Multinucleated podocytes as a clue to diagnosis of juvenile nephropathic cystinosis.

BACKGROUND  : Cystinosis is a rare autosomal recessive lysosomal disorder that mainly affects the kidney and eye. Early treatment with cysteamine significantly improves the prognosis. However, early diagnosis of cystinosis, especially the juvenile nephropathic form, remains challenging because typical symptoms only become apparent in adulthood. We herein describe a 13-year-old girl who presented with proteinuria only but was diagnosed with juvenile nephropathic cystinosis based on multinucleated podocytes in her kidney biopsy specimen. We also studied the nephropathology of another case to determine the features of the multinucleated podocytes. CASE DIAGNOSIS: A previously healthy 13-year-old girl presented to our hospital because proteinuria had been detected in her school urine screening. She had been noted to have proteinuria on her school urine screening when she was 11 years of age but there was no consultation with her physician at that time. She was asymptomatic and had no other abnormalities on examination other than a relatively high urinary ß-2 microglobulin level. Her kidney biopsy showed 15 multinucleated podocytes in 34 glomeruli, and the mean number of nuclei per multinucleated podocyte was 4.4. Ophthalmological examination showed cystine crystals in her cornea. Her white blood cell cystine level was high, and she was diagnosed with juvenile nephropathic cystinosis. She started oral cysteamine treatment and showed almost no progression of the disease after 2 years. In another patient with juvenile nephropathic cystinosis, there were 25 multinucleated podocytes in 63 glomeruli, and the mean number of nuclei per multinucleated podocyte was 2.9. CONCLUSION: Early diagnosis is crucial to improve the prognosis of patients with cystinosis. This report emphasizes the importance of recognizing the unique pathological feature of multinucleated podocytes as an essential clue to the diagnosis of cystinosis.

Aggressive immunotherapy combined with bortezomib and rituximab for membranous nephropathy associated with enzyme replacement therapy in Pompe disease.

BACKGROUND: Pompe disease (PD) is a lysosomal glycogen storage disorder caused by a deficiency in acid α-glucosidase (GAA) activity. Various organs, including the skeletal muscle, cardiac muscle, and liver, are commonly involved. Early initiation of enzyme replacement therapy (ERT) with recombinant human α-glucosidase (rhGAA) can improve the outcome. However, some patients experience a poor clinical course despite ERT because of the emergence of anti-rhGAA antibodies that neutralize rhGAA. Treatment against anti-rhGAA antibodies is challenging. CASE-DIAGNOSIS/TREATMENT: A 14-year-old boy with late-onset PD was referred to our hospital with proteinuria detected by school urinalysis screening. He was diagnosed with PD at the age of 4 years based on muscle biopsy and decreased GAA activity. Treatment with rhGAA was initiated, but anaphylaxis occurred frequently. Anti-rhGAA antibodies were detected and immune tolerance therapy was therefore given, but his antibody titer remained high. Kidney biopsy revealed stage II membranous nephropathy. Immunohistochemistry staining revealed anti-rhGAA antibody/rhGAA immune complexes along the glomerular capillary loop. Aggressive immunotherapy combined with bortezomib and rituximab was then initiated. Serum levels of anti-rhGAA antibodies decreased significantly and his proteinuria finally resolved. CONCLUSIONS: There have been few reports of membranous nephropathy associated with ERT for PD. We clarified the cause in the current patient. Bortezomib and rituximab effectively suppressed anti-rhGAA antibody production resulting in the resolution of proteinuria and maintenance of ERT efficacy.

Intraprocedurally EOB-MRI/US fusion imaging focusing on hepatobiliary phase findings can help to reduce the recurrence of hepatocellular carcinoma after radiofrequency ablation.

