Takamichi Igarashi

Association of RAB5 overexpression in pancreatic cancer with cancer progression and poor prognosis via E-cadherin suppression

Pancreatic cancer is a common type of cancer with poor prognosis worldwide. Postoperative survival depends on the existence of metastasis. Elucidation of the mechanism underlying cancer progression is important to improve prognosis. The RAS-associated protein RAB5 activates intracellular membrane trafficking, and RAB5 expression is correlated to progression and epithelial mesenchymal transition in various cancers. The expression of RAB5 and E-cadherin in 111 pancreatic cancer samples was investigated by immunohistochemical staining, and the relationship among RAB5 expression, clinicopathological factors, and E-cadherin expression was assessed. Furthermore, RAB5 suppression analysis by siRNA was performed to determine the roles of RAB5 in morphological change, proliferation potency, cell migration ability, and invasiveness of the pancreatic cancer cell line. High RAB5 expression correlated with the presence of lymphatic invasion and venous invasion and low E-cadherin expression. Patients with high RAB5 expression had a poorer prognosis than those with low RAB5 expression. RAB5 suppression in pancreatic cancer cells enhanced E-cadherin expression; changed cell morphology from spindle to round; and inhibited proliferation, invasion, and cell migration. RAB5 contributes to poor prognosis and progression in pancreatic cancer patients. It may be a promising candidate for individualized therapy in refractory pancreatic cancer.

Laparoscopic resection of a paraganglioma located on the border of the thoracic and abdominal cavities using a transabdominal-transdiaphragmatic approach

We treated a 64‐year‐old woman with high blood pressure. Catecholamine metabolite levels were elevated in the blood and urine. CT revealed a densely stained tumor on the right side of the descending aorta dorsal to the inferior vena cava. PET‐CT revealed abnormal accumulation of 18F‐fluorodeoxyglucose, and 123I‐meta‐iodo‐benzylguanidine uptake was apparent on scintigraphy. The tumor was determined to be a paraganglioma located on the border between the thoracic and abdominal cavities, and laparoscopic tumorectomy was performed. The patient was placed in the left lateral position. The right lobe of the liver was turned over, and we cut the diaphragm to expose the front of the tumor. We resected the straight artery flowing in from the aorta and removed the tumor safely. Herein, we describe the removal of a paravertebral paraganglioma located in the border of the thoracic and abdominal cavities with a laparoscopic transabdominal‐transdiaphragmatic approach.

Perioperative management of hepatectomy in patients with interstitial pneumonia: a report of three cases and a literature review

PurposeInterstitial pneumonia (IP) is a progressive and irreversible fibrosis and can be fatal if acute exacerbation (AE) occurs. While a useful risk-scoring system has been established for lung surgery, no risk evaluation exists for AE of IP related to non-pulmonary surgery. The objective of this review is to describe the management for patients with IP.MethodsWe experienced three hepatectomy cases with IP. The first was a 72-year-old male patient diagnosed with hepatocellular carcinoma. Preoperative computed tomography (CT) revealed IP with reticular shadow at the base of both lungs. After hepatectomy, his IP became acutely exacerbated and did not improve with steroid or sivelestat treatment. The second was a 74-year-old male patient diagnosed with hepatocellular carcinoma, and the third was a 75-year-old male patient with liver metastasis. In both these cases, CT revealed a reticular shadow in the lung fields, with increased serum KL-6 levels. We administered pirfenidone for perioperative management, during which time no respiratory complications occurred.ResultsPerioperative management with pirfenidone for hepatectomy accompanied by IP was successful in our cases.ConclusionWe reviewed reports on the perioperative prevention, intraoperative risk factors, and treatment of postoperative AE of IP and summarized the perioperative management techniques for IP patients undergoing non-pulmonary surgery.

