Changes on food intake, body weight and salivary amylase synthesis in the submandibular gland of wistar rats treated with bevacizumab and cytostatics / Cambios en la ingesta de alimentos, peso corporal y síntesis de amilasa salival en la glándula submandibular de ratas wistar tratadas con bevacizumab y citostáticos

Background: Bevacizumab together with 5-fluorouracil and oxaliplatin inhibit microvascular growth of tumor blood vessels and tumor proliferation. Few reports state the effect of these therapeutic schemes on salivary glands. Materials and Methods: Food consumption, body weight and salivary amylase activity were assessed in the submandibular gland of rats. Adult male Wistar rats, of three months old with 350/400 grams body weight, under 12-hour light/dark cycles respectively, were divided into the following experimental groups: G1) Control group, G2) 5-Fluorouracil and leucovorin calcium treated group, G3) Bevacizumab treated group, G4) Oxaliplatin treated group, G5) Bevacizumab, oxaliplatin, 5-fluorouracil and leucovorin calcium treated group and G6) Drug-free paired feeding treated group. Assessment of treatment effect was performed by one-way ANOVA. A value of p<0.05 was set for statistical significance. Results: Salivary amylase activity in gland homogenate was G1: 137.9 ± 4.64, G2: 60.95±4.64, G3: 120.93 ± 4.96, G4: 26.17 ±4.64, G5: 10.77 ±4.64 and G6: 82.87 ±4.64 U/mg protein (mean ± S.D.) Amylase activity in the G1 group was higher relative to the other experimental groups p<0.0001. Conclusions: The drugs 5-fluorouracil and oxaliplatin altered salivary amylase activity by serous granules of the submandibular gland interpreted as a mechanism of impaired acinar function. Bevacizumab administered in isolation did not alter salivary amylase activity compared to the control group. While the lower intake of the matched feeding group affected salivary amylase activity compared to the control group, the effect was significantly greater in animals treated with the oncology drugs used in the present animal model.

Antecedentes: Bevacizumab, junto con 5-fluorouracilo y oxaliplatino, inhiben el crecimiento microvascular de los vasos sanguíneos tumorales y la proliferación tumoral. Pocos reportes establecen el efecto de estos esquemas terapéuticos sobre las glándulas salivales. Materiales y Métodos: Se evaluaron el consumo de alimentos, el peso corporal y la actividad de amilasa salival en la glándula submandibular de ratas Wistar macho adultas, de tres meses de edad con 350/400 gramos de peso corporal, bajo ciclos de luz/oscuridad de 12 horas respectivamente, se dividieron en los siguientes grupos experimentales: G1) Grupo control, G2) Grupo tratado con 5-Fluorouracilo y Leucovorina cálcica. , G3) Grupo tratado con bevacizumab, G4) Grupo tratado con oxaliplatino, G5) Grupo tratado con bevacizumab, oxaliplatino, 5-fluorouracilo y leucovorina cálcica y G6) Grupo tratado con alimentación emparejada sin fármacos. La evaluación del efecto del tratamiento se realizó mediante ANOVA unidireccional. Se estableció un valor de p<0,05 para significación estadística. Resultado: La actividad de amilasa salival en homogeneizado de glándula fue G1: 137,9 ± 4,64, G2: 60,95 ± 4,64, G3: 120,93 ± 4,96, G4: 26,17 ± 4,64, G5: 10,77 ± 4,64 y G6: 82,87 ± 4,64 U/mg de proteína (media ± S.E.). La actividad de amilasa en el grupo G1 fue mayor en relación con los otros grupos experimentales p<0,0001. Conclusión: Los fármacos 5-fluorouracilo y oxaliplatino alteraron la actividad de la amilasa salival mediante gránulos serosos de la glándula submandibular interpretados como un mecanismo de deterioro de la función acinar. Bevacizumab administrado de forma aislada no alteró la actividad de la amilasa salival en comparación con el grupo de control. Mientras que la menor ingesta del grupo de alimentación combinada afectó la actividad de la amilasa salival en comparación con el grupo de control, el efecto fue significativamente mayor en los animales tratados con los medicamentos oncológicos utilizados en el grupo. modelo animal actual.

The efficacy and side effects of rigosertib combined with chemotherapy in KRAS mutant colorectal cancer mice / 中华肿瘤杂志

Objective: To investigate the effect of rigosertib (RGS) combined with classic chemotherapy drugs including 5-fluorouracil, oxaliplatin, and irinotecan in colorectal cancer. Methods: Explore the synergy effects of RGS and 5-fluorouracil (5-FU), oxaliplatin (OXA), and irinotecan (IRI) on colorectal cancer by subcutaneously transplanted tumor models of mice. The mice were randomly divided into control group, RGS group, 5-FU group, OXA group, IRI group, 5-FU+ RGS group, OXA+ RGS group and IRI+ RGS group. The synergy effects of RGS and OXA on KRAS mutant colorectal cancer cell lines in vitro was detected by CCK-8. Ki-67 immunohistochemistry and TdT-mediated dUTP nick-end labeling (TUNEL) staining were performed on the mouse tumor tissue sections, and the extracted tumor tissue was analyzed by western blot. The blood samples of mice after chemotherapy and RGS treatment were collected, blood routine and liver and kidney function analysis were conducted, and H&E staining on liver sections was performed to observe the side effects of chemotherapy and RGS. Results: The subcutaneously transplanted tumor models were established successfully in all groups. 55 days after administration, the fold change of tumor size of OXA+ RGS group was 37.019±8.634, which is significantly smaller than 77.571±15.387 of RGS group (P=0.029) and 92.500±13.279 of OXA group (P=0.008). Immunohistochemical staining showed that the Ki-67 index of tumor tissue in control group, OXA group, RGS group and OXA+ RGS group were (100.0±16.8)%, (35.6±11.3)%, (54.5±18.1)% and (15.4±3.9)%, respectively. The Ki-67 index of OXA+ RGS group was significantly lower than that in control group (P=0.014), but there was no significant difference compared to OXA group and RGS group (OXA: P=0.549; RGS: P=0.218). TUNEL fluorescence staining showed that the apoptotic level of OXA+ RGS group was 3.878±0.547, which was significantly higher than 1.515±0.442 of OXA group (P=0.005) and 1.966±0.261 of RGS group (P=0.008). Western blot showed that the expressions of apoptosis related proteins such as cleaved-PARP, cleaved-caspase 3 and cleaved-caspase 8 in the tumor tissues of mice in the OXA+ RGS group were higher than those in control group, OXA group and RGS group. After the mice received RGS combined with chemotherapy drugs, there was no significant effect on liver and kidney function indexes, but the combined use of oxaliplatin and RGS significantly reduced the white blood cells [(0.385±0.215)×10(9)/L vs (5.598±0.605)×10(9)/L, P<0.001] and hemoglobin[(56.000±24.000)g/L vs (153.333±2.231)g/L, P=0.001] of the mice. RGS, chemotherapy combined with RGS and chemotherapy alone did not significantly increase the damage to liver cells. Conclusions: The combination of RGS and oxaliplatin has a stronger anti-tumor effect on KRAS mutant colorectal cancer. RGS single agent will not cause significant bone marrow suppression and hepatorenal injury in mice, but its side effects may increase correspondingly after combined with chemotherapy.