BACKGROUND & AIMS: To explore the ability of gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid magnetic resonance imaging (EOB-MRI)/ultrasound (US) fusion imaging (FI) to improve the prognosis of radiofrequency ablation (RFA) by ablating the characteristic findings of hepatocellular carcinoma (HCC) in hepatobiliary phase (HBP) imaging. METHODS: We retrospectively recruited 115 solitary HCC lesions with size of (15.9 ± 4.6) mm. They were all treated by RFA and preoperative EOB-MRI. According to the modalities guiding RFA performance, the lesions were grouped into contrast enhanced US (CEUS)/US guidance group and EOB-MRI/US FI guidance group. For the latter group, the ablation scope was set to cover the HBP findings (peritumoral hypointensity and irregular protruding margin). The presence of HBP findings, the modalities guided RFA, the recurrence rate were observed. RESULTS: After an average follow-up of 377 days, local tumor progression (LTP) and intrahepatic distant recurrence (IDR) were 14.8% and 38.4%, respectively. The lesions having HBP findings exhibited a higher recurrence rate (73.7%) than the lesions without HBP findings (42.9%) (p = 0.002) and a low overall recurrence-free curve using the Kaplan-Meier method (p = 0.038). Using EOB-MRI/US FI as guidance, there was no difference in the recurrence rate between the groups with and without HBP findings (p = 0.799). In lesions with HBP findings, RFA guided by EOB-MRI/US FI (53.8%) produced a lower recurrence rate than CEUS/US (84.0%) (p = 0.045). CONCLUSIONS: The intraprocedurally application of EOB-MRI/US FI to determine ablation scope according to HBP findings is feasible and beneficial for prognosis of RFA.

Myoepithelioma-like tumor of the vulvar region showing infiltrative growth and harboring only a few estrogen receptor-positive cells: A case report.

Recently, a new entity "myoepithelioma-like tumor of the vulvar region (MELTVR)" was proposed as a rare mesenchymal neoplasm arising in vulvar regions of adult women. While MELTVRs morphologically resemble soft tissue myoepitheliomas and extraskeletal myxoid chondrosarcomas, they have a unique immunohistochemical profile (positive for epithelial membrane antigen and estrogen receptor, negative for S100 protein and glial fibrillary acidic protein, and loss of INI1/SMARCB1 expression), and lack EWSR1 and NR4A3 gene rearrangement, as seen by fluorescence in situ hybridization. MELTVRs are usually well-demarcated tumors, with no reports of extensive infiltrative growth. In the current report, we present an unusual case of MELTVR showing infiltrative growth and harboring only a few estrogen receptor-positive cells, which might indicate a variation in this rare tumor.

Diagnostic challenge in a patient with nephropathic juvenile cystinosis: a case report.

BACKGROUND: Cystinosis is a rare autosomal recessive lysosomal disorder characterized by the accumulation of cystine in lysosomes. Cystinosis is much rarer in Asian than Caucasian populations. There are only 14 patients have with cystinosis alive in Japan. Most cystinosis is the nephropathic infantile form, as indicated by its apparent and severe clinical manifestations, including renal and ocular symptoms. Patients with the nephropathic juvenile form account for 5% of those with cystinosis. Their diagnosis is frequently delayed and difficult because of slower progression to end-stage renal disease and fewer cystine crystals in the cornea. Molecular analysis and a cysteine-binding protein assay should be performed when patients with proximal tubulopathy of an unknown origin are encountered. CASE PRESENTATION: A 12-year-old boy had been suffering from Fanconi syndrome since he was 3 years old. He was only recently diagnosed despite repeated ophthalmological examinations. Corneal cystine crystals were found when he was 12 years old, and he was diagnosed with cystinosis by high free cystine content in granulocytes (6.36 nmol half-cystine/mg protein, normal: <0.15). Analysis of the CTNS gene showed two novel heterozygous single nucleotide substitutions of c.329G > C and c.329 + 2 T > C. Both were splicing site variants causing exon 6 skipping proven by transcript analysis, although the functional prediction site showed c.329G > C, p.(Gly110Ala) as a benign missense substitution. The patient's estimated glomerular filtration rate was 66.8 mL/min/1.73 m2. He was immediately treated with cysteamine after diagnosis. CONCLUSIONS: Even if no ophthalmological abnormalities are present, nephropathic juvenile cystinosis should be suspected in children with Fanconi syndrome. Transcript analysis was useful to detect pathogenic splicing variants in this patient.