Enhanced karyopherin-α2 expression is associated with carcinogenesis in patients with intraductal papillary mucinous neoplasms

BACKGROUND/OBJECTIVES Intraductal papillary mucinous neoplasms (IPMN) can become malignant. Karyopherin-α2 (KPNA2) plays a central role in nucleocytoplasmic transport and is associated with various types of cancer. The current study examined pancreatic KPNA2 expression in cancer patients and evaluated its association with clinicopathological factors, cancer cell proliferation. METHODS KPNA2 expression was investigated by immunohistochemistry in 40 surgically resected IPMN samples and its association with clinicopathological factors and Ki-67 expression were examined. RESULTS Eighteen IPMN samples (45% of patients) showed positive KPNA2 expression. KPNA2 expression levels in IPMN tissue with invasive carcinoma were significantly higher than those in adjacent normal tissues and in IPMN tissue with low-to high-grade dysplasia. KPNA2 expression correlated with pathological malignancy and Ki-67 labeling index and KPNA2 and Ki-67 expression was co-localized in nuclei. E2F were co-localized with KPNA2 in the IPMN tissues with high expression of KPNA2. KPNA2 expression was enhanced in the invasion front and in proliferating Ki-67-positive cells. In addition, KPNA2 expression in IPMN tissues was associated with older age, dilation of main pancreatic duct diameter, the presence of nodules, and histological type. CONCLUSION KPNA2 expression is associated with carcinogenesis of IPMN through the adenoma-carcinoma sequence.

Presence of Cytokeratin 19-Expressing Cholangiocarcinoma-Like Tumour in a Liver Metastatic Lesion of Rectal Neuroendocrine Tumour

Introduction: Tumours with adenocarcinoma and neuroendocrine components have often been reported, although the reason underlying the dual components remains unclear. Case Presentation: A 43-year-old woman with multiple liver metastatic lesions of rectal neuroendocrine tumour underwent primary tumour resection and subsequent liver transplantation. Pathological examination indicated a cholangiocarcinoma-like tumour with gland formation, adjacent to a liver metastatic lesion of the neuroendocrine tumour. This tumour comprised atypical columnar epithelium, and stained positively for neuroendocrine markers and the ductal marker cytokeratin 19, indicating amphicrine properties and a partial cholangiocarcinoma phenotype – features not observed in the primary and metastatic neuroendocrine tumours. Conclusion: The presence of adenocarcinoma only at the metastatic site indicated that neuroendocrine tumour cells acquired stemness and differentiated into adenocarcinoma through metastasis, or that the adenocarcinoma newly arose from the adjacent epithelium influenced by the neuroendocrine tumour. We propose a novel mechanism for the pathogenesis of mixed tumours in neuroendocrine tumours.

Successful surgical treatment of left atrioesophageal fistula following atrial ablation

A 69-year-old male had catheter-based ablation for atrial fibrillation. He was admitted with high fever and had neurological disorder; he was diagnosed with atrioesophageal fistula by CT scan. Intraoperative findings showed that the fistula existed adjacent to the left lower pulmonary vein with a vegetation. The esophageal fistula was repaired, and the left atrial fistula was closed. A nasogastric tube tip was placed in the esophagus for decompression and advanced into the stomach for nutritional support. After vomiting, the patient showed loss of consciousness and left hemiplegia. CT scan revealed a micro-air embolism to the brain. The nasogastric tube tip was pulled back into the esophagus. Gastrointestinal fiberscopy showed a pinhole at the fistula, and a percutaneous endoscopic gastrostomy was made. After conservative treatment, the esophageal fistula was closed and mediastinitis was improved. He was discharged with a little neurological deficit.

Fairly rare clear cell adenocarcinoma mimicking liver cancer: a case report

BackgroundClear cell carcinoma commonly occurs in the ovary and kidney, and clear cell cholangiocarcinoma was rarely reported. Differential diagnosis which the origin of the tumor located on the liver surface is intrahepatic or extrahepatic was difficult. Herein, we report a case of clear cell adenocarcinoma mimicking liver cancer.Case presentationThis was a 55-year-old female who had the tumor with cystic component in the liver. She was performed hepatectomy and diagnosed as clear cell adenocarcinoma. Histopathological evaluation revealed intra-cystic clear cell adenocarcinoma. The tumor has ductal structure including mucin and atypical nuclear with clear cytoplasm. The tumor was separated from the liver and the diaphragm. The expression of Pax8 was positive, but the expression CK7 and HNF1β was positive and that of CD10 and ER was negative, which indicate that the tumor has the feature of clear cell carcinoma of ovary, not renal cell carcinoma nor cholangiocarcinoma.ConclusionsOur experience with this patient suggests that this tumor may originate from the endometriosis onto the diaphragm from the detailed results of immunohistochemical staining.

