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Radiotherapy is an effective treatment method for cervical cancer and is typically administered as external beam radiotherapy followed by intracavitary brachytherapy. In Japan, center shielding is used in external beam radiotherapy to shorten treatment time and reduce the doses delivered to the rectum or bladder. However, it has several challenges, such as uncertainties in calculating the cumulative dose. Recently, external beam radiotherapy has been increasingly performed with intensity-modulated radiotherapy, which reduces doses to the rectum or bladder without center shielding. In highly conformal radiotherapy, uncertainties in treatment delivery, such as inter-fractional anatomical structure movements, affect treatment outcomes; therefore, image-guided radiotherapy is essential for appropriate and safe performance. Regarding intracavitary brachytherapy, the use of magnetic resonance imaging-based image-guided adaptive brachytherapy is becoming increasingly widespread because it allows dose escalation to the tumor and accurately evaluates the dose delivered to the surrounding normal organs. According to current evidence, a minimal dose of D90% of the high-risk clinical target volume is significantly relevant to local control. Further improvements in target coverage have been achieved with combined interstitial and intracavity brachytherapy for massive tumors with extensive parametrical involvement. Introducing artificial intelligence will enable faster and more accurate generation of brachytherapy plans. Charged-particle therapies have biological and dosimetric advantages, and current evidence has proven their effectiveness and safety in cervical cancer treatment. Recently, radiotherapy-related technologies have advanced dramatically. This review provides an overview of technological innovations and future perspectives in radiotherapy for cervical cancer.
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OBJECTIVE: Blood flow in the hepatic veins and superior vena cava (SVC) reflects right heart filling; however, their Doppler profiles are often not identical, and no studies have compared their diagnostic efficacies. We aimed to determine which venous Doppler profile is reliable for detecting elevated right atrial pressure (RAP). METHODS: In 193 patients with cardiovascular diseases who underwent cardiac catheterization within 2 d of echocardiography, the hepatic vein systolic filling fraction (HV-SFF) and the ratio of the peak systolic to diastolic forward velocities of the SVC (SVC-S/D) were measured. HV-SFF < 55% and SVC-S/D < 1.9 were regarded as elevated RAP. We also calculated the fibrosis 4 index (FIB-4) as a serum liver fibrosis marker. RESULTS: HV-SFF and SVC-S/D were feasible in 177 (92%) and 173 (90%) patients, respectively. In the 161 patients in whom both venous Doppler waveforms could be measured, HV-SFF and SVC-S/D were inversely correlated with RAP (r = -0.350, p < 0.001; r = -0.430, p < 0.001, respectively). SVC-S/D > 1.9 showed a significantly higher diagnostic accuracy of RAP elevation compared with HV-SFF < 55% (area under the curve, 0.842 vs. 0.614, p < 0.001). Multivariate analyses showed that both FIB-4 (ß = -0.211, p = 0.013) and mean RAP (ß = -0.319, p < 0.001) were independent determinants of HV-SFF. In contrast, not FIB-4 but mean RAP (ß = -0.471, p < 0.001) was an independent determinant of SVC-S/D. The diagnostic accuracy remained unchanged when HV-SFF < 55% was considered in conjunction with the estimated RAP based on the inferior vena cava morphology. Conversely, SVC-S/D showed an incremental diagnostic value over the estimated RAP. CONCLUSIONS: SVC-S/D enabled a more accurate diagnosis of RAP elevation than HV-SFF.