O-linked glycosylation determines the nephritogenic potential of IgA rheumatoid factor.

Deficient glycosylation of O-linked glycans in the IgA1 hinge region is associated with IgA nephropathy in humans, but the pathogenic contribution of the underlying structural aberrations remains incompletely understood. We previously showed that mice implanted with cells secreting the class-switch variant 6-19 IgA anti-IgG2a rheumatoid factor, but not 46-42 IgA anti-IgG2a rheumatoid factor, develop glomerular lesions resembling IgA nephropathy. Because the levels of O-linked glycosylation in the hinge region and the structures of N-linked glycans in the CH1 domain differ in 6-19 IgA and 46-42 IgA, we determined the respective contributions of O- and N-linked glycans to the nephritogenic potential of the 6-19 IgA rheumatoid factor in mice. Wild-type 6-19 IgA secreted by implanted cells induced significant formation of glomerular lesions, whereas poorly O-glycosylated 6-19 IgA glycovariants or a 6-19 IgA hinge mutant lacking O-linked glycans did not. However, we observed no apparent heterogeneity in the structure of N-linked glycans attached to three different sites of the Fc regions of nephritogenic and non-nephritogenic 6-19 IgAs. Collectively, our data suggest a critical role of O-linked glycans attached to the hinge region in the development of IgA nephropathy-like GN induced by 6-19 IgA rheumatoid factor in mice.

Tubulointerstitial nephritis with IgG4-positive plasma cell infiltration and tertiary lymphoid tissue in a patient with cryoglobulinemic vasculitis: a case report.

Tertiary lymphoid tissue (TLT) develops at sites of chronic immune stimulation, including infection, autoimmune disease, transplant rejection, and cancer. Recently, TLT has been focused on an indicator for poor renal prognosis in various kidney diseases. In cryoglobulinemic vasculitis (CV), specific glomerular and vascular lesions are seen; however, tubulointerstitial lesions are usually nonspecific. We herein report the case of a 74-year-old man with idiopathic CV with rare tubulointerstitial lesions, such as tubulointerstitial nephritis (TIN) with IgG4-positive plasma cell infiltration and TLT. To our knowledge, this is the first report identifying TLT in the kidney biopsy in a patient with CV. Glucocorticoid improved the renal outcome. The association between CV and TIN with TLT remains unknown.

O-glycosylated IgA rheumatoid factor induces IgA deposits and glomerulonephritis.

Structural aberrations of O-linked glycans present in the IgA1 hinge region are associated with IgA nephropathy, but their contribution to its pathogenesis remains incompletely understood. In this study, mice implanted with hybridoma secreting 6-19 IgA anti-IgG2a rheumatoid factor, but not 46-42 IgA rheumatoid factor bearing the same IgA allotype, developed mesangial deposits consisting of IgA, IgG2a, and C3. Studies in immunoglobulin- and C3-deficient mice revealed that the development of these glomerular lesions required the formation of IgA-IgG2a immune complexes and subsequent activation of complement. The proportion of polymeric and monomeric forms, the IgG2a-binding affinity, and the serum levels of IgA-IgG2a immune complexes were similar between 6-19 IgA- and 46-42 IgA-injected mice. In contrast, the analysis of oligosaccharide structures revealed highly galactosylated O-linked glycans in the hinge region of 6-19 IgA and poorly O-glycosylated in the hinge region of 46-42 IgA. Furthermore, the structure of N-linked glycans in the CH1 domain was the complex type in 6-19 IgA and the hybrid type in 46-42 IgA. In summary, this study demonstrates the presence of O-linked glycans in the hinge region of mouse IgA and suggests that 6-19 IgA rheumatoid factor-induced GN could serve as an experimental model for IgA nephropathy.

