BRAF V600E-mutant colorectal cancer with CNS metastases treated successfully with encorafenib, binimetinib and cetuximab.

This report describes a case of BRAF V600E-mutated colorectal cancer with CNS metastases in which treatment with encorafenib, binimetinib and cetuximab was effective. There is limited information on the ability of encorafenib, binimetinib and cetuximab to enter the CNS.The patient was a 53-year-old man was diagnosed with ascending colon cancer (cT3N3M1c stage IVc). BRAF V600E mutation was confirmed. FOLFOX was started, but CNS metastases soon appeared. Encorafenib, binimetinib and cetuximab were administered and had a favorable effect on the CNS lesions. The patient initially responded well, but his disease progressed 2 months later. Further research is needed to improve management strategies for BRAF V600E-mutated colorectal cancer with CNS metastases.

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Improvement in aged liver regeneration using cell transplantation with chemically induced liver progenitors.

BACKGROUND: A decrease in the regenerative capacity of age-damaged liver tissue has been reported. Liver progenitor cells may play an important role in the regeneration of injured livers. In the present study we aimed to investigate improvements in the regenerative capacity of age-damaged livers using chemically induced liver progenitors (CLiPs) derived from mature hepatocytes. METHODS: Old (>90 weeks) and young (<20 weeks) mice underwent 70% hepatectomy, with or without trans-splenic CLiP administration. The residual liver/bodyweight (LW/BW) ratio was measured on postoperative days 1 and 7, and changes in liver regeneration and histology were evaluated. RESULTS: At 7 days post-hepatectomy, LW/BW ratios were significantly better in CLiP-treated old mice than in untreated old mice (p = .02). By contrast, no effect of CLiP transplantation was observed in young mice (p = .62). Immunofluorescence staining of liver tissue after CLiP administration showed an increase in Ki67-positive cells (p < .01). Flow cytometry analysis of green fluorescent protein-labeled CLiPs indicated that transplanted CLiPs differentiated into mature hepatocytes and were present in the recipient liver. CONCLUSIONS: CLiP transplantation appears to ameliorate the age-related decline in liver regeneration in mice.

Clinical Validation of Computer-Aided Diagnosis Software for Preventing Retained Surgical Sponges.

BACKGROUND: We previously reported the successful development of a computer-aided diagnosis (CAD) system for preventing retained surgical sponges with deep learning using training data, including composite and simulated radiographs. In this study, we evaluated the efficacy of the CAD system in a clinical setting. STUDY DESIGN: A total of 1,053 postoperative radiographs obtained from patients 20 years of age or older who underwent surgery were evaluated. We implemented a foreign object detection application software on the portable radiographic device used in the operating room to detect retained surgical sponges. The results of the CAD system diagnosis were prospectively collected. RESULTS: Among the 1,053 images, the CAD system detected possible retained surgical items in 150 images. Specificity was 85.8%, which is similar to the data obtained during the development of the software. CONCLUSIONS: The validation of a CAD system using deep learning in a clinical setting showed similar efficacy as during the development of the system. These results suggest that the CAD system can contribute to the establishment of a more effective protocol than the current standard practice for preventing the retention of surgical items.

Feasibility of Organ Transportation by a Drone: An Experimental Study Using a Rat Model.

BACKGROUND: Recently, the successful delivery of organs for transplantation using drones was reported. We investigated the influence of transportation by drones on the quality of liver grafts using a rat model. METHODS: Livers of 12 rats (8 and 32 weeks old) were divided into 2 groups of six. Livers were split into 2 parts and allocated to the drone or control groups (both n = 12). The drone experiment was conducted between islands in Nagasaki Prefecture, Japan. The distance between the islands was 12 km. Livers of the drone group were transported by a multicopter at a speed of 30 km-40 km/h over 60 m above sea level. Transported liver quality was analyzed by histology, and biochemistry data were compared between groups. RESULTS: Cold ischemia time did not differ between groups (902 min and 909 min, respectively). There were no differences in macroscopic findings regarding coloration and damage between groups. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) in preservation fluid were graft weight-corrected and compared, and no significant differences were found between groups: AST/g (4.61 vs 4.81 IU/L), ALT/g (2.78 vs 2.92 IU/L), and ALP/g (39.1 vs 37.0 IU/L). Immunochemical staining showed no significant difference between groups for terminal deoxynucleotidyl transferase dUTP nick and labeling staining (141 vs 113 cells), CD163 (818 vs 870 cells), and TNF-α (1.25 vs 1.41 scores). CONCLUSIONS: The simulation experiment of organ transport for transplantation by drones was successfully conducted. There were no differences in the quality of livers transported by drones or other means. Further studies including large-animal experiments could lead to future clinical applications.

Percutaneous Direct Puncture of Retropancreatic Splenic Vein and Portal Thrombectomy in a Patient With Liver Transplantation and Simultaneous Splenectomy.

