CANE, a Component of the NLRP3 Inflammasome, Promotes Inflammasome Activation.

The nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3, also called cryopyrin) inflammasome is an intracellular innate immune complex, which consists of the pattern-recognition receptor NLRP3, the adaptor apoptosis-assciated speck-like protein containing a caspase recruitment domain, and procaspase-1. Aberrant activation of the NLRP3 inflammasome causes an autoinflammatory disease called cryopyrin-associated periodic syndrome (CAPS). CAPS is caused by gain-of-function mutations in the NLRP3-encoding gene CIAS1; however, the mechanism of CAPS pathogenesis has not been fully understood. Thus, unknown regulators of the NLRP3 inflammasome, which are associated with CAPS development, are being investigated. To identify novel components of the NLRP3 inflammasome, we performed a high-throughput screen using a human protein array, with NLRP3 as the bait. We identified a NLRP3-binding protein, which we called the cryopyrin-associated nano enhancer (CANE). We demonstrated that CANE increased IL-1ß secretion after NLRP3 inflammasome reconstitution in human embryonic kidney 293T cells and formed a "speck" in the cytosol, a hallmark of NLRP3 inflammasome activity. Reduced expression of endogenous CANE decreased IL-1ß secretion upon stimulation with the NLRP3 agonist nigericin. To investigate the role of CANE in vivo, we developed CANE-transgenic mice. The PBMCs and bone marrow-derived macrophages of CANE-transgenic mice exhibited increased IL-1ß secretion. Moreover, increased autoinflammatory neutrophil infiltration was observed in the s.c. tissue of CANE-transgenic versus wild-type mice; these phenotypes were consistent with those of CAPS model mice. These findings suggest that CANE, a component of the NLRP3 inflammasome, is a potential modulator of the inflammasome and a contributor to CAPS pathogenesis.

Reduced chemokine C-C motif ligand 1 expression may negatively regulate colorectal cancer progression at liver metastatic sites.

Colorectal cancer (CRC) liver metastasis, albeit a stage-IV disease, is completely curable by surgical resection in selected patients. In addressing the molecular basics of this phenomenon, differentially expressed genes at primary and liver metastatic sites were screened by RNA sequencing with the use of paraffin-embedded surgical specimens. Chemokine C-C motif ligand 1 (CCL1), a chemotactic factor for a ligand of the chemokine C-C motif receptor 8 (CCR8), was isolated as one of the differentially expressed genes. Histological analysis revealed that the number of CCL1-positive cells, mainly tumour associated macrophages (TAMs) located in the stroma of CRC, decreased significantly at liver metastatic sites, while the expression level of CCR8 on CRC remained unchanged. To explore the biological significance of the CCL1-CCR8 axis in CRC, CCR8-positive CRC cell line Colo320DM was used to assess the effect of the CCL1-CCR8 axis on major signalling pathways, epithelial mesenchymal transition induction and cell motility. Upon stimulation of recombinant CCL1 (rCCL1), phosphorylation of AKT was observed in Colo320DM cells; on the other hand, the corresponding significant increase in MMP-2 levels demonstrated by RT-qPCR was nullified by siRNA (siCCR8). In the scratch test, rCCL1 treatment significantly increased the motility of Colo320DM cells, which was similarly nullified by siCCR8. Thus, the activation of the CCL1-CCR8 axis is a positive regulator of CRC tumour progression. Reduced CCL1 expression of TAMs at liver metastatic sites may partly explain the unique slow tumour progression of CRC, thus providing for a grace period for radical resection of metastatic lesions.

An Analysis of 10,000 Cases of Living Donor Liver Transplantation in Japan: Special Reference to the Graft-Versus-Recipient Weight Ratio and Donor Age.