Sialylation determines the nephritogenicity of IgG3 cryoglobulins.

Monoclonal 6-19 IgG3 anti-IgG2a rheumatoid factor derived from lupus-prone MRL-Fas(lpr) mice can induce GN and cryoglobulinemia, but the features that confer nephritogenic potential are not completely understood. Asparagine-linked oligosaccharide chains of 6-19 IgG3 mAb are poorly galactosylated and hardly sialylated, possibly contributing to the pathogenic potential of 6-19 IgG3 rheumatoid factors. Here, we used the 6-19 model of cryoglobulin-associated GN to define the relative contributions of galactosylation and sialylation, in relation to cryoglobulin activity, to the nephritogenic potential of IgG3 antibodies. We generated one highly sialylated and two distinct more galactosylated 6-19 IgG3 rheumatoid factor variants. Although the mere extent of galactosylation had no effect on either the cryogenic and nephritogenic activities of 6-19 IgG3 rheumatoid factor, terminal sialylation attenuated the nephritogenic potential of 6-19 IgG3 by limiting its cryoglobulin activity. These data suggest a protective role of IgG sialylation against the development of cryoglobulin-mediated GN, highlighting the anti-inflammatory activity of sialylated IgG antibodies.

Successful fertility preservation by expectant management of a cervico-isthmic pregnancy with fetal death in the second trimester: A case report.

In a cervico-isthmic pregnancy, the risk of placenta accreta increases with advancing gestational age. Previous reports have detailed cases that required hysterectomy at delivery or artificial abortion at an early gestational age. However, to the best of our knowledge, there have been no previous reports on the management of a cervico-isthmic pregnancy with fetal death during the second trimester. A 33-year-old primigravid woman was diagnosed with a cervico-isthmic pregnancy and fetal death at 15 weeks of gestation. Placenta accreta was suspected; hence, we chose expectant management and to observe the patient for placental tissue regression. After 5 weeks of expectant management, the ultrasonographic findings suggested remission of placenta accreta. Therefore, we performed a cesarean delivery and terminated the pregnancy. All uterine contents were removed, and the uterus was preserved. In cervico-isthmic pregnancy cases with fetal death, as in the current case, the possibility of fertility preservation could be increased by observing for placental tissue regression through expectant management.

Streptococcal Infection-related Glomerulonephritis in an Elderly Diabetic Patient Complicated by Hemophagocytic Syndrome and Cytomegalovirus Nephritis.

There has been a significant shift in epidemiology and renal outcomes of infection-related glomerulonephritis (IRGN) in recent years. The renal prognosis of IRGN is often poor in adults, especially in the elderly and diabetics. We herein report an elderly diabetic patient with IRGN due to streptococcal infection complicated by hemophagocytic syndrome and cytomegalovirus nephritis, which is uncommon among non-transplant patients. Infection control and steroids did not recover the patient's renal function. For elderly IRGN patients with diabetes, a further investigation of the most effective treatment for related renal outcomes is needed.

A rare case of intra-articular synovial sarcoma of the hip joint: a case report with intra-articular findings via hip arthroscopy.

Although synovial sarcoma is a relatively common soft tissue sarcoma, primary intra-articular cases are extremely rare. Herein, we report a case of primary intra-articular synovial sarcoma arising from the hip joint, that was initially treated with hip arthroscopy. A 42-year-old male presented with a history of pain in the left hip for 7 years. Radiography and magnetic resonance imaging revealed the primary intra-articular lesion and simple excision with an arthroscopy was performed. Histological findings revealed spindle cell proliferation with abundant psammoma bodies. SS18 gene rearrangement was confirmed by fluorescence in situ hybridization, and the tumor was diagnosed as synovial sarcoma. Adjuvant chemotherapy and radiotherapy were performed. Local control without metastasis was achieved 6 months after excision. This is the first case of intra-articular synovial sarcoma of the hip joint excised via hip arthroscopy. When an intra-articular lesion is identified, malignancies such as synovial sarcoma should be included in the differential diagnosis.

