Histopathological analysis of tumor microenvironment in adrenocortical carcinoma: Possible effects of in situ disorganized glucocorticoid production on tumor immunity.

Adrenocortical carcinoma (ACC) patients with glucocorticoid excess have been reported to be associated with decreased tumor-infiltrating immune cells, but the effects of in situ glucocorticoid production on tumor immunity have remained unknown. In addition, ACC was also known to harbor marked intra-tumoral heterogeneity of steroidogenesis or disorganized steroidogenesis. Therefore, in this study, we immune-profiled tumor-infiltrating lymphocytes (TILs) and tumor-associated macrophages (TAMs) and pivotal steroidogenic enzymes of glucocorticoid biosynthesis (CYP17A and CYP11B1) to explore the potential effects of in situ glucocorticoid production and intra-tumoral heterogeneity/disorganized steroidogenesis on tumor immunity of ACC. We also studied the correlations of the status of tumor immunity with that of angiogenesis and tumor grade to further explore the tumor tissue microenvironment of ACC. TILs (CD3, CD4, CD8, and FOXP3), TAMs (CD68 and CD163), key steroidogenic enzymes of glucocorticoid (CYP17A and CYP11B1), angiogenesis (CD31 and vasohibin-1 (VASH-1)), tumor grade (Ki-67 and Weiss score) were immunohistochemically evaluated in 34 ACCs. Increased CYP17A immunoreactivity in the whole tumor area was significantly positively correlated with FOXP3-positive TILs (p = 0.021) and negatively with CD4/CD3 ratio (p = 0.001). Increased CYP11B1 immunoreactivity in the whole tumor area was significantly positively correlated with CD8/CD3 (p = 0.039) and CD163/CD68 ratios (p = 0.006) and negatively with CD4-positive TILs (p = 0.036) and CD4/CD3 ratio (p = 0.001). There were also significant positive correlations between CYP17A and CD8 (r = 0.334, p < 0.001) and FOXP3-positive TILs (r = 0.414, p < 0.001), CD8/CD3 ratio (r = 0.421, p < 0.001), and CD68-positive TAMs (r = 0.298, p < 0.001) in randomly selected areas. Significant positive correlations were also detected between CYP11B1 and CD8/CD3 ratio (r = 0.276, p = 0.001) and negative ones detected between CYP11B1 and CD3- (r = -0.259, p = 0.002) and CD4-positive TILs (r = -0.312, p < 0.001) in those areas above. Increased micro-vessel density (MVD) -VASH-1 was significantly positively correlated with CD68- (p = 0.015) and CD163-positive TAMs (p = 0.009) and CD163/CD68 ratio and the high VASH-1 with CD163-positive TAMs (p = 0.042). Ki-67 labeling index was significantly positively correlated with MAD-VASH-1 (p = 0.006) and VASH-1 (p = 0.006) status. Results of our present study indicated that in situ glucocorticoid production did influence the status of tumor immunity in ACC. In particular, increased levels of CYP17A and CYP11B1, both involved in glucocorticoid producing immunoreactivity played different effects on tumor immunity, i.e., reflecting the involvement of intra-tumoral heterogeneity and disorganized steroidogenesis of ACC, which also did indicate the importance of in situ approaches when analyzing tumor immunity of ACC.

Small Intestinal Adenocarcinoma Arising at the Anastomotic Site after Kasai Operation for Biliary Atresia: A Case Report and Literature Review.

