Anaplastic thyroid cancer (ATC) is a rarely occurring refractory disease. While recent clinical trials have demonstrated the efficacy of tyrosine kinase inhibitor (TKI) therapy for ATC, evidence is scarce in clinical practice. In this study, we reviewed our initial experiences with TKI treatment in ATC patients with the aim of revealing the efficacy and safety of the same in clinical practice. We retrospectively reviewed our experiences with TKI treatment use in ATC patients diagnosed at our institute from 2014 to 2019. Changes in the patients' neutrophil-to-lymphocyte ratio (NLR) by TKI therapy introduction as well as their clinical factors to indicate the efficacy were examined. Seven patients showed no indication for TKI treatment, while 13 (65%) received treatment. The median duration of TKI treatment was 1.9 months. All patients died, and the overall survival period from diagnosis was 4.7 (95% confidence interval: 2.0–11.5) months. Adverse events ≥Grade 3 were observed commonly (92.3%), and resulted in the termination of TKI treatment in six cases (46.1%). Existence of multiple unfavorable characteristics (higher Prognostic Index) was associated with poor survival. The NLR decreased after the introduction of TKIs and increased again when treatment failed. The response rate to TKI among the ATC patients were approximately 30% in practice. Although the duration of the response was short, several patients demonstrated long survival durations when TKI treatment was provided after successful multidisciplinary treatment to control local disease. Decreases in high NLR values during treatment may suggest the continued effect of TKIs.
Abstract Accumulating evidence indicates that alterations of gut microbiota are associated with colorectal cancer (CRC). Therefore, the use of gut microbiota for the diagnosis of CRC has received attention. Recently, several studies have been conducted to detect the differences in the gut microbiota between healthy individuals and CRC patients using machine learning‐based gut bacterial DNA meta‐sequencing analysis, and to use this information for the development of CRC diagnostic model. However, to date, most studies had small sample sizes and/or only cross‐validated using the training dataset that was used to create the diagnostic model, rather than validated using an independent test dataset. Since machine learning‐based diagnostic models cause overfitting if the sample size is small and/or an independent test dataset is not used for validation, the reliability of these diagnostic models needs to be interpreted with caution. To circumvent these problems, here we have established a new machine learning‐based CRC diagnostic model using the gut microbiota as an indicator. Validation using independent test datasets showed that the true positive rate of our CRC diagnostic model increased substantially as CRC progressed from Stage I to more than 60% for CRC patients more advanced than Stage II when the false positive rate was set around 8%. Moreover, there was no statistically significant difference in the true positive rate between samples collected in different cities or in any part of the colorectum. These results reveal the possibility of the practical application of gut microbiota‐based CRC screening tests.
Background: Human scirrhous gastric carcinoma (SGC) is also known as diffusely infiltrating carcinoma, type 4 on Borrmann's criteria, and linitis plastica-type carcinoma. SGC is characterized by frequent peritoneal metastasis, high proliferation and infiltration activity with extensive fibrosis in the tumor stroma. We previously reported that a soluble factor(s) from SGC cells changed the peritoneum to pre-metastatic niche such as round shape of mesothelial cells and peritoneal fibrosis, which is a favorable environment for cancer cells to metastasize. Extracellular vesicles (EVs; Exosomes) might be one of soluble factor(s) which might change the peritoneal component to pre-metastatic niche. In this study, we investigated the effect of EVs from SGC cells on the pre-metastatic niche formation of the peritoneum.Methods: Four SGC cell lines, OCUM-2M, OCUM-2MD3, OCUM-12, KATO-III, 2 non-SGC cell lines, MKN74, MKN45, and peritoneal mesothelial cells (PM cells) were used. The effect of EVs from gastric cancer cells on the peritoneum was examined in vitro and in vivo, as follows. PKH26-labeled EVs from OCUM-2MD3 cells were intravenously injected into nude mice for 3 weeks, then we examined the distribution of PKH26-labeled EVs by a fluorescence microscope. Next, we injected EVs intraperitoneally into nude mice, and investigated the morphology of peritoneum. Effect of EVs on the gene expression of PM cells was examined by RT-PCR. Clinical significance of EVs markers, CD9 and CD63, was evaluated by immunohistochemistry using 63 human gastric cancer specimens.Results: PKH26-labeled EVs frequently distributed to peritoneum and the liver. The morphology of PM cells changed from round shape to spindle shape by EVs addiction in vitro and in vivo. mRNA expression level of ZEB and N-cadherin of PM cells was significantly increased following the addiction of EVs. The high expression of EVsmarkers, CD9 and CD63, was significantly correlated with frequent peritoneal metastasis.Conclusion: EVs from SGC cells might frequently distribute to mesothelial cells of peritoneum. EVs from SGC cells might play an important role for the formation of a pre-metastatic niche on peritoneum by the morphologic change of peritoneal mesothelial cells.Citation Format: Tomohisa Okuno, Masakazu Yashiro, Shuhei Kushiyama, Sadaaki Nishimura, Shingo Togano, Kenji Kuroda, Tatsuro Tamura, Takahiro Toyokawa, Hiroaki Tanaka, Kazuya Muguruma, Kosei Hirakawa, Masaichi Ohira. Extracellular vesicles from scirrhous gastric cancer cells induce premetastatic niche formation for peritoneal metastasis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 5160.