Granulomatous mastitis in a male breast: A case report and review of literature.

Granulomatous mastitis (GM) is a rare disease, particularly among men. Herein, we present a case of GM diagnosed in a 63-year-old male patient who showed reduction in the tumor size during 3 months of observation.

Inflammatory bowel disease-specific findings are common morphological changes in the ileal pouch with ulcerative colitis.

Why inflammation is common in ileal pouches with ulcerative colitis (UC) is unclear. We therefore clarified the morphological changes in pouches and afferent limbs (AL) of patients with UC and explored the relationship between these findings. We evaluated the morphological findings (histological and endoscopic inflammation as the Pouchitis Disease Activity Index [PDAI] histology subscore [hPDAI] and endoscopy subscore [ePDAI], inflammatory bowel disease [IBD]-specific findings using the IBD score [SIBD], colonic metaplasia using the colonic metaplasia score [CMS], and goblet cell [GC] ratio) in the pouch and AL of patients with UC. A total of 261 pouchoscopies were analyzed. The pouch body had a higher hPDAI (p < 0.001), SIBD (p < 0.001), CMS (p < 0.001), GC ratio (p < 0.001), and ePDAI (p < 0.001) than the AL. The hPDAI was correlated with the SIBD (Spearman's coefficient r = 0.538; p < 0.001), CMS (r = 0.687; p < 0.001), and the ePDAI (r = 0.552; p < 0.001), but not with GC ratio (r = 0.175; p < 0.001) or the pouch usage duration (r = -0.057; p = 0.107). The incidence of histological inflammation was higher in specimens showing basal plasmacytosis with severe mononuclear cell infiltration (BP) than in those without BP (odds ratio [OR] 6.790, p < 0.001), BP was commonly found with crypt hyperplasia (OR 3.414, p < 0.001) and the crypt length correlated with neutrophil infiltration (r = 0.469; p < 0.001). Histological inflammation, colonic metaplasia, the GC ratio, endoscopic inflammation, and IBD-specific findings were commonly present in the pouch than in the AL. Histological inflammation occurs with IBD-specific findings and colonic metaplasia, and these signify endoscopic inflammation.

Infantile hepatic hemangioma and hepatic mesenchymal hamartoma in an infant associated with placental mesenchymal dysplasia: a case report.

BACKGROUND: Although infantile hepatic hemangioma and hepatic mesenchymal hamartoma are relatively common in benign pediatric liver tumors, coexistence of the two tumors is rare. Placental mesenchymal dysplasia is also a rare disorder. We report the case of a baby girl born after a pregnancy complicated by placental mesenchymal dysplasia, who developed both infantile hepatic hemangioma and hepatic mesenchymal hamartoma. CASE PRESENTATION: The patient was born at 32 weeks and 5 days of gestation for impending placental abruption, weighing 1450 g. Liver tumors, composed of both hypervascular solid and large cystic lesions, were detected after birth and markedly increased to create abdominal distention within 9 months. Diagnostic imaging suspected the coexistence of infantile hepatic hemangioma and cystic hepatic mesenchymal hamartoma. Following propranolol therapy for infantile hepatic hemangioma and needle puncture of a large cyst, the cystic lesions and adjacent hypervascular lesions were partially resected via laparotomy. Pathological findings confirmed the coexistence of hepatic mesenchymal hamartoma and infantile hepatic hemangioma, which had no association with androgenetic/biparental mosaicism. The postoperative course was uneventful, and the tumor had not regrown after 3 years. CONCLUSIONS: Although the coexistence of infantile hepatic hemangioma and hepatic mesenchymal hamartoma associated with placental mesenchymal dysplasia is extremely rare, the pathological and pathogenetic similarities between these disorders suggest that they could have derived from similar embryologic origins rather than being a mere coincidence. Further follow-up is required, with careful attention to the potential for malignant hepatic mesenchymal hamartoma transformation.