Biliary atresia is an obliterative cholangiopathy of unknown etiology. Hepatic portoenterostomy, in which obliterated extrahepatic bile ducts are resected and bile flow is restored, known as Kasai operation, is performed within 3 months after birth. While this operation enhances long-term survival of patients, the occurrence of primary malignant hepatic tumors has been increasing. We report a case of small intestinal adenocarcinoma arising at the anastomotic site after Kasai operation. A 49-year-old man, who underwent Kasai operation for biliary atresia when he was 2 months old, experienced rapidly progressive jaundice and liver dysfunction. Deceased-donor liver transplantation was performed for liver failure. Macroscopically, there was a white-yellow tumor located at the anastomotic site of hepatic portoenterostomy of the resected liver. Pathological examination revealed a well-differentiated adenocarcinoma with some Paneth cells in the neoplastic lesion. Immunohistochemically, the tumor cells were negative for cytokeratin 7 (CK7) but positive for cytokeratin 20 (CK20) and a homeobox domain-containing transcription factor (CDX2). Mucin expression in tumor cells was negative for mucin 1 (MUC1) and mucin 6 (MUC6) and positive for mucin 2 (MUC2) and mucin 5AC (MUC5AC). The pathological diagnosis was small intestinal adenocarcinoma originating from the jejunum. The patient was discharged 48 days after the operation. The patient had not experienced recurrence at 10 months after the operation. This is the first report of small intestinal adenocarcinoma arising at the anastomotic site after Kasai operation for biliary atresia. Special care should be taken for the patients after Kasai operation with acute progressive jaundice and liver dysfunction because there is a possibility of malignancy in their native liver.

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.

Tumor-to-Tumor Metastasis of Medullary Thyroid Carcinoma to Paraganglioma in a Multiple Endocrine Neoplasia Type 2B Patient: A Case Report and Literature Review.

Tumor-to-tumor metastasis is a rare phenomenon in which primary tumor cells metastasize to other tumors. Herein, we report an extremely rare case of tumor-to-tumor metastasis of medullary thyroid carcinoma to a paraganglioma in a patient with multiple endocrine neoplasia type 2B. Based on genetic examination, a 36-year-old woman was diagnosed with multiple endocrine neoplasia type 2B when she was 24 years old. She had a history of total thyroidectomy for medullary thyroid carcinoma and bilateral adrenalectomy for pheochromocytomas, which were performed when she was 15 years and 29 years old, respectively. Follow-up computed tomography demonstrated a retroperitoneal tumor of 30 mm in diameter beside the left kidney and a liver tumor of 16 mm in diameter located in segment 6. The retroperitoneal and liver tumors were surgically resected and examined by a pathologist. Histological examination revealed the classic Zellballen pattern in the retroperitoneal tumor, rendering the diagnosis of a paraganglioma recurrence. Inside the tumor, a white nodule positive for carcinoembryonic antigen, weakly positive for calcitonin, and negative for tyrosine hydroxylase, was identified and diagnosed as a metastatic medullary thyroid carcinoma with high malignant potential. The liver lesion was diagnosed as a metastasis of the medullary thyroid carcinoma. This is the first report of tumor-to-tumor metastasis of medullary thyroid carcinoma to paraganglioma in a patient with multiple endocrine neoplasia type 2B twenty years after total thyroidectomy.

Ideal Duration of Pretreatment Using a Gelatin Hydrogel Nonwoven Fabric Prior to Subcutaneous Islet Transplantation.

