Emerging evidence supports the theory that tumor cell clusters efficiently metastasize to distant organs. However, the roles of epithelial‐to‐mesenchymal transition (EMT) in metastasizing tumor cell clusters have not yet been fully elucidated. To investigate this issue, tumor fragments were dissected from 40 colorectal cancer (CRC) patients and implanted subcutaneously into immunodeficient mice. We observed that tumors developed from the tumor fragments obtained from 28 of the 40 CRC patients. The tumors were then dissociated into cell suspensions to be orthotopically injected into secondary mice. The tumors from 13 of the 28 patients progressed. Furthermore, metastases formed spontaneously in the liver and lungs from the tumor fragments obtained from 8 of these 13 patients. Moreover, employing a mathematical analysis, we showed that tumor cell clusters seeded these metastases significantly more often than did single tumor cells. Membrane E‐cadherin‐ and nuclear ZEB1‐positive tumor cells indicating the hybrid epithelial/mesenchymal state were also detected in primary tumors of various CRC patients, and in the corresponding patient‐derived xenografts (PDXs) and circulating tumor cell clusters in the bloodstreams of mice. In contrast, ZEB1 staining was barely detectable in the patient‐matched liver metastases presumably developing through mesenchymal‐to‐epithelial transition. Inhibition of E‐cadherin or ZEB1 expression by shRNA notably prevented the PDX‐derived tumor organoids from colonizing the liver, when injected intrasplenically into mice, indicating E‐cadherin and ZEB1 expressions to be required for their metastatic colonization. Taken together, these findings suggest that the epithelial/mesenchymal state mediates metastatic seeding of human CRC cell clusters into distant organs.

Background/AimsSclerotherapy with aluminum potassium sulfate and tannic acid (ALTA) has a potent effect on internal hemorrhoids. In this retrospective study, we compared the effects of endoscopic ALTA therapy and standard ALTA therapy. MethodsWe investigated patients who underwent treatment for internal hemorrhoids at our institution between 2014 and 2016. They were divided into a standard ALTA group (n=33, treated using proctoscopy) and an endoscopic ALTA group (n=48). We compared the clinical findings between the 2 groups. ResultsThere were no intergroup differences in background factors. The mean ALTA dose was 21.9±7.2 mL and 17.8±3.4 mL in the standard and endoscopic ALTA groups, respectively (p<0.01). Adverse events occurred in 4 patients (12.1%) from the standard ALTA group and 6 patients (12.5%) from the endoscopic ALTA group. In both groups, the patients reported good satisfaction with the therapeutic effect at 1 month after the procedure. Hemorrhoids recurred in 2 patients (6.3%) from the standard ALTA group and 4 patients (8.3%) from the endoscopic ALTA group. ConclusionsEndoscopic ALTA sclerotherapy is equivalent to standard ALTA therapy in terms of efficacy, adverse events, and recurrence. Therefore, it is a useful non-surgical option for patients with internal hemorrhoids who prefer a less invasive treatment.

This case involved an 80-year-old man who was seen for melena. Further testing revealed a tubular adenocarcinoma 50 mm in size in the rectum. In addition, an anal fistula was noted behind the anus along with induration. A biopsy of tissue from the external (secondary) opening of the fistula also revealed adenocarcinoma. Nodules suspected of being metastases were noted in both lung fields. The patient was diagnosed with rectal cancer, a cancer arising from an anal fistula, and a metastatic pulmonary tumor, and neoadjuvant chemotherapy was begun. A laparoscopic abdominoperineal resection was performed 34 days after 6 cycles of mFOLFOX-6 therapy. Based on pathology, the rectal cancer was diagnosed as moderately differentiated adenocarcinoma, and this adenocarcinoma had lymph node metastasis (yp T3N2aM1b). There was no communication between the rectal lesion and the anal fistula, and a moderately differentiated tubular adenocarcinoma resembling the rectal lesion was noted in the anal fistula. Immunohistochemical staining indicated that both the rectal lesion and anal fistula were cytokeratin 7 (CK7) (−) and cytokeratin 20 (CK20) (+), and the patient’s condition was diagnosed as implantation of rectal cancer in an anal fistula.In instances where an anal fistula develops in colon cancer, cancer implantation in that fistula must also be taken into account, and further testing should be performed prior to surgery.

HighlightsClear cell adenocarcinoma arising from endometriosis is very rare.Preoperative diagnosis of the malignant transformation in endometriosis is very difficult.The patient was undergone low anterior resection under the diagnosis of rectal carcinoma.Sampson's criteria are useful for diagnosis of the malignant transformation in endometriosis.The prognosis of malignant transformation in endometriosis is poor.

Despite current advances in human colorectal cancer (CRC) treatment, few radical therapies are effective for the late stages of CRC. To overcome this clinical challenge, tumor xenograft mouse models using long-established human carcinoma cell lines and many transgenic mouse models with tumors have been developed as preclinical models. They partially mimic the features of human carcinomas, but often fail to recapitulate the key aspects of human malignancies including invasion and metastasis. Thus, alternative models that better represent the malignant progression in human CRC have long been awaited. We herein show generation of patient-derived tumor xenografts (PDXs) by subcutaneous implantation of small CRC fragments surgically dissected from a patient. The colon PDXs develop and histopathologically resemble the CRC in the patient. However, few spontaneous micrometastases are detectable in conventional cross-sections of affected distant organs in the PDX model. To facilitate the detection of metastatic dissemination into distant organs, we extracted the tumor organoid cells from the colon PDXs in culture and infected them with GFP lentivirus prior to injection into highly immunodeficient NOD/Shi-scid IL2Rγ (NOG) mice. Orthotopically injected PDX-derived CRC organoid cells consistently form primary tumors positive for GFP in recipient mice. Moreover, spontaneously developing micrometastatic colonies expressing GFP are notably detected in the lungs of these mice by fluorescence microscopy. Moreover, intrasplenic injection of CRC organoids frequently produces hepatic colonization. Taken together, these findings indicate GFP-labelled PDX-derived CRC organoid cells to be visually detectable during a multistep process termed the invasion-metastasis cascade. The described protocols include the establishment of PDXs of human CRC and 3D culture of the corresponding CRC organoid cells transduced by GFP lentiviral particles.