A rat-based preclinical platform facilitating transcatheter hepatic arterial infusion in immunodeficient rats with liver xenografts of patient-derived pancreatic ductal adenocarcinoma.

Liver metastases from pancreatic ductal adenocarcinoma (PDAC) are highly fatal. A rat-based patient-derived tumor xenograft (PDX) model is available for transcatheter therapy. This study aimed to create an immunodeficient rat model with liver xenografts of patient-derived primary PDAC and evaluate efficacy of hepatic arterial infusion chemotherapy with cisplatin in this model. Three patient-derived PDACs were transplanted into the livers of 21 rats each (totally, 63 rats), randomly assigned into hepatic arterial infusion, systemic venous infusion, and control groups (n = 7 each) four weeks post-implantation. Computed tomography evaluated tumor volumes before and four weeks after treatment. Post-euthanasia, resected tumor specimens underwent histopathological examination. A liver-implanted PDAC PDX rat model was established in all 63 rats, with first CT identifying all tumors. Four weeks post-treatment, arterial infusion groups exhibited significantly smaller tumor volumes than controls for all three tumors on second CT. Xenograft tumors histologically maintained adenocarcinoma features compared to original patient tumors. Ki67 expression was significantly lower in arterial infusion groups than in the other two for the three tumors, indicating reduced tumor growth in PDX rats. A liver-implanted PDAC PDX rat model was established as a rat-based preclinical platform. Arterial cisplatin infusion chemotherapy represents a potential therapy for PDAC liver metastasis.

CXCR2 signaling might have a tumor-suppressive role in patients with cholangiocarcinoma.

BACKGROUND: We reported that chemokine C-X-C motif receptor 2 (CXCR2) signaling appears to play an important role in the pathogenic signaling of gastric cancer (GC), and although CXCR2 may have a role in other solid cancers, the significance of CXCR2 in cholangiocarcinoma (CCA) has not been evaluated. Herein, we determined the clinicopathologic significance of CXCL1-CXCR2 signaling in CCA. MATERIALS AND METHODS: Two human CCA cell lines, OCUG-1 and HuCCT1, were used. CXCR2 expression was examined by western blotting. We investigated the effects of CXCL1 on the proliferation (by MTT assay) and migration activity (by a wound-healing assay) of each cell line. Our immunohistochemical study of the cases of 178 CCA patients examined the expression levels of CXCR2 and CXCL1, and we analyzed the relationship between these expression levels and the patients' clinicopathologic features. RESULTS: CXCR2 was expressed on both CCA cell lines. CXCL1 significantly inhibited both the proliferative activity and migratory activity of both cell lines. CXCL1 and CXCR2 were immunohistochemically expressed in 73% and 18% of the CCA cases, respectively. The CXCL1-positive group was significantly associated with negative lymph node metastasis (p = 0.043). The CXCR2-positive group showed significantly better survival (p = 0.042, Kaplan-Meier). A multivariate logistic regression analysis revealed that CXCR2 expression (p = 0.031) and lymph node metastasis (p = 0.004) were significantly correlated with the CCA patients' overall survival. CONCLUSION: CXCR2 signaling might exert a tumor-suppressive effect on CCA cells. CXCR2 might be a useful independent prognostic marker for CCA patients after surgical resection.

[Surgical Resection of Pulmonary Oligometastases of Ampullary Cancer-A Case Report and Review of Seven Cases].