Clinical Anslysis of Primary Adrenal NK/T-Cell Lymphoma / 中国实验血液学杂志

OBJECTIVE@#To investigate the clinical characteristics, diagnosis, and treatment of one patient with primary adrenal natural killer/T-cell lymphoma (PANKTCL), and to strengthen the understanding of this rare type of lymphoma.@*METHODS@#The clinical manifestations, diagnosis and treatment process, and prognosis of the patient admitted in our hospital were retrospectively analyzed.@*RESULTS@#Combined with pathology, imaging, bone marrow examination， etc, the patient was diagnosed with PANKTCL (CA stage, stage II; PINK-E score 3, high-risk group). Six cycles of "P-GemOx+VP-16" regimen（gemcitabine 1 g/m2 d1 + oxaliplatin 100 mg/m2 d 1 + etoposide 60 mg/m2 d 2-4 + polyethylene glycol conjugated asparaginase 3 750 IU d 5） was performed, and complete response was assessed in 4 cycles. Maintenance therapy with sintilimab was administered after the completion of chemotherapy. Eight months after the complete response, the patient experienced disease recurrence and underwent a total of four courses of chemotherapy, during which hemophagocytic syndrome occurred. The patient died of disease progression 1 month later.@*CONCLUSION@#PANKTCL is rare, relapses easily, and has a worse prognosis. The choice of the "P-GemOx+VP-16" regimen combined with sintilimab help to improve the survival prognosis of patient with non-upper aerodigestive tract natural killer /T-cell lymphoma.

The efficacy of chemotherapy re-challenge in third-line setting for metastatic colorectal cancer patients: a real-world study / 中华肿瘤杂志

Objective: To explore the efficacy of chemotherapy re-challenge in the third-line setting for patients with metastatic colorectal cancer (mCRC) in the real world. Methods: The clinicopathological data, treatment information, recent treatment efficacy, adverse events and survival data of mCRC patients who had disease progression after treatment with oxaliplatin-based and/or irinotecan-based chemotherapy and received third-line chemotherapy re-challenge from January 2013 to December 2020 at Tianjin Medical University Cancer Institute and Hospital were retrospectively collected. Survival curves were plotted with the Kaplan-Meier method, and the Cox proportional hazard model was used to analyze the prognostic factors. Results: A total of 95 mCRC patients were included. Among them, 32 patients (33.7%) received chemotherapy alone and 63 patients (66.3%) received chemotherapy combined with targeted drugs. Eighty-three patients were treated with dual-drug chemotherapy (87.4%), including oxaliplatin re-challenge in 35 patients and irinotecan re-challenge in 48 patients. The remaining 12 patients were treated with triplet chemotherapy regimens (12.6%). Among them, as 5 patients had sequential application of oxaliplatin and irinotecan in front-line treatments, their third-line therapy re-challenged both oxaliplatin and irinotecan; 7 patients only had oxaliplatin prescription before, and these patients re-challenged oxaliplatin in the third-line treatment. The overall response rate (ORR) and disease control rate (DCR) reached 8.6% (8/93) and 61.3% (57/93), respectively. The median progression free survival (mPFS) and median overall survival (mOS) were 4.9 months and 13.0 months, respectively. The most common adverse events were leukopenia (34.7%) and neutropenia (34.7%), followed by gastrointestinal adverse reactions such as nausea (32.6%) and vomiting (31.6%). Grade 3-4 adverse events were mostly hematological toxicity. Cox multivariate analysis showed that gender (HR=1.609, 95% CI: 1.016-2.548) and the PFS of front-line treatments (HR=0.598, 95% CI: 0.378-0.947) were independent prognostic factors. Conclusion: The results suggested that it is safe and effective for mCRC patients to choose third-line chemotherapy re-challenge, especially for patients with a PFS of more than one year in front-line treatments.

The efficacy of chemotherapy re-challenge in third-line setting for metastatic colorectal cancer patients: a real-world study / 中华肿瘤杂志

Objective: To explore the efficacy of chemotherapy re-challenge in the third-line setting for patients with metastatic colorectal cancer (mCRC) in the real world. Methods: The clinicopathological data, treatment information, recent treatment efficacy, adverse events and survival data of mCRC patients who had disease progression after treatment with oxaliplatin-based and/or irinotecan-based chemotherapy and received third-line chemotherapy re-challenge from January 2013 to December 2020 at Tianjin Medical University Cancer Institute and Hospital were retrospectively collected. Survival curves were plotted with the Kaplan-Meier method, and the Cox proportional hazard model was used to analyze the prognostic factors. Results: A total of 95 mCRC patients were included. Among them, 32 patients (33.7%) received chemotherapy alone and 63 patients (66.3%) received chemotherapy combined with targeted drugs. Eighty-three patients were treated with dual-drug chemotherapy (87.4%), including oxaliplatin re-challenge in 35 patients and irinotecan re-challenge in 48 patients. The remaining 12 patients were treated with triplet chemotherapy regimens (12.6%). Among them, as 5 patients had sequential application of oxaliplatin and irinotecan in front-line treatments, their third-line therapy re-challenged both oxaliplatin and irinotecan; 7 patients only had oxaliplatin prescription before, and these patients re-challenged oxaliplatin in the third-line treatment. The overall response rate (ORR) and disease control rate (DCR) reached 8.6% (8/93) and 61.3% (57/93), respectively. The median progression free survival (mPFS) and median overall survival (mOS) were 4.9 months and 13.0 months, respectively. The most common adverse events were leukopenia (34.7%) and neutropenia (34.7%), followed by gastrointestinal adverse reactions such as nausea (32.6%) and vomiting (31.6%). Grade 3-4 adverse events were mostly hematological toxicity. Cox multivariate analysis showed that gender (HR=1.609, 95% CI: 1.016-2.548) and the PFS of front-line treatments (HR=0.598, 95% CI: 0.378-0.947) were independent prognostic factors. Conclusion: The results suggested that it is safe and effective for mCRC patients to choose third-line chemotherapy re-challenge, especially for patients with a PFS of more than one year in front-line treatments.

Research progress on oxaliplatin-induced neurotoxicity in traditional Chinese medicine (TCM) and western medical cognition and prevention and treatment by TCM / 中国中药杂志

Chemotherapy is one of the main options in clinical tumor treatment. Although chemotherapy drugs have a good therapeutic effect, they can also cause a series of adverse reactions, such as neurotoxicity. Chemotherapy-induced neurotoxicity is a dose-limi-ting adverse reaction that significantly affects patients' long-term treatment and quality of life. This article reviewed literature from 2000 to the present on chemotherapy-induced neurotoxicity and found that oxaliplatin was the most frequently used chemotherapy drug. Based on the clinical characteristics of oxaliplatin-induced neurotoxicity, this article summarized the understanding of its pathogenesis from both traditional Chinese medicine(TCM) and western medicine perspectives, discussed the role and mechanism of TCM compounds and monomeric components, and explored the research direction of using cutting-edge biotechnology to reveal the mechanism of oxaliplatin-induced neurotoxicity from a temporal-spatial perspective of intercellular communication and the application prospects of an interdisciplinary model combining TCM pathogenesis, western medicine manifestations, and artificial intelligence in precise intervention decision-making for TCM, aiming to provide research ideas for the prevention and treatment of oxaliplatin-induced neurotoxicity and the development of new drugs.