OBJECTIVE: To analyze 10,000 cases of living donor liver transplantation (LDLT) recipient data to elucidate outcomes with special reference to the graft-versus-recipient weight ratio (GRWR), based on the Japanese Liver Transplantation Society (JLTS) registry. BACKGROUND: The JLTS registry has been accurate and complete in characterizing and following trends in patient characteristics and survival of all patients with LDLT. METHODS: Between November 1989 and August 2021, 10,000 patients underwent LDLT in Japan. The procedures performed during the study period included pediatric liver transplantation (age <18 years, n = 3572) and adult liver transplantation (age ≥18 years, n=6428). Factors related to patient survival (PS) and graft survival (GS) were also analyzed. RESULTS: The GRWR was <0.7, 0.7 to <0.8, 0.8 to <3, 3 to <5, and ≥5 in 0.2%, 2.0%, 61.8%, 31.8%, and 2.6% of pediatric patients and <0.6, 0.6 to <0.7, 0.7 to <0.8, and ≥0.8 in 8.0%, 12.7%, 17.7%, and 61.5% of adult patients, respectively. Among pediatric recipients, the PS rate up to 5 years was significantly better in cases with a GRWR ≤5 than in those with a GRWR >5. When the GRWR and donor age were combined, among adult recipients 50 to 60 years old, the early PS and GS up to 5 years were significantly better in cases with a GRWR ≥0.7, than in those with a GRWR <0.7. (P = 0.02). In adults, a multivariate analysis showed that GRWR <0.6, transplant era (<2011), donor age (>60 years), recipient age (>60 years), model for end-stage liver disease score (≥20), and center volume (<10) were significant prognostic factors for long-term PS. CONCLUSION: Although a satisfactory long-term PS and GS, especially in the recent era (2011-2021), was achieved in the JLTS series, a GRWR ≥5 in pediatric cases and relatively old donors with a GRWR <0.7 in adult cases should be managed with caution.

Impact of the inferior vena cava morphology on fluid dynamics of the hepatic veins.

We reported previously that a large vertical interval between the hepatic segment of the inferior vena cava (IVC) and right atrium (RA), referred to as the IVC-RA gap, was associated with more intraoperative bleeding during hemi-hepatectomy. We conducted a computational fluid dynamics (CFD) study to clarify the impact of fluid dynamics resulting from morphologic variations around the liver. The subjects were 10 patients/donors with a large IVC-RA gap and 10 patients/donors with a small IVC-RA gap. Three-dimensional reconstructions of the IVC and hepatic vessels were created from CT images for the CFD study. Median pressure in the middle hepatic vein was significantly higher in the large-gap group than in the small-gap group (P = 0.008). Differences in hepatic vein pressure caused by morphologic variation in the IVC might be one of the mechanisms of intraoperative bleeding from the hepatic veins.

Prolonged warm ischemia time in the recipient is associated with post-transplant biliary stricture following living-donor liver transplantation.

PURPOSE: Post-transplant biliary stricture (PBS) is a common and important complication following orthotopic liver transplantation (LT). This study clarified the incidence of PBS and identified its risk factors. METHODS: We retrospectively reviewed the medical records of 67 patients who underwent living-donor LT (LDLT) at our institute between June 2010 and July 2022 and analyzed their clinical characteristics, prognosis, and risk factors for PBS. RESULTS: Of the 67 patients, 26 (38.8%) developed PBS during the observation period. Multivariate analyses revealed the following independent risk factors for PBS formation: increased red cell transfusion volume per body weight (> 0.2 U/kg; hazard ratio [HR], 3.8; P = 0.002), increased portal vein pressure (PVP) at the end of LT (> 16 mmHg; HR, 2.88; P = 0.032), postoperative biliary leakage (HR, 4.58; P = 0.014), and prolonged warm ischemia time (WIT) (> 48 min; HR, 4.53; P = 0.008). In patients with PBS, the cumulative incidence of becoming stent free was significantly higher in patients with a WIT ≤ 48 min than in those with a WIT > 48 min (P = 0.038). CONCLUSION: Prolonged WIT is associated with intractable PBS following LDLT.

The histone demethylase Utx controls CD8+ T-cell-dependent antitumor immunity via epigenetic regulation of the effector function.

CD8+ T cells play a central role in antitumor immune responses. Epigenetic gene regulation is essential to acquire the effector function of CD8+ T cells. However, the role of Utx, a demethylase of histone H3K27, in antitumor immunity remains unclear. In this study, we examined the roles of Utx in effector CD8+ T-cell differentiation and the antitumor immune response. In a murine tumor-bearing model, an increased tumor size and decreased survival rate were observed in T-cell-specific Utx KO (Utx KO) mice compared with wild-type (WT) mice. The number of CD8+ T cells in tumor-infiltrating lymphocytes (TILs) was significantly decreased in Utx KO mice. We found that the acquisition of effector function was delayed and attenuated in Utx KO CD8+ T cells. RNA sequencing revealed that the expression of effector signature genes was decreased in Utx KO effector CD8+ T cells, while the expression of naïve or memory signature genes was increased. Furthermore, the expression of Cxcr3, which is required for the migration of effector CD8+ T cells to tumor sites, was substantially decreased in Utx KO CD8+ T cells. These findings suggest that Utx promotes CD8+ T-cell-dependent antitumor immune responses partially through epigenetic regulation of the effector function.

