Publications by authors named "Shinichiro Ikeda"

24 Publications

  • Page 1 of 1

A Novel Case of Spontaneous Coronary Artery Dissection During Cabergoline Therapy for Prolactinoma.

JACC Case Rep 2020 Sep 15;2(11):1684-1687. Epub 2020 Sep 15.

Division of Cardiothoracic Surgery, Department of Surgery, Maimonides Medical Center, Brooklyn, New York.

We present a case of spontaneous coronary artery dissection associated with cabergoline treatment for prolactinoma. A 31-year-old woman with history of hypertension and prolactinoma, treated with cabergoline, presented with chest pain. She had non-ST-segment elevation myocardial infarction with double vessel coronary artery dissection and was treated with coronary artery bypass grafting. ().
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http://dx.doi.org/10.1016/j.jaccas.2020.07.024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8312105PMC
September 2020

Prognostic Impact of Lymphocyte-C-Reactive Protein Ratio in Patients Who Underwent Surgical Resection for Hepatocellular Carcinoma.

J Gastrointest Surg 2021 Jul 13. Epub 2021 Jul 13.

Department of Surgery, Hiroshima Red Cross Hospital and Atomic-bomb Survivors Hospital, Hiroshima, 730-0052, Japan.

Background: Systemic inflammation-related factors, either independently or in combination, are recognized as prognostic factors for various cancers. The ratio of lymphocyte count to C-reactive protein concentration (lymphocyte-CRP ratio; LCR) is a recently identified prognostic marker for several cancers. Here, we examined the prognostic value of the LCR in patients with hepatocellular carcinoma (HCC).

Methods: This was a single-center retrospective study of patients who underwent surgical resection for HCC between 2004 and 2017. Patients were divided into high- and low-LCR status groups, and the relationships between LCR status, prognosis, and other clinicopathological characteristics were analyzed.

Results: A total of 454 patients with HCC were enrolled and assigned to the high- (n=245) or low- (n=209) LCR groups. Compared with the high-LCR group, patients in the low-LCR group had a significantly lower serum albumin level (median 4.1 vs. 3.9 g/dL, P <0.0001), lower platelet count (median 14.0 vs. 12.0 ×10/μL, P=0.0468), lower prothrombin time (median 93.2 vs. 89.6 %, P=0.0006), and larger tumor size (median 2.3 vs. 2.5 cm, P=0.0056). Patients with low-LCR status had significantly worse outcomes of overall survival and disease-free survival than patients with high-LCR status (P=0.0003 and P=0.0069, respectively). Low-LCR status was significantly associated with worse overall survival in multivariate analysis (hazard ratio 1.57, 95% confidence interval 1.14-2.17, P=0.0058).

Conclusions: Low-LCR status may predict worse outcomes in patients with HCC. Measurement of LCR is routine and can easily be applied for risk stratification in the assessment of patients with HCC.
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http://dx.doi.org/10.1007/s11605-021-05085-zDOI Listing
July 2021

Amplatzer Vascular Plug for Complicated Residual DeBakey Type 1 Aortic Dissection in the Aortic Arch.

Innovations (Phila) 2021 Mar-Apr;16(2):192-194. Epub 2021 Jan 22.

2042 Department of Surgery, Maimonides Medical Center, Brooklyn, NY, USA.

Surgical treatment of acute DeBakey type I aortic dissection does not address the entire aorta, which can leave anatomically complex residual aortic dissection in the aortic arch and descending aorta. Open repair has been the standard treatment for this pathology. When the lesions are located in the aortic arch, re-do total arch replacement needs to be performed. Plug placement to close small entry tears in the aortic arch has been reported. This article reports about a 79-year-old man who underwent hemiarch replacement for acute DeBakey type I aortic dissection. One year later, his proximal descending aorta dilated to 6.3 cm. The patient was treated with Amplatzer plug in the false lumen, and a stent graft was placed in the true lumen. Follow-up computed tomography scan confirmed complete thrombosis of the false lumen in the descending aorta which had decreased from 6.3 to 4.0 cm. Plug placement in the false lumen in the aortic arch is a potential treatment strategy for anatomically complex residual aortic dissection to induce thrombosis of the false lumen and encourage remodeling.
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http://dx.doi.org/10.1177/1556984520983790DOI Listing
January 2021

Ventricular septal defect concomitant with patent ductal arteriosus complicated with pulmonary hypertension in adulthood.