Portal vein thrombosis following liver transplantation is generally managed by endovascular treatment. Although several techniques are available for portal venous access, trans-splenic access is of interest because it avoids damage to the liver graft. However, the spleen cannot be punctured to access the portal vein after splenectomy. We herein report a case of portal vein thrombosis following living donor liver transplantation with simultaneous splenectomy successfully treated by percutaneous intervention with direct puncture of the retropancreatic splenic vein. The splenic vein was punctured under computed tomography guidance in the prone position. Portal venography revealed a contrast defect due to a thrombus in the extrahepatic to intrahepatic portal vein. The portal vein was reopened after thrombectomy, and the portal vein thrombosis did not recur for 2 y. The technique and advantages of our approach are described.

Transplantation of chemically-induced liver progenitor cells ameliorates hepatic fibrosis in mice with diet-induced nonalcoholic steatohepatitis.

Chemically-induced liver progenitors (CLiPs) have promising applications in liver regenerative medicine. We aimed to clarify the efficacy of CLiPs for ameliorating fibrosis in a diet-induced nonalcoholic steatohepatitis rat model, since nonalcoholic fatty liver disease is currently recognized as the most common form of chronic liver disease in developed countries. METHODS: Primary mature hepatocytes were isolated from 7-week-old male Wistar rats. To establish CLiPs, isolated hepatocytes were cultured in differentiation medium composed of Y-27632, A-83-01, and CHIR99021 (YAC medium). As an animal model that reproduces NASH pathophysiology, 6-week-old severe combined immunodeficient (SCID) mice were carefully selected and prepared and fed with choline-deficient, L-amino acid-defined, high-fat diet (HFD). After 12 weeks' HFD feeding, the mice were assigned to continue HFD with or without the administration of rat CLiPs (HFD + CLiPs and HFD-CLiPs, respectively). Rat CLiPs were administered from the spleen. Hepatic fibrosis was semi-quantitatively evaluated according to histology. Liver parenchyma and blood samples were collected for biochemical analyses. RESULTS: Rat CLiPs were positive for CK19 and EpCAM were successfully delivered to the liver. At 8 weeks after CLiPs transplantation, the HFD + CLiPs group showed significantly less positive staining than the HFD-CLiPs group. Alanine aminotransferase significantly improved in the HFD + CLiPs group, as demonstrated by Azan staining and αSMA immunostaining. RT qPCR showed that the liver expression of MMP2 and 9 tended to be higher in the HFD + CLiPs group. CONCLUSIONS: The anti-fibrotic effect of CLiPs was demonstrated in the immunodeficient NASH animal model and may have therapeutic applications in humans.

The Efficacy of Acoustic Radiation Force Impulse Elastography for Predicting Clinical Outcomes in Living Donor Liver Transplant.

PURPOSE: Acoustic radiation force impulse (ARFI) elastography is widely used for evaluating liver fibrosis. Here we evaluated the efficacy of ARFI elastography for estimating graft quality and clinical outcomes in living donor liver transplant (LDLT). METHODS: We retrospectively evaluated the cases of 87 LDLT donors who preoperatively underwent ARFI elastography at Nagasaki University Hospital between August 2010 and June 2016. We analyzed whether the velocity of shear wave (Vs) obtained by ARFI elastography affected the regeneration rate of each donor's remnant liver and the 1-year survival rate of the recipients. RESULTS: There were no significant correlations between Vs value and the donors' age. Only 1 donor (1.1%) showed significant fibrosis, F2 (portal fibrosis with few septa) in zero-biopsy. The 7 donors (8.0%), including 1 case, showed a high Vs value (> 1.33) that was equal to F2, although there was no abnormal pathologic finding except in 1 case. In those cases, the regeneration rate of the remnant liver after hepatectomy was significantly lower compared to other cases. The 1-year survival rate of the recipients paired with the high-Vs donors was also significantly poorer than that of the other cases (high-Vs: 57.1%, others: 84.2%, P = .04). CONCLUSIONS: ARFI elastography might be an effective examination for the preoperative evaluation of the graft quality in LDLT.

A comparison of postoperative pain between transumbilical and suprapubic incision in laparoscopic liver resection.

BACKGROUND: In laparoscopic liver resection, few reports have investigated the influence of type of incision on postoperative pain in laparoscopic liver resection. We therefore conducted the present study to clarify the difference in postoperative pain between two types of incision. METHODS: Nineteen patients who underwent laparoscopic lateral sectionectomy were enrolled. In 11 patients with a transumbilical incision and eight with a suprapubic incision, the operation duration, blood loss, length of incision, duration of intravenous fentanyl infusion immediately after surgery and rescue dosage, and period of regular oral nonsteroidal anti-inflammatory drugs were evaluated. RESULTS: There was no significant difference between the two groups in patients' background characteristics, operation time, or amount of blood loss. The length of suprapubic incision was significantly longer than the umbilical incision. Concerning the postoperative pain management, the duration of intravenous fentanyl administration was 1 day (1-2 days) for umbilical incisions and 1.5 days (1-2 days) for suprapubic incisions, showing no significant difference. Regarding the rescue dosage of fentanyl, the results were comparable between the groups. Regarding the postoperative duration of regular nonsteroidal anti-inflammatory drug administration, there was also no significant difference between the groups (transumbilical: 14 