Demethylation in promoter region of severely damaged hepatocytes enhances chemokine receptor CXCR4 gene expression.

The liver is known to possess remarkable regenerative potential, but persistent inflammation or severe acute injury can lead to liver fibrosis and incomplete regeneration, ultimately resulting in liver failure. Recent studies have shown that the axis of two types of CXCL12 receptors, CXCR4 and CXCR7, plays a crucial role in liver fibrosis and regeneration. The present study aimed to investigate the regulatory factors involved in CXCR4 expression in injured liver. Immunohistochemical screening of liver tissue samples collected during liver transplantation revealed a reciprocal expression pattern between CXCR4 and MeCP2. An in vitro system involving cultured cell lines and H2O2 treatment was established to study the impact of oxidative stress on signaling pathways and epigenetic alterations that affect CXCR4 mRNA expression. Operating through distinct signaling pathways, H2O2 treatment induced a dose-dependent increase in CXCR4 expression in both hepatocyte- and intrahepatic cholangiocyte-derived cells. Treatment of the cells with trichostatin and azacytidine modulated CXCR4 expression in hepatocytes by modifying the methylation status of CpG dinucleotides located in a pair of TA repeats adjacent to the TATA box of the CXCR4 gene promoter. Only MeCP2 bound to oligonucleotides representing the TATA box region when the cytosine residues within the sequence were methylated, as revealed by electrophoretic mobility shift assay (EMSA). Methylation-specific PCR analysis of microdissected samples revealed a correlation between the loss of CpG methylation and the upregulation of CXCR4 in injured hepatocytes, replicating the findings from the in vitro study. Besides the conventional MEK/ERK and NF-κB signaling pathways that activate CXCR4 in intrahepatic cholangiocytes, the unique epigenetic modifications observed in hepatocytes might also contribute to a shift in the CXCR4-CXCR7 balance towards CXCR4, leading to irreversible liver injury and fibrosis. This study highlights the importance of epigenetic modifications in regulating CXCR4 expression in liver injury and fibrosis.

Intramuscular Adipose Tissue Content as a Predictor of Incisional Hernia after Hepatic Resection.

BACKGROUND: Incisional hernia (IH) is a common surgical complication, with an incidence of 6-31% following major abdominal surgery. This study aimed to investigate the impact of intramuscular adipose tissue content (IMAC) on the incidence of IH in patients who underwent hepatic resection. METHODS: Data of 205 patients who underwent open hepatic resection between 2007 and 2019 at Ehime University Hospital were retrospectively analyzed. Patient characteristics, perioperative findings, and body composition were compared between patients with IH and those without IH. The quantity and quality of skeletal muscle, calculated as skeletal muscle index and IMAC, were evaluated using preoperative computerized tomography images. RESULTS: Forty (19.5%) patients were diagnosed with IH. The cumulative incidence rates were 15.6% at 1 year and 19.6% at 3 years. On univariate analysis, body mass index, areas of subcutaneous and visceral fat, and IMAC were significantly higher in the IH group than in the non-IH group (p = 0.0023, 0.0070, 0.0047, and 0.0080, respectively). No significant difference in skeletal muscle index was found between the groups (p = 0.3548). The incidence of diabetes mellitus, intraoperative transfusion, and postoperative wound infection was significantly higher in the IH group than in the non-IH group (p = 0.0361, 0.0078, and 0.0299, respectively). On multivariate analysis, a high IMAC and wound infection were independent risk factors for IH (adjusted odds ratio, 2.83 and 4.52, respectively; p = 0.0152 and 0.0164, respectively). CONCLUSION: IMAC can predict the incidence of IH in patients undergoing hepatic resection.

Postoperative arterial lactate levels can predict postoperative pancreatic fistula following pancreaticoduodenectomy: A single cohort retrospective study.