Synergistic effects of dendrosomal nanocurcumin and oxaliplatin on oncogenic properties of ovarian cancer cell lines by down-expression of MMPs

BACKGROUND: Contrary to the advantageous anticancer activities of curcumin (Cur), limited bioavailability and solubility hindered its efficacy. Here, nontoxic dendrosomal nano carrier with Cur was used to overcome these problems. Despite considerable antitumor properties of Oxaliplatin (Oxa), the limiting factors are drug resistance and adverse side-effects. The hypothesis of this study was to evaluate the possible synergism between dendrosomal nanocurcumin (DNC) and Oxa and these agents showed growth regulatory effects on SKOV3 and OVCAR3 cells. METHODS: and materials In the present study, colony formation, wound healing motility, cell adhesion, transwell invasion and migration assay and cell cycle arrest with or without DNC, Oxa and Combination were defined. In addition to, real time PCR and Western blot were used to analyze AKT, PI3K, PKC, JNK, P38 and MMPs mRNAs and proteins expressions. Docking of MMP-2-Cur, MMP-2-DNC and MMP-2-Oxa was performed and the results of all three complexes were simulated by molecular dynamics. RESULTS: Our findings illustrated that DNC had the greatest effect on cell death as compared to the Cur alone. Moreover, the growth inhibitory effects (such as cell death correlated to apoptosis) were more intense if Oxa was added followed by DNC at 4 h interval. However, insignificant effects were observed upon simultaneous addition of these two agents in both cell lines. Besides, a combination of agents synergistically alters the relative expression of MMP-9. CONCLUSIONS: The docking results showed that His70 and Asp100 may play a key role at the MMP-2 binding site. The matrigel invasion as well as cell viability of ovarian cancer cell lines SKOV3 and OVCAR3 by DNC alone or in combination with Oxa was inhibited significantly. The inhibitory effects of these agents were due to the differential expression levels of MMP 2 and MMP 9 regulated by multiple downstream signaling cascades. From the molecular dynamic simulation studies, it was confirmed that DNC established a strong interaction with MMP-2.

Oxaliplatin versus Irinotecan no câncer colorretal avançado / Oxaliplatin versus Irinotecan in advanced colorectal cancer

O câncer colorretal é uma neoplasia com alta prevalência e letalidade. A razão desse elevado número de mortes é a detecção da doença em estágios metastáticos, de difícil cura e que necessitam de terapia quimioterápica adjuvante ou paliativa. Na atualidade, o principal tratamento quimioterápico dessa neoplasia tem como base as drogas Oxaliplatina ou Irinotecano, isolados ou combinados com outros medicamentos. O objetivo desta revisão sistemática é avaliar se há superioridade do esquema quimioterápico com Irinotecano sobre o regime com Oxaliplatina. Foi realizada a análise de ensaios clínicos randomizados, fase II ou III, nas bases de dados eletrônicas Central e PubMed. Critérios de inclusão: ensaios clínicos randomizados comparando regimes à base de irinotecano ou oxaliplatina como tratamentos de primeira linha para câncer colorretal metastático. O desfecho primário analisado foi a superioridade entre os quimioterápicos sobre a sobrevida global. Os desfechos secundários incluíram sobrevida livre de progressão, taxa de resposta e efeitos colaterais. Registro na PROSPERO: CRD42019130339. Não houve diferença significativa nos 13 estudos sobre a sobrevida dos pacientes. Sobre os efeitos colaterais dos medicamentos, os regimes baseados em irinotecano foram associados a uma alta incidência de neutropenia e diarreia grave. Já os associados com oxaliplatin cursaram com alta incidência de neuropatia sensitiva. Não houve diferença estatisticamente significativa sobre a sobrevida global, sobrevivência livre de progressão e na taxa de resposta quando comparamos os pacientes que receberam oxaliplatina e irinotecano (AU)

Colorectal cancer is a highly prevalent and lethal neoplasm. The reason for this high number of deaths is the detection of the disease in metastatic stages, which are difficult to cure and require adjuvant or palliative chemotherapy therapy. Currently, the main chemotherapeutic treatment of this neoplasm is based on the drugs Oxaliplatin or Irinotecan, alone or combined with other drugs. The objective of this systematic review is to evaluate whether there is superiority of the chemotherapy regimen with Irinotecan over that with Oxaliplatin. Analysis of randomized clinical trials, phase II or III, was performed in the electronic databases Central and PubMed. Inclusion criteria: randomized clinical trials comparing irinotecan- or oxaliplatin-based regimens as first-line treatments for metastatic colorectal cancer. The primary endpoint analyzed was the superiority between chemotherapies on overall survival. Secondary endpoints included progression-free survival, response rate, and side effects. PROSPERO registration: CRD42019130339. There was no significant difference in the 13 studies on patient survival. On drug side effects, irinotecan-based regimens were associated with a high incidence of neutropenia and severe diarrhea. Those associated with oxaliplatin were associated with a high incidence of sensory neuropathy. There was no statistically significant difference in overall survival, progression-free survival, and response rate when comparing patients receiving oxaliplatin and irinotecan (AU)

Caracterización clínico-epidemiológica de la urolitiasis / Clinical-epidemiological description of urolithiasis

Introducción: Las urolitiasis ocasionan dolor, deterioro funcional renal y notorias erogaciones económicas. Objetivos: Identificar las características clínico-epidemiológicas de la nefrolitiasis. Métodos: Estudio descriptivo, transversal. Se estudiaron 2 923 personas pertenecientes a tres consultorios del Policlínico Plaza; municipio Plaza de la Revolución, provincia La Habana, Cuba., seleccionados por muestreo simple aleatorio de los 16 con que cuenta el área de salud. Los datos se obtuvieron mediante encuesta y entrevista estructurada. La información fue procesada de forma automatizada (IBMSPSS 22.0). Se utilizó análisis de distribución de frecuencias, se calcularon tasas de prevalencia, y fue empleado el test de homogeneidad. Resultados: La prevalencia de urolitiasis fue de 4,99 por cada 100 habitantes, de 6,3 entre los varones y de 5,7 en los de piel blanca. La edad promedio al diagnóstico fue de 39,3 años. Entre los factores de riesgo de litiasis predominó la alta ingestión de oxalatos (97,3 por ciento). La ecografía fue la forma de diagnóstico más usada (67,8 por ciento). La fitoterapia fue el tratamiento médico más utilizado (69,2 por ciento). Al 16,4 por ciento de los pacientes se les expidió certificado médico en los últimos dos años. Conclusiones: La prevalencia de litiasis urinaria en el Policlínico Docente Plaza de la Revolución es elevada, con predominio en el sexo masculino, en sujetos de piel blanca y en las edades medias de la vida. La alta ingestión de oxalato es el factor de riesgo de litiasis urinaria más frecuente encontrado. La forma de diagnóstico más utilizada es la ecografía y el tratamiento más empleado es la fitoterapia(AU)

