Cancer Stem Cells Persist Despite Cellular Damage, Emergence of the Refractory Cell Population.

PURPOSE: Cancer stem cells (CSCs) are responsible for chemotherapy resistance and have unique properties that protect them from chemotherapy. Investigating CSCs may help to identify the population that is more resistant to treatments, leading to recurrence. We evaluated persisting CSCs, emerging after chemotherapy that cause tumor recurrence. METHODS: Using human colorectal cancer organoids prepared from surgical specimens, we looked at changes in CSCs, the emergence and changes in the original population, which single-cell analysis identified. RESULTS: With regards to changes in cancer stem cell markers, CD44 showed low levels after 5-fluorouracil administration. Once the CD44-ve population was sorted and cultured, the CD44+ve population gradually emerged, and the CD44-ve population decreased. Compared with the CD44-ve population of an organoid parent, the CD44-ve population proliferated after chemotherapeutic agent stimulation. The CD44-ve population was derived from the CD44+ve population before chemotherapeutic agents. In addition, when the CD44 variants were evaluated, the CD44v9 population remained. In single-cell analysis, we found that POU5F1 was highly expressed in the CD44low population. Velocity analysis showed that the CD44-ve population was induced after chemotherapy and expressed POU5F1. POU5F1-EGFP-Casp9 transfected organoids resulted in the appearance of a CD44-ve population after administration of a chemotherapeutic reagent. Both in vivo and in vitro, the dimerizer administration inhibited tumor growth significantly. CONCLUSIONS: POU5F1 is involved in chemotherapy resistance in relation to stemness. For the treatment against refractory tumors, such as the recurrence after chemotherapy, the treatment should target the emerging specific population such as CD44 (or CD44v9) and proliferative cancer cells.

[Negative Pressure Wound Therapy for Advanced Recurrent Rectal Cancer].

The incidence of perineal wound complications after extended pelvic surgeries for locally advanced or locally recurrent cancer is high. The management of these refractory complications is usually difficult. Extended pelvic surgeries are commonly associated with severe infectious complications owing to pre-operative chemoradiation therapy, the tissue damage during surgery, and the dead space after radical resections. Negative pressure wound therapy(NPWT)is widely used for the management ofseveral wounds. Recently, the utility ofNPWT has been reported on the management ofinf ectious wound complications post-surgery. Some authors reported the drainage effect of NPWT on pelvic abscess after surgery. However, so far, only a few reports have been published on the usefulness of NPWT in the management of perineal wound disruption or pelvic abscess. We performed NPWT on patients with perineal wound disruption or intractable lymphorrhoea. In these cases, NPWP was effective in early successful treatment. In summary, NPWT is an effective treatment option for perineal disruption and pelvic abscess after surgery for locally advanced or locally recurrent cancers.

[Palliative Radiotherapy and Sequential Nivolumab Administration for Recurrent Gastric Cancer-A Case Report].

A 52-year-old man underwent total gastrectomy for advanced gastric cancer. The postoperative diagnosis was por1>muc >por2>tub2, pT4a(SE)N3bM0H0P0CY0, pStage ⅢC. He underwent 6 courses of adjuvant chemotherapy with capecitabine plus oxaliplatin. Six months after the surgery, CT showed 2 recurrent lesions: a tumor behind the esophago-jejunal anastomosis and another in the mesentery around the jejuno-jejunal anastomosis. Endoscopy showed intrajejunal invasion. Second-line therapy with paclitaxel and ramucirumab were administered for 3 courses, resulting in rapid progression of the disease. Palliative radiotherapy(39.6 Gy/22 Fr)for both lesions was performed for local control. Sequential administration of nivolumab was started 9 days after terminating radiotherapy. After 6 courses, both tumors markedly reduced PR, and the oral intake of food improved. After 10 courses, there was hyper-progression of the tumor behind the esophago-jejunal anastomosis and shrinkage of the other tumor. Surgery (left upper abdominal exenteration and enucleation of the tumor in the mesentery)was performed to release the jejunal limb obstruction. The tumor behind the esophago-jejunal anastomosis was a poorly differentiated adenocarcinoma, and no viable cancer cells were seen in the tumor in the mesentery. Radiotherapy and immune checkpoint inhibitors may be effective for gastric cancers, although the mechanism of action should be elucidated.