J Card Surg 2020 Sep 27;35(9):2359-2360. Epub 2020 Jul 27.

Division of Cardiothoracic Surgery, Department of Surgery, Maimonides Medical Center, Brooklyn, New York.

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http://dx.doi.org/10.1111/jocs.14811DOI Listing
September 2020

Hepatic resection for recurrent hepatocellular carcinoma during pregnancy: a case report.

Surg Case Rep 2020 Sep 29;6(1):229. Epub 2020 Sep 29.

Department of Surgery, Hiroshima Red Cross Hospital and Atomic-Bomb Survivors Hospital, 1-9-6 Senda-machi, Naka-ku, Hiroshima, 730-8619, Japan.

Background: Hepatocellular carcinoma (HCC) during pregnancy is extremely rare. Treatment strategies for cancers detected during pregnancy have been controversial. We herein report a case of recurrent HCC detected at 20 weeks of pregnancy, which subsequently prompted hepatic resection after abortion.

Case Presentation: A 36-year-old woman underwent laparoscopic partial hepatectomy for HCC (20 mm in diameter) in segment 5 of the liver during follow-up after being determined as a hepatitis B virus carrier two and a half years ago. Post-surgery follow-up abdominal ultrasonography revealed a 36-mm tumor in segment 7 of the liver. Abdominal contrast-enhanced computed tomography revealed a well-enhanced tumor with a 40-mm diameter in segment 7 adjacent to the inferior vena cava and right hepatic vein, suggesting HCC recurrence. Laboratory data revealed total bilirubin (0.4 mg/dL), aspartate aminotransferase (28 IU/L), alanine aminotransferase (30 IU/L), glutamyltransferase (16 IU/L), prothrombin time (115.3%), and indocyanine green retention rate at 15 min (7.0%). α-Fetoprotein (AFP) (12,371.5 ng/mL; normal range < 10 ng/mL) and PIVKA-II (208 mAU/mL; normal range < 40 mAU/mL) were both significantly elevated. After discussions with a cancer board consisting of experts from the departments of gastroenterology, obstetrics and gynecology, and surgery, as well as obtaining appropriate informed consent from the patient and her family, we decided to perform a hepatic resection after abortion. Subsequently, abortion surgery was performed at 21 weeks and 2 days of pregnancy. After 6 days, subsegmentectomy of liver segment 7 was performed under general and epidural anesthesia, with a pathological diagnosis which was moderately differentiated HCC being established. Given the good postoperative course, without particular complications, the patient was subsequently discharged 10 days after the operation. Approximately 2 years after the surgery, the patient remains alive without recurrence, while both AFP and PIVKA-II were within normal limits.

Conclusions: Treatment strategies for HCC detected during pregnancy remain controversial. As such, decisions should be made based on HCC growth and fetal maturity after thorough multidisciplinary team discussions and obtaining appropriate informed consent from the patient and her family.
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http://dx.doi.org/10.1186/s40792-020-00985-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7524929PMC
September 2020

Correction to: Post-transplant inflow modulation for early allograft dysfunction after living donor liver transplantation.

Surg Case Rep 2020 Aug 4;6(1):198. Epub 2020 Aug 4.

Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.

An amendment to this paper has been published and can be accessed via the original article.
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http://dx.doi.org/10.1186/s40792-020-00958-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7403266PMC
August 2020

TEVAR for a Marfan patient during COVID-19 pandemic.

J Card Surg 2020 09 17;35(9):2444. Epub 2020 Jul 17.

Department of Surgery, Maimonides Medical Center, Brooklyn, New York.

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http://dx.doi.org/10.1111/jocs.14862DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7405328PMC
September 2020

Large surgically resected leiomyosarcoma of the liver: a case report.

Surg Case Rep 2020 Jul 9;6(1):168. Epub 2020 Jul 9.

Department of Surgery, Hiroshima Red Cross Hospital and Atomic-bomb Survivors Hospital, 1-9-6 Senda-machi, Naka-ku, Hiroshima 730-8619, Japan.

