Incorporation of human iPSC-derived stromal cells creates a pancreatic cancer organoid with heterogeneous cancer-associated fibroblasts.

The aggressiveness of pancreatic ductal adenocarcinoma (PDAC) is affected by the tumor microenvironment (TME). In this study, to recapitulate the PDAC TME ex vivo, we cocultured patient-derived PDAC cells with mesenchymal and vascular endothelial cells derived from human induced pluripotent stem cells (hiPSCs) to create a fused pancreatic cancer organoid (FPCO) in an air-liquid interface. FPCOs were further induced to resemble two distinct aspects of PDAC tissue. Quiescent FPCOs were drug resistant, likely because the TME consisted of abundant extracellular matrix proteins that were secreted from the various types of cancer-associated fibroblasts (CAFs) derived from hiPSCs. Proliferative FPCOs could re-proliferate after anticancer drug treatment, suggesting that this type of FPCO would be useful for studying PDAC recurrence. Thus, we generated PDAC organoids that recapitulate the heterogeneity of PDAC tissue and are a potential platform for screening anticancer drugs.

Laparoscopic ileo-transverse bypass may contribute to achieving curative resection for locally advanced right colon cancer: a case report.

BACKGROUND: The strategy for treating obstructive colon cancers with metastatic lesions remains unclear. Herein, we report a case of laparoscopic ileo-transverse colon bypass (LITB) before preoperative chemotherapy for an obstructive right colon cancer. CASE PRESENTATION: A 59-year-old woman was referred to our institution (Department of Gastroenterological Surgery, Chiba Cancer Center) for liver tumors detected on ultrasound. The clinical diagnosis was ascending colon cancer with multiple liver metastases. Based on the criteria of the International Union against Cancer Committee, 8th edition, the staging was confirmed as cT4aN1M1a(H), cStage IV. Although the primary tumor in the ascending colon extended beyond the colonic wall, curative resection was possible for both primary and metastatic tumors. We planned to administer chemotherapy before the radical surgery to obtain tumor-free resection margins; however, as the obstruction was fatal, LITB was prioritized and performed using five ports. An intracorporeal side-to-side anastomosis was performed between the ileum, 25 cm from the terminal ileum, and the transverse colon. The patient was discharged on postoperative day 18 without any complications. After LITB, for preoperative chemotherapy, five courses of capecitabine plus oxaliplatin (CapeOX) + bevacizumab were administered. Six weeks after the preoperative chemotherapy, right hemicolectomy with D3 lymph node dissection and right hepatectomy were performed. Pathological findings of the resected specimen confirmed curative resection of both lesions, and a favorable effect of chemotherapy was obtained. The patient has been alive for over 8 months after the surgery, with no evidence of cancer recurrence. CONCLUSIONS: This case report demonstrates the effectiveness of LITB for obstructive right colon cancer in patients who need preoperative chemotherapy.

[Intracorporeal Anastomosis in Laparoscopic Colectomy with Blood Flow Confirmation by Fluorescence Angiography].

We verified the significance of intestinal blood flow evaluation by indocyanine green(ICG)fluorescence during intracorporeal anastomosis in laparoscopic colectomy which was performed from July 2019 to December 2019 in our institute. For 11 cases of intracorporeal anastomosis, we examined the patient background, surgical results such as operation time and blood loss, evaluation of intraoperative ICG blood flow, and perioperative complications. In all cases, after the mesentery treatment in the abdominal cavity and before the intestinal incision, the blood flow of the planned anastomosis site was evaluated by ICG fluorescence observation. No cases were required to be changed the anastomosis site. The average operation time was 240 minutes and the average blood loss was 10 mL. There were no perioperative complications such as anastomotic leakage, stenosis, bleeding, nor wound infection. It was suggested that the intraoperative evaluation of ICG blood flow during intracorporeal anastomosis in laparoscopic colectomy may contribute to the suppression of complications such as anastomotic leakage.

[A Study of Laparoscopic Stoma Creation for Patients with Colorectal Cancer].