Subject(s)
Hepatic Veins , Vena Cava, Superior , Humans , Female , Male , Hepatic Veins/diagnostic imaging , Hepatic Veins/physiopathology , Vena Cava, Superior/diagnostic imaging , Vena Cava, Superior/physiopathology , Middle Aged , Blood Flow Velocity/physiology , Aged , Atrial Pressure/physiology , Reproducibility of Results , Predictive Value of Tests , Heart Atria/diagnostic imaging , Heart Atria/physiopathology , Echocardiography, Doppler/methodsABSTRACT
Right ventricular (RV) diastolic stiffness is an independent predictor of survival and is strongly associated with disease severity in patients with precapillary pulmonary hypertension (PH). Therefore, a fully validated echocardiographic method for assessing RV diastolic stiffness needs to be established. This study aimed to compare echocardiography-derived RV diastolic stiffness and invasively measured pressure-volume loop-derived RV diastolic stiffness in patients with precapillary PH. We studied 50 consecutive patients with suspected or confirmed precapillary PH who underwent cardiac catheterization, magnetic resonance imaging, and echocardiography within a 1-week interval. Single-beat RV pressure-volume analysis was performed to determine the gold standard for RV diastolic stiffness. Elevated RV end-diastolic pressure (RVEDP) was defined as RVEDP ≥ 8 mmHg. Using continuous-wave Doppler and M-mode echocardiography, an echocardiographic index of RV diastolic stiffness was calculated as the ratio of the atrial-systolic descent of the pulmonary artery-RV pressure gradient derived from pulmonary regurgitant velocity (PRPGDAC) to the tricuspid annular plane movement during atrial contraction (TAPMAC). PRPGDAC/TAPMAC showed significant correlation with ß (r = 0.54, p < 0.001) and RVEDP (r = 0.61, p < 0.001). A cut-off value of 0.74 mmHg/mm for PRPGDAC/TAPMAC showed 83% sensitivity and 93% specificity for identifying elevated RVEDP. Multivariate analyses indicated that PRPGDAC/TAPMAC was independently associated with disease severity in patients with precapillary PH, including substantial PH symptoms, stroke volume index, right atrial size, and pressure. PRPGDAC/TAPMAC, based on pulmonary regurgitation velocity waveform analysis, is useful for the noninvasive assessment of RV diastolic stiffness and is associated with prognostic risk factors in precapillary PH.
Subject(s)
Cardiac Catheterization , Diastole , Echocardiography, Doppler , Hypertension, Pulmonary , Predictive Value of Tests , Pulmonary Valve Insufficiency , Ventricular Function, Right , Ventricular Pressure , Humans , Hypertension, Pulmonary/physiopathology , Hypertension, Pulmonary/diagnostic imaging , Male , Female , Middle Aged , Reproducibility of Results , Aged , Pulmonary Valve Insufficiency/physiopathology , Pulmonary Valve Insufficiency/diagnostic imaging , Adult , Ventricular Dysfunction, Right/physiopathology , Ventricular Dysfunction, Right/diagnostic imaging , Ventricular Dysfunction, Right/etiology , Pulmonary Artery/physiopathology , Pulmonary Artery/diagnostic imaging , ROC Curve , Area Under Curve , Arterial Pressure , Severity of Illness IndexABSTRACT
BACKGROUND: Methylmalonic acidemia (MMA) is an autosomal recessive disorder caused by defects in propionyl-CoA (P-CoA) catabolism; of note, liver neoplasms rarely occur as a long-term complication of the disorder. Herein, we report the case of a patient with MMA and hepatocellular carcinoma (HCC) who was successfully treated with a living-donor liver transplant (LDLT) following prior kidney transplantation. CASE REPORT: A 25-year-old male patient with MMA underwent LDLT with a left lobe graft because of metabolic instability and liver neoplasms. He had presented with chronic symptoms of MMA, which had been diagnosed by genetic testing. Additionally, he had undergone living-donor kidney transplantation with his father as the donor due to end-stage kidney disease 6 years before the LDLT. He had an episode of metabolic decompensation triggered by coronavirus disease in 2019. Imaging studies revealed an intrahepatic neoplasm in the right hepatic lobe. Due to concerns about metabolic decompensation after hepatectomy, LDLT was performed using a left lobe graft obtained from the patient's mother. Pathological findings were consistent with the characteristics of well-to-moderately differentiated HCC. The postoperative course was uneventful, and the patient was discharged 48 days after the LDLT without any complications. At the 9-month follow-up, the patient's condition was satisfactory, with sufficient liver graft function and without metabolic decompensation. CONCLUSION: This case indicates that although HCC is a rare complication in patients with MMA, clinicians should be aware of hepatic malignancies during long-term follow-up.
Subject(s)
Amino Acid Metabolism, Inborn Errors , Carcinoma, Hepatocellular , Liver Neoplasms , Liver Transplantation , Male , Humans , Adult , Carcinoma, Hepatocellular/complications , Carcinoma, Hepatocellular/surgery , Living Donors , Liver Neoplasms/complications , Liver Neoplasms/surgeryABSTRACT
Liver transplantation (LT) has become a vital treatment option for children with end-stage liver disease. Left lateral segment (LLS) grafts are particularly common in split and living donor LT for pediatric patients. However, challenges arise in small infants receiving LLS grafts, primarily due to graft-size mismatches, resulting in "large-for-size" grafts. To overcome this issue, the practice of further reducing grafts from the LLS to diminish graft thickness has been explored. Currently, the indication for reducing the thickness of LLS grafts includes recipients with a body weight (BW) under 5.0 kg, neonates with acute liver failure, or those with metabolic liver disease. At the National Center for Child Health and Development in Tokyo, Japan, among 131 recipients of reduced-size LLS grafts, a remarkable 15-year graft survival rate of 89.9% has been achieved in small infants. This success indicates that with experience and refinement of the technique, there's a trend towards improved graft survival in recipients with reduced-thickness LLS grafts. This advancement underscores the importance of BW-appropriate methods in graft selection to ensure exceptional outcomes in vulnerable pediatric patients in need of LT. These techniques' ongoing development and refinement are crucial in enhancing the survival rates and overall outcomes for these young patients.