BACKGROUND: /Objectives: Postoperative pancreatic fistula (POPF) is a serious complication after pancreaticoduodenectomy (PD). Thus, identification of the risk factors for POPF is urgently needed. In this study, we aimed to identify whether arterial lactate (LCT) levels following PD might be a marker of the potential risk of POPF. METHODS: Between September 2009 and December 2020, 151 patients who underwent elective PD were retrospectively enrolled. Patient characteristics, perioperative clinicopathological variables, postoperative blood biochemistry data were analyzed in univariable and multivariable analyses. Pancreatic fistula of Grade B and C was considered as POPF. RESULTS: Patients were divided into the POPF group (n = 33, 21.9%) and non-POPF group (n = 118, 78.1%). Higher body mass index (p = 0.017), increased estimated blood loss (p = 0.047), soft textured pancreas (p = 0.007), smaller main pancreatic duct (p = 0.016), higher LCT levels (p < 0.001), higher aspartate aminotransferase levels (p = 0.023) and higher procalcitonin levels (p = 0.024) were significantly associated with POPF. Receiver operating characteristic curve analysis revealed that 2.1 mmol/L was the optimal cut-off value of LCT (sensitivity = 78.8%, specificity = 61.2%) for predicting POPF occurrence. Univariate and multivariate analyses confirmed that an LCT of ≥2.1 mmol/L was independently associated with the risk of POPF following PD (odds ratio = 6.78, 95% confidence interval = 2.22-20.74; p = 0.001). CONCLUSIONS: Higher LCT is a predictive marker for POPF following PD.

Transmediastinal, intrapericardial inferior vena cava approach based on anatomical landmarks for hepatectomy using total hepatic vascular exclusion.

BACKGROUND: Total hepatic vascular exclusion (THVE) is an essential technique to control hemorrhage during surgical treatment of advanced liver tumors or injury. However, surgeons often have difficulty securing the intrapericardial inferior vena cava (IVC) because few reports have described the anatomy around the supra-diaphragmatic IVC or the techniques and surgical outcomes for this procedure. This study presents our safe and feasible intrapericardial IVC approach, which is based on anatomical landmarks, and reports the surgical outcomes of this procedure. METHODS: We performed THVE using our technique for hepatectomy, accompanied by resection of the hepatic vein confluence or tumor thrombectomy of the supra-hepatic IVC, in five patients between August 2011 and March 2018. RESULTS: The mean operative time was 568 min (range: 240-820 min). The mean THVE time was 10 min (range: 5-15 min), with a mean blood loss of 1882 mL (range: 1010-3100 mL). Postoperatively, one patient was classified as Clavien-Dindo grade II due to medication for tachycardia, and two patients were classified as grade IIIa due to drainage of bile and pleural effusion, including one patient with tachycardia. The mean postoperative hospital stay was 26 days (range: 18-34 days). No patient exhibited decreased cardiac function during surgery or postoperatively, and no patient experienced thoracotomy or phrenic nerve paralysis. CONCLUSIONS: Anatomical landmarks are important to ensure a safe approach to the intrapericardial IVC. Incising the pericardium does not lead to serious problems. The transmediastinal, intrapericardial IVC approach for THVE is a feasible method to secure the supra-diaphragmatic intrapericardial IVC.

Importance of reconstruction of middle hepatic vein tributaries of right-lobe grafts in living donor liver transplantation: demonstration of the reconstruction technique.

PURPOSE: The aim of the present study on living donor liver transplantation (LDLT) using a right-lobe graft without the middle hepatic vein (MHV) was to investigate the clinical impact of MHV tributary reconstruction using our criteria and techniques. METHODS: The medical records of 40 patients who underwent adult LDLT using a right-lobe graft without the MHV between April 2008 and December 2020 were retrospectively reviewed. In this cohort, the criterion for MHV tributary reconstruction was estimated drainage volume of each MHV tributary greater than 100 mL. The drainage vein of segment 8 (V8) was reconstructed as the common orifice of the right hepatic vein and V8 using a venous patch graft, and that of segment 5 was reconstructed using artificial vascular grafts. The outcomes were compared between the groups with and without MHV tributary reconstruction. Factors associated with postoperative massive ascites were also investigated. RESULTS: Twenty patients underwent MHV tributary reconstruction. There were no significant differences in the amount of postoperative ascites, Clavien-Dindo classification ≥ III postoperative complications, and 90-day in-hospital mortality between the groups (P = 0.678, P = 1.000, and P = 0.244, respectively). On multivariate analyses, a low-estimated functional graft-to-recipient weight ratio, which was calculated using estimated graft volume minus the territory of MHV tributaries that was not reconstructed, was identified as an independent predictor of postoperative massive ascites (odds ratio, 40.479; 95% confidence interval, 3.823-428.622). CONCLUSION: The present study suggests that selective MHV tributary reconstruction might be useful for achieving successful graft function.