Subcutaneous islet transplantation is a promising treatment for severe diabetes; however, poor engraftment hinders its prevalence. We previously revealed that a gelatin hydrogel nonwoven fabric (GHNF) markedly improved subcutaneous islet engraftment in comparison with intraportal islet transplantation. We herein investigated whether the duration of pretreatment using GHNF affected the outcome of subcutaneous islet transplantation. A silicone spacer with GHNF was implanted into the subcutaneous space of healthy mice at 2, 4, 6, or 8 weeks before transplantation, and then diabetes was induced 7 days before transplantation. Syngeneic islets were transplanted into the pretreated space. Blood glucose, intraperitoneal glucose tolerance, immunohistochemistry, inflammatory mediators, and gene expression were evaluated. The 6-week group showed significantly better blood glucose changes than the other groups (P < 0.05). The cure rate of the 6-week group (60.0%) was the highest among the groups (2-week = 0%, 4-week = 50.0%, 8-week = 15.4%). The number of von Willebrand factor (vWF)-positive vessels in the 6-week group was significantly higher than in the other groups at pre-islet and post-islet transplantation (P < 0.01 [vs 2-and 4-week groups] and P < 0.05 [vs all other groups], respectively). Notably, this beneficial effect was also observed when GHNF was implanted into diabetic mice injected with streptozotocin 7 days before GHNF implantation. The positive rates for laminin, collagen III, and collagen IV increased as the duration of pretreatment became longer and were significantly higher in the 8-week group (P < 0.01). Inflammatory mediators, including interleukin (IL)-1b, granulocyte colony-stimulating factor (G-CSF), and interferon (IFN)-γ, were gradually downregulated according to the duration of GHNF pretreatment and re-elevated in the 8-week group. Taken together, the duration of GHNF pretreatment apparently had an impact on the outcomes of subcutaneous islet transplantation, and 6 weeks appeared to be the ideal duration. Islet graft revascularization, extracellular matrix compensation of the islet capsule, and the inflammatory status at the subcutaneous space would be crucial factors for successful subcutaneous islet transplantation.

Clinical Significance of the Mac-2 Binding Protein Glycosylated Isomer as a Surrogate Marker of Graft Fibrosis After Pediatric Liver Transplantation.

BACKGROUND: After pediatric liver transplantation, liver fibrosis may occur during long-term follow-up. Noninvasive markers for assessing this liver fibrosis are desired. Mac-2 binding protein glycosylated isomer (M2BPGi) has recently been reported as a useful biomarker for liver fibrosis. However, its usefulness in the pediatric population is yet to be established. This study investigated the clinical significance of M2BPGi levels as a surrogate marker of graft fibrosis after pediatric liver transplantation. METHODS: We retrospectively identified 96 patients who underwent pediatric liver transplantation at our institution between 1991 and 2015. The association between M2BPGi levels and other fibrosis markers was analyzed in 60 patients in whom fibrosis markers were measured. The association between fibrosis marker levels and graft fibrosis was assessed in 42 patients who underwent biopsies between 2016 and 2022. RESULTS: The M2BPGi levels were statistically correlated with the hyaluronic acid and type-IV collagen levels. None of the fibrosis markers were significantly associated with liver graft fibrosis, although the levels of these markers were slightly higher in patients with severe liver fibrosis than in those with mild fibrosis. CONCLUSIONS: The M2BPGi levels had a limited ability to assess liver graft fibrosis after pediatric liver transplantation, similar to other fibrosis markers. Further studies with larger cohorts are required to validate these findings externally.

Detailed Courses and Pathological Findings of Colonic Perforation without Diverticula in Sisters with Musculocontractural Ehlers-Danlos Syndrome Caused by Pathogenic Variant in CHST14 (mcEDS-CHST14).

Musculocontractural Ehlers-Danlos syndrome (mcEDS) is a heritable connective tissue disorder characterized by multiple congenital malformations and progressive connective-tissue-fragility-related manifestations in the cutaneous, skeletal, cardiovascular, visceral, ocular, and gastrointestinal systems. It is caused by pathogenic variants in the carbohydrate sulfotransferase 14 gene (mcEDS-CHST14) or in the dermatan sulfate epimerase gene (mcEDS-DSE). As gastrointestinal complications of mcEDS-CHST14, diverticula in the colon, small intestine, or stomach have been reported, which may lead to gastrointestinal perforation, here, we describe sisters with mcEDS-CHST14, who developed colonic perforation with no evidence of diverticula and were successfully treated through surgery (a resection of perforation site and colostomy) and careful postoperative care. A pathological investigation did not show specific abnormalities of the colon at the perforation site. Patients with mcEDS-CHST14 aged from the teens to the 30s should undergo not only abdominal X-ray photography but also abdominal computed tomography when they experience abdominal pain.

First Multicenter Clinical Trial on Machine Perfusion Preservation for Marginal Donor Kidney Transplantation in Japan.