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BACKGROUND: COACH syndrome is a rare autosomal recessive genetic disease characterized by liver fibrosis, which leads to severe complications related to portal hypertension. However, only a few patients with COACH syndrome undergoing liver transplantation (LT) have been reported. MATERIALS AND METHODS: We herein report the outcomes of four children who underwent LT for COACH syndrome at our institute and review three previously reported cases to elucidate the role of LT in COACH syndrome. RESULTS: All four patients in our institute were female, and three received living donors LT. All patients were diagnosed with COACH syndrome by genetic testing. LT was performed in these patients at 3, 7, 9, and 14 years old. The indication for LT was varices related to portal hypertension in all patients. One showed an intrapulmonary shunt. Blood tests revealed renal impairment due to nephronophthisis in three patients, and one developed renal insufficiency after LT. The liver function was maintained in all patients. A literature review revealed detailed information for three more patients. The indication for LT in these three cases was portal hypertension, such as bleeding from esophageal varices. One patient had chronic renal failure on hemodialysis at LT and underwent combined liver and kidney transplantation. Of these three previous patients, one died from hepatic failure due to de novo HCV infection 3 years after LT. CONCLUSIONS: LT should be considered an effective treatment for COACH syndrome in patients with severe portal hypertension. However, a detailed follow-up of the renal function is necessary.
Subject(s)
Abnormalities, Multiple , Ataxia , Brain , Cholestasis , Coloboma , Eye Abnormalities , Genetic Diseases, Inborn , Hypertension, Portal , Kidney Diseases, Cystic , Liver Diseases , Liver Transplantation , Renal Insufficiency , Child , Female , Humans , Brain/abnormalities , Cerebellum/abnormalities , Hypertension, Portal/complications , Hypertension, Portal/surgery , Kidney Diseases, Cystic/complications , Liver Cirrhosis/complications , Liver Cirrhosis/surgery , Liver Transplantation/adverse effects , Renal Insufficiency/complications , Renal Insufficiency/surgery , RetinaABSTRACT
PURPOSE: To validate the effectiveness of Deflux® treatment for vesicoureteral reflux (VUR) following pediatric renal transplantation (RT), based on our single-institution experience. METHOD: A retrospective study was conducted using the medical records of pediatric patients who underwent Deflux® treatment for VUR after RT from April 2008 to March 2022. RESULTS: Sixty-eight pediatric patients underwent RT. VUR was subsequently detected in 22 (32 %) of these patients. Seven of the 22 patients (32 %) underwent Deflux® treatment to avoid renal dysfunction due to urinary infection (UTI). The median age at the time of RT was 4 years (range:2-12). All 7 patients had urinary UTIs before Deflux® treatment. The median estimated glomerular filtration rate (eGFR) before Deflux® treatment was 67 ml/min/1.73 m2 (range:42-138 ml/min/1.73 m2). After Deflux® treatment, VUR was downgraded in three cases (43 %). Four patients (57 %) experienced postoperative UTI, two of who underwent a second Deflux® treatment, one underwent submuscular tunnel reconstruction, and the other one experienced UTI without VUR after 1st Deflux® treatment but did not reoccur. All seven patients continued prophylactic medication after Deflux® treatment, without any history of recurrent UTIs during the observation period after treatment (median 37 months [range 7-86 months]). Furthermore, the eGFRs did not significantly decrease after Deflux® treatment (median eGFR 58 ml/min/1.73 m2 [range:33-99 ml/min/1.73 m2], p > 0.1). CONCLUSION: Deflux® treatment for VUR after RT is technically challenging because the new ureteral orifice is ventrally anastomosed at the bladder. We believe our results indicate the possibility of reducing the frequency of UTIs and contributing to preservation of the renal function after RT. TYPE OF STUDY: Retrospective Study. LEVEL OF EVIDENCE: Level III.