Introduction: Urolithiasis causes pain, renal functional deterioration and notorious economic expenses. Objectives: To identify the clinical-epidemiological characteristics of nephrolithiasis. Methods: A descriptive, cross-sectional study was conducted in a total of 2,923 people from to three clinics of Plaza de la Revolution Teaching Community Clinic, Plaza de la Revolution municipality, Havana province, Cuba. They were selected by simple random sampling from the 16 clinics that the health area has. The data was obtained through a survey and structured interview. The information was processed automatically (IBMSPSS 22.0). Frequency distribution analysis was used, prevalence rates were calculated and the homogeneity test was used. Results: The prevalence of urolithiasis was 4.99 per 100 inhabitants, 6.3 among men and 5.7 among white-skinned men. The average age at diagnosis was 39.3 years. Among the risk factors for lithiasis, the high intake of oxalates prevailed (97.3 percent). Ultrasound was the most used form of diagnosis (67.8 percent). Phytotherapy was the most used medical treatment (69.2 percent). A medical permit was issued to 16.4 percent of the patients in the last two years. Conclusions: The prevalence of urinary lithiasis in Plaza de la Revolution Teaching Community Clinic is high, prevailing in males, in white-skinned and middle aged subjects. High oxalate intake is the most common risk factor for urinary lithiasis found. The most used form of diagnosis is ultrasound and the most used treatment is phytotherapy(AU)

Disseminated intravascular coagulation from Intraperitoneal Oxaliplatin for Appendiceal Carcinoma: A case report

@#This is a case of a 65-year-old female diagnosed with appendiceal carcinoma, who underwent cytoreductive surgery with hyperthermic intraperitoneal chemotherapy. Profuse bleeding through the peritoneal drains, with hemodynamic instability, warranted a re-exploration on the fourth postoperative day. Intraoperatively, there was 500 mL of blood clots mostly on the right upper quadrant, diffuse muscle oozing along the previously-stripped right hemidiaphragm and right paracolic gutter, and a non-expanding hematoma on the right anterior abdominal wall. Bleeding parameters were checked postoperatively, and derangements pointing to a disseminated intravascular coagulation were noted. The patient was managed with multiple blood transfusions of packed red blood cells, fresh frozen plasma, platelet concentrates, and cryoprecipitate. Dexamethasone and tranexamic acid were given intravenously. The patient was discharged well on postoperative day 14 after clinical resolution of the bleeding. Eight days after discharge, however, patient succumbed to myocardial infarction.

Overexpression of NAT10 induced platinum drugs resistance in breast cancer cell / 中华肿瘤杂志

Objective: To observe the platinum drugs resistance effect of N-acetyltransferase 10 (NAT10) overexpression in breast cancer cell line and elucidate the underlining mechanisms. Methods: The experiment was divided into wild-type (MCF-7 wild-type cells without any treatment) group, NAT10 overexpression group (H-NAT10 plasmid transfected into MCF-7 cells) and NAT10 knockdown group (SH-NAT10 plasmid transfected into MCF-7 cells). The invasion was detected by Transwell array, the interaction between NAT10 and PARP1 was detected by co-immunoprecipitation. The impact of NAT10 overexpression or knockdown on the acetylation level of PARP1 and its half-life was also determined. Immunostaining and IP array were used to detect the recruitment of DNA damage repair protein by acetylated PARP1. Flow cytometry was used to detect the cell apoptosis. Results: Transwell invasion assay showed that the number of cell invasion was 483.00±46.90 in the NAT10 overexpression group, 469.00±40.50 in the NAT10 knockdown group, and 445.00±35.50 in the MCF-7 wild-type cells, and the differences were not statistically significant (P>0.05). In the presence of 10 μmol/L oxaliplatin, the number of cell invasion was 502.00±45.60 in the NAT10 overexpression group and 105.00±20.50 in the NAT10 knockdown group, both statistically significant (P<0.05) compared with 219.00±31.50 in wild-type cells. In the presence of 10 μmol/L oxaliplatin, NAT10 overexpression enhanced the binding of PARP1 to NAT10 compared with wild-type cells, whereas the use of the NAT10 inhibitor Remodelin inhibited the mutual binding of the two. Overexpression of NAT10 induced PARP1 acetylation followed by increased PARP1 binding to XRCC1, and knockdown of NAT10 expression reduced PARP1 binding to XRCC1. Overexpression of NAT10 enhanced PARP1 binding to LIG3, while knockdown of NAT10 expression decreased PARP1 binding to LIG3. In 10 μmol/L oxaliplatin-treated cells, the γH2AX expression level was 0.38±0.02 in NAT10 overexpressing cells and 1.36±0.15 in NAT10 knockdown cells, both statistically significant (P<0.05) compared with 1.00±0.00 in wild-type cells. In 10 μmol/L oxaliplatin treated cells, the apoptosis rate was (6.54±0.68)% in the NAT10 overexpression group and (12.98±2.54)% in the NAT10 knockdown group, both of which were statistically significant (P<0.05) compared with (9.67±0.37)% in wild-type cells. Conclusion: NAT10 overexpression enhances the binding of NAT10 to PARP1 and promotes the acetylation of PARP1, which in turn prolongs the half-life of PARP1, thus enhancing PARP1 recruitment of DNA damage repair related proteins to the damage sites, promoting DNA damage repair and ultimately the survival of breast cancer cells.

Protective Mechanism of Electroacupuncture on Peripheral Neurotoxicity Induced by Oxaliplatin in Rats / 中国结合医学杂志

OBJECTIVE@#To study the effect of electroacupuncture (EA) on oxaliplatin-induced peripheral neuropathy (OIPN) in rats.@*METHODS@#Male Sprague-Dawley rats were equally divided into 3 groups using a random number table: the control group, the OIPN group, and the EA (OIPN + EA) group, with 10 rats in each. The time courses of mechanical, cold sensitivity, and microcirculation blood flow intensity were determined. The morphology of the dorsal root ganglion (DRG) was observed by electron microscopic examination. The protein levels of nuclear factor E2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), and the transient receptor potential (TRP) protein family in DRGs were assayed by Western blot.@*RESULTS@#EA treatment significantly reduced mechanical allodynia and cold allodynia in OIPN rats (P<0.01). Notably, oxaliplatin treatment resulted in impaired microcirculatory blood flow and pathomorphological defects in DRGs (P<0.01). EA treatment increased the microcirculation blood flow and attenuated the pathological changes induced by oxaliplatin (P<0.01). In addition, the expression levels of Nrf2 and HO-1 were down-regulated, and the TRP protein family was over-expressed in the DRGs of OIPN rats (P<0.01). EA increased the expression levels of Nrf2 and HO-1 and decreased the level of TRP protein family in DRG (P<0.05 or P<0.01).@*CONCLUSION@#EA may be a potential alternative therapy for OIPN, and its mechanism may be mainly mediated by restoring the Nrf2/HO-1 signaling pathway.

Foot drop - an uncommon presentation of FOLFOX toxicity

A quimioterapia com FOLFOX (oxaliplatina, leucovorina e 5-fluorouracilo) é frequentemente utilizada em doentes com cancro colorretal. Os sais de platina são conhecidos por serem uma classe de quimioterápicos que comumente induzem neurotoxicidade periférica. Na toxicidade induzida pela oxaliplatina, os sintomas sensitivos são os mais frequentes. Neste artigo, apresentamos dois casos clínicos de pacientes com adenocarcinoma de cólon, ambos submetidos à quimioterapia com FOLFOX4, e que desenvolveram neurotoxicidade incomum, apresentando pé pendente após o terceiro ciclo de tratamento. Esta manifestação clínica pode ser explicada por dano axonal nos neurônios motores periféricos do nervo peroneal comum (fibular), que fornece inervação motora aos músculos do pé. A paralisia do nervo fibular causa fraqueza súbita nos músculos do pé, que parece ser temporária. Ambos os doentes recuperaram completamente do evento sem necessidade de ajustes no tratamento, nem introdução de medicamentos diferentes. A apresentação de pé pendente como toxicidade da quimioterapia ainda é pouco compreendida. Os casos relatados mostram o pé pendente como uma manifestação grave e incomum de neuropatia induzida por FOLFOX, que pode ser transitória, e não requer necessariamente intervenção específica.