A 62-year-old woman underwent a subtotal stomach-preserving pancreatoduodenectomy for ampullary carcinoma (T3bN0M0, Stage Ⅱb). Histopathologically, the tumor was a tubular adenocarcinoma with mixed features, predominantly the intestinal type, following which adjuvant chemotherapy was not performed. Computed tomography performed 32 months after surgery showed a tumor measuring 6.7 mm in diameter at the apex of the right lung. The tumor had gradually increased in size and measured 10 mm in diameter, 47 months postoperatively. Since other metastatic lesions were absent, partial resection of the right lung under video-assisted thoracic surgery was performed 48 months postoperatively. Histopathological testing confirmed a diagnosis of lung metastasis from the resected specimen of ampullary carcinoma without mediastinal lymph node metastasis. Adjuvant chemotherapy was not performed, and recurrence was not observed even after 53 months following the partial lung resection. Previously, 7 resected cases of solitary lung metastasis from ampullary cancer have been reported. The histopathological sub-type of these 7 cases were intestinal type in 5 and pancreatobiliary type in 2 cases, respectively. No mortality or recurrence was observed for 8-119 months in any of the 7 cases(median, 19 months). In conclusion, owing to the good prognosis, solitary lung metastasis from an ampullary cancer can be classified as an oligometastatic disease, based on the concept proposed by Hellman and Weichselbaum.

Establishment of a Liver Transplant Patient-derived Tumor Xenograft (PDX) Model Using Cryopreserved Pancreatic Ductal Adenocarcinoma.

BACKGROUND/AIM: There is rapid progression and widespread use of patient-derived tumor xenografts (PDX) in translational pancreatic cancer research. This study aimed to establish a liver transplant PDX model using cryopreserved primary pancreatic ductal adenocarcinoma (PDAC). PATIENTS AND METHODS: Primary PDAC from 10 patients were cryopreserved and transplanted into immunodeficient mice using the liver pocket method. H&E staining and immunohistochemical staining, such as Ki-67, p53, Smad4, and MUC1 were used to evaluate engraftment and histological similarities. RESULTS: Patient-derived xenograft placement was successful in six cases (60%), and 10 mice (33.3%). The Ki-67 index of primary PDAC and the cryopreservation duration were significantly related to successful engraftment (p=0.003 and p=0.007, respectively). CONCLUSION: In this study, we succeeded in establishing a liver transplant PDX mouse model as a preclinical platform. The successful engraftment was affected by the cryopreservation duration and could be detected by the Ki-67 index.

Preoperative Neutrophil-to-lymphocyte Ratio Predicts Tumor-infiltrating CD8+ T Cells in Biliary Tract Cancer.

BACKGROUND/AIM: This study evaluated the prognostic significance of preoperative neutrophil-to-lymphocyte ratio (NLR) and CD8+ tumor-infiltrating lymphocytes (TILs), and whether preoperative NLR was associated with CD8+ TILs in biliary tract cancers (BTCs). PATIENTS AND METHODS: A total of 154 patients with BTCs who underwent surgery were enrolled in this study. We obtained neutrophil and lymphocyte counts, and calculated NLR from preoperative peripheral blood samples. CD8+ TILs were identified by immunohistochemical staining. RESULTS: The overall survival (OS) and recurrence-free survival (RFS) of patients with high NLR were shorter than those with low NLR. The OS and RFS of patients with high CD8+ TILs were longer than those with low CD8+ TILs. Preoperative NLR and CD8+ TILs were negatively correlated. CONCLUSION: NLR and CD8+ TILs were associated with OS and RFS in BTCs. NLR can predict CD8+ TILs infiltrating the cancer microenvironment.

[Descending Colon Cancer with Synchronous Solitary Small Intestinal Metastasis-A Case Report].

A 77-year-old man presented with biliary colic and was diagnosed with descending colon cancer and cholelithiasis.During the surgery, a mass was detected in the upper jejunum, located 5 cm from the Treitz ligament on the anal side.Open left hemicolectomy with partial jejunal resection was performed.The mass in the small intestine was diagnosed as solitary small intestinal metastasis of colon cancer through immunohistopathological examination.Isolated intestinal metastases of colorectal cancers are rare.Furthermore, synchronous metastases are rare among these cases.A previous study reported poor prognosis in patients with small intestinal metastasis; therefore, more studies on the small intestinal metastasis of colorectal cancer are necessary.

[A Case of Disturbance of Consciousness Due to Hyperammonemia during Chemotherapy for Metastasis of Sigmoid Colon Cancer].