Subject(s)
Kidney Transplantation , Urinary Tract Infections , Vesico-Ureteral Reflux , Child , Humans , Infant , Child, Preschool , Vesico-Ureteral Reflux/etiology , Vesico-Ureteral Reflux/surgery , Kidney Transplantation/adverse effects , Retrospective Studies , Dextrans/therapeutic use , Hyaluronic Acid/therapeutic use , Urinary Tract Infections/etiology , Urinary Tract Infections/prevention & control , Urinary Tract Infections/drug therapyABSTRACT
BACKGROUND/PURPOSE: Whether Roux-en-Y hepatic jejunectomy (HJ) or duct-to-duct biliary reconstruction (DD) is more useful in pediatric living donor liver transplantation has not yet been fully investigated. Therefore, to assess the feasibility and safety of DD, we compared the surgical outcomes of DD to HJ. METHODS: We divided 45 patients, excluding those with biliary atresia, into the DD group (n = 20) and the HJ group (n = 25), according to the type of biliary reconstruction they received. RESULTS: The 5-year survival rates (DD vs. HJ = 79.7% vs. 83.6%, p = 0.70) and the incidence of biliary complications, including bile leakage and stricture (DD vs. HJ = 1 [5.0%] vs. 1 [4.0%], p = 0.87) were not significantly different between the groups. However, intestinal complications, including bowel perforation or ileus, were significantly common in the HJ group (9/25 [36.0%]) than in the DD group (1/20 [5.0%]; p = 0.01). The three patients in the HJ group with intestinal perforation all suffered perforation at the anastomosed site in the Roux-en-Y procedure. The subgroup analysis showed the non-inferiority of DD to HJ for biliary or intestinal complications in patients weighting < 10 kg. CONCLUSION: With a proper selection of cases, DD should be a safe method for biliary reconstruction in pediatric recipients with little risk of biliary complications equivalent to HJ and a reduced risk of intestinal complications.
Subject(s)
Biliary Tract Diseases , Biliary Tract Surgical Procedures , Liver Transplantation , Humans , Child , Liver Transplantation/methods , Living Donors , Liver/surgery , Anastomosis, Roux-en-Y/methods , Biliary Tract Diseases/surgery , Bile Ducts/surgery , Biliary Tract Surgical Procedures/methods , Anastomosis, Surgical , Postoperative Complications/etiology , Retrospective StudiesABSTRACT
Background: Endoscopic surgery also has been becoming widespread in the field of pediatric surgery. However, most disease treated by pediatric surgery in a single institution are small number of cases. Besides, the variety of operative procedures that need to be performed in this field is quite wide. For these reasons, pediatric surgeons have limited opportunities to perform endoscopic surgery. Therefore, it is difficult to introduce advanced endoscopic surgery at a single local hospital. To educate pediatric surgeons in local hospitals, for widespread advanced pediatric endoscopic surgery safely, and to eliminate the need for patient centralization, we have introduced a proctoring system. We compared the surgical results of our institution, a center hospital, with other local institutions, to investigate the feasibility of our proctoring system. Methods: The experienced pediatric surgeon of our institution visits local hospitals to provide onsite coaching and supervises pediatric surgeons on the learning curve. All patients who underwent laparoscopic cyst excision and hepaticojejunostomy for choledochal cysts, one of the advanced pediatric endoscopic surgeries was retrospectively reviewed. Results: Thirty-four cases were evaluated (14 cases in our institution, 20 cases in 9 other institutions). The procedures of all 34 cases were performed by surgeons with 0-2 cases of experience in the procedure. There were no open conversion cases. There was no significant difference in the operative date. There was 1 case (6.7%) of postoperative complications during hospitalization at our institution and 3 cases (14.3%) at other institutions (P = .47). Two cases of late complications (13.3%) occurred at our institution, whereas 6 cases (28.6%) occurred at other institutions (P = .28). Conclusion: With the proctoring system, the performance and completion of advanced pediatric endoscopic surgery at local institutions was feasible. This has important implications given the ever-growing demand for pediatric endoscopic surgery and the increasing need for competent pediatric endoscopic surgeons.
