Rapid deterioration of steatotic liver disease due to portal vein stenosis after pancreaticoduodenectomy.

Steatotic liver disease after pancreatoduodenectomy occurs due to various factors, such as exocrine pancreatic insufficiency, impaired intestinal absorption, and malnutrition. The mechanism of steatogenesis differs to that of conventional steatotic liver disease associated with obesity and insulin resistance. We experienced a rare case of rapidly progressive steatotic liver disease accompanied by portal vein stenosis in the early postoperative period after subtotal stomach-preserving pancreaticoduodenectomy for distal cholangiocarcinoma. Although there was a complication due to postoperative drain infection, the patient was discharged from hospital with no nutritional problems. Two months postoperatively, the patient presented to the emergency room with dyspnea. CT showed a markedly steatotic liver, ascites, and portal vein stenosis. A portal vein stent was inserted transhepatically and the steatotic liver disease gradually improved. During the postoperative course, there were no problems indicated by nutritional markers; although the patient had diarrhea associated with postoperative pancreatic exocrine insufficiency, the symptoms were mild and improved after administration of oral pancrelipase. Before the intervention, the patient had intestinal edema, exacerbation of diarrhea, and a low serum zinc concentration, suggesting that impaired absorption caused by intestinal blood stasis and gut barrier dysfunction contributed to the development of steatotic liver disease.

Two Cases of a Portal Annular Pancreas in Patients Undergoing Pancreaticoduodenectomy.

Introduction: Portal annular pancreas (PAP) is a congenital anomaly resulting from aberrant fusion of the ventral and dorsal pancreatic buds around the portal vein (PV). PAP was classified into three types by Joseph et al., based on the location of the main pancreatic duct around the PV. The presence of PAP is important for the surgical procedure because it is associated with the postoperative pancreatic fistula. There are no standardized surgical procedures of resection and reconstruction for PAP. Case Presentation: We report 2 cases of subtotal stomach-preserving pancreatoduodenectomy in patients with PAP. One case of PAP was discovered coincidentally intraoperatively, and the other case was diagnosed before surgery. The first case was an 84-year-old male patient who underwent surgery for distal bile duct cancer. PAP was noticed intraoperatively when the uncinate process of the pancreas was detached from behind the PV. The second case was an 84-year-old female patient who also underwent surgery for distal bile duct cancer. We recognized PAP from preoperative computed tomography images. In both cases, the ductal anatomy was consistent with type IIIA PAP, and the dorsal pancreas was resected using a stapling device. During the postoperative period, there was no clinically relevant postoperative pancreatic fistula. Conclusion: PAP is rarely encountered intraoperatively; however, it is important to recognize it before surgery and take it into consideration when deciding upon the procedures for resection and reconstruction.

Living-Donor Liver Transplantation for Erythropoietic Protoporphyria: A Case Report and Literature Review.

Erythropoietic protoporphyria (EPP) is a very rare disease with an estimated prevalence of 1 in 200,000 individuals. Decreased ferrochelatase activity causes the accumulation of protoporphyrin in the body, and light exposure results in the generation of active oxygen, causing photosensitivity. Liver damage has the greatest influence on the prognosis, and liver transplantation is the only treatment option for patients with decompensated liver cirrhosis. We report a case of living-donor liver transplantation for decompensated liver cirrhosis associated with EPP. The patient was a 52-year-old male who led a normal life except for mild photosensitivity. When the patient was 37-year-old, hepatic dysfunction was noticed. At 48-year-old, high erythrocyte protoporphyrin levels, skin biopsy, and genetic tests resulted in a diagnosis of EPP. The patient underwent living- donor liver transplantation because of decompensated liver cirrhosis. In the operating room and intensive care unit, a special light-shielding film was applied to all light sources to block light with harmful wavelengths during treatment. Due to the need for special measures, a lecture on patients with EPP was given before surgery to deepen understanding among all medical professionals involved in the treatment. As a result, no adverse events occurred during the perioperative period, and the patient was discharged on the 46th post-operative day. Currently, the transplanted liver is functioning extremely well, and the patient is alive 3 years post-transplant. Herein, we describe a case of living donor liver transplantation for EPP with a brief literature review.

Recurrence of Adult Granulosa Cell Tumor in the Greater Omentum 11 Years after Surgery.