Added Value of Ultrasound-Based Multimodal Imaging to Diagnose Hepatic Sclerosed Hemangioma before Biopsy and Resection.

Imaging methods have the overwhelming advantage of being non-invasive in the diagnosis of hepatic lesions and, thanks to technical developments in the field of ultrasound (US), radiation exposure can also be avoided in many clinical situations. In particular, contrast-enhanced US (CEUS) outperforms other radiological methods in regard to real-time images, repeatability, and prompt reporting and demonstrates relatively few contraindications and adverse reactions. In this study, we reported in detail a rare benign tumor: hepatic sclerosed hemangioma (HSH). We described US-based multimodal imaging (B-flow imaging, US elastography, and Sonazoid CEUS) features of this HSH case. Furthermore, by summarizing the recently published literature on the imaging diagnosis of HSH, we offered readers comprehensive knowledge of conventional imaging methods (CT, MRI) and CEUS in the diagnosis of HSH and preliminarily discussed their mechanism of pathology-based diagnosis. Our multimodal imaging approach may provide a diagnostic strategy for HSH, thus avoiding unnecessary biopsy or resection.

Identification of CT Values That Could Be Predictive of Necrosis (N-CTav) in Hepatocellular Carcinoma after Lenvatinib Treatment.

Purpose: To assess the utility of measurement of the computed tomography (CT) attenuation value (CTav) in predicting tumor necrosis in hepatocellular carcinoma (HCC) patients who achieve a complete response (CR), defined using modified Response Evaluation Criteria in Solid Tumors (mRECIST), after lenvatinib treatment. Method: We compared CTav in arterial phase CT images with postoperative histopathology in four patients who underwent HCC resection after lenvatinib treatment, to determine CTav thresholds indicative of histological necrosis (N-CTav). Next, we confirmed the accuracy of the determined N-CTav in 15 cases with histopathologically proven necrosis in surgical specimens. Furthermore, the percentage of the tumor with N-CTav, i.e., the N-CTav occupancy rate, assessed using Image J software in 30 tumors in 12 patients with CR out of 571 HCC patients treated with lenvatinib, and its correlation with local recurrence following CR were examined. Results: Receiver operating characteristic (ROC) curve analysis revealed an optimal cut-off value of CTav of 30.2 HU, with 90.0% specificity and 65.0% sensitivity in discriminating between pathologically identified necrosis and degeneration, with a CTav of less than 30.2 HU indicating necrosis after lenvatinib treatment (N30-CTav). Furthermore, the optimal cut-off value of 30.6% for the N30-CTav occupancy rate by ROC analysis was a significant indicator of local recurrence following CR with 76.9% specificity and sensitivity (area under the ROC curve; 0.939), with the CR group with high N30-CTav occupancy (≥30.6%) after lenvatinib treatment showing significantly lower local recurrence (8.3% at 1 year) compared with the low (<30.6%) N30-CTav group (p < 0.001, 61.5% at 1 year). Conclusion: The cut-off value of 30.2 HU for CTav (N30-CTav) might be appropriate for identifying post-lenvatinib necrosis in HCC, and an N30-CTav occupancy rate of >30.6% might be a predictor of maintenance of CR. Use of these indicators have the potential to impact systemic chemotherapy for HCC.

A study on the inconsistency of arterial phase hypervascularity detection between contrast-enhanced ultrasound using sonazoid and gadolinium-ethoxybenzyl-diethylenetriamine penta-acetic acid magnetic resonance imaging of hepatocellular carcinoma lesions.