BACKGROUND: Machine perfusion has not been widely used because of its low demand in Japan; however, we believe its advantages may increase the number of organ transplants. METHODS: Here, we report the first clinical trial of machine perfusion for kidney transplantation in Japan. We used the CMP-X08 perfusion device (Chuo-Seiko Co, Ltd, Asahikawa, Hokkaido, Japan) to preserve the donated organs. The flow rate, perfusion pressure, renal resistance, and temperature were monitored during continuous hypothermic perfusion. RESULTS: From August 2020 to the present, 13 cases of perfusion-preserved kidney transplantation have been performed. Of these, ten and 3 cases were performed using organs donated after brain death (DBD) and cardiac death (DCD), respectively. The average age of the recipients was 55.9 ± 7.3 (45-66) years. The average dialysis period was 14.8 ± 8.4 (0-26) years. The donor's final creatinine level before organ retrieval was 1.58 ± 1.0 (0.46-3.07) mg/dL. The warm ischemic times of the 3 DCD donors were 3, 12, and 18 minutes. The average total ischemic time was 12.0 ± 3.7 (7.17-19.88) hours. The average MP time was 140 (60-240) minutes. A total of 7 cases had delayed graft function. The best creatinine level during hospitalization was 1.17 ± 0.43 (0.71-1.85) mg/dL. There were no primary non-functional cases, and perfusion preservation was safely performed in all cases. CONCLUSIONS: Therefore, we present this report as the first clinical trial on machine perfusion for kidney transplantation from marginal donors with DBD and DCD in Japan.

Postreperfusion Syndrome Presenting as Posttransplant Portal Hypertension due to Prolonged Elevation of Pulmonary Vascular Resistance and the Role of Nitroglycerin in Diagnosis and Treatment: A Case Report of Budd-Chiari Syndrome.

Postreperfusion syndrome is one of the responsible mechanisms of portal hypertension in patients undergoing liver transplantation. And post-transplant portal hypertension causes graft dysfunction. Postreperfusion syndrome is characterized by a decrease in arterial pressure and cardiac output, and an increase in central venous pressure, pulmonary artery pressure, and pulmonary vascular resistance that occurs after the release of the portal vein clamp. Although early recovery from postreperfusion syndrome is desired, there is a little medication therapy such as the administration of calcium chloride, sodium bicarbonate, and beta-agonist for postreperfusion syndrome. We present a case of postreperfusion syndrome manifested as post-transplant portal hypertension and reversed after nitroglycerin administration. A 49-year-old Asian woman was scheduled for liver transplantation because of Budd-Chiari syndrome. After portal vein reperfusion, she experienced severe postreperfusion syndrome. Administration of ephedrine and calcium restored arterial pressure; however, pulmonary artery pressure, pulmonary vascular resistance, and central venous pressure elevations were sustained, causing right ventricular overload. This condition did not improve after hepatic artery reperfusion, and caused post-transplant portal hypertension. After nitroglycerin administration, pulmonary vascular resistance and central venous pressure decreased, mean arterial pressure increased, right heart contractility recovered, and portal hypertension disappeared. Hemodynamic improvement by nitroglycerin administration helped in diagnosing postreperfusion syndrome and avoiding unnecessary splenectomy. If portal vein pressure increases after liver transplantation, the change in hemodynamic parameters by nitroglycerin administration should be assessed, which will lead to accurate diagnosis and appropriate treatment. Furthermore, postreperfusion syndrome should be listed as a differential diagnosis of post-transplant portal hypertension.

A Gelatin Hydrogel Nonwoven Fabric Enhances Subcutaneous Islet Engraftment in Rats.