Adult-type ovarian granulosa cell tumors (AGCTs) are very rare tumors that account for <5% of all ovarian carcinomas. AGCTs have low malignancy potential and rarely metastasize 5-30 years after the initial diagnosis. Because time has passed from the first surgery and because recurrence develops in various locations, the differential diagnosis is difficult. In particular, tumors developing in the greater omentum are encountered rarely, and it is necessary to carefully consider the differential diagnosis, including primary and secondary neoplasms. Although CT is useful to detect omental tumors, the diagnosis requires invasive procedures. We report a case of AGCT recurrence in the greater omentum that was resected during laparoscopic cholecystectomy. A patient visited our hospital with right-sided abdominal pain. The CT revealed gallbladder stones, a ureteral stone, and a right abdominal mass. The diagnosis of the abdominal tumor was difficult on the basis of blood biochemical testing, gastrointestinal endoscopy, or image inspection. Although the patient underwent several previous surgeries and there were no findings of malignancy with positron emission tomography, we chose to resect the tumor for combined diagnosis and treatment during laparoscopic cholecystectomy. Intraoperative findings showed that the tumor originated from the greater omentum, and the tumor was diagnosed as AGCT recurrence by pathology. A recurrence of AGCT in the greater omentum is very rare, and laparoscopic surgery was safe and useful for resection, in our case.

Living donor liver transplantation for Budd‒Chiari syndrome with right posterior segment graft and patch plasty using the superficial femoral vein: a case report.

BACKGROUND: In living donor liver transplantation (LDLT) for patients with Budd‒Chiari syndrome (BCS), there are several concerns about reconstruction of the inferior vena cava (IVC) and hepatic veins. Herein, we report the case of a patient with BCS who underwent LDLT with right posterior segment graft (RPSG) and patch plasty for reconstruction of the hepatic venous outflow, using the patient's own superficial femoral vein (SFV). CASE PRESENTATION: A 19-year-old man, who was diagnosed with primary BCS, underwent LDLT. His main hepatic veins were totally obstructed, and membranous stenosis was seen in the IVC. The LDLT donor was his mother; however, liver volumetric analysis showed that only her RPSG was appropriate. In the recipient surgery, 16 cm of the left SFV was harvested and was cut longitudinally and opened. The right hepatic vein (RHV) of the RPSG was anastomosed to the sidewall of the SFV graft. After explantation of native diseased liver was completed, the stenotic and thickened wall of the IVC was widely resected, and a large anastomotic orifice was created. Patch cavoplasty was performed with the RHV‒SFV graft patch. After portal reperfusion started, hepatic venous outflow was satisfactory, and there was no venous graft congestion. Both his postoperative course and his long-term course after discharge were uneventful. CONCLUSIONS: In LDLT for BCS patients, ingenuity is required for the reconstruction of venous outflow. The SFV patch can be safely harvested from liver transplant recipients and is suitable for venous reconstruction. In addition, RPSG is an alternative type of liver graft for LDLT if a conventional right- or left-lobe graft cannot be used.

Laparoscopic liver cyst fenestration with real-time indocyanine green fluorescence-guided surgery: a case report.

Laparoscopic fenestration (LF) has recently been considered a standard procedure for nonparasitic symptomatic liver cysts. Here, we report a case of LF that was safely performed using real-time indocyanine green (ICG) fluorescence-guided surgery. A 74-year-old woman presented with right upper abdominal pain and poor dietary intake. The patient was diagnosed with symptomatic liver cysts and underwent LF. One hour before surgery, ICG (2.5 mg) was intravenously administered to the patient. ICG fluorescence imaging clearly showed the biliary ducts and distinguished the cysts from the liver parenchyma. We could resect only the cyst walls as wide as possible under the guidance of both white light and fluorescence imaging. There were no signs of postoperative symptom recurrence. Detection of ICG fluorescence in the liver parenchyma is as important as ICG cholangiography for fenestration. Laparoscopic liver cyst fenestration with real-time ICG fluorescence-guided surgery is safe and can be used as a standard procedure.

The anti-angiogenic agent lenvatinib induces tumor vessel normalization and enhances radiosensitivity in hepatocellular tumors.