A Surgically Resected Pancreatic Schwannoma with Obstructive Jaundice with Special Reference to Differential Diagnosis from Other Cystic Lesions in the Pancreas

Pancreatic schwannomas are uncommon. About 60% of pancreatic schwannomas develop cystic lesions, and the differential diagnosis from other cystic pancreatic tumors is difficult. A 43-year-old man presented for evaluation of liver dysfunction detected during a medical checkup. Blood testing detected obstructive jaundice. A computed tomography scan revealed a well-defined polycystic tumor of about 5 cm at the pancreatic head. We performed surgical resection to treat the patient’s symptoms and facilitate long-term management. Histopathological examination revealed spindle-shaped cells. Immunohistochemical studies showed S100 protein expression and the absence of CD34 and c-kit protein expression. Finally, we diagnosed a schwannoma. Pancreatic schwannoma is usually asymptomatic. The present case presented with obstructive jaundice, which is reportedly a rare symptom. Pancreatic schwannomas should be considered as a differential diagnosis of pancreatic cystic tumors. Dilatation of the pancreatic duct and the 18-fluorodeoxyglucose positron emission tomography findings are important for the differential diagnosis.

The Feature of Solitary Small Nodular Type of Hepatic Epithelioid Hemangioendothelioma

Hepatic epithelioid hemangioendothelioma (HEHE) is a rare tumor. Preoperative diagnosis of HEHE is difficult because it does not manifest specific symptoms or tumor markers. We report a resected case of small and solitary HEHE. The patient, a 74-year-old man, had undergone surgical resection for left renal cell carcinoma 20 years ago. During follow-up, a tumor approximately 1.3 cm in diameter was detected by computed tomography (CT) at liver segment VIII. It showed isodensity in the arterial phase, low density in the portal venous phase, and homogeneous enhancement in the late phase on CT and magnetic resonance imaging (MRI). We performed hepatic resection of the right hepatic vein drainage area. A pathological diagnosis of HEHE was made. Although small and solitary HEHE is rare, an enhancement pattern in each phase on CT and MRI, using contrast media, can yield clues for the diagnosis of HEHE.

Conophylline suppresses pancreatic cancer desmoplasia and cancer‐promoting cytokines produced by cancer‐associated fibroblasts

Despite recent advances in cancer treatment, pancreatic cancer is a highly malignant tumor type with a dismal prognosis and it is characterized by dense desmoplasia in the cancer tissue. Cancer‐associated fibroblasts (CAF) are responsible for this fibrotic stroma and promote cancer progression. We previously reported that a novel natural compound conophylline (CnP) extracted from the leaves of a tropical plant reduced liver and pancreatic fibrosis by suppression of stellate cells. However, there have been no studies to investigate the effects of CnP on CAF, which is the aim of this work. Here, we showed that CAF stimulated indicators of pancreatic cancer malignancy, such as proliferation, invasiveness, and chemoresistance. We also showed that CnP suppressed CAF activity and proliferation, and inhibited the stimulating effects of CAF on pancreatic cancer cells. Moreover, CnP strongly decreased the various cytokines involved in cancer progression, such as interleukin (IL)‐6, IL‐8, C‐C motif chemokine ligand 2 (CCL2), and C‐X‐C motif chemokine ligand 12 (CXCL12), secreted by CAF. In vivo, CAF promoted tumor proliferation and desmoplastic formation in a mouse xenograft model, CnP reduced desmoplasia of tumors composed of pancreatic cancer cells + CAF, and combination therapy of CnP with gemcitabine remarkably inhibited tumor proliferation. Our findings suggest that CnP is a promising therapeutic strategy of combination therapy with anticancer drugs to overcome refractory pancreatic cancers.