Background: Primary hepatic leiomyosarcoma (PHL) is an extremely rare type of tumor. We herein report a case of a large surgically resected leiomyosarcoma of the liver.

Case Presentation: A 69-year-old man with a feeling of epigastric compression was referred for examination of an abdominal mass. He had no history of liver disease or alcohol abuse. Liver function tests indicated Child-Pugh class A. Tumor markers were negative. Computed tomography (CT) and magnetic resonance imaging (MRI) revealed a relatively well-contrasted 12 × 11 × 8 cm tumor with well-defined boundary replacing the lateral segment of the liver alongside multiple intrahepatic metastases. Several nodules up to 12 mm were found in both lungs, suggestive of metastasis. SUVmax of the liver mass and lung tumor in positron emission tomography were 10.4 and 1.5, respectively. Hepatocellular carcinoma was primarily suspected. Lateral segmentectomy of the liver was performed to confirm diagnosis and prevent tumor rupture. Macroscopically, the lateral segment of the liver had been replaced by a lobular or multinodular tumor with a maximum diameter of 15 cm. In pathological findings, the tumor consisted of bundle-like proliferation of complicated banding spindle-like cells with clear cytoplasm, accompanied by storiform pattern and compressed blood vessels. Nuclear fission images were observed in 8/10 HPF. Partial necrosis was present, with associated venous invasion and intrahepatic metastasis. Immunohistochemical staining for tumor cells revealed desmin, α-smooth muscle actin (αSMA), and h-caldesmon were all positive, informing a final diagnosis of PHL. The postoperative course was uneventful, and he was discharged on the 12th postoperative day.

Conclusions: PHL is a rare malignant disease with relatively poor prognosis. To confirm a diagnosis of PHL, immunohistochemical analysis as well as histopathological findings is important. The preferred treatment is surgical resection, sometimes in combination with adjuvant chemotherapy and radiotherapy. Further studies are needed to elucidate and better understand this uncommon clinical entity.
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http://dx.doi.org/10.1186/s40792-020-00934-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7347740PMC
July 2020

Post-transplant inflow modulation for early allograft dysfunction after living donor liver transplantation.

Surg Case Rep 2020 Jul 8;6(1):164. Epub 2020 Jul 8.

Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.

Background: To treat small-for-size syndrome (SFSS) after living donor liver transplantation (LDLT), many procedures were described for portal flow modulation before, during, or after transplantation. The selection of the procedure as well as the best timing remains controversial.

Case Presentation: A 43-year-old female with end-stage liver disease underwent LDLT with extended left with caudate lobe graft from her donor who was her 41-year-old brother (graft volume/standard liver volume (GV/SLV), 35.7%; graft to recipient weight ratio (GRWR), 0.67%). During the surgery, splenectomy could not be performed owing to severe peri-splenic adhesions to avoid the ruined bleedings. The splenic artery ligation was not also completely done because it was dorsal to the pancreas and difficult to be approached. Finally, adequate portal vein (PV) inflow was confirmed after portal venous thrombectomy. As having post-transplant optional procedures that are accessible for PV flow modulation, any other procedures for PV modulation during LDLT were not done until the postoperative assessment of the graft function and PV flow for possible postoperative modulation of the portal flow accordingly. Postoperative PV flow kept as high as 30 cm/s. By the end of the 1st week, there was a progressive deterioration of the total bilirubin profile (peak as 19.4 mg/dL) and ascitic fluid amount exceeded 1000 mL/day. Therefore, splenic artery embolization was done effectively and safely on the 10th postoperative day (POD) to reverse early allograft dysfunction as PV flow significantly decreased to keep within 20 cm/s and serum total bilirubin levels gradually declined with decreased amounts of ascites below 500 mL on POD 11 and thereafter. The patient was discharged on POD 28 with good condition.

Conclusions: SFSS can be prevented or reversed by the portal inflow modulation, even by post-transplant procedure. This case emphasizes that keeping accessible angiographic treatment options for PV modulation, such as splenic artery embolization, after LDLT is quite feasible.
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http://dx.doi.org/10.1186/s40792-020-00897-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7343689PMC
July 2020

Mixed adenoneuroendocrine carcinoma of the distal bile duct: a case report.

Surg Case Rep 2020 Jul 6;6(1):160. Epub 2020 Jul 6.