The evaluation of angiogenesis inhibitors requires the analysis of the precise structure and function of tumor vessels. The anti-angiogenic agents lenvatinib and sorafenib are multi-target tyrosine kinase inhibitors that have been approved for the treatment of hepatocellular carcinoma (HCC). However, the different effects on tumor vasculature between lenvatinib and sorafenib are not well understood. In this study, we analyzed the effects of both drugs on vascular structure and function, including vascular normalization, and investigated whether the normalization had a positive effect on a combination therapy with the drugs and radiation using micro X-ray computed tomography with gold nanoparticles as a contrast agent, as well as immunohistochemical analysis and interstitial fluid pressure (IFP) measurement. In mice subcutaneously transplanted with mouse HCC cells, treatment with lenvatinib or sorafenib for 14 days inhibited tumor growth and reduced the tumor vessel volume density. However, analysis of integrated data on vessel density, rates of pericyte-covering and perfused vessels, tumor hypoxia, and IFP measured 4 days after drug treatment showed that treatment with 3 mg/kg of lenvatinib significantly reduced the microvessel density and normalized tumor vessels compared to treatment with 50 mg/kg of sorafenib. These results showed that lenvatinib induced vascular normalization and improved the intratumoral microenvironment in HCC tumors earlier and more effectively than sorafenib. Moreover, such changes increased the radiosensitivity of tumors and enhanced the effect of lenvatinib and radiation combination therapy, suggesting that this combination therapy is a powerful potential application against HCC.

Surgical resection for liver metastasis and local recurrence of pheochromocytoma 16 years after primary surgery: A case report.

INTRODUCTION AND IMPORTANCE: Pheochromocytomas arise from the adrenal medulla and are rare. Pheochromocytomas metastasize to bone, lung and liver, and surgery might be the curative treatment. However, few cases are detected when they are resectable lesions because of difficulty in diagnosis and rapid growth. We herein report a patient who underwent resection of liver metastasis and local recurrence of pheochromocytoma. CASE PRESENTATION: A 74-year-old woman visited our hospital for treatment for liver and retroperitoneal tumors. She had undergone left adrenal gland resection for pheochromocytoma 16 years earlier. Eleven years after primary surgery, breast cancer was diagnosed and resected. During the breast cancer follow-up, a liver tumor was identified with computed tomography. Breast cancer recurrence and metastasis were considered, so chemotherapy was administered first. However, the liver tumor gradually enlarged, and another lesion appeared in the retroperitoneum. The tumors were diagnosed as pheochromocytoma recurrence using 123I-metaiodobenzylguanidine scintigraphy, and she underwent resection of the local recurrence and liver metastasis. She was discharged on postoperative day 25 without complications, and no evidence of recurrence occurred more than 3.5 years postoperatively. CLINICAL DISCUSSION: All pheochromocytomas have metastatic potential; however, there are no reliable markers to predict malignancy. Early detection of recurrence by regular imaging and complete resection are important in the treatment. If the recurrence was oligometastasis and tumor growth is slow, surgical resection may be eligible. CONCLUSION: A favorable outcome resulted from complete resection for liver metastasis and local recurrence of pheochromocytoma.

Quantitative analyses of amount and localization of radiosensitizer gold nanoparticles interacting with cancer cells to optimize radiation therapy.

Previous studies showed that gold nanoparticles (AuNPs) are useful radiosensitizers which optimize radiation therapy under low-dose radiation. However, the mechanisms of AuNP radiosensitization, including the amount and localization of the AuNPs interacting with cancer cells, has not yet been quantified. To answer these questions, we prepared AuNPs conjugated with anti-human epidermal growth factor receptor type 2 (HER2) antibody via polyethylene glycol (PEG) chains (AuNP-PEG-HER2ab). AuNP-PEG-HER2ab specifically bound to the HER2-expressing cancer cells and entered the cells via endocytosis. Whether endocytosis of AuNP-PEG-HER2ab occurred had no effect on radiosensitization efficacy by AuNP-PEG-HER2ab in vitro. The radiosensitization efficacy in vitro depended on dose of AuNP-PEG-HER2ab or dose of X-ray. Moreover, AuNP-PEG-HER2ab administrated into tumor-bearing mice was localized to both the periphery of the tumor tissue and near the nuclei in cancer cells in tumor deep tissue. The localization of AuNP-PEG-HER2ab in tumor tissues was important factors for in vivo powerful radiosensitization efficacy.

Surgical resection of recurrent extrahepatic hepatocellular carcinoma with tumor thrombus extending into the right atrium under cardiopulmonary bypass: a case report and review of the literature.