Chemotherapy based on FOLFOX (oxaliplatin, leucovorin, and 5-fluorouracil) regimen is frequently used in colorectal cancer patients. Oxaliplatin and other platinum agents are known to be a class of chemotherapy drugs that commonly induce peripheral neurotoxicity. The most frequent oxaliplatin related neurotoxicity is sensitive symptoms. Here, we present two cases of patients with colon adenocarcinoma, both undergoing chemotherapy with FOLFOX4, who developed uncommon neurotoxicity, presenting with foot drop after the third treatment cycle. Foot drop may be explained by axonal damage of peripheral motor neurons of the common peroneal (fibular) nerve, which provides motor innervation to the foot muscles. Peroneal nerve palsy causes sudden weakness in the muscles of the foot that seems to be temporary. Both patients completely recovered from the event. There was no need for treatment adjustments, neither introduction of different drugs. Foot drop as chemotherapy toxicity is still poorly understood. The reported cases show foot drop as a severe and uncommon manifestation of FOLFOX-induced neuropathy, that might be transitory, and does not necessarily requires specific intervention.

Índice pronóstico nutricional en pacientes con cáncer de páncreas avanzado tratados con nimotuzumab combinado a quimioterapia / Nutritional prognostic index in patients with advanced pancreatic cancer treated with nimotuzumab combined with chemotherapy

Introducción: El índice pronóstico nutricional es un marcador inmuno-nutricional que puede ser útil como factor pronóstico en tumores gastrointestinales. Objetivo: Evaluar supervivencia de pacientes con adenocarcinoma pancreático avanzado tratados con quimioinmunoterapia según índice pronóstico nutricional, según parámetros clínico-patológicos y tratamiento. Métodos: Se realizó estudio retrospectivo y observacional en pacientes que recibieron quimioterapia gemcitabina-oxaliplatino combinado a nimotuzumab (n=118), en el Hospital Ameijeiras, entre 2014 y 2019. Se evaluó supervivencia por método Kaplan-Meier, y regresión de Cox, para determinar los factores pronósticos independientes de supervivencia. Resultados: El punto de corte seleccionado fue 40 (sensibilidad 52,9 por ciento y especificidad 85,7 por ciento (p = 0,019), con área bajo la curva de 0,693. Para pacientes con índice menor de 40, la supervivencia fue más baja respecto a los pacientes con índice ≥ 40 (11,4 meses frente a 16,0 meses; p=0,001), con un HR de 1,7 (1,13-2,60; p=0,011). Las variables mayormente asociadas con índice pronóstico nutricional altos son pacientes con sesenta años o menos; ECOG cero, índice de masa corporal ≥25 Kg/m2 y albúmina sérica >3,5g/dL (x² < 0,05). Los pacientes con índice ≥ 40 tienen medianas de supervivencia más altas que pacientes con índice < 40 en las variables seleccionadas con p < 0,05, excepto el índice de masa corporal. Conclusiones: Este trabajo constituye el primer reporte nacional de utilización del índice pronóstico nutricional como pronóstico de supervivencia en pacientes con cáncer de páncreas avanzado(AU)

Background: The nutritional prognostic index is an immuno-nutritional marker that can be useful as a prognostic factor in gastrointestinal tumors. Aim: To evaluate the survival of patients with advanced pancreatic adenocarcinoma treated with chemoimmunotherapy according to the nutritional prognostic index, according to clinical-pathological parameters and treatment. Methods: A retrospective and observational study was carried out in patients who received gemcitabine-oxaliplatin chemotherapy combined with nimotuzumab (n=118), at the Ameijeiras Hospital, between 2014 and 2019. Survival was evaluated by the Kaplan-Meier method, and Cox regression, for determine independent prognostic factors for survival. Results: The selected cut-off point was 40 (52.9 percent sensitivity and 85.7 percent specificity) (p=0,019), with an area under the curve of 0,693. For patients with an index less than 40, survival was lower compared to patients with index ≥ 40 (11, 4 months vs. 16, 0 months; p=0,001), with a HR of 1, 7 (1, 13-2, 60; p=0,011). The variables mostly associated with nutritional prognostic index patients with 60 years or less, ECOG 0, body mass index ≥ 25 kg/m2 and serum albumin >3,5g/dL (x2 < 0, 05). Patients with index ≥ 40 have higher median survival than patients with index < 40 in the selected variables with p < 0, 05, except body mass index. Conclusions: This work constitutes the first national report on the use of the nutritional prognostic index as a prognosis of survival in patients with advanced pancreatic cancer(AU)

Hepatectomía en dos tiempos por metástasis hepáticas bilobares de origen colorrectal: reporte de un caso / Two-stage hepatectomy for bilobar colorectal liver metastases: case report / Hepatectomia em dois estágios para metástases hepáticas bilobares de origem colorretal: relato de um caso

La mitad de los pacientes con cáncer de origen colorrectal desarrollan metástasis hepáticas durante el curso de su enfermedad y de esas el 80% son irresecables. La resecabilidad se define no por la extensión de la hepatectomía, sino por la función del hígado remanente, por lo que para pacientes con ciertos factores favorables se pueden realizar técnicas de remodelación hepática para aumentar el volumen del hígado remanente para que este sea suficiente. La hepatectomía en dos tiempos se basa en procedimientos secuenciales que buscan tratar metástasis hepáticas colorrectales consideradas inicialmente irresecables, logrando la resección completa de las mismas dejando un remanente hepático funcionante suficiente, lo cual no sería posible en un solo acto quirúrgico. El objetivo de este trabajo es presentar el caso clínico de un paciente portador de metástasis hepáticas sincrónicas de origen colorrectal irresecables, que luego de una quimioterapia de conversión, con el fin de aumentar el futuro remanente hepático y evitar falla hepática postoperatoria y realizar una resección oncológica, fue sometido a una hepatectomía en dos tiempos, técnica utilizada con baja frecuencia en nuestro medio, destacando una evolución favorable, con marcadores tumorales en valores normales y sin evidencia imagenológica de recaída local ni sistémica.

Half of colorectal cancer patients develop liver metastases during the course of their disease, 80% of which are unresectable. Resectability is defined not by the extent of the hepatectomy, but by the function of the liver remnant. Therefore, for patients with certain factors, liver remodeling techniques can be performed to increase volume of the remaining liver so that it is sufficient. Two-stage hepatectomy is performed on colorectal liver metastases which are initially considered unresectable in one stage resection procedures, in which sequential procedures are performed in order to achieve complete resection and preserve a sufficient functioning liver remnant. The objective of this paper is to present the case of a patient with unresectable synchronous colorectal liver metastases, in which after conversion chemotherapy, in order to increase the future liver remnant, avoid postoperative liver failure and perform an oncological resection underwent a two-stage hepatectomy, a technique used with low frequency in our setting, highlighting a favorable evolution, with tumor markers in normal values and without imaging evidence of local or systemic relapse.