Laparoscopic clamp-crushing enucleation with a pancreatic duct stent for tumors located close to the main pancreatic duct.

The perioperative management and technical details of laparoscopic clamp-crushing enucleation for low-malignant-potential pancreatic neuroendocrine neoplasms (PNENs) located close to the main pancreatic duct (MPD) in the body/tail of the pancreas using a perioperative MPD stent are reported. The procedure was performed in two patients with PNEN (13 and 10 mm in diameter) in the body/tail of the pancreas. A naso-pancreatic stent (NPS) was placed preoperatively in both patients. Resection was performed using Maryland-type bipolar forceps. The surgical duration was 139 and 55 min, and the estimated blood loss was 5 and 0 mL, respectively. One patient was discharged uneventfully on postoperative day (POD) 12. The other patient developed a grade B pancreatic fistula, but was discharged on POD 22. Laparoscopic clamp-crushing enucleation with an NPS might be a viable treatment option for tumors located close to the MPD.

Computer-Aided Detection of Quantitative Signatures for Breast Fibroepithelial Tumors Using Label-Free Multi-Photon Imaging.

Fibroadenomas (FAs) and phyllodes tumors (PTs) are major benign breast tumors, pathologically classified as fibroepithelial tumors. Although the clinical management of PTs differs from FAs, distinction by core needle biopsy diagnoses is still challenging. Here, a combined technique of label-free imaging with multi-photon microscopy and artificial intelligence was applied to detect quantitative signatures that differentiate fibroepithelial lesions. Multi-photon excited autofluorescence and second harmonic generation (SHG) signals were detected in tissue sections. A pixel-wise semantic segmentation method using a deep learning framework was used to separate epithelial and stromal regions automatically. The epithelial to stromal area ratio and the collagen SHG signal strength were investigated for their ability to distinguish fibroepithelial lesions. An image segmentation analysis with a pixel-wise semantic segmentation framework using a deep convolutional neural network showed the accurate separation of epithelial and stromal regions. A further investigation, to determine if scoring the epithelial to stromal area ratio and the SHG signal strength within the stromal area could be a marker for differentiating fibroepithelial tumors, showed accurate classification. Therefore, molecular and morphological changes, detected through the assistance of computational and label-free multi-photon imaging techniques, enable us to propose quantitative signatures for epithelial and stromal alterations in breast tissues.

[A Case of Breast Cancer during Pregnancy Treated with Neoadjuvant Chemotherapy during Pregnancy].

Although breast cancer during pregnancy is relatively rare, the number of such cases has risen in recent years owing to an increase in mean childbirth age and the increasing prevalence of breast cancer. Here we report the case of a 37-year-old breast cancer patient who received neoadjuvant chemotherapy during pregnancy. The woman previously consulted an outside physician after noting a mass in her right breast at 25 weeks' gestation. Breast ultrasonography revealed a right breast tumor and axillary lymphadenopathy. A histopathological examination indicated right breast cancer and axillary lymph node metastasis. She was referred to our department for pregnancy management. Chest X-rays and abdominal ultrasonography were utilized in the search for metastases. She received 2 courses of doxorubicin and cyclophosphamide(AC)therapy during pregnancy and gave birth via cesarean section at 35 weeks' gestation. After delivery, the AC was resumed. The patient completed a total of 4 courses of AC followed by 4 courses of docetaxel (dosed every 3 weeks). She underwent total right mastectomy and axillary dissection; because the tumor was BRCA2 mutation-positive, a risk-reducing salpingo- oophorectomy was also performed. Adjuvant therapy included radiotherapy and tamoxifen but no luteinizing hormone- releasing hormone agonists. At the time of this writing more than 1 year post-surgery, she has not experienced recurrence; although the infant has a congenital clubfoot, she suffers from no other cognitive or developmental delays.