[A Case of Hepatic Resection after Neoadjuvant Chemotherapy for Single Liver Metastasis from Gastric Cancer with Positive Human Epidermal Growth Factor Receptor 2].

A man in his 70s was diagnosed with gastric cancer and underwent total gastrectomy with D2 lymphadenectomy. The final diagnosis was T3(SS)N2M0, Stage ⅢA. After surgery, S-1 was administered for 1 year. One year and 6 months after surgery, abdominal computed tomography showed a single liver tumor(S4: 30mm). Based on overexpression of the human epidermal growth factor receptor 2(HER2)protein in the primary tumor, we selected capecitabine plus cisplatin plus trastuzumab as the combination chemotherapy. After the second course, the therapeutic response was stable. S4 partial liver resection was performed. The liver tumor was histologically evaluated as Grade Ⅰb metastatic gastric adenocarcinoma. After surgery, capecitabine plus trastuzumab was administered for 1 year. One year after resection of liver metastasis, the patient is alive without any relapse.

Treatment response prediction of neoadjuvant chemotherapy for rectal cancer by deep learning of colonoscopy images.

In current clinical practice, several treatment methods, including neoadjuvant therapy, are being developed to improve overall survival or local recurrence rates for locally advanced rectal cancer. The response to neoadjuvant therapy is usually evaluated using imaging data collected before and after preoperative treatment or postsurgical pathological diagnosis. However, there is a need to accurately predict the response to preoperative treatment before treatment is administered. The present study used a deep learning network to examine colonoscopy images and construct a model to predict the response of rectal cancer to neoadjuvant chemotherapy. A total of 53 patients who underwent preoperative chemotherapy followed by radical resection for advanced rectal cancer at the Osaka University Hospital between January 2011 and August 2019 were retrospectively analyzed. A convolutional neural network model was constructed using 403 images from 43 patients as the learning set. The diagnostic accuracy of the deep learning model was evaluated using 84 images from 10 patients as the validation set. The model demonstrated a sensitivity, specificity, accuracy, positive predictive value and area under the curve of 77.6% (38/49), 62.9% (22/33), 71.4% (60/84), 74.5% (38/51) and 0.713, respectively, in predicting a poor response to neoadjuvant therapy. Overall, deep learning of colonoscopy images may contribute to an accurate prediction of the response of rectal cancer to neoadjuvant chemotherapy.

Fibroblast Activation Protein and Tertiary Lymphoid Structure in Colorectal Cancer Recurrence.

BACKGROUND/AIM: Fibroblast activation protein (FAP) is known to have prognostic significance in colorectal cancer (CRC). However, FAP and tertiary lymphoid structures (TLSs) have not been associated with each other in predicting the prognosis of CRC recurrence. PATIENTS AND METHODS: FAP expression was evaluated by real-time reverse transcription polymerase chain reaction in 195 CRC patients at Osaka International Cancer Institute (first data set). Immunohistochemistry (IHC) was then performed to stain FAP at the invasive margin (IM) and in the central tumour (CT) in 159 CRC patients at Osaka University Hospital (second data set). Consecutive slides were used to evaluate the presence of TLSs in 159 CRC patients from Osaka University Hospital. RESULTS: The high FAP mRNA expression group (n=82) was associated with poor recurrence-free survival (RFS) compared with the low FAP expression group (n=83) (p=0.004). In the second data set, patients with high FAP expression in CT and TLS absence (n=49) showed significantly poorer RFS compared with those with low expression of FAP in CT and presence of TLSs (n=101) (p=0.002). CONCLUSION: FAP in the CT combined with TLSs was shown to have significant prognostic value in predicting CRC recurrence after curative resection.