Department of Surgery, Hiroshima Red Cross Hospital and Atomic-bomb Survivors Hospital, 1-9-6 Senda-machi, Naka-ku, Hiroshima, 730-8619, Japan.

Background: Mixed adenoneuroendocrine carcinoma (MANEC) of the common bile duct (CBD) is very rare, with only 10 reported cases. Here, we report a case of MANEC of the distal bile duct (DBD) that was surgically resected under a diagnosis of cholangiocarcinoma (CCA).

Case Presentation: A 60-year-old male had epigastric pain and was admitted to our hospital for the treatment of a suspected CBD stone. Upon admission, laboratory findings revealed elevated hepatobiliary enzymes including serum aspartate aminotransferase, serum alanine aminotransferase, serum glutamyltransferase, and serum alkaline phosphatase. Both carcinoembryonic antigen and carbohydrate antigen 19-9 were negative. Computed tomography (CT) showed dilation of the CBD. Endoscopic retrograde cholangiopancreatography (ERCP) showed circumferential stenosis and a 5-mm elevated lesion in the DBD. Brush cytology showed atypical ductal cells, indicating adenocarcinoma (AC) of the DBD. Under a diagnosis of CCA of the DBD, a subtotal stomach-preserving pancreaticoduodenectomy was performed. Neither peritoneal dissemination nor lymph node metastasis was found. Microscopically, the lesion was seen to be composed of predominantly well-differentiated tubular AC in the superficial layer of the tumor, admixed with neuroendocrine carcinoma (NEC) in the deeper portion, indicating a diagnosis of MANEC of the DBD. After immunohistochemical staining, NEC components were positive for synaptophysin and CD56 and were for SSTR2, SSTR5, and mammalian target of rapamycin (mTOR). Three months postsurgery, postoperative adjuvant chemotherapy with S-1 was started. More than 3 years postsurgery, he is alive without recurrence.

Conclusions: MANEC is highly malignant, progresses rapidly, and has a poor prognosis. Preoperative diagnosis is difficult; therefore, identifying NEC components by immunohistochemical staining using resected specimens is important.
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http://dx.doi.org/10.1186/s40792-020-00921-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7338298PMC
July 2020

Acute complicated type B aortic dissection during the New York City COVID-19 surge.

J Card Surg 2020 Jul 4;35(7):1736-1739. Epub 2020 Jun 4.

Department of Surgery, Maimonides Medical Center, Brooklyn, New York.

The impact of the coronavirus disease 2019 (COVID-19) pandemic in New York City (NYC) is dramatic. COVID-19 cases surged, hospitals expanded to meet capacity, and NYC remains the global epicenter of this pandemic. During this unprecedented time, a young woman with known Marfan syndrome presented with an acute complicated type B aortic dissection to our Aortic Center. Using the provisional extension to induce a complete attachment technique, we treated this patient and quickly discharged her the next day to decrease the risk of COVID-19 infection. Her progress was monitored using frequent phone calls and one office visit at two weeks.
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http://dx.doi.org/10.1111/jocs.14678DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7300946PMC
July 2020

The treatment of tuberculous aortic pseudoaneurysm.

J Card Surg 2018 Dec;33(12):840-852

Department of Surgery, Division of Cardiothoracic Surgery, Maimonides Medical Center, Brooklyn, New York.

Objective: Our aim was to compare the outcomes of tuberculous aortic aneurysms treated with endovascular aortic repair (TEVAR) or open surgery.

Methods: An electronic search of the National Library of Medicine PubMed database for tuberculous aortic aneurysm was performed between January 1998 through December 2017. Cases were screened for completeness of information and outcomes were recorded and analyzed.

Results: A total of 56 studies were reviewed, with 61 (20 TEVAR, 41 open surgical repair) having adequate case details and follow-up. The in-hospital/30-day mortality was 0% (0 out of 20) in the TEVAR group and 7% (three out of 41) in the open surgery group (P = .54). Overall mortality was 5% (1/20) in the TEVAR group and 10% (4/41) in the open surgery group (P = .53). Two-year survival and freedom from aneurysm recurrence were comparable in the two groups, P = .45 and P = .94, respectively. One patient in the TEVAR group and one patient in the open surgery group died due to a rupture of a recurrent aortic aneurysm 16 and 28 months after surgery, respectively.