Metade dos pacientes com câncer colorretal desenvolve metástases hepáticas durante o curso da doença e, desses, 80% são irressecáveis. A ressecabilidade é definida não pela extensão da hepatectomia, mas pela função do fígado remanescente; portanto, para pacientes com certos fatores favoráveis, técnicas de remodelação hepática podem ser realizadas para aumentar o volume do fígado remanescente de forma que seja suficiente. A hepatectomia em dois estágios é baseada em procedimentos sequenciais que buscam tratar metástases hepáticas colorretais inicialmente consideradas irressecáveis, obtendo ressecção completa, deixando um remanescente hepático funcional suficiente, o que não seria possível em um único ato cirúrgico. O objetivo deste trabalho é apresentar o caso clínico de um paciente com metástases hepáticas sincrônicas irressecáveis ​​de origem colorretal, que após quimioterapia de conversão, com o objetivo de aumentar o futuro remanescente hepático e evitar insuficiência hepática pós-operatória e realizar uma ressecção oncológica, foi submetido a dois Hepatectomia em estágio, técnica utilizada com baixa frequência em nosso meio, evidenciando evolução favorável, com marcadores tumorais em valores normais e sem evidências de imagem de recidiva local ou sistêmica.

Protocolo de desensibilización rápida en pacientes con reacción moderada a severa de hipersensibilidad a citostáticos / Rapid desensitization protocol in patients with moderate to severe hypersensitivity reaction to cytostatics

Introducción: La desensibilización rápida a medicamentos induce una tolerancia temporal a los quimioterapéuticos que provocan reacciones de hipersensibilidad. Objetivo: Evaluar el protocolo de desensibilización rápida en escenario ambulatorio en pacientes que presentaron reacciones de hipersensibilidad a fármacos citotóxicos. Métodos: Se realizó un estudio observacional, y retrospectivo, de 30 pacientes con cáncer que desarrollaron reacciones de hipersensibilidad entre los años 2016 y 2018, tratados en el Hospital de Día del Servicio de Oncología del Clínico Quirúrgico Hermanos Ameijeiras. Se clasificaron según su intensidad, y se analizaron variables demográficas, características clínicas, y síntomas presentados. Se utilizó un protocolo en doce etapas basado en tres diluciones del fármaco. Se administró premedicación en todos los casos. Se realizó estadística descriptiva, y para la asociación entre variables, se utilizó la prueba estadística Chi-cuadrado. Resultados: La mediana de edad fue 54 años (23;77). Predominaron las mujeres; los menores de 60 años; tumor primario de colon; antecedentes de alergia; el oxaliplatino como fármaco más implicado; las RHS durante la infusión; e intensidad moderada. Fueron más frecuentes los síntomas cutáneos y gastrointestinales. Con la aplicación del protocolo se completó la quimioterapia planificada a los 30 pacientes (145 ciclos adicionales). Solo se presentaron ocho desensibilizaciones con reacciones leves de tipo cutáneas. El 94,5 por ciento de las desensibilizaciones no presentaron reacción alguna. Conclusiones: Constituye el primer reporte nacional de la utilización exitosa de un protocolo de desensibilización rápida a citostáticos que demostró ser eficaz y seguro en el escenario ambulatorio, con un manejo multidisciplinario(AU)

Introduction: Rapid desensitization to drugs induces a temporary tolerance to chemotherapeutics causing hypersensitivity reactions. Objective: To evaluate the rapid desensitization protocol in an outpatient setting in patients who had hypersensitivity reactions to cytotoxic drugs. Methods: An observational and retrospective study was carried out in 30 cancer patients, who developed hypersensitivity reactions, from 2016 to 2018. They were treated in the outpatient Oncology service at Hermanos Ameijeiras Surgical Clinical Hospital. These subjects were classified according to intensity; demographic variables, clinical characteristics, and symptoms were analyzed. A twelve-step protocol based on three dilutions of the drug was used. Premedication was administered in all cases. Descriptive statistics and for the association between variables were performed. Chi-square statistical test was used. Results: The median age was 54 years (23; 77). Predominance was observed in women, those under 60 years of age, primary colon tumor, history of allergy, oxaliplatin as the drug most implicated, HRH during infusion, and moderate intensity. Skin and gastrointestinal symptoms were more frequent. The planned chemotherapy was completed with the application of the protocol, in all 30 patients (145 additional cycles). There were only eight desensitization with mild skin-type reactions. 94.5 percent of desensitizations did not show any reaction. Conclusions: It constitutes the first national report of successful use of a rapid desensitization protocol to cytostatics that proved to be effective and safe in the outpatient setting with multidisciplinary management(AU)

Neoadjuvant chemoradiotherapy combined with surgery versus direct surgery in the treatment of Siewert type II and III adenocarcinomas of the esophagogastric junction: long-term prognostic analysis of a prospective randomized controlled trial / 中华胃肠外科杂志