There are few reports on laparoscopic stoma creation; we report here our experience with laparoscopic stoma creation. PATIENTS AND METHODS: Seven patients who underwent laparoscopic stoma creation between April 2019 and December 2019 were studied and their clinical outcome was evaluated retrospectively. Operation approach: We performed a colostomy in the transverse colon. At first, we insert a 12 mm first port into the site of stoma marking. And more, we insert three 5 mm ports on the opposite side of the first port. We remove the adhesions of the intestinal tract and create a colostomy. RESULT: We changed open method 2 cases out of 7 cases due to extensive adhesion. In laparoscopically, we had an operation time of 97 (42-130) minutes and a blood loss of 5(2-40) mL. We had no postoperative complications or stoma problems. CONCLUSION: Laparoscopic stoma creation was useful due to few postoperative complications and can be rapidly transferred to chemotherapy.

Residual esophageal necrosis after radical esophagectomy for esophagogastric cancer: A case report.

A 66-year-old man was diagnosed with advanced esophagogastric junction cancer and referred to our institution (Department of Gastroenterological Surgery, Chiba Cancer Center) for treatment. Computed tomography imaging confirmed the presence of a tumor, extending from the lower thoracic esophageal to the esophagogastric junction, with swelling of the upper mediastinal lymph nodes. Based on the criteria of the International Union against Cancer Committee (UICC, 8th Edition), the staging was confirmed as follows: 101R, 107 and 106 pre. Based on these findings, a clinical diagnosis of EGJ cancer was made, with a UICC 8th classification of cT3N1M0 c-stage-III. Preoperative chemotherapy was performed, with tumor shrinkage obtained after three courses of chemotherapy (using S-1 plus oxaliplatin). Subsequently, esophagectomy with three-field lymph node dissection and gastric tube reconstruction, via the intrathoracic route, was performed. On postoperative day 2, the patient developed an idiopathic pneumothorax, with brown-green drainage from the chest tube. A repeat thoracotomy was performed, confirming the presence of brown-green pleural fluid and necrosis of esophageal tissue. The area of necrosis was situated 4 cm on the oral side of the anastomosis, with greater necrosis of the right than left side. There was no evidence of necrosis of the gastric tube. The necrotic residual esophagus was excised and reconstructed, as an external fistula on the left side of the neck. On day 38, after the second surgery, reconstruction of the esophageal conduit and gastric tube, via the jejunum, was performed. At 7 months after discharge, the patient was symptom free, with no evidence of cancer recurrence.

[Significance of Surgery for Multidisciplinary Treatment Including Neoadjuvant Chemotherapy for Locally Advanced Colorectal Cancer].

Neoadjuvant chemotherapy has been performed for locally advanced colorectal cancer with invasion to other organs or lateral lymph node metastasis in to control local recurrence and distant metastasis. We evaluated the treatment results and the significance of surgery in 53 patients(36 rectal cancer cases and 17 sigmoid colon cancer cases)who underwent surgery after chemotherapy by XELOX plus bevacizumab for 3 months. As pretreatment diagnosis, 42 cases were T4b and 39 cases were lymph node positive. Combined resection was performed in 34 cases including 12 cases of total pelvic exenteration. Pathological diagnosis showed 27 cases of ypT4b and 34 cases of ypN0. Pathological curative resection was performed in 90.4%. Histological effect by chemotherapy was 31 cases in Grade(Gr)1a, 10 cases in Gr 1b, 8 cases in Gr 2, and 4 cases in Gr 3, respectively. The 5-year survival rate was 60.9% in Gr 1a or lower and 100% in Gr 1b or higher. Tumor markers( CEA and CA19-9)were reduced into normal range after neoadjuvant chemotherapy in all 4 patients with Gr 3. Pathological CR could not be predicted from clinical findings after neoadjuvant chemotherapy. It was suggested that neoadjuvant chemotherapy for locally advanced rectal cancer with invasion to other organs or lateral lymph node metastasis is useful for improving the prognosis, surgical resection is indispensable as a multidisciplinary treatment, and that the pathological therapeutic effect leads to prognosis prediction.

[Postoperative Recurrence of Pancreatic Cancer Successfully Treated with the Gemcitabine plus Oxaliplatin Regimen Resulting in Long-Term Survival-ACase Report].