Conclusions: TEVAR and anti-tuberculosis (TB) medications are reasonable initial treatment options for tuberculous aortic aneurysm especially in high-risk patients; however, careful follow-up is necessary.
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http://dx.doi.org/10.1111/jocs.13952DOI Listing
December 2018

One-stage repair using a frozen elephant trunk technique for acute type A intramural hematoma with an ulcer-like projection in the dilated proximal descending aorta.

J Card Surg 2017 Aug 23;32(8):504-505. Epub 2017 Jul 23.

Department of Cardiothoracic Surgery, Maimonides Medical Center, Brooklyn, New York.

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http://dx.doi.org/10.1111/jocs.13180DOI Listing
August 2017

Aorto-right ventricular fistula from iatrogenic rupture of the right coronary ostia following percutaneous coronary intervention.

J Card Surg 2017 06 8;32(6):364-365. Epub 2017 May 8.

Department of Cardiothoracic Surgery, Maimonides Medical Center, Brooklyn, New York.

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http://dx.doi.org/10.1111/jocs.13142DOI Listing
June 2017

Cardiac resynchronization therapy for ischemic myopathy.

Asian Cardiovasc Thorac Ann 2017 Jun 25;25(5):383-385. Epub 2016 May 25.

Cardiovascular Surgery Department, Hiroshima City Hospital, Hiroshima, Japan.

We performed coronary artery grafting, mitral valve plasty, and tricuspid plasty in a 75-year-old man who had double-vessel coronary disease and moderate mitral and tricuspid insufficiency. Preoperative transthoracic echocardiography revealed an ejection fraction of 34% and dyssynchronous wall motion of the septum and free wall. We placed pacing leads on the right ventricular outlet and posterior left ventricular wall for cardiac resynchronization therapy. The dyssynchrony disappeared postoperatively and the New York Heart Association functional class improved from IV to I.
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http://dx.doi.org/10.1177/0218492316652056DOI Listing
June 2017

A simple and safe procedure to repair rectal prolapse perineally using stapling devices.

Case Rep Gastroenterol 2014 Jan 23;8(1):39-43. Epub 2014 Jan 23.

Sapporo Ishiyama Hospital, Sapporo, Japan.

Rectal prolapses are not life-threatening, however the bleeding and fecal incontinence associated with them significantly erode quality of life and can cause concern among patients' caregivers in nursing homes. Many procedures have been reported that repair rectal prolapses, and the procedure used depends on the severity of the prolapse; however, the treatments are yet to be established. Here we report a simple and safe procedure to repair rectal prolapse perineally using stapling devices. We performed this procedure on 5 patients within a short time. All patients were followed up for over 24 months and none had any recurrences of their rectal prolapses. No complications occurred during the operations and postoperative periods. Most patients who have prolapses are elderly and fragile, so the treatment must be easy, safe, and rapid. While rectal prolapse is not life-threatening, the goal of treatment is to alleviate its symptoms. The procedure we describe is consistent with this concept. We suggest that this procedure, which uses surgical stapling devices, might be a better option for the treatment of complete rectal prolapse. We will continue to surgically correct complete rectal prolapses and investigate the long-term outcomes of the procedure.
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http://dx.doi.org/10.1159/000354970DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3934783PMC
January 2014

A case of sarcoidosis with severe acute renal failure requiring dialysis.

Clin Nephrol 2014 Oct;82(4):273-7

We report here a 79-year-old male having sarcoidosis without presentation of typical findings, such as respiratory symptoms, ocular signs, or skin lesions. Two weeks prior to admission to our hospital, he presented to a different hospital with acute renal failure, with blood urea nitrogen (BUN) and serum creatinine (Cr) levels of 67.9 mg/dl and 7.97 mg/dl, respectively, and was initiated on hemodialysis. The patient also exhibited fever, severe anorexia, and fatigue. We initially experienced difficulty in performing kidney biopsy due to a thrombocytopenia complication and severe general debility. Tuberculosis and other malignancies were not found. However, bone marrow biopsy revealed noncaseating granuloma with multinucleated giant cells, and the patient's serum angiotensin converting enzyme (ACE) level was slightly elevated at 24.3 U/l. We informed the patient and his family of the risk of a kidney biopsy and subsequently received informed consent for the procedure. The biopsy showed many epitheloid granulomas with multinucleated giant cells in the interstitium, from which we diagnosed sarcoidosis. The thrombocytopenia was subsequently found to be due to heparin-induced thrombocytopenia (HIT). After administering 20 mg/day of oral prednisolone, the patient's general condition improved rapidly. Therefore, it is important to take sarcoidosis into account as a differential diagnosis of acute renal failure, and kidney biopsy offers useful information in these cases.
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http://dx.doi.org/10.5414/CN107717DOI Listing
October 2014