Background/Aim: Neoadjuvant chemotherapy (NAC) using 5-FU (5-fluorouracil)/CDDP (cisplatin) is a standard therapy for stage II/III thoracic esophageal squamous cell carcinoma (ESCC) in Japan. The aim of this study was to investigate whether 5-FU/CDDP could induce immunogenic cell death in ESCC cell lines. Materials and Methods: Tumor samples for immunohistochemistry were obtained from 50 patients (mean age=63.1 years) with pathological stage 0-IVa ESCC who underwent NAC followed by surgery. Cell lines T.T and KYSE30 were used for the in vitro experiments. Results: The concentrations of HMGB1 were elevated in the cell line supernatants treated with 5-FU/CDDP. 5-FU/CDDP treated dendritic cells (DCs) showed a mature phenotype, and enhanced T cell proliferation capacity. In addition, mature DCs were observed in surgical specimens with a histological response after treatment with 5-FU/CDDP chemotherapy. Conclusion: 5-FU/CDDP could induce immunogenic cell death in the tumor microenvironment of ESCC.
In patients undergoing mastectomy for locally advanced breast cancer, surgical skin flap reconstruction is sometimes required in order to cover large skin defects. Generally, we reconstruct by using latissimus dorsi or rectus abdominis when the direct closure is difficult. These constructions are difficult and have various complications. Our facility started rhomboid flap reconstruction after mastectomy. We report the result of rhomboid flap reconstruction. Five patients were performed rhomboid flap reconstruction. Three of 5 patients were cutaneous invasion, 1 patient was skin metastasis after mastectomy, and the other patient was Paget's disease. Regarding post operative complications, there were 2 cases of surgical site infection, 2 cases of skin necrosis and 1 case of seroma. The median length of postoperative hospital stay was 9 days. Median follow-up period was 381 days(221-508 days). Only 1 patient progressed. The median progression-free survival was 332 days(221-508 days). Rhomboid flap reconstruction is effective way for the improvement of the QOL of the patients with advanced breast cancer because the long term result was not bad and we can repair large skin defect easily.
A 66-year-old man underwent laparoscopic right nephrectomy for renal cell carcinoma (T2b, N0, M1, clear cell, Grade 3). He was treated with targeted therapy for lung metastases after nephrectomy. Despite the targeted therapy, he was paralyzed in the lower half of the body due to the spinal metastases. Therefore, an osteoplastic laminectomy and domelaminectomy for the spinal metastases was performed. The FDG-PET examination, which was performed after the operation, revealed lung, liver, bone, and small intestinal metastases. After a while, he suffered from continuous massive melena. Double balloon enteroscopy revealed a hemorrhagic tumor in the small intestine, and an emergency operation was performed. A partial resection of the small intestine was performed for the 3 tumors. The histopathological diagnosis was small intestinal metastasis from renal cell carcinoma. It is well known that renal cell carcinoma often develops metastases to the lung, bone, and liver. However, small intestinal metastasis from renal cell carcinoma is rare. Although small intestinal metastasis from renal cell carcinoma often accompanies metastases to other organs, a palliative operation might improve the quality of life in patients with symptomatic tumors.
The frequency of rectal gastrointestinal stromal tumor (GIST) is relatively low. We have experienced three cases of giant rectal GIST. Case 1 was treated with sunitinib after imatinib failed by Stevens-Johnson syndrome as neoadjuvant therapy. Case 2 was treated with imatinib as neoadjuvant therapy. These neoadjuvant therapies had no effect on tumor size. All patients underwent an abdominoperineal resection. The mean major axis was 11 .7 cm. Immnohistochemical staining showed that CD34 and KIT were positive. The term of follow-up is short, but no recurrences have been found in all cases. It has been reported that imatinib as neoadjuvant therapy is useful for radical resection in cases of giant rectal GIST. Furthermore, neoadjuvant therapy seems to be one of the treatment options for locally advanced rectal GIST. However, in cases of GIST patients not responding to imatinib, we should perform a surgical resection immediately.
48 Background: Programmed cell death (PD) -1, one of immune checkpoint molecules, expresses on T cells and induces immune tolerances in tumor microenvironment by binding to the ligand PDL-1 on the cancer cells. The clinical effect of immune checkpoint inhibitors such as anti-PD-1/PDL-1 antibody was demonstrated in various cancer including malignant melanoma, lung cancer and gastric cancer. The development of biomarkers for case selection that these inhibitors are effective will be in urgent need. We previously showed that neutrophil-lymphocyte ratio (NLR), a marker for general immune response, was related with postoperative recurrence and advanced stage of gastric cancer. In this study, we report the association of pretreatment NLR with PD-1/PDL-1 expression in the primary tumor of gastric cancer. Methods: Using immunohistochemistry, we retrospectively examined the expression of PDL-1 and infiltration of PD-1 + cells in primary tumor from 180 patients who had undergone surgery for gastric cancer between 2007 and 2010 at the Department of Surgical Oncology of Osaka City University. Results: Positive expression of PDL-1 was observed in 78 (43%) patients. PDL-1 expression was correlated with tumor infiltrated PD-1 + cells and related poor prognosis of the patients with Stage II/III. NLR was correlated with pathological stage and lymph node metastasis. In the positive PDL-1 group, NLR was significantly increased compared with negative group. However, the number of infiltrated PD-1+ cells was not correlated with NLR. Conclusions: PDL-1 expression in gastric cancer tissues was associated with pretreatment NLR, indicating that local immune suppression could be reflected in the systemic immune responses. Our data also suggested that NLR might be one of surrogate marker for PD-1/PDL-1 blockade therapy for gastric cancer.
