , Neoplasias Colorretais/patologia , Microambiente Tumoral
19.
Curr Oncol ; 31(2): 660-671, 2024 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-38392042

RESUMO

Multidisciplinary strategies have transformed the management of advanced ovarian cancer. We aimed to evaluate the effectiveness of paclitaxel in hyperthermic intraperitoneal chemotherapy (HIPEC) following surgical cytoreduction for ovarian peritoneal metastases in a randomized phase III trial conducted between August 2012 and December 2019. Seventy-six patients were randomized to either the HIPEC or no HIPEC group. Although median values for the primary endpoints (recurrence-free survival (RFS) and overall survival (OS)) revealed superior outcomes for the HIPEC (RFS: 23 months, OS: 48 months) over the control group (RFS: 19 months, OS: 46 months), these differences were not statistically significant (p = 0.22 and p = 0.579). Notably, the HIPEC group demonstrated significantly higher 5-year OS and 3-year RFS rates (47.2% and 47.5%) compared to patients without HIPEC (34.5% and 21.3%). Stratification according to Peritoneal Surface Disease Severity Score (PSDSS) showed improved OS and RFS for patients with lower PSDSS (I-II) in the HIPEC-treated group (p = 0.033 and p = 0.042, respectively). The Clavien-Dindo classification of adverse event grades revealed no significant differences between HIPEC and controls (p = 0.482). While overall results were not statistically significant, our long-term follow-up emphasized the potential benefit of HIPEC-associated cytoreduction with paclitaxel, particularly in selected ovarian cancer patients with lower PSDSS indices.


Assuntos
Hipertermia Induzida , Neoplasias Ovarianas , Neoplasias Peritoneais , Feminino , Humanos , Paclitaxel/uso terapêutico , Quimioterapia Intraperitoneal Hipertérmica , Terapia Combinada , Procedimentos Cirúrgicos de Citorredução , Neoplasias Peritoneais/tratamento farmacológico , Neoplasias Peritoneais/cirurgia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Seguimentos , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/cirurgia
20.
BMC Cancer ; 24(1): 252, 2024 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-38395832

RESUMO

BACKGROUND: Immune checkpoint inhibitor (ICI) or irinotecan-based chemotherapy is frequently used after failure of second-line paclitaxel plus ramucirumab treatment for patients with locally advanced unresectable or metastatic advanced gastric cancer (AGC). This study aimed to compare the efficacy between ICI and irinotecan-based chemotherapy as third-line treatment in patients with AGC. METHODS: We retrospectively reviewed patients with AGC, whose third-line treatment started between July 2019 and June 2021 at 17 institutions in Korea. The ICI group included patients who received nivolumab or pembrolizumab, and the irinotecan-based chemotherapy group included patients who received irinotecan or FOLFIRI (5-fluorouracil, leucovorin and irinotecan). RESULTS: A total of 363 patients [n = 129 (ICI) and n = 234 (irinotecan-based chemotherapy)] were analyzed. The median progression-free survival was 2.3 and 2.9 months in ICI and irinotecan-based chemotherapy groups, respectively (p = 0.802). The median overall survival (OS) was 5.5 and 6.0 months in ICI and irinotecan-based chemotherapy groups, respectively (p = 0.786). For all patients included in this study, multivariable analysis showed that weight loss, peritoneal metastasis, low serum sodium or albumin, and short duration of second-line treatment were associated with inferior OS (p < 0.05). ICI showed significantly longer OS than irinotecan-based chemotherapy in patients without peritoneal metastasis. Whereas ICI showed significantly shorter OS in patients without PD-L1 expression than irinotecan-based chemotherapy. CONCLUSIONS: No significant difference in survival outcome was observed between ICI and irinotecan-based chemotherapy as third-line treatment for AGC patients. ICI might be preferred for patients without peritoneal metastasis and irinotecan-based chemotherapy for patients with tumors without PD-L1 expression. TRIAL REGISTRATION: This study was registered in the Clinical Trial Registry of Korea ( https://cris.nih.go.kr : KCT 0007732).


Assuntos
Niacinamida/análogos & derivados , Neoplasias Peritoneais , Neoplasias Gástricas , Humanos , Irinotecano , Neoplasias Gástricas/patologia , Inibidores de Checkpoint Imunológico/efeitos adversos , Antígeno B7-H1 , Camptotecina , Estudos Retrospectivos , Neoplasias Peritoneais/tratamento farmacológico , Fluoruracila , Leucovorina , República da Coreia/epidemiologia , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos
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