Hepatic organoid formation in collagen sponge of cells isolated from human liver tissues.

Tissue Eng 2005 Mar-Apr;11(3-4):626-33

Department of Gastroenterological Surgery, Kyoto University Graduate School of Medicine, Japan.

We examined whether small hepatocytes (SHs), which are hepatic progenitor cells, could be isolated from a normal human liver and whether human hepatic cells could form hepatic organoids in a collagen sponge. Normal liver tissues were obtained from resected specimens from nine patients who underwent hepatic resection. Isolated hepatic cells were plated on dishes and a collagen sponge. More than 1 month later, SH-like cells appeared and proliferated on the dishes, whereas cell aggregates were formed in the sponge and showed characteristic tissue architecture: columnar and/or cuboidal epithelial cells lined the surface of the sponge. Clusters of epithelial cells with a large cytoplasm and ductular structures were observed under the lining cells. The lining and ductular cells were positive for cytokeratins 7 and 19, which indicated they were biliary epithelial cells (BECs), and the epithelial cells forming clusters were positive for the anti-human hepatocyte antibody, identifying them as hepatocytes. Some lining cells were positive for both the hepatic marker and the BEC markers. The cells in the collagen sponge actively proliferated and the hepatocytes excreted albumin into the medium. Thus, hepatic organoids could be reconstructed in a collagen sponge by normal human liver cells.
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http://dx.doi.org/10.1089/ten.2005.11.626DOI Listing
August 2005

Bile canalicular formation in hepatic organoid reconstructed by rat small hepatocytes and nonparenchymal cells.

J Cell Physiol 2004 May;199(2):252-61

Department of Pathophysiology, Cancer Research Institute, Sapporo Medical University School of Medicine, Sapporo, Japan.

The morphogenesis and movement of bile canaliculi (BC) are not well understood. This is because culture of hepatocytes that maintain polarity of cell membranes and possess highly differentiated functions has never been successful. We found that small hepatocytes (SHs), which are known to be hepatic progenitor cells, could proliferate and differentiate into mature hepatocytes and that BC-like structures developed between rising/piled-up cells. We investigated how BC-like structures developed with maturation of SHs and whether the structures were functionally active as BC. Hepatic cells, including SHs, were isolated from an adult rat liver and cultured. Immunocytochemistry and immunoblotting for BC proteins, such as ectoATPase, 5'-nucleotidase, dipeptidylpeptidase IV, and multidrug-resistance associated protein 2, were examined and time-lapse microscopy was used for the observation of BC contractions. Secretion of bilirubin into the reconstructed BC was also observed. The results of immunocytochemistry, immunoblots, and immunoelectron micrographs revealed that BC proteins were localized in the intercellular space that coincided with BC-like structures reconstructed between rising/piled-up cells. Tight junction-associated protein ZO-1 was also expressed along the BC-like structures. Bilirubin added to the medium were secreted into BC-like structure and accumulated without leakage. Time-lapse microscopy showed continuous contractions of reconstructed BC. In conclusion, BC-like structures reconstructed by SHs may be functional with membrane polarity, secretory ability, and motility. These results show that this culture system may suitable for investigating the mechanism of the formation of BC and their functions.
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http://dx.doi.org/10.1002/jcp.10407DOI Listing
May 2004

Rapid formation of hepatic organoid in collagen sponge by rat small hepatocytes and hepatic nonparenchymal cells.

J Hepatol 2003 Nov;39(5):716-23

Department of Pathophysiology, Cancer Research Institute, Sapporo Medical University School of Medicine, S-1, W-17, Chuo-Ku, Sapporo 060-8556, Japan.

