The expression analysis of SerpinB9 in hepatoblastoma microenvironment.

PURPOSE: In this research, we analyzed the expression of serpinB9 in hepatoblastoma and investigated the factors which enhance its expression. METHOD: SerpinB9 expression in hepatoblastoma cell lines and macrophages co-cultured with each other or stimulated by anticancer agents was examined using RT-qPCR and western blotting. Immunohistochemistry for SerpinB9 in hepatoblastoma specimens was performed. Single-cell RNA-sequence data for hepatoblastoma from an online database were analyzed to investigate which types of cells express SerpinB9. RESULT: HepG2, a hepatoblastoma cell line, exhibited increased expression of SerpinB9 when indirectly co-cultured with macrophages. Immunohistochemistry for the specimens demonstrated that serpinB9 is positive not in hepatoblastoma cells but in macrophages. Single-cell RNA sequence analysis in tissues from hepatoblastoma patients showed that macrophages expressed SerpinB9 more than tumor cells did. Co-culture of macrophages with hepatoblastoma cell lines led to the enhanced expression of SerpinB9 in both macrophages and cell lines. Anticancer agents induced an elevation of SerpinB9 in hepatoblastomas cell lines. CONCLUSION: In hepatoblastoma, SerpinB9 is thought to be more highly expressed in macrophages and enhanced by interaction with hepatoblastoma cell.

Overexpression of SerpinB9 in non-seminomatous germ cell tumors.

Serpinb9 is an inhibitor of granzyme B and is potentially involved in the immune escape of tumor cells. In the present study, bioinformatics analysis using open databases suggested that SerpinB9 is overexpressed in testicular embryonal carcinoma. Immunohistological analysis was performed on 28 cases of testicular germ cell tumors to investigate the relationship between SerpinB9 expression in testicular germ cell tumors and the tumor immune environment. SerpinB9 was significantly upregulated in the non-seminoma group and inversely correlated with the number of tumor-infiltrating CD8-positive cells. In addition, yolk sac tumors were characterized by the loss of human leukocyte antigen-class I expression. These findings suggest that SerpinB9 contributes to the immune escape of testicular germ cell tumors. Targeting therapy for SerpinB9 might therefore be useful in immunotherapy for testicular germ cell tumors resistant to immune checkpoint inhibitors.

Reappraisal of anatomical liver resection for hepatoblastoma in children.

Background: The principle of hepatoblastoma (HB) treatment is complete resection. The removal of tumor-bearing section(s) or hemiliver is widely accepted. However, neither the standardized anterior approach for right hepatectomy nor parenchymal sparing anatomical liver resection has been described for HB. Methods: We retrospectively reviewed the clinical course of two pediatric HB patients who underwent extended right hepatectomy using the anterior approach with the liver hanging maneuver and one who underwent parenchymal sparing anatomical liver resection of S4 apical+S8 ventral/dorsal+S7. The critical aspects of surgical techniques are described in detail. Results: In all three patients, R0 resection was achieved without complications and are currently alive without recurrence after an average follow-up of 23 months. Intraoperative cardiac hemodynamics were stable, even in a trisomy 18 patient with cardiac disease. Conclusions: Our findings suggest that these innovative techniques established in adults are safe and feasible for HB in children. These techniques also allow optimal anatomical liver resection to accomplish curative surgery while maintaining the functional reserve of the remnant liver.

Potential involvement of IL-32 in cell-to-cell communication between macrophages and hepatoblastoma.

PURPOSE: This study investigated the expression of interleukin 32 (IL-32) in hepatoblastoma, the most common primary pediatric liver tumor, and its possible roles in tumorigenesis. METHODS: IL-32 expression was investigated in two hepatoblastoma cell lines (Hep G2 and HuH 6) in the steady state and after co-culture with macrophages by RNA-seq analysis and RT-qPCR, and after stimulation with chemotherapy. Cultured macrophages were stimulated by IL-32 isoforms followed by RT-qPCR and western blot analysis. IL-32 immunohistochemical staining (IHC) was performed using specimens from 21 hepatoblastoma patients. Clustering analysis was also performed using scRNA-seq data downloaded from Gene Expression Omnibus. RESULTS: The IL-32 gene is expressed by hepatoblastoma cell lines; expression is upregulated by paracrine cell-cell communication with macrophages, also by carboplatin and etoposide. IL-32 causes protumor activation of macrophages with upregulation of PD-L1, IDO-1, IL-6, and IL-10. In the patient pool, IHC was positive only in 48% of cases. However, in the downloaded dataset, IL-32 gene expression was negative. CONCLUSION: IL-32 was detected in hepatoblastoma cell lines, but not in all hepatoblastoma patients. We hypothesized that stimulation such as chemotherapy might induce expression of IL-32, which might be a critical mediator of chemoresistance in hepatoblastoma through inducing protumor activation in macrophages.

Precision anatomy for minimally invasive spleen-preserving distal pancreatectomy in children: A case report of solid-pseudopapillary neoplasm in a 12-year-old girl.