Objective: To investigate the effectiveness, safety, and prognosis of neoadjuvant chemoradiotherapy (nCRT) for Siewert type II and III adenocarcinomas of the esophagogastric junction (AEG). Methods: This study is a prospective randomized controlled clinical study (NCT01962246). AEG patients who were treated at the Third Department of Surgery of the Fourth Hospital of Hebei Medical University from February 2012 to June 2016 were included. All of the enrolled patients were diagnosed with type II or III locally advanced AEG gastric cancer (T2-4N0-3M0 or T1N1-3M0) by gastroscopy and CT before operation; the longitudinal axis of the lesion was ≤ 8 cm; no anti-tumor treatment was previously given and no contraindications of chemotherapy and surgery were found. Case exclusion criteria: serious diseases accompanied by liver and kidney, cardiovascular system and other vital organs; allergy to capecitabine or oxaliplatin drugs or excipients; receiving any form of chemotherapy or other research drugs; pregnant or lactating women; patients with diseases resulting in difficulty to take capecitabine or with concurrent tumors. Based on sample size estimation, a total of 150 AEG patients were enrolled. Using the random number table method, the enrolled patients were divided into the nCRT group and the direct operation group with 75 cases in each group. The nCRT group received XELOX chemotherapy (capecitabine+ oxaliplatin) before surgery and concurrent radiotherapy (45 Gy, 25 times, 1.8 Gy/d, 5 times/week). Clinical efficacy of the nCRT group was evaluated by the solid tumor efficacy evaluation standard (RECIST1.1) and the tumor volume reduction rate was measured on CT. After completing the preoperative examination in the direct operation group, and 8-10 weeks after the end of nCRT in the nCRT group, surgery was performed. Laparoscopic exploration was initially performed. According to the Japanese "Regulations for the Treatment of Gastric Cancer", a transabdominal radical total gastrectomy combined with perigastric lymph node dissection was performed. The primary outcome was the 3-year overall survival (OS) and disease-free survival rate (DFS); the secondary outcomes were R0 resection rate, the toxicity of chemotherapy, and surgical complications. The follow-up ended on December 31, 2019. The postoperative recurrence, metastasis and survival time of the two groups were collected. Results: After excluding patients with incomplete clinical data, patients or family members requesting to withdraw informed consent, and those failing to follow the treatment plan, 63 cases in the nCRT group and 69 cases in the direct operation group were finally enrolled in the study. There were no statistically significant differences in baseline characteristics of the two groups (all P>0.05). Sixty-three patients in the nCRT group were evaluated by RECIST1.1 after treatment, the image based effective rate was 42.9% (27/63), and the stable disease rate was 98.4% (62/63); the tumor volume before and after nCRT measured on CT was (58.8±24.4) cm(3) and (46.6±25.7) cm(3), respectively, the effective rate of tumor volume reduction measured by CT was 47.6% (30/63). Incidences of neutrophilopenia [65.1% (41/63) vs. 40.6% (28/69), χ(2)=7.923, P=0.005], nausea [81.0% (51/63) vs. 56.5% (39/69), χ(2)=9.060, P=0.003] and fatigue [74.6% (47/63) vs. 42.0% (29/69), χ(2)=14.306, P=0.001] in the nCRT group were significantly higher than those in the direct surgery group. Radiation gastritis/esophagitis and radiation pneumonia were unique adverse reactions in the nCRT group, with incidences of 52.4% (33/63) and 15.9%(10/63), respectively. The classification of tumor regression of 63 patients in nCRT group presented as 11 cases of grade 0 (17.5%), 20 cases of grade 1 (31.7%), 28 cases of grade 2 (44.4%), and 5 cases of grade 3 (7.9%). Eleven (17.5%) patients achieved pathologic complete response. Sixty-one (96.8%) patients in the nCRT group underwent R0 resection, which was higher than 87.0% (60/69) in the direct surgery group (χ(2)=4.199, P=0.040). The mean number of harvested lymph nodes in the specimens in the nCRT group and the direct operation group was 27.6±12.4 and 26.8±14.6, respectively, and the difference was not statistically significant (t=-0.015, P=0.976). The pathological lymph node metastasis rate and lymph node ratio in the two groups were 44.4% (28/63) vs. 76.8% (53/69), and 4.0% (70/1 739) vs. 21.9% (404/1 847), respectively with statistically significant differences (χ(2)=14.552, P<0.001, and χ(2)=248.736, P<0.001, respectively). During a median follow-up of 52 (27-77) months, the 3-year DFS rate in the nCRT group and the direct surgery group was 52.4% and 39.1% (P=0.049), and the 3-year OS rate was 63.4% and 52.2% (P=0.019), respectively. According to whether the tumor volume reduction rate measured by CT was ≥ 12.5%, 63 patients in the nCRT group were divided into the effective group (n=30) and the ineffective group (n=33). The 3-year DFS rate of these two subgracps was 56.6% and 45.5%, respectively without significant difference (P=0.098). The 3-year OS rate was 73.3% and 51.5%,respectively with significant difference (P=0.038). The 3-year DFS rate of patients with the tumor regression grades 0, 1, 2 and 3 was 81.8%, 70.0%, 44.4%, and 20.0%, repectively (P=0.024); the 3-year OS rate was 81.8%, 75.0%, 48.1% and 40.0%, repectively (P=0.048). Conclusion: nCRT improves treatment efficacy of Siewert type II and III AEG patients, and the long-term prognosis is good.

Safety and effectiveness of oxaliplatin combined with capecitabine or oxaliplatin combined with S-1 neoadjuvant chemotherapy in the treatment of advanced gastric cancer / 中华胃肠外科杂志

Objective: To explore the safety and efficacy of oxaliplatin plus capecitabine (CapeOX) or oxaliplatin plus S-1 (SOX) regimen neoadjuvant chemotherapy in the treatment of advanced gastric cancer. Methods: A retrospective cohort study was performed. Clinical data of patients diagnosed as advanced gastric cancer undergoing CapeOX/SOX neoadjuvant chemotherapy and standard laparoscopic radical operation for gastric cancer in Ruijin Hospital of Shanghai Jiaotong University School of Medicine from April 2016 to April 2019 were retrospectively collected. Inclusion criteria were as follows: (1) age≥18 years; (2) gastric adenocarcinoma was confirmed by histopathology and the clinical stage was T3-4aN+M0; (3) tumor could be resectable; (4) preoperative neoadjuvant chemotherapy was CapeOX or SOX regimen without radiotherapy or other regimen chemotherapy; (5) no other concurrent malignant tumor; (6) the Eastern Cooperative Oncology Group (ECOG) score ≤ 1; (7) no bone marrow suppression; (8) normal liver and kidney function. Exclusion criteria were as follows: (1) patients with recurrent gastric cancer; (2) patients receiving emergency surgery due to tumor perforation, bleeding, obstruction, etc.; (3) allergy to oxaliplatin, S-1, capecitabine or any drug excipients; (4) diagnosed with coronary heart disease, cardiomyopathy, or the New York Heart Association class III or IV; (5) pregnant or lactating women. A total of 118 patients were enrolled as the neoadjuvant chemotherapy group, and 379 patients with locally advanced gastric cancer who received surgery combined with postoperative adjuvant chemotherapy over the same period simultaneously were included as the adjuvant chemotherapy group. After propensity score matching was performed including gender, age, ECOG score, tumor site, clinical stage, chemotherapy regimen and other factors by 1:1 ratio, there were 40 cases in each group. The differences between the two groups in general conditions, efficacy of neoadjuvant chemotherapy, intraoperative conditions, postoperative conditions, histopathological results, chemotherapy-related adverse events, and survival status were compared and analyzed. Results: Comparison of baseline demographics between the two groups showed no statistically significant difference (all P>0.05). In the neoadjuvant chemotherapy group, 5.0% (2/40) of patients achieved clinical complete response, 57.5% (23/40) achieved partial response, 32.5% (13/40) remained stable disease, and 5.0% (2/40) had disease progression before surgery. Objective response rate was 62.5% (25/40), and disease control rate was 95.0% (38/40). There were no statistically significant differences between neoadjuvant chemotherapy group and adjuvant chemotherapy group in terms of operation time, intraoperative blood loss, number of lymph node harvested, length of postoperative hospital stay, and postoperative mortality and morbidity (all P>0.05). Postoperative complications were well managed with conservative treatment. No Clavien-Dindo IV or V complications were observed in both groups. Pathological results showed that the proportion of patients with pathological stage T1 in the neoadjuvant chemotherapy group was significantly higher than that in the adjuvant chemotherapy group [27.5% (11/40) vs. 5.0% (2/40)], while the proportion of patients with pathological stage T3 was significantly lower than that in the adjuvant chemotherapy group [20.0% (8/40) vs. 45.0% (18/40)], with statistically significant difference (χ(2)=15.432, P=0.001). In the neoadjuvant chemotherapy group, there were 4 cases of tumor regression grade 0, 8 cases of grade 1, 16 cases of grade 2, and 12 cases of grade 3. The pathological complete response rate was 10% (4/40), the overall pathological response rate was 70.0% (28/40). There was no statistically significant difference in the incidence of chemotherapy-related adverse events between neoadjuvant chemotherapy group and adjuvant chemotherapy group [40% (16/40) vs. 37.5% (15/40), P>0.05). There were no statistically significant differences in OS (43 months vs. 40 months) and 3-year OS rate (66.1% vs. 59.8%) between neoadjuvant chemotherapy group and adjuvant chemotherapy group (P=0.428). The disease-free survival (DFS) and 3-year DFS rates of the neoadjuvant chemotherapy group were significantly superior to those of the adjuvant chemotherapy group (36 months vs. 28 months, 51.4% vs. 35.8%, P=0.048). Conclusion: CapeOX or SOX regimen neoadjuvant chemotherapy is a safe, effective and feasible treatment mode for advanced gastric cancer without increasing surgical risk and can improve the DFS of patients.