BACKGROUND: Recurrent hepatocellular carcinoma accompanied by a right atrial tumor thrombus is rare. No standard treatment modality has been established. Surgical treatment may be the only curative treatment; however, surgery has been considered high risk. We herein describe a patient who underwent resection of a recurrent right atrial tumor thrombus under normothermic cardiopulmonary bypass on a beating heart. CASE PRESENTATION: A 60-year-old man underwent a right hepatectomy for hepatocellular carcinoma with diaphragm invasion. During the preoperative cardiac screening, he was diagnosed with an old myocardial infarction with triple-vessel coronary disease. Percutaneous coronary intervention was performed for the left anterior descending artery and left circumflex coronary artery. High-grade stenosis remained in his right coronary artery. Nine months later, computed tomography showed recurrent hepatocellular carcinoma in the diaphragm and a tumor thrombus extending from the suprahepatic inferior vena cava into the right atrium. Surgical resection of the recurrent tumor was performed through a right subcostal incision with xiphoid extension and median sternotomy. The recurrent tumor was incised with the diaphragm and pericardium. Intraoperative ultrasonography revealed that the tumor thrombus was free from right atrium wall invasion and that the right atrium could be clamped just proximal to the tumor thrombus. The right atrium, infrahepatic vena cava, left and middle hepatic veins, and hepatoduodenal ligament were encircled. Cardiopulmonary bypass was performed to prevent ischemic heart disease caused by intraoperative hypotension. Total hepatic vascular exclusion was then performed under normothermic cardiopulmonary bypass on heart beating. The inferior vena cava wall was incised. The tumor thrombus with the diaphragmatic recurrent tumor was resected en bloc. The patient had a favorable clinical course without any complications. CONCLUSION: The recurrent hepatocellular carcinoma in the diaphragm and the right atrial tumor thrombus were safely resected using normothermic cardiopulmonary bypass on heart beating.

Methionine adenosyltransferase II-dependent histone H3K9 methylation at the COX-2 gene locus.

BACKGROUND: MATII biosynthesizes AdoMet, which supplies methyl group for methylation of molecules, including histone. RESULTS: MATII interacts with histone methyltransferase SETDB1 and inhibits COX-2 gene expression. CONCLUSION: AdoMet synthesis and histone methylation are coupled on chromatin by a physical interaction of MATII and SETDB1 at the MafK target genes. SIGNIFICANCE: MATII may be important for both gene-specific and epigenome-wide regulation of histone methylation. Methionine adenosyltransferase (MAT) synthesizes S-adenosylmethionine (AdoMet), which is utilized as a methyl donor in transmethylation reactions involving histones. MATIIα, a MAT isozyme, serves as a transcriptional corepressor in the oxidative stress response and forms the AdoMet-integrating transcription regulation module, affecting histone methyltransferase activities. However, the identities of genes regulated by MATIIα or its associated methyltransferases are unclear. We show that MATIIα represses the expression of cyclooxygenase 2 (COX-2), encoded by Ptgs2, by specifically interacting with histone H3K9 methyltransferase SETDB1, thereby promoting the trimethylation of H3K9 at the COX-2 locus. We discuss both gene-specific and epigenome-wide functions of MATIIα.

Methionine adenosyltransferase II serves as a transcriptional corepressor of Maf oncoprotein.

Protein methylation pathways comprise methionine adenosyltransferase (MAT), which produces S-adenosylmethionine (SAM) and SAM-dependent substrate-specific methyltransferases. However, the function of MAT in the nucleus is largely unknown. MafK represses or activates expression of heme oxygenase-1 (HO-1) gene, depending on its heterodimer partners. Proteomics analysis of MafK revealed its interaction with MATIIα, a MAT isozyme. MATIIα was localized in nuclei and found to form a dense network with chromatin-related proteins including Swi/Snf and NuRD complexes. MATIIα was recruited to Maf recognition element (MARE) at HO-1 gene. When MATIIα was knocked down in murine hepatoma cell line, expression of HO-1 was derepressed at both basal and induced levels. The catalytic activity of MATIIα, as well as its interacting factors such as MATIIß, BAF53a, CHD4, and PARP1, was required for HO-1 repression. MATII serves as a transcriptional corepressor of MafK by interacting with chromatin regulators and supplying SAM for methyltransferases.