INTRODUCTION: Solid pseudopapillary neoplasm (SPN) is a rare and low malignant tumor found mainly in young females. There is no standardized procedure for SPN of the pancreatic body and tail in children. In adults, an international consensus on precision anatomy for minimally invasive distal pancreatectomy (MIDP) was established recently (PAM-HBP Surgery Project). The aim of this study is to demonstrate that precision anatomy can also be safely and effectively implemented in the pediatric population. PRESENTATION OF CASE: A 12-year-old girl with an incidentally found SPN located in the pancreatic tail was referred to our hospital. She successfully underwent an R0 resection by laparoscopic spleen-preserving distal pancreatectomy (LSPDP) under the concept of precision anatomy. The patient recovered uneventfully and was discharged on day 7. DISCUSSION: This is the first successful report of LSPDP under the concept of precision anatomy in children. In accordance with the recommendations from the international consensus, the "anterior approach" was selected to dissect and encircle the splenic artery based on the vascular anatomy identified by preoperative imaging. The dorsal dissection border of the pancreas along the anterior layer above the Gerota's fascia was carefully maintained and the splenic vessels were preserved taking into consideration the low malignant potential of SPN and to decrease the risk of complications associated with splenectomy, which were also the essential issues of the consensus. CONCLUSION: The implementation of precision anatomy for pediatric pancreas surgery should facilitate the safe diffusion of MIDP for SPN and other benign or low-malignant tumors in children.

Preoperative serum CA19-9 predicts postoperative pancreatic fistula in PDAC patients: retrospective analysis at a single institution.

BACKGROUND: Postoperative pancreatic fistula (POPF) is a critical complication of pancreatectomy in patients with pancreatic ductal adenocarcinoma (PDAC). Recent papers reported that serum carbohydrate antigen (CA)19-9 levels predicted long-term prognosis. We investigated whether preoperative serum CA19-9 levels were associated with POPF in PDAC patients. METHODS: This cohort study was conducted at a single institution retrospectively. Clinicopathologic features were determined using medical records. RESULTS: Among of 196 consecutive patients who underwent pancreatectomy against PDAC, 180 patients whose CA19-9 levels were above the measurement sensitivity, were registered in this study. The patients consisted of 122 patients who underwent pancreaticoduodenectomy and 58 patients who underwent distal pancreatectomy. Several clinicopathological factors, including CA 19-9 level, as well as surgical factors were determined retrospectively based on the medical records. Patients with high CA19-9 levels had a significantly higher incidence of POPF than those with low levels (43.9 vs. 13.0%, P < 0.0001). The receiver operating characteristic curves calculated that the cutoff CA19-9 value to predict POPF was 428 U/mL. CA19-9, BMI, curability, and histology were statistically significant risk factors for POPF by univariate analysis. Multivariate analysis showed that CA19-9 and BMI levels were statistically significant independent risk factors for POPF. CA19-9 levels were correlated with both histology and curability. Disease free survival and overall survival of patients with higher levels of CA19-9 were significantly shorter than that of patients with lower levels of preoperative serum CA19-9. CONCLUSIONS: In patients undergoing pancreatectomy for PDAC, higher preoperative CA19-9 levels are a significant predictor for POPF.

A case of right hepatic duct entering cystic duct successfully treated by laparoscopic subtotal cholecystectomy through preoperatively placed biliary stent.

BACKGROUND: Laparoscopic cholecystectomy is a well-established surgical procedure and is one of the most commonly performed gastroenterological surgeries. Therefore, strategy for the management of rare anomalous cystic ducts should be determined. CASE PRESENTATION: A 56-year-old woman was admitted to our hospital owing to upper abdominal pain and diagnosed with acute cholecystitis. Magnetic resonance cholangiopancreatography suspected that several small stones in gallbladder and the right hepatic duct drained into the cystic duct. Endoscopic retrograde cholangiopancreatography confirmed the cystic duct anomaly, and an endoscopic nasobiliary drainage catheter (ENBD) was placed at the right hepatic duct preoperatively. Intraoperative cholangiography with ENBD confirmed the place of division in the gallbladder, and laparoscopic subtotal cholecystectomy was safely performed. CONCLUSIONS: The present case exhibited rare right hepatic duct anomaly draining into the cystic duct, which might have caused biliary tract disorientation and bile duct injury (BDI) intraoperatively. Any surgical technique without awareness of this anomaly preoperatively might insufficiently prevent BDI, and preoperative ENBD would facilitate safe and successful surgery.

Nivolumab exerts therapeutic effects against metastatic lesions from early gastric adenocarcinoma with a small proportion of neuroendocrine carcinoma after gastrectomy: a case report.

Gastric neuroendocrine carcinoma (NEC) is an aggressive disease with high metastatic ability. Gastric cancer has intra-tumoral and intra-patient heterogeneity and may contain NEC. We discuss the case of a 75-year-old man who underwent distal gastrectomy for early gastric cancer. Tumor pathology revealed that nearly all of the tumor (> 95%) was well-differentiated adenocarcinoma, with NEC detected in a small area (< 5%) at the invasion front. No metastasis was identified in the dissected lymph nodes (LN). Multiple liver metastases were detected 3 months after surgery. The metastatic lesion was resistant to both chemotherapy regimens; namely, SOX (S-1 combined with oxaliplatin) and ramucirumab combined with paclitaxel. However, tumor regression was detected after nivolumab treatment. The tumor regression continued for 26 cycles (13 months). Irinotecan treatment was then administered. After 18 irinotecan treatment cycles for 11 months, the para-aortic LN rapidly enlarged. Following biopsy, the swollen para-aortic LN was diagnosed as the recurrence of NEC components of the gastric cancer. Treatment with carboplatin combined with etoposide has been effective and continued. We report a case of NEC para-aorta LN metastases from early gastric cancer with a low proportion of NEC (< 5%). A partial response of the distant metastatic lesions was observed with nivolumab therapy.