Background/aims: Hybrid bioartificial liver devices supporting a large mass of metabolically active hepatocytes are thought to be necessary for the successful treatment of patients with severe acute liver failure. However, it is very difficult to obtain cells with both growth activity and differentiated functions. Rat small hepatocytes (SHs), which are hepatic progenitor cells, can differentiate into mature hepatocytes and reconstruct a hepatic organoid by interacting with hepatic nonparenchymal cells (NPCs).

Methods: Colonies of SHs were collected and replated on a collagen sponge. Hepatic functions were examined by ELISA, immunoblotting, and Northern blotting. Cells in the sponge were characterized by immunocytochemistry and transmission electron microscopy. Urea synthesis was measured and metabolization of fluorescein diacetate was examined.

Results: SHs could proliferate and expand to form a hepatic organoid in the sponge. Albumin secretion and other hepatic protein production of the cells in the sponge increased with time in culture and the amounts were much larger than for those obtained from cells grown on dishes. Morphologically and functionally differentiated hepatocytes were observed and some CK19-positive cells formed duct-like structures within the sponge. Excretion of fluorescein was observed in bile canaliculi.

Conclusions: Hepatic organoids can be rapidly reconstructed in a collagen sponge by rat SHs and NPCs.
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http://dx.doi.org/10.1016/s0168-8278(03)00412-4DOI Listing
November 2003

Surgical influence on TH1/TH2 balance and monocyte surface antigen expression and its relation to infectious complications.

World J Surg 2003 May 28;27(5):522-8. Epub 2003 Apr 28.

First Department of Surgery, Sapporo Medical University School of Medicine, South 1, West 16, Chuo-ku, Sapporo 060-8543, Japan.

Malignancy and operation for it cause several alterations in immune function that are considered to be concerned with the development of infectious complications. Forty-three patients who underwent curative surgery for gastrointestinal malignancies were entered into this study and were divided into two groups, those with and those without postoperative infection. Changes in the proportion of Th1/Th2 subsets in CD4(+) T cells and the expression of human leukocyte antigen (HLA)-DR and CD16a molecules on monocytes were measured by flow cytometry before and after surgery. We performed intracellular cytokine stainings to exactly detect Th1/Th2 subsets. The proportions of interferon- gamma-producing CD4(+) T (Th1) cells in the preoperative state were almost equal in the two groups, and the proportion decreased on postoperative day (POD) 1 in both groups. On POD 7, the proportion of Th1 cells recovered to the preoperative level in the noninfection group, while the suppression was further reinforced in the infection group (26.8% versus 18.3%, p < 0.005). In contrast, the proportion of interleukin-4-producing CD4(+) T (Th2) cells in the infection group (11.3%) was already suppressed in the preoperative state when compared with the noninfection group (17.3%, p < 0.005). Changes in HLA-DR and CD16a expression on monocytes were similar to the changes in the proportion of Th1 cells. These results indicate that the suppression of Th1 cell and monocyte functions during the early phase of the postoperative course was directly related to the occurrence of infectious complications and that several immunological impairments have already occurred in the preoperative state in cancer patients.
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http://dx.doi.org/10.1007/s00268-003-6813-2DOI Listing
May 2003

Tumor necrosis factor-alpha and interleukin-6 reduce bile canalicular contractions of rat hepatocytes.

Surgery 2003 Jan;133(1):101-9

First Department of Surgery, Cancer Research Institute, Sapporo Medical University School of Medicine, Sapporo, Japan.

Background: Surgeons sometimes encounter hyperbilirubinemia without mechanical obstruction of the biliary tree postoperatively. Many of these patients have bacterial infections and endotoxemia. Kupffer's cells stimulated by endotoxin secrete inflammatory cytokines such as tumor necrosis factor (TNF)-alpha and interleukin (IL)-6. We hypothesized that TNF-alpha and IL-6 might be involved in the pathogenesis of hyperbilirubinemia.

Methods: Effects of TNF-alpha and IL-6 on the contractions of bile canaliculi (BC) of rat hepatocyte couplets were examined and time-lapse images using phase-contrast microscopy were taken. Bile was collected from rats treated with or without the cytokines. The livers, perfused with lanthanum after the injection of cytokines, were examined ultrastructurally using electron microscopy.