Although subcutaneous islet transplantation has many advantages, the subcutaneous space is poor in vessels and transplant efficiency is still low in animal models, except in mice. Subcutaneous islet transplantation using a two-step approach has been proposed, in which a favorable cavity is first prepared using various materials, followed by islet transplantation into the preformed cavity. We previously reported the efficacy of pretreatment using gelatin hydrogel nonwoven fabric (GHNF), and the length of the pretreatment period influenced the results in a mouse model. We investigated whether the preimplantation of GHNF could improve the subcutaneous islet transplantation outcomes in a rat model. GHNF sheets sandwiching a silicone spacer (GHNF group) and silicone spacers without GHNF sheets (control group) were implanted into the subcutaneous space of recipients three weeks before islet transplantation, and diabetes was induced seven days before islet transplantation. Syngeneic islets were transplanted into the space where the silicone spacer was removed. Blood glucose levels, glucose tolerance, immunohistochemistry, and neovascularization were evaluated. The GHNF group showed significantly better blood glucose changes than the control group (p < 0.01). The cure rate was significantly higher in the GHNF group (p < 0.05). The number of vWF-positive vessels was significantly higher in the GHNF group (p < 0.01), and lectin angiography showed the same tendency (p < 0.05). The expression of laminin and collagen III around the transplanted islets was also higher in the GHNF group (p < 0.01). GHNF pretreatment was effective in a rat model, and the main mechanisms might be neovascularization and compensation of the extracellular matrices.

Probable posttransplant lymphoproliferative disorder after pediatric living donor liver transplantation: Is a biopsy still needed?

Posttransplant lymphoproliferative disorder (PTLD) is a complication of solid organ transplantation and is associated with Epstein-Barr virus (EBV). Recently, EBV-related PTLD was defined as probable PTLD or proven PTLD. Probable PTLD involves significant lymphadenopathy, hepatosplenomegaly, or other end-organ manifestations, without a histological diagnosis, together with significant EBV DNAemia. Proven PTLD is the detection of EBV-encoded proteins in a tissue specimen, together with symptoms and/or signs originating from the affected organ. Probable PTLD after pediatric liver transplantation has not been well documented. Therefore, here, we aimed to describe cases of five pediatric patients with probable PTLD after liver transplantation, who were successfully treated with preemptive immunosuppression reduction with or without rituximab. All five patients (age range, 1-4 years; two girls and three boys) had EBV DNAemia. Three patients developed probable PTLD within 12 months of transplantation. Further, three patients had a significantly high EBV viral load, but the other two patients with lymphadenopathy and end-organ manifestation had a relatively low EBV viral load. Early onset pediatric PTLD with significant EBV DNAemia is almost universally EBV-related. Biopsy was not performed in any patient due to the relative inaccessibility of the lesion and young age of the patients. If the patient's symptoms are too mild, if excisional biopsy is too difficult to perform, or if the patient is too sick to undergo an invasive procedure, initiating preemptive treatment without a histological diagnosis could be the treatment option.

A potential preventive method for scar stenosis after esophageal endoscopic mucosal resection using human amniotic epithelial cells in a porcine model.

Objectives: The current methods employed for esophageal endoscopic mucosal resection (EMR) involve the risk of adverse postprocedural complications. Therefore, this study aimed to develop a new method to prevent stenosis following a resection procedure using human amniotic epithelial cells in a porcine model. Methods: With the consent of a woman who underwent a cesarean section, amniotic epithelial cells were isolated from the amniotic membrane of the delivered placenta. Six swine were used for this study. Under general anesthesia, four EMRs using cap-fitted microscope ulcers were performed on each porcine esophagus. Of the four ulcers, the two on the oral side were treated by injecting human amniotic epithelial (AE group) cells, and the remaining two on the anal side were left untreated (control group). One week after the procedure, the swine were sacrificed, and the ulcers were evaluated. The epithelialization rate was calculated by dividing the length of the epithelialized portion of each section by the length of the ulcer, which was determined using an optical microscope. Moreover, the mucosal thickening in each section was measured in terms of diameter. Results: The epithelialization rate was significantly higher in the AE group than in the control group. Mucosal thickening was not significantly different between the groups. Conclusions: Transplanting amniotic epithelial cells into the ulcer promoted ulcer epithelialization. Amniotic epithelial cell transplantation is a potential method for the management of ulcer scar stenosis following esophageal endoscopic submucosal dissection.