Subject(s)
Choledochal Cyst , Laparoscopy , Child , Humans , Choledochal Cyst/surgery , Retrospective Studies , Laparoscopy/methods , Anastomosis, Surgical , Liver/surgery , Treatment OutcomeSubject(s)
Liver Neoplasms , Liver Transplantation , Rhabdoid Tumor , Child , Humans , Abdomen , Liver Neoplasms/surgery , Living Donors , Rhabdoid Tumor/surgery , Rhabdoid Tumor/pathologyABSTRACT
The in vitro growth transformation of primary B cells by Epstein-Barr virus (EBV) is the initial step in the development of posttransplant lymphoproliferative disorder (PTLD). We performed electron microscopic analysis and immunostaining of primary B cells infected with wild-type EBV. Interestingly, the nucleolar size was increased by two days after infection. A recent study found that nucleolar hypertrophy, which is caused by the induction of the IMPDH2 gene, is required for the efficient promotion of growth in cancers. In the present study, RNA-seq revealed that the IMPDH2 gene was significantly induced by EBV and that its level peaked at day 2. Even without EBV infection, the activation of primary B cells by the CD40 ligand and interleukin-4 increased IMPDH2 expression and nucleolar hypertrophy. Using EBNA2 or LMP1 knockout viruses, we found that EBNA2 and MYC, but not LMP1, induced the IMPDH2 gene during primary infections. IMPDH2 inhibition by mycophenolic acid (MPA) blocked the growth transformation of primary B cells by EBV, leading to smaller nucleoli, nuclei, and cells. Mycophenolate mofetil (MMF), which is a prodrug of MPA that is approved for use as an immunosuppressant, was tested in a mouse xenograft model. Oral MMF significantly improved the survival of mice and reduced splenomegaly. Taken together, these results indicate that EBV induces IMPDH2 expression through EBNA2-dependent and MYC-dependent mechanisms, leading to the hypertrophy of the nucleoli, nuclei, and cells as well as efficient cell proliferation. Our results provide basic evidence that IMPDH2 induction and nucleolar enlargement are crucial for B cell transformation by EBV. In addition, the use of MMF suppresses PTLD. IMPORTANCE EBV infections cause nucleolar enlargement via the induction of IMPDH2, which are essential for B cell growth transformation by EBV. Although the significance of IMPDH2 induction and nuclear hypertrophy in the tumorigenesis of glioblastoma has been reported, EBV infection brings about the change quickly by using its transcriptional cofactor, EBNA2, and MYC. Moreover, we present here, for the novel, basic evidence that an IMPDH2 inhibitor, namely, MPA or MMF, can be used for EBV-positive posttransplant lymphoproliferative disorder (PTLD).
Subject(s)
Epstein-Barr Virus Infections , Lymphoproliferative Disorders , Humans , Herpesvirus 4, Human/genetics , Epstein-Barr Virus Infections/genetics , Epstein-Barr Virus Nuclear Antigens/genetics , Epstein-Barr Virus Nuclear Antigens/metabolism , Viral Proteins/genetics , Hypertrophy , IMP DehydrogenaseABSTRACT
BACKGROUND: Progressive familial intrahepatic cholestasis type 1 (PFIC1) is an autosomal recessive cholestatic liver disorder caused by ATP8B1 gene mutations. Although liver transplantation (LT) is indicated for progressive liver disease, postoperative complications, including severe diarrhea and graft steatohepatitis leading to graft loss, have been reported. CASES: The first patient had jaundice, pruritus, diarrhea, and growth retardation (weight z-score: -2.5; height z-score: -3.7). She underwent LT with total internal biliary diversion (TIBD) to the colon at 2 years of age. Graft biopsy at the 7-year follow-up examination revealed microvesicular steatosis (60%). Her diarrhea improved, and her growth failure was recovering (weight z-score: -1.0; height z-score: -1.7). The second patient underwent sequential intestine-liver transplantation at 8 years of age due to end-stage liver disease (ESLD) and short bowel syndrome caused by massive bowel resection for internal hernia after partial external biliary diversion (PEBD) at 21 months of age. She developed severe pancreatitis induced by steroid-bolus therapy for rejection after transplantation. She died 1.7 years after intestinal transplantation due to an uncontrollable pancreatic abscess and acute respiratory distress syndrome. The third patient underwent PEBD at 15 months of age and received LT with TEBD at 15 years of age due to ESLD with hepatic encephalopathy. Throughout the perioperative period, she showed no abdominal symptoms, including diarrhea and pancreatitis. Graft biopsy at the 2-year follow-up examination revealed macrovesicular steatosis (60%) with inflammation. CONCLUSIONS: The patients showed different outcomes. Effective therapeutic options to mitigate post-LT complications in patients with PFIC1 must be considered individually.