PURPOSE: By analyzing possible factors contributing to imaging misevaluation of arterial phase (AP) vascularity, we aimed to provide a more proper way to detect AP hypervascularity of hepatocellular carcinomas (HCCs) using the noninvasive imaging modalities magnetic resonance imaging (MRI) and contrast-enhanced ultrasound (CEUS). METHODS: We retrospectively recruited 164 pathologically confirmed HCC lesions from 128 patients. Using CEUS with Sonazoid (SCEUS) and gadolinium-ethoxybenzyl-diethylenetriamine penta-acetic acid MRI (EOB-MRI), AP vascularity of the lesions was evaluated and inconsistencies in interpretation were examined. Indicators of margin, echogenicity, and halo and mosaic signs of lesions on grayscale US; depth of lesions on SCEUS; and tumoral homogeneity, signal contrast ratio of lesions to the surrounding area on precontrast and AP images on EOB-MRI, and histological grade were investigated. RESULTS: When precontrast images were used to adjust the AP enhancement ratio, the proportion of inconsistent interpretations of AP vascularity declined from 26.2% (43/164; 29 non-hypervascularity instances using EOB-MRI and 14 using SCEUS) to 16.5% (27/164; 7 using EOB-MRI and 20 using SCEUS). Greater lesion depth (P = 0.017), ill-defined tumoral margin (P = 0.028), absence of halo sign (P = 0.034), and histologically early HCC (P = 0.007) on SCEUS, and small size (P = 0.012) and heterogeneity (P = 0.013) of lesions and slight enhancement (low AP enhancement ratio) (P = 0.018 and 0.009 before and after adjustment) on EOB-MRI, may relate to undetectable hypervascularity. CONCLUSIONS: SCEUS and EOB-MRI may show discrepancies in evaluating AP vascularity in the case of deep, ill-defined, heterogeneous, slightly enhanced lesions, and histologically early HCCs. We recommend adjusting AP with precontrast images in EOB-MRI, and combining both modalities to detect hypervascularity.

Liver Injury and Use of Contrast-Enhanced Ultrasound for Evaluating Intrahepatic Recurrence in a Case of TACE-Refractory Hepatocellular Carcinoma Receiving Atezolizumab-Bevacizumab Combination Therapy: A Case Report.

A 67-year-old male with type 2 diabetes (T2DM) was diagnosed with postoperative intrahepatic recurrence for hepatocellular carcinoma (HCC). Nine sessions of transarterial chemoembolization (TACE) proved ineffective, and the patient was diagnosed as having TACE-refractory disease and received seven cycles of atezolizumab-bevacizumab combination therapy. After that, the patient developed hyperglycemia with the HbA1c elevation and the marked fasting serum C-peptide reduction and was diagnosed with developed immune-mediated diabetes (IMD) (T2DM exacerbation with insulin-dependent diabetes development). Subsequently, the hepatobiliary enzyme levels, which were high before the systemic therapy, worsened. Thus, we clinically diagnosed an exacerbation of liver injury due to TACE-induced liver injury complicated by drug-induced liver injury such as immune-mediated hepatotoxicity (IMH). Meanwhile, after contrast-enhanced computed tomography revealed complete response, contrast-enhanced ultrasound was performed to assess intrahepatic recurrence. We found that the latter modality allowed earlier and more definitive diagnosis of intrahepatic recurrence of HCC. Subsequently, despite systemic therapy discontinuation and steroids administration, the liver injury worsened, and the patient died. The autopsy revealed intrahepatic recurrence of HCC and extensive arterial obstruction by the beads used for TACE within the liver, which indicated that disturbed circulation was the primary cause of the liver injury and histopathologically confirmed IMD, but not IMH.

A case of successful pregnancy in a septate uterus after discharge of decidual tissue in the second trimester.

In pregnant patients with a divided uterine cavity, the decidual tissue on the nonpregnant side may be discharged prior to the delivery of the fetus. The pregnancy can continue if the uterine contractions and vaginal bleeding are controlled and the fetus is not in distress.