[A Case of Unresectable Hepatocellular Carcinoma Treated using Lenvatinib and Conversion Surgery].

A 57-year-old man was treated with lenvatinib for unresectable hepatocellular carcinoma(HCC). Thereafter, the tumor marker levels decreased, and the tumor became resectable. The patient underwent portal vein embolization followed by laparoscopic extended left lobectomy. The patient's postoperative course was uneventful, and the tumor marker levels remained within the normal range. No recurrence was observed 3 months after surgery. In recent years, the use of systemic chemotherapy with drugs, such as lenvatinib, followed by conversion surgery has been reported in some cases of unresectable HCC. The present case reports successful conversion surgery following lenvatinib treatment.

Immunohistochemically Detected Expression of ATRX, TSC2, and PTEN Predicts Clinical Outcomes in Patients With Grade 1 and 2 Pancreatic Neuroendocrine Tumors.

OBJECTIVE: The goal of this retrospective study was to clarify the clinical implications of immunohistochemically detected protein expression for genes that are frequently mutated in pancreatic neuroendocrine tumors (PNETs). BACKGROUND: The clinical management of PNETs is hindered by their heterogenous biological behavior. Whole-exome sequencing recently showed that 5 genes (DAXX/ATRX, MEN1, TSC2, and PTEN) are frequently mutated in PNETs. However, the clinical implications of the associated alterations in protein expression remain unclear. METHODS: We collected Grade 1 and 2 (World Health Organization 2017 Classification) primary PNETs samples from 100 patients who underwent surgical resection. ATRX, DAXX, MEN1, TSC2, and PTEN expression were determined immunohistochemically to clarify their relationships with prognosis and clinicopathological findings. RESULTS: Kaplan-Meier analysis indicated that loss of TSC2 (n = 58) or PTEN (n = 37) was associated with significantly shorter overall survival, and that loss of TSC2 or ATRX (n = 41) was associated with significantly shorter recurrence-free survival. Additionally, loss of ATRX or TSC2 was significantly associated with nodal metastasis. In a multivariate analysis, combined loss of TSC2 and ATRX (n = 31) was an independent prognostic factor for shorter recurrence-free survival (hazard ratio 10.1, 95% confidence interval 2.1-66.9, P = 0.003) in G2 PNETs. CONCLUSIONS: Loss of ATRX, TSC2, and PTEN expression might be useful as a method of clarifying the behavior and clinical outcomes of Grade 1 and 2 PNETs in routine clinical practice. Combined loss of TSC2 and ATRX had an especially strong, independent association with shorter recurrence-free survival in patients with G2 PNETs. Loss of pairs in ATRX, TSC2, or PTEN would be useful for selecting the candidate for postoperative adjuvant therapy.

Uhrf1 is indispensable for normal limb growth by regulating chondrocyte differentiation through specific gene expression.

Transcriptional regulation can be tightly orchestrated by epigenetic regulators. Among these, ubiquitin-like with PHD and RING finger domains 1 (Uhrf1) is reported to have diverse epigenetic functions, including regulation of DNA methylation. However, the physiological functions of Uhrf1 in skeletal tissues remain unclear. Here, we show that limb mesenchymal cell-specific Uhrf1 conditional knockout mice (Uhrf1ΔLimb/ΔLimb ) exhibit remarkably shortened long bones that have morphological deformities due to dysregulated chondrocyte differentiation and proliferation. RNA-seq performed on primary cultured chondrocytes obtained from Uhrf1ΔLimb/ΔLimb mice showed abnormal chondrocyte differentiation. In addition, integrative analyses using RNA-seq and MBD-seq revealed that Uhrf1 deficiency decreased genome-wide DNA methylation and increased gene expression through reduced DNA methylation in the promoter regions of 28 genes, including Hspb1, which is reported to be an IL1-related gene and to affect chondrocyte differentiation. Hspb1 knockdown in cKO chondrocytes can normalize abnormal expression of genes involved in chondrocyte differentiation, such as Mmp13 These results indicate that Uhrf1 governs cell type-specific transcriptional regulation by controlling the genome-wide DNA methylation status and regulating consequent cell differentiation and skeletal maturation.

Pure Laparoscopic Right Hepatectomy for Hepatocellular Carcinoma with Bile Duct Tumor Thrombus (with Video).