Results: The number of BC contractions decreased in the couplets treated with both cytokines. The rapid movement of a droplet from BC was observed at the intercellular space of the hepatocyte couplet treated with TNF-alpha. Systolic blood pressure and hepatic tissue blood flow of rats injected with TNF-alpha were not changed, whereas the hepatic tissue blood flow of rats treated with IL-6 decreased (Dunnett test, P <.05). Bile secretion was reduced in both groups of rats (Dunnett test, P <.05). In rats treated with TNF-alpha the total serum bile acid concentration increased and lanthanum temporarily accumulated in BC.

Conclusions: These results suggest that TNF-alpha and IL-6 may reduce BC contractions and thereby decrease bile flow.
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http://dx.doi.org/10.1067/msy.2003.91DOI Listing
January 2003

Morphological changes induced by extracellular matrix are correlated with maturation of rat small hepatocytes.

J Cell Biochem 2002 ;87(1):16-28

Department of Pathology, Cancer Research Institute, Sapporo Medical University School of Medicine, Chuo-Ku, S-1, W-17, Sapporo 060-8556, Japan.

Small hepatocytes (SHs), which are known to be hepatic progenitor cells, were isolated from an adult rat liver. SHs in a colony sometimes change their shape from small to large and from flat to rising/piled-up. The aim of the present study is to clarify whether the alteration of cell shape is correlated with the maturation of SHs and whether extracellular matrix (ECM) can induce the morphological changes of SHs. We used liver-enriched transcription factors (LETFs) such as hepatocyte nuclear factor (HNF) 4 alpha, HNF6, CCAAT/enhancer binding proteins (C/EBP) alpha, and C/EBP beta, tryptophan 2,3-dioxygenase (TO), and serine dehydratase (SDH) as markers of hepatic maturation. To enrich the number of SH colonies, the colonies were isolated from dishes and replated. Replated colonies proliferated and the average number of cells per colony was about five times larger at day 9 than at day 1. When the cells were treated with laminin, type IV collagen, a mixture of laminin and type IV collagen, Matrigel or collagen gel (CG), only the cells treated with Matrigel dramatically changed their shape within several days and had reduced growth activity, whereas the cells treated with other ECM did not. HNF4 alpha, HNF6, C/EBP alpha, C/EBP beta, and TO were well expressed in the cells treated with Matrigel. Furthermore, addition of both glucagon and dexamethasone dramatically induced the expression of SDH mRNA and protein in the cells treated with Matrigel. In conclusion, morphological changes of SHs may be correlated with hepatic maturation and basement membrane (BM)-like structure may induce the morphological changes of SHs.
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http://dx.doi.org/10.1002/jcb.10274DOI Listing
April 2003

Proliferation of rat small hepatocytes after long-term cryopreservation.

J Hepatol 2002 Jul;37(1):7-14

Department of Pathology, Cancer Research Institute, Sapporo Medical University School of Medicine, Chu-Ku, S-1, W-17, Sapporo, Japan.

Background/aims: The demand for clinical use of hepatocytes is escalating because cell transplantation will be an alternative to orthotopic liver transplantation and the shortage of liver donors is a serious problem throughout the world. However, the supply of fresh differentiated hepatocytes is limited and methods for cryopreservation of hepatocytes that can proliferate with hepatic functions are not satisfactorily established.

Methods: Colonies of small hepatocytes were collected and then maintained at -80 degrees C for more than 6 months. Albumin secretion and mRNA expression of thawed cells were measured by enzyme linked immunosorbent assay and Northern blotting, respectively, and the expression of hepatic functions was examined by immunoblotting. The ultrastructure of cryopreserved cells was also examined.

Results: About 60% of the cryopreserved colonies attached on dishes and then proliferated. The average area of small hepatocyte colonies was about 7.5 times larger at day 15 than at day 1. Albumin production increased with time in culture. In addition, the cells produced other serum proteins such as transferrin and fibrinogen, and expressed carbamoyl phosphate synthetase I and tryptophan 2,3-dioxygenase.

Conclusions: Small hepatocytes maintain growth ability and hepatic differentiated functions even after long-term cryopreservation.
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http://dx.doi.org/10.1016/s0168-8278(02)00069-7DOI Listing
July 2002
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