A New Strategy of Liver Transplantation for Locally Advanced Unresectable Perihilar Cholangiocarcinoma Using Living Grafts With Simultaneous Resection of Recipients' Hepatic Artery and Portal Vein Without Neoadjuvant Radiation: A Case Report.

BACKGROUND: Perihilar cholangiocarcinoma (pCCA) is often unresectable, because it includes crucial blood vessels in portal area. The prognosis of locally advanced unresectable cholangiocarcinomas is extremely poor. Recently, there have been several reports of the prognosis improving drastically with transplantation and combined chemoradiation therapy. However, liver transplantation for pCCA has 2 big problems. The first is that pCCA is located at a lethal position and its progress is sometimes rapid; therefore, the optimal timing of transplantation is sometimes lost. The second is vascular complications associated with neoadjuvant radiation, especially in living donor liver transplantation (LDLT). To overcome these problems, we performed conversion surgery using LDLT with simultaneous resection of the hepatic artery and portal vein, instead of neoadjuvant radiation. Herein, we report our experience of interposition reconstruction. METHODS: A 31-year-old man with primary sclerosing cholangitis (PSC) was diagnosed with locally advanced unresectable pCCA. The patient underwent radical chemotherapy (gemcitabine/cisplatin/S-1) and avoided radiation because of PSC. After 6 months, positron emission tomography-computed tomography revealed no lymph node metastasis. There was no time to wait. We immediately performed LDLT with simultaneous resection of hepatic artery and portal vein, and microsurgical reconstruction using auto-vessel grafts. RESULTS: The recipient recovered and was discharged 31 days posttransplant. His liver function improved, and he has had no recurrence after LDLT. CONCLUSION: LDLT with neoadjuvant radiation is associated with high risk of vascular complications. In some cases, conversion surgery after radical chemotherapy using good timing LDLT without radiation may increase chances of transplantation for locally advanced pCCA.

Long-term survival of an adult patient with undifferentiated embryonal sarcoma of the liver with multidisciplinary treatment: a case report and literature review.

BACKGROUND: Undifferentiated embryonal sarcoma of the liver (UESL) primarily occurs in children; it is rarely seen in adults and appears to have a poor prognosis. However, in recent years, some cases indicated that long-term survival was possible due to a combination of multiple surgeries, chemotherapy, and liver transplantation. CASE PRESENTATION: A 33-year-old female patient presented with a complaint of epigastric pain, for which she underwent a medical examination. Computed tomography (CT) and magnetic resonance imaging showed a cystic tumor in the right hepatic lobe, approximately 10 cm in size. During observation, the abdominal pain worsened, and a contrast-enhanced CT revealed that the tumor's peripheral solid components increased in size and volume, suggesting a malignant tumor threatening hepatic rupture. Subsequently, transcatheter arterial embolization of the anterior and posterior segmental branches of the hepatic artery was performed, followed by right trisectionectomy. Histopathological and immunohistochemical examinations of the lesion revealed UESL. Two months after the surgery, we initiated sarcoma-directed chemotherapy with doxorubicin because of multiple metastases to the liver. After initiating the chemotherapy, she received another regimen using gemcitabine/docetaxel, eribulin, trabectedin, ifosfamide/mesna, pazopanib, and cisplatin. During the chemotherapy, she underwent palliative surgery twice due to the progressive disease. She lived for 49 months after the initial operation. CONCLUSIONS: Improved long-term survival was achieved in an adult patient with UESL after multidisciplinary therapy, involving a combination of three surgical procedures and several chemotherapies.

Cholesterol Granuloma of the Liver Mimicking Malignant Tumor: A Case Report.