BACKGROUND: Laparoscopic liver resection has been increasingly utilized due to its less invasiveness approach compared with open surgery,1-3 but often creates challenges. Hepatocellular carcinoma (HCC) with bile duct tumor thrombus (BDTT) portends a poorer prognosis and often precludes patients from potential liver resection.4-6 We herein report a case of laparoscopic hepatectomy and thrombectomy in a patient with HCC and BDTT. METHODS: CT, ERCP, and POCS showed a 40-mm tumor located in the right lobe with BDTT. A five 12-mm trocar was inserted at the umbilicus for laparoscope, the epigastrium, both sides of the hypochondrium, and right lateral region. Moreover, a 5-mm trocar was inserted at left hypochondrium. After cholecystectomy, hepatoduodenal ligament was encircled using the tourniquet through 5-mm trocar site. The right portal vein was transected by stapler following transection of the right hepatic artery. After ICG staining (0.5 mg/body i.v.),7 hepatic parenchymal transection was performed using clamp-crashing technique. Moreover, CUSA also was used near Glissonian sheath. BDTT was removed from the right BD. Moreover, the cholangioscopy confirmed no BDTT remnants. The resection stump was then sutured. Finally, the right hepatic vein was divided with a stapler. A drainage tube was placed in the right subphrenic space. Operation time was 496 min, and blood loss was 91 ml. The patient was discharged without complications on postoperative day 11. Pathological diagnosis showed moderately differentiated HCC, tumor size 40 × 45 mm with negative surgical margins. CONCLUSIONS: Pure laparoscopic resection for HCC with BDTT is a radical, yet feasible procedure.

An analysis of the outcomes in living donor liver transplantation for pediatric malignant hepatic tumors using nationwide survey data in Japan.

Malignant hepatic tumors (MHTs) in children are rare and account for approximately 5% of candidates for pediatric liver transplantation (LT) in Japan. We conducted a national survey of pediatric patients undergoing living donor LT for MHTs between October 1990 and April 2018. In total, 116 children underwent LT for MHTs during this study period: 100 hepatoblastomas (HBLs), 10 hepatocellular carcinomas (HCCs), and six other MHTs. The overall patient survival rate at 5 years was 81.3% for HBL, 60.0% for HCC, and 80.0% for other MHTs (P = 0.047). In patients with HBL, there was no significant difference in the 1- and 5-year patient survival rates between patients undergoing primary LT and those who received salvage LT for tumor recurrence (89.7%, 81.6% vs. 88.0%, 76%; P = 0.526). The 5-year overall survival rate after LT for HBL significantly improved from 63.2% in 1996-2008 to 89.8% in 2009-2018 (P = 0.018). The presence of lung metastasis before LT had no significant influence on the long-term survival (P = 0.742). Five patients with HCC died, including two who fell outside the Milan criteria. In conclusion, LT for pediatric MHTs, especially HBL, is a valuable treatment option for select patients.

Metaplastic carcinoma of the breast and BRCA1 germline mutation: a case report and review.

BACKGROUND: Metaplastic carcinoma of the breast consists of both invasive ductal carcinoma and metaplastic carcinoma. This rare subtype of cancer has a poor prognosis. The development of metaplastic breast cancer and relationship with BRCA1 are not well known. Here, we report a rare case of germline BRCA1 mutation-positive breast cancer with chondroid metaplasia. CASE PRESENTATION: A 39-year-old Japanese woman with a family history of breast cancer in her mother and ovarian cancer in her maternal grandmother consulted at our hospital with a left breast mass. Needle biopsy for the mass was performed, leading to a diagnosis of invasive breast cancer with chondroid metaplasia. We performed left mastectomy + sentinel lymph node biopsy + tissue expander insertion and replaced with a silicone implant later. Pathological examination revealed that the patient had triple-negative breast cancer. Four courses of doxorubicin+ cyclophosphamide therapy were performed as adjuvant therapy after surgery. We performed genetic counseling and genetic testing, and the results suggested the germline BRCA1 mutation 307 T> A (L63*). She has currently lived without a relapse for 2 years post-surgery. CONCLUSIONS: There have been only 6 cases of metaplastic breast carcinoma with germline BRCA1 mutations including our case. Patients with BRCA1 mutations may develop basal-like subtypes or M type of triple-negative breast cancer besides metaplastic breast cancers.