Gastric cancer: histological response of tumor and metastatic lymph nodes for perioperative chemotherapy.

BACKGROUND: Gastric cancer is the fourth cancer most common in the world and the second cause of cancer-related deaths. Perioperative chemotherapy may reduce tumor burden and decrease lymph node invasion, improving R0 resections rates. On the other hand, administered before surgery, chemotherapy may cause fibrosis and tissue edema, with potential increase of surgical difficulty and in the number of post-operative complications. Therefore, we aim to investigate the effect of perioperative chemotherapy for tumor burden and metastatic lymph nodes of gastric cancer. METHODS: Retrospective analysis of all patients submitted to perioperative chemotherapy and surgery, between January 2010 and June 2020, which showed lymph node regression and tumor regression (Becker's classification). RESULTS: A total of 112 patients with an average age of 61.9 years were analyzed. About 90.2% completed three cycles of perioperative chemotherapy. Good tumor response to chemotherapy (<10% residual tumor) was achieved in 21.3% of patients. Only three patients obtained a complete pathological response. A median lymph node response of 33.3% was achieved in our series. CONCLUSION: Despite no evident outstanding regression rate was observed, perioperative chemotherapy seems to be useful in obtaining a R0 resection in gastric cancer, even in advanced gastric cancer.

INTRODUCCIÓN: El cáncer de estómago es el cuarto tipo de cáncer más común y la segunda causa de muerte relacionada con el cáncer. La quimioterapia perioperatoria puede reducir la carga tumoral y disminuir la invasión de los ganglios linfáticos. Por otro lado, administrada antes de la cirugía, la quimioterapia puede causar fibrosis y edema tisular, aumentando potencialmente la dificultad quirúrgica y el número de complicaciones posoperatorias. Nuestro objetivo es investigar el efecto de la quimioterapia perioperatoria sobre la carga tumoral y los ganglios metastásicos en el cáncer gástrico. MÉTODOS: Análisis retrospectivo de todos los pacientes sometidos a quimioterapia y cirugía, entre enero de 2010 y junio de 2020. RESULTADOS: Se analizaron 112 pacientes con una edad media de 61.9 años. El 90.2% completó 3 ciclos de quimioterapia perioperatoria. Se logró una buena respuesta tumoral a la quimioterapia (< 10% de tumor residual) en el 21.3% de los pacientes. Tres pacientes lograron una respuesta patológica completa. En nuestra serie se logró una mediana de respuesta de los ganglios linfáticos del 33.3%. CONCLUSIÓN: Aunque no se observó una tasa de regresión manifiesta, la quimioterapia perioperatoria parece ser útil para lograr una resección R0 en el cáncer gástrico, incluso en el cáncer gástrico avanzado.

Does MTA provide a more favourable histological response than other materials in the repair of furcal perforations? A systematic review.

BACKGROUND: There is no consensus on which furcal perforation repair material induces a more favourable histological response. This systematic review of laboratory studies provides an overview of the studies comparing repair materials in animal models. OBJECTIVES: To evaluate whether mineral trioxide aggregate (MTA) yields a more favourable histological response than other materials when used to repair furcal perforations in animal experimental models. METHODS: This review followed the PRISMA checklist. The studies included various materials used to repair furcal perforations and compared the histological responses with MTA. An electronic search was conducted in EMBASE, PubMed, Scopus and Web of Science up to 2 September 2020, with no language or publication date restrictions. Studies whose full text was unavailable were excluded. The ARRIVE and SYRCLE tools were used to assess the methodological quality and risk of bias (RoB) of the studies. RESULTS: The studies included in the qualitative synthesis were conducted in rat (n = 3) and dog (n = 17) models. They were classified as having a low quality, high methodological heterogeneity and high RoB. MTA and Biodentine, the materials most often compared, reduced the inflammatory reaction to mild over time. In addition, a mineralized tissue was formed in all studies. The response yielded by MTA was better than or equivalent to that of the other tested materials. DISCUSSION: This review confirmed that MTA is the reference standard material for furcal perforation repair. However, research using animal models has inherent limitations, and the substantial methodological heterogeneity across the studies included should be considered. Therefore, the knowledge generated by this systematic review should be translated into clinical practice cautiously. CONCLUSIONS: Features described in the report and quality assessment guidelines, such as PRIASE, ARRIVE and SYRCLE, should guide researchers. Despite the high RoB and the low methodological quality of the studies included, findings indicated that MTA yields a more favourable histological response than other materials in the repair of furcal perforations. REGISTRATION: PROSPERO (CRD42020181297).

10 ns PEFs induce a histological response linked to cell death and cytotoxic T-lymphocytes in an immunocompetent mouse model of peritoneal metastasis.

PURPOSE: The application of nanosecond pulsed electric fields (nsPEFs) could be an effective therapeutic strategy for peritoneal metastasis (PM) from colorectal cancer (CRC). The aim of this study was to evaluate in vitro the sensitivity of CT-26 CRC cells to nsPEFs in combination with chemotherapeutic agents, and to observe the subsequent in vivo histologic response. METHODS: In vitro cellular assays were performed to assess the effects of exposure to 1, 10, 100, 500 and 1000 10 ns pulses in a cuvette or bi-electrode system at 10 and 200 Hz. nsPEF treatment was applied alone or in combination with oxaliplatin and mitomycin. Cell death was detected by flow cytometry, and permeabilization and intracellular calcium levels by fluorescent confocal microscopy after treatment. A mouse model of PM was used to investigate the effects of in vivo exposure to pulses delivered using a bi-electrode system; morphological changes in mitochondria were assessed by electron microscopy. Fibrosis was measured by multiphoton microscopy, while the histological response (HR; hematoxylin-eosin-safran stain), proliferation (KI67, DAPI), and expression of immunological factors (CD3, CD4, CD8) were evaluated by classic histology. RESULTS: 10 ns PEFs exerted a dose-dependent effect on CT-26 cells in vitro and in vivo, by inducing cell death and altering mitochondrial morphology after plasma membrane permeabilization. In vivo results indicated a specific CD8+ T cell immune response, together with a strong HR according to the Peritoneal Regression Grading Score (PRGS). CONCLUSIONS: The effects of nsPEFs on CT-26 were confirmed in a mouse model of CRC with PM.

HCV virological response during treatment of chronic hepatitis C is associated with liver histological Improvement in patients with HCV/HIV co-infection

Liver histological improvement after treatment for chronic hepatitis C in patients co-infected with human immunodeficiency virus-1 (HIV-1) has been described. Paired liver biopsies in twenty six HCV/HIV co-infected patients were compared to determine factors possibly associated with histological improvement. The patients were submitted to a liver biopsy before treatment for hepatitis C and 25 months after the end of treatment. Fragments of the liver biopsy obtained before and after treatment were compared regarding the following parameters: histological activity index (HAI) and degree of fibrosis (Knodell); intensity of collagen deposits (Sirius Red staining) and degree of stellate cell activation (alpha-smooth muscle actin labeling). The ratios of the post and pre-treatment variables were related through logistic regression to body mass index (BMI), alcohol ingestion, HCV genotype, HCV viremia, presence of hepatic iron and pre-treatment hepatic steatosis. A negative RNA test in the 24th week of treatment was associated with improvement in fibrosis, collagen deposits and stellate cell numbers. The other variables analyzed did not correlate to an improvement in hepatic histology after hepatitis C treatment. Reduction in HCV viremia during treatment may result in reduced hepatic fibrosis even in patients without a sustained virological response.