Cholesterol granuloma is a benign, tumor-like lesion with an accumulation of cholesterol crystals in the tissue and is a consequence of a chronic inflammatory reaction. It commonly occurs in the middle ear but rarely in the liver. There is only one previous case report of cholesterol granuloma of the liver, which was caused by cholesterol hepatolithiasis. We report a case of cholesterol granuloma of the liver in a patient with no intrahepatic cholesterol stones; it was difficult to rule out malignant liver tumor preoperatively. The patient was a 79-year-old woman in whom a lesion in the liver was detected on abdominal ultrasonography. She was referred to our hospital for detailed examination and treatment. Abdominal contrast-enhanced computed tomography showed a 20 mm lesion with ring enhancement in the lateral segment of the liver during the arterial and delayed phases. Since a malignant tumor could not be ruled out radiologically, laparoscopic lateral segment hepatectomy was performed for definitive diagnosis and treatment. The resection specimen showed a yellowish-white lesion measuring 15 mm in diameter. Pathological examination showed a granulomatous lesion with cholesterol crystals surrounded by foreign body giant cells. The lesion was diagnosed as cholesterol granuloma of the liver. The postoperative course was good, and the patient was discharged on postoperative day 5. She was healthy, and no recurrence of the cholesterol granuloma was detected at the 5-month follow-up. This is the first case report of cholesterol granuloma of the liver mimicking a malignant liver tumor in a patient with no intrahepatic cholesterol stones.

Optimal Conditions for Oxygenated Subnormothermic Machine Perfusion for Liver Grafts Using a Novel Perfusion Device.

BACKGROUND: Liver transplantation from donors after cardiac death (DCD) resolves donor shortages. PURPOSE: We investigated the optimal time for subnormothermic oxygenated perfusion in DCD liver transplantation. METHODS: Ten F1 pigs (body weight: 27-32 kg) were allocated to 2 groups: the heart beating group (n = 6), from which livers were retrieved while the heart was beating, and the donation after cardiac death (DCD) group (n = 4), in which liver retrieval was performed on pigs under apnea-induced cardiac arrest for 20 minutes. In both groups, the livers were kept in cold storage for 2 hours after retrieval and perfused with a subnormothermic oxygenated Krebs-Henseleit buffer for 120 minutes. We used a novel perfusion device, which can set maximum perfusion pressures of arteries and portal vein, developed by Asahikawa Medical University and Chuo Seiko Co. Bile production, liver enzymes, and inflammatory cytokines were measured and the sinusoidal space, using tissue specimens taken from liver grafts, was measured at 30, 60, 90, and 120 minutes after the start of perfusion. RESULTS: Bile production peaked at 90 minutes. Significantly higher levels of liver enzymes and inflammatory cytokines were found in the DCD group (P < .05). The release of liver enzymes peaked at 60 minutes and that of inflammatory cytokines peaked at 90 minutes. The hepatic sinusoidal space was wide at 90 minutes and narrowed after 120 minutes. CONCLUSIONS: The results suggest that subnormothermic oxygenation perfusion may maintain optimal graft condition until around 90 minutes and perfusion for more than 120 minutes may be counterproductive.

Adult Living Donor Liver Transplantation for the Carryover Patients After Kasai Operation Who Have a History of Multiple Laparotomies.

OBJECTIVE: Approximately 50 years have passed since the Kasai operation announcement for biliary atresia. In adult liver failure cases, the so-called "the carryover cases after Kasai operation" have increased. These patients often underwent polysurgery. In such cases, adult living-donor liver transplantation (LDLT) is occasionally difficult. Many complications have been reported to be caused by severe cholangitis, hepatic portal regional inflammation, and adhesion. We investigated the complications of adult LDLT in post-Kasai biliary atresia cases with polysurgery. METHODS: Between 1991 and 2021, we performed 205 LDLT cases. We investigated the outcome of adult LDLT for post-Kasai biliary atresia cases (transplanted over 16 years old) (n = 20) and the risk factors for complications after LDLT. RESULTS: On 5 years overall survival, there were no significant differences between "adult LDLT for post-Kasai" group and the others (81.8% vs 81.2%). Adult LDLT for post-Kasai was not found to be a risk factor for complications. However, polysurgery before LDLT was an independent risk factor for biliary stenosis and portal stenosis, as identified in our univariate and multivariate analysis. We analyzed the relationship between biliary stenosis and the frequency of laparotomies using a receiver operating characteristic curve. The analysis showed that the cutoff point (maximum point of sensitivity plus specificity) was more than 3 times that of laparotomies before LDLT. CONCLUSIONS: In our study, adult LDLT for post-Kasai cases was not a risk factor for any complications. However, polysurgery before LDLT has been identified as a risk factor for biliary stenosis and portal vein stenosis.

Distribution of Amniotic Epithelial Cells After Intraportal Infusion in a Rat Model.

BACKGROUND: Human amniotic epithelial cells (hAECs) are increasingly gaining attention as novel sources for cell transplantation. In clinical practice, intraportal infusion is considered one of the leading approaches for transplantation; however, this has not yet been validated for in vivo transplantation of hAECs. Thus, this study aims to investigate the distribution of hAECs post intraportal infusion and compare this distribution with other cell administration routes. METHODS: Wistar/ST rats were divided into 4 groups (n = 3 for each) based on cell administration route: group 1, intraportal; group 2, the spleen; group 3, tail veins; and group 4, penile veins. Subsequently, hAECs (1 × 107) stained with XenoLight DiR were infused into each recipient. Cell distribution was evaluated using an in vivo imaging system. RESULTS: DiR signals were detected in the rat livers of groups 1 and 2 with those in group 2 being much weaker than those in group 1. Necrosis of small intestine was observed in 2 cases in group 2. DiR signals were detected in the lungs in groups 3 and 4 because of systemic circulation; however, all the animals died within 20 minutes of infusions. CONCLUSIONS: Intraportal infusion is potentially applicable for safe and efficient transplantation of hAECs into the liver, whereas hAECs administration via the spleen carries a risk of thrombosis in a narrow portal vein system. Our results also indicate that hAECs administration via the systemic circulation could cause pulmonary embolism in clinical settings.

Oxygenated Hypothermic Machine Perfusion of Kidney Transplantation from Donors After Cardiac Death Due to Long-Term Low Blood Pressure and Hypoxia: The First Case Report of a Clinical Trial Using a New Japanese Perfusion System.

BACKGROUND: Machine perfusion of marginal kidney grafts obtained from donors after cardiac death (DCD) has become a standard therapy worldwide. However, the use of grafts from DCD due to long-term low blood pressure is associated with a high incidence of primary graft nonfunction. Furthermore, the importance of oxygenation in machine perfusion remains unclear. We report the first case of a clinical trial of a kidney transplant obtained from a DCD using a Japanese oxygenated hypothermic perfusion system (CMX-08W, Chuo Seiko Co Ltd, Asahikawa, Japan). PATIENTS AND METHODS: The donor was a 61-year-old man with amyotrophic lateral sclerosis. His SpO2 decreased to 80% to 90%, his blood pressure remained consistently low for 4 hours and 30 minutes, and he suffered a cardiac arrest. Subsequently, we carried him to the operating room. The warm ischemic time was 12 minutes, and the cold ischemic time was 418 minutes. The recipient was a 58-year-old man who had been undergoing hemodialysis for 26 years. He was diagnosed with nephrosclerosis and multiple renal cysts. Oxygenated hypothermic machine perfusion was used on the kidney transplant obtained from the DCD. RESULTS: The recipient gradually recovered and was withdrawn from hemodialysis therapy 14 days post transplantation. His renal function improved, and he was discharged on postoperative day 36. Currently, his renal function remains good (phosphocreatine, 1.7). CONCLUSIONS: Oxygenated machine perfusion is used to preserve organs and determine if an organ is suitable for transplantation. This may provide the possibility of perfusion preservation and expand the criteria for cardiac arrest-associated renal transplantation.