A 76-year-old woman had underwent 5-fluorouracil(5-FU), oxaliplatin(L-OHP)combination therapy(mFOLFOX6)as first-line chemotherapy for peritoneal recurrence after resection of sigmoid colon cancer. She showed severe general fatigue and disturbance of consciousness on the second day of the 12th course of chemotherapy. Computed tomography of the head detected no abnormal findings in the central nervous system. The laboratory results revealed a marked hyperammonemia. She was diagnosed as a disturbance of consciousness due to hyperammonemia and treated her with branched- chain amino acid solution. Then the disturbance of consciousness resolved on the following day. After changing the regimen of chemotherapy, the disturbance of consciousness was not found. Recently, it has been reported that high-dose 5-FU regimen such as mFOLFOX6 causes hyperammonemia as a rare adverse event. We should take hyperammonemia into account when disturbance of consciousness occurs during high-dose 5-FU chemotherapy.

[A Resected Case of Retroperitoneal Metastasis and Small Bowel Metastasis from HCC].

A 71-year-old man underwent right hemi-hepatectomyfor a hepatocellular carcinoma(HCC)measuring 18 cm in diameter. The pathological diagnosis was poorlydifferentiated HCC. Ten months after the surgery, computed tomographyrevealed a nodule 12mm in diameter in the right lung as well as 2 nodules measuring 19 and 11mm in diameter in the retroperitoneum at the cranial aspect of the left kidney. Four months later, the nodule in the right lung had enlarged to 44 mm, while the 2 nodules in the retroperitoneum had enlarged to 68mm and 34 mm. These nodules were resected and histopathologicallydiagnosed as metastasis from HCC. Twenty-one months after liver resection, computed tomographyrevealed nodules 16 and 25mm in diameter in the retroperitoneum around the urinarybladder and jejunum, respectively. One month later, intussusception resulted from the jejunal tumor. Laparoscopic surgerywas performed for both tumors, which were diagnosed as metastases from HCC. Twenty-five months after liver resection, metastasis from the HCC appeared in the left adrenal grand, at the site of the jejunal anastomosis, and in the fattytissue around the right scapula. Twenty-nine months after liver resection, the patient died of respiratoryfailure from multiple metastases in the left lung.

[A Case of Rupture of Esophageal Varices during a Course of CAPOX with Bevacizumab Therapy for Sigmoid Colon Cancer with Multiple Liver Metastases].

The patient was a 67-year-old man with multiple liver metastases from sigmoid colon cancer and had received capecitabine, oxaliplatin, and bevacizumab(CAPOX plus Bev)combination chemotherapy. After 11 courses of this therapy, he had a rupture of esophageal varices and was treated with endoscopic variceal ligation(EVL). Esophageal varices are rare during the course of oxaliplatin-based chemotherapy. More studies are necessary for early detection of esophageal varices during this therapy.

Double-balloon endoscopy WAS effective in diagnosing small intestinal duplication: a case report.

INTRODUCTION: Ileal duplications are encountered infrequently in adults, because symptoms including abdominal pain, intussusception, hemorrhage, and perforation usually present in early childhood. In this report, we present an adult case of ileal duplication that was revealed by double-balloon endoscopy (DBE). CASE DESCRIPTION: A 73-year-old Japanese man presented with anemia and melena. Anal DBE detected the narrow opening of an extra lumen in the ileum about 100 cm proximal to the ileocecal valve. Enteroclysis via DBE showed a 5-cm-long ileal diverticulum-like structure at the mesenteric side of the ileum. No ectopic gastric mucosa was detected by technetium-99m pertechnetate scintigraphy. The final diagnosis was ileal duplication. DISCUSSION AND EVALUATION: This is the first report of tubular ileal duplication diagnosed by using DBE. The small intestinal duplication opening was not detected by using VCE and plane CT in this case, but was found by using DBE. CONCLUSIONS: The present case demonstrates that DBE was useful in the diagnosis of an adult small intestinal duplication that was not visualized by other modalities.