A 38-year-old woman who presented with complaints of back pain was diagnosed with cancer of the pancreatic body. Since invasion of the celiac artery/superior mesenteric artery was suspected, she was referred to our department for chemotherapy. She received 4 courses of gemcitabine plus S-1(GS), and she underwent distal pancreatectomy with en bloc celiac axis resection/portal vein resection/reconstruction using a left renal vein graft(OP-CAR). Histopathological examination of the resected specimen revealed a positive margin(R1). She received 11 courses of GS as postoperative adjuvant chemotherapy. She developed marked abdominal distension due to metastatic ovarian enlargement, and bilateral salpingo-oophorectomy was performed. The intraoperative findings revealed multiple peritoneal dissemination. Peritoneocentesis was performed, and the patient was started on gemcitabine plus oxaliplatin(GEMOX)for control of the ascites. This treatment was followed by a rapid decrease in the size of the ascites and resolution of the symptoms of stenosis. The serum tumor marker levels decreased over the following 18months. She received a total of 35 courses of GEMOX. This patient showed long-term survival after the start of treatment: she survived for 5 years and 11 months after the initial examination and for 5 years and 6 months after the surgery. Our experience in this case suggests that GEMOX could be a useful treatment option to improve prognosis.

An increased neutrophil-to-lymphocyte ratio predicts poorer survival following recurrence for patients with breast cancer.

The aim of the present study was to evaluate the association between changes in the neutrophil-to-lymphocyte ratio and the survival rate, as well as tumor subtype, in recurrent breast cancer. Patients with recurrent breast cancer following surgery were included in this study. NLR was calculated and compared between two time points: Pre-treatment and recurrence. The associations between the longitudinal NLR change, the NLR at the time of recurrence and overall survival following recurrence (OSrec) were evaluated. A total of 89 patients were evaluated. NLR increased by 0.59 at recurrence, as compared with the initial treatment (P<0.05). The triple negative (TN) type demonstrated 4.59 in NLR, which was the highest among the four subtypes at the time of recurrence (P<0.05). The highest change (an increase of 2.0) was observed in TN type cancer (P<0.05). Patients with high NLR upon recurrence demonstrated significantly shorter OSrec rates (P<0.05). On the other hand, patients with an NLR increased by more than a third quartile demonstrated a shorter OSrec rate (P=0.06). When adjusted by covariates, the NLR and tumor subtype were determined to be associated with OSrec (P<0.05). Therefore, an increased NLR predicts survival, even in patients with recurrent breast cancer, and the NLR is potentially useful as an inflammation marker for TN breast cancer.

[Long-Term Survivors after Resection for Primary Pancreatic Carcinoma Stage IV].

We discuss the prognosis of cases of Stage IV pancreatic carcinoma with distant metastases(7th Edition of General Rules for the Study of Pancreatic Cancer, Japan Pancreas Society)for which any treatment was performed at our hospital. Fiftythree patients were radiographically or pathologically diagnosed as having Stage IV pancreatic carcinoma with definite prognosis, and received treatments, includingsurg ery or chemotherapy, at our department. Twenty-two cases showed more metastases, and celiac artery or superior mesenteric artery invasion was suspected in 28 cases. The 5-year survival rate of all 53 cases was 3.8%, and the median survival time(MST)was 6.2 months. The MST in the palliative surgery cases was 6.7 months, and that in the cases given best supportive care(BSC)was only 1.9 months. There were no 2-year survivors in the group given chemotherapy without any other treatments and in the group given BSC alone, while the longest survival time and MST were 66.9 and 31.3 months(p<0.001), respectively, in the 10 patients treated by primary tumor resection. There was only 1 patient who showed relapse-free survival. Primary site resection and chemotherapy over 4 cycles was revealed as an independent prognostic factor by multivariable analysis. Patients with Stage IV pancreatic carcinoma have a poor prognosis. However, the possibility of achievingimproved prognosis was noted with combined-modality therapy, including aggressive resection in limited cases showinga good response to chemotherapy or cases in whom preoperative metastasis assessment was difficult.