Safety and efficacy of adjuvant chemotherapy with oxaliplatin and S-1 for patients with locally advanced gastric cancer after D2 lymph nodes dissection / 中华胃肠外科杂志

Objective: To investigate the safety and efficacy of oxaliplatin combined with S-1 (SOX) as adjuvant chemotherapy after D2 radical gastrectomy for locally advanced gastric cancer. Methods: A descriptive case series study was applied. Case inclusion criteria: (1) locally advanced gastric cancer confirmed by endoscopic biopsy or surgical specimen pathology as gastric adenocarcinoma; (2) receiving D2 radical gastric resection followed by SOX regimen adjuvant chemotherapy. Case exclusion criteria: (1) postoperative pathological TNM stage I or IV; (2) acute complications and emergency surgeries; (3) receiving neoadjuvant therapy; (4) concurrent malignancies and complications compromising patients' treatment or survival; (5) without receiving adjuvant SOX chemotherapy. A total of 94 patients with stage II-III gastric cancer who underwent D2 radical gastrectomy and postoperative adjuvant SOX chemotherapy at department of Gastrointestinal Surgery, Peking University People's Hospital from January 2014 to December 2019 were retrospectively enrolled. Chemotherapy-related adverse events, overall survival (OS) and progression-free survival (PFS) were analyzed. Kaplan-Meier survival analysis was performed and log rank test was used to analyze the difference between groups. P<0.2 or clinically significant indicators in univariate analysis were included in Cox regression model for multivariate survival analysis. Results: Among these 94 patients, there were 65 males and 29 females with an average age of (58.2±12.1) years; 33 patients with hypertension, diabetes mellitus, or cardiovascular and cerebrovascular diseases, 11 patients with family history of gastrointestinal tumors; 59 patients with tumors locating in the antrum or pylorus, 16 patients in the gastric body, 19 patients in the gastric fundus or cardia; 29 patients underwent total gastrectomy, 5 patients underwent proximal subtotal gastrectomy, and 60 patients underwent distal subtotal gastrectomy. In this study, 73 patients (77.7%) completed at least 5 cycles of adjuvant SOX regimen chemotherapy. Grade 3-4 adverse reactions included thrombocytopenia (23.4%, 22/94), nausea and vomiting (18.1%, 17/94) and peripheral neurotoxicity (6.4%, 6/94). Eighty-nine patients (94.7%) completed follow-up with a median follow-up time of 32 months. The 3-year and 5-year OS rates were 89.8% and 83.7%, respectively, and the 3-year and 5-year PFS rates were 81.4% and 78.1%, respectively. Taking 5 chemotherapy cycles as the cut-off point, the 3-year OS rate and 3-year PFS rate were 72.2% and 53.9% in the adjuvant chemotherapy < 5 cycles group, and 93.7% and 87.1% in the adjuvant chemotherapy ≥5 cycles group, respectively; the differences were statistically significant (P=0.029, P=0.006). Univariate analysis showed that the adjuvant chemotherapy < 5 cycles group was associated with worse 3-year OS (P=0.029). Multivariate analysis showed that insufficient chemotherapy cycle (HR=9.419, 95% CI: 2.330-38.007, P=0.002) was an independent risk factor for 3-year OS. Meanwhile, univariate analysis showed that the adjuvant chemotherapy <5 cycles (P=0.006), preoperative CEA > 4.70 μg/L (P=0.035) and adjacent organ resection (P=0.024) were associated with worse 3-year PFS. Multivariate analysis showed that adjuvant chemotherapy <5 cycles (HR=10.493, 95% CI: 2.466-44.655, P=0.001) and adjacent organ resection (HR=127.518, 95% CI: 8.885-1 830.136, P<0.001) were independent risk factors for 3-year PFS. Conclusions: Oxaliplatin combined with S-1 as an adjuvant chemotherapy regimen for locally advanced gastric cancer has high efficacy and low incidence of adverse reactions. At least 5 cycles of SOX regimen adjuvant chemotherapy can significantly improve prognosis of patients with stage II-III gastric cancer.

Safety and short-term efficacy of apatinib combined with oxaliplatin and S-1 in the conversion treatment for gastric cancer with peritoneal metastasis / 中华胃肠外科杂志

Objective: To investigate the safety and short-term efficacy of apatinib combined with oxaliplatin and S-1 in the conversion treatment for gastric cancer with different types of peritoneal metastasis. Methods: A prospective study "one arm exploratory clinical study of conversion therapy of apatinib with S-1 and oxaliplatin in the treatment of advanced gastric cancer" (clinical registration ChiCTR-ONC-17010430) from medical record database was retrospectively analyzed. Patients aged 18-70 years with gastric cancer peritoneal metastasis confirmed by histology and laparoscopic exploration, and had not receive radiotherapy, chemotherapy, targeted therapy or immunotherapy before were enrolled. Before operation, the patients received 6 cycles of S-1 (80-120 mg/d, d1-d14) and oxaliplatin (130 mg/m(2), d1), and 5 cycles of apatinib (500 mg/d, d1-d21) conversion regimen. Three weeks after chemotherapy, whether the operation was performed or not depending on re-evaluation and patient preference. The main outcome were adverse reactions, and the secondary outcome were objective remission rate (ORR), disease control rate (DCR), and overall survival (OS) rate. The follow-up period was up to May 2020. Results: A total of 27 patients with gastric cancer peritoneal metastasis were enrolled in this study. There were 13 males and 14 females, with a median age of 58 (30-68) years old. There were 9 cases of P1a, 5 cases of P1b, and 13 cases of P1c. There were 14 cases with 1-5 scores of PCI (peritoneal cancer index), and 13 cases with 6 scores or above. The incidence of adverse reactions was 100%. The most common adverse reactions were hematological events including leucopenia (70.4%, 19/27) and granulocytopenia (74.1%, 20/27). Non-hematological adverse events included fatigue (51.9%, 14/27) and oral mucositis (37.0%, 10/27). One patient was withdrawn due to grade 4 thrombocytopenia. Among 26 patients with feasible efficacy evaluation, 18 (69.2%) achieved partial remission, 3 (11.5%) achieved stable disease, and 5 (19.2%) disease progression. The objective remission rate was 69.2% (18/26) and the disease control rate was 80.8% (21/26). Fourteen patients underwent surgery, including 6 patients undergoing R0 resection with the R0 resection rate of 42.9% (6/14). The postoperative pathological response rate was 64.3% (9/14). The follow-up time was 12-40 months, and the follow-up rate was 100%. The 1-year OS rate was 65.2% and the survival time was (14.0±1.7) months. The 1-year OS rates of P1a/P1b group and P1c group were 81.8% and 42.0% respectively, whose difference was statistically significant (P=0.041). The 1-year OS rates of PCI 1-5 group and PCI ≥6 group were 67.3% and 38.5% respectively, whose difference was statistically significant (P=0.022). Conclusion: In the conversion treatment of gastric cancer peritoneal metastasis, the safety of apatinib combined with oxaliplatin and S-1 is acceptable, and this regimen shows a good short-term survival efficacy in patients with P1a/P1b and PCI of 1-5.