Subject(s)
Cholestasis, Intrahepatic , Fatty Liver , Liver Transplantation , Female , Humans , Infant , Liver Transplantation/methods , Treatment Outcome , Cholestasis, Intrahepatic/complications , Cholestasis, Intrahepatic/surgery , Fatty Liver/etiology , Intestines/pathology , Diarrhea/complicationsABSTRACT
Measles virus (MeV), the causative agent of measles, is an enveloped RNA virus of the family Paramyxoviridae, which remains an important cause of childhood morbidity and mortality. MeV has two envelope glycoproteins, the hemagglutinin (H) and fusion (F) proteins. During viral entry or virus-mediated fusion between infected cells and neighboring susceptible cells, the head domain of the H protein initially binds to its receptors, signaling lymphocytic activation molecule family member 1 (SLAM) and nectin-4, and then the stalk region of the H protein transmits the fusion-triggering signal to the F protein. MeV may persist in the human brain and cause a fatal neurodegenerative disease, subacute sclerosing panencephalitis (SSPE). Recently, we showed, using in vitro cell culture, that cell adhesion molecule (CADM) 1 and CADM2 are host factors that trigger hyperfusogenic mutant F proteins, causing cell-to-cell fusion and the transfer of the MeV genome between neurons. Unlike conventional receptors, CADM1 and CADM2 interact in cis (on the same membrane) with the H protein and then trigger membrane fusion. Here, we show that alanine substitutions in part of the stalk region (positions 171-175) abolish the ability of the H protein to mediate membrane fusion triggered by CADM1 and CADM2, but not by SLAM. The recombinant hyperfusogenic MeV carrying this mutant H protein loses its ability to spread in primary mouse neurons as well as its neurovirulence in experimentally infected suckling hamsters. These results indicate that CADM1 and CADM2 are key molecules for MeV propagation in the brain and its neurovirulence in vivo. IMPORTANCE Measles is an acute febrile illness with skin rash. Despite the availability of highly effective vaccines, measles is still an important cause of childhood morbidity and mortality in many countries. The World Health Organization estimates that more than 120,000 people died from measles worldwide in 2021. Measles virus (MeV), the causative agent of measles, can also cause a fatal progressive neurological disorder, subacute sclerosing panencephalitis (SSPE), several years after acute infection. There is currently no effective treatment for this disease. In this study, using recombinant MeVs with altered receptor usage patterns, we show that cell adhesion molecule (CADM) 1 and CADM2 are host factors critical for MeV spread in neurons and its neurovirulence. These findings further our understanding of the molecular mechanism of MeV neuropathogenicity.
Subject(s)
Measles , Neurodegenerative Diseases , Subacute Sclerosing Panencephalitis , Cricetinae , Humans , Mice , Animals , Measles virus/physiology , Subacute Sclerosing Panencephalitis/genetics , Hemagglutinins/metabolism , Neurodegenerative Diseases/metabolism , Viral Fusion Proteins/genetics , Viral Fusion Proteins/metabolism , Cell Adhesion Molecules/genetics , Cell Adhesion Molecules/metabolism , Recombinant Proteins/metabolism , Neurons , Cell Adhesion Molecule-1/metabolismABSTRACT
PURPOSE: The aim of this study was to clarify the appropriate management after birth for congenital biliary dilatation (CBD, choledochal cyst) patients with a prenatal diagnosis. METHOD: Thirteen patients with a prenatal diagnosis of CBD who underwent liver biopsy during excision surgery were divided into two groups and retrospectively analyzed: group A, with liver fibrosis above F1 and group B, without liver fibrosis. RESULTS: Excision surgery was performed earlier in group A (F1-F2), at a median of 106 days old (p = 0.04). There were significant differences between the two groups in the presence symptoms and sludge, the cyst size, and the level of serum bilirubin and gamma glutamyl transpeptidase (GGT) before excision surgery (p < 0.05). Especially, in group A, prolonged serum GGT elevation and larger cysts were consistently observed from birth. The cut-off values of predictions for the presence of liver fibrosis in serum GGT and cyst size were 319 U/l and 45 mm. No significant differences were observed in the postoperative liver function or complications during the follow-up period. CONCLUSION: In patients with prenatally diagnosed CBD, the postnatal serial changes of serum GGT values and cyst size, in addition to symptoms, could help to prevent progressive liver fibrosis. LEVEL OF EVIDENCE: â ¢. TYPE OF STUDY: Treatment Study.
Subject(s)
Choledochal Cyst , Pregnancy , Female , Humans , Choledochal Cyst/diagnosis , Choledochal Cyst/surgery , Retrospective Studies , Prenatal Diagnosis , Biopsy , gamma-Glutamyltransferase , Liver CirrhosisABSTRACT
N6-methyladenosine (m6A) is a post-transcriptional modification of RNA involved in transcript transport, degradation, translation, and splicing. We found that HBV RNA is modified by m6A predominantly in the coding region of HBx. The mutagenesis of methylation sites reduced the HBV mRNA and HBs protein levels. The suppression of m6A by an inhibitor or knockdown in primary hepatocytes decreased the viral RNA and HBs protein levels in the medium. These results suggest that the m6A modification of HBV RNA is needed for the efficient replication of HBV in hepatocytes.
Subject(s)
Hepatitis B virus , Hepatitis B , Humans , Hepatitis B virus/genetics , Hepatitis B virus/metabolism , Viral Regulatory and Accessory Proteins/genetics , Trans-Activators/genetics , Trans-Activators/metabolism , Virus Replication/genetics , RNA, Viral/genetics , RNA, Viral/metabolismABSTRACT
AIM: To review the current institutional practice to treat patients with congenital extrahepatic portosystemic shunt (CEPS) and to determine the optimal strategy. METHODS: We retrospectively reviewed the records of 55 patients diagnosed with CEPS at our center between December 2008 and March 2022. RESULTS: Among these 55 patients, 44 (80.0%) received treatment for CEPS at a median age of 4.7 years. The most common indication for treatment was cardiopulmonary complications (45.5%). Therapeutic intervention included shunt closure by endovascular techniques (50.0%) or surgery (40.9%), and liver transplantation (9.1%). A total of 11 were classified as short shunt types, and surgical ligation was performed in all to preserve the major vascular system and prevent complications (p < 0.001). Children who received a surgical ligation were more likely to develop complications after shunt closure (p = 0.02). Among seven patients with portopulmonary hypertension (POPH), one patient, who received a shunt ligation at <1 year-of-age, was only able to completely discontinue medication. Most other CEPS-related complications were completely resolved. Post-treatment complications, including thrombosis and symptoms of portal hypertension, were seen in 16 patients. After shunt closure, one patient was scheduled to undergo liver transplantation for progressive POPH and large residual hepatocellular adenoma. During follow-up, one patient without any treatment for CEPS developed POPH 16 years from the diagnosis. CONCLUSION: Earlier therapeutic interventions should be strongly considered for patients with POPH related to CEPS. However, in view of the invasiveness and treatment complications, special attention should be paid to the management of patients with short shunt types.
ABSTRACT
Measles virus (MeV), which is usually non-neurotropic, sometimes persists in the brain and causes subacute sclerosing panencephalitis (SSPE) several years after acute infection, serving as a model for persistent viral infections. The persisting MeVs have hyperfusogenic mutant fusion (F) proteins that likely enable cell-cell fusion at synapses and "en bloc transmission" between neurons. We here show that during persistence, F protein fusogenicity is generally enhanced by cumulative mutations, yet mutations paradoxically reducing the fusogenicity may be selected alongside the wild-type (non-neurotropic) MeV genome. A mutant F protein having SSPE-derived substitutions exhibits lower fusogenicity than the hyperfusogenic F protein containing some of those substitutions, but by the wild-type F protein coexpression, the fusogenicity of the former F protein is enhanced, while that of the latter is nearly abolished. These findings advance the understanding of the long-term process of MeV neuropathogenicity and provide critical insight into the genotype-phenotype relationships of en bloc transmitted viruses.
Subject(s)
Subacute Sclerosing Panencephalitis , Humans , Subacute Sclerosing Panencephalitis/genetics , Subacute Sclerosing Panencephalitis/metabolism , Viral Fusion Proteins/genetics , Viral Fusion Proteins/metabolism , Measles virus/genetics , Brain/metabolism , MutationABSTRACT
BACKGROUND: Epstein-Barr virus (EBV) infection and posttransplant lymphoproliferative disorders (PTLDs) after pediatric liver transplantation (LT) account for significant morbidity and mortality. Knowledge of EBV kinetics, epidemiology, and outcomes among pediatric living-donor LT cases is largely lacking. This study aims to provide clinical information related to EBV infection, chronic high EBV load (CHL) carriage, and PTLD at a living-donor-dominant pediatric LT center. METHODS: A total of 5827 EBV load measurements from 394 LT recipients fulfilling inclusion criteria and their clinical data were analyzed. EBV loads >1000 copies/µg DNA (742 IU/µg DNA) were considered "high," and CHL was defined by persistence >6 mo. RESULTS: The highlighted results were as follows: (1) 94% of recipients underwent living-donor LT; (2) 80% of EBV seronegative recipients developed first EBV infection <2 y post-LT, and their EBV loads were consistently higher than those of seropositive recipients within <3 y post-LT but did not differ thereafter; (3) 61 (15%) recipients met CHL criteria, but none developed PTLD; (4) age <5 y, cytomegalovirus seronegative donors, and early development of EBV DNAemia <6 mo post-LT were independent risk factors for CHL; (5) the incidence of rejections after 1-y post-LT was comparably low among CHL carriers whose immunosuppression was minimized. CONCLUSIONS: Early detection of EBV following LT and CMV seronegative donors would facilitate risk stratification to prevent PTLD while titrating immunosuppression among pediatric LT recipients.
Subject(s)
Epstein-Barr Virus Infections , Liver Transplantation , Lymphoproliferative Disorders , Child , Humans , Herpesvirus 4, Human , Liver Transplantation/adverse effects , Living Donors , Viral Load , Risk Factors , DNA, ViralABSTRACT
BACKGROUND: Surgical management of tumor thrombus extending to the major vascular system for children with hepatoblastoma is challenging and insufficiently discussed. METHODS: We conducted a retrospective review of hepatoblastoma with tumor thrombus extending to the major vascular system (inferior vena cava, 3 hepatic veins, and portal vein trunk) treated at our center between May 2010 and June 2021. We describe our preoperative assessment, surgical strategies, and outcomes. RESULTS: We identified 9 patients (median age at the diagnosis: 3.4 years). All patients received chemotherapy before liver surgery. At the time of the diagnosis, tumor thrombus extended to the portal vein trunk (n = 6), inferior vena cava (n = 3), and 3 hepatic veins (n = 2). Among the 9 patients, 4 underwent liver resection. Liver transplantation was performed in 5 patients. The inferior vena cava wall was circumferentially resected for tumor removal in 1 patient and partially resected in 2 patients. One patient underwent liver transplantation using veno-venous bypass. Patients with tumor thrombus extending to the portal vein trunk were more likely to be managed by liver transplantation in comparison to those with tumor thrombus spreading to the inferior vena cava. The median follow-up period was 5.5 years. One patient underwent transhepatic balloon dilatation for biliary stricture after liver resection. Tumor recurrence was seen in 3 patients (33.3%; lung, n = 2; lymph node and liver, n = 1). No patients died during the follow-up period. CONCLUSION: Surgical intervention for pediatric hepatoblastoma with tumor thrombus extending into the major vascular system is safe, feasible, and achieves excellent outcomes.
Subject(s)
Hepatoblastoma , Liver Neoplasms , Thrombosis , Child , Humans , Child, Preschool , Hepatoblastoma/surgery , Liver Neoplasms/surgery , Liver Neoplasms/pathology , Neoplasm Recurrence, Local/pathology , Hepatic Veins/surgery , Vena Cava, Inferior/surgery , Vena Cava, Inferior/pathology , Thrombosis/etiology , Thrombosis/surgeryABSTRACT
Background: Currently, the standard curative treatment for ventricular tachycardia (VT) and ventricular fibrillation (VF) is radiofrequency catheter ablation. However, when the VT circuit is deep in the myocardium, the catheter may not be delivered, and a new, minimally invasive treatment using different energies is desired. Methods: This is a protocol paper for a feasibility study designed to provide stereotactic radiotherapy for refractory VT not cured by catheter ablation after at least one catheter ablation. The primary end point is to evaluate the short-term safety of this treatment and the secondary endpoint is to evaluate its efficacy as assessed by the reduction in VT episode. Cyberknife M6 radiosurgery system will be used for treatment, and the prescribed dose to the target will be 25Gy in one fraction. The study will be conducted on three patients. Conclusion: Since catheter ablation is the only treatment option for VT that is covered by insurance in Japan, there is currently no other treatment for VT/VF that cannot be cured by catheter ablation. We hope that this feasibility study will provide hope for patients who are currently under the stress of ICD activation. Trial registration: The study has been registered in the Japan Registry of Clinical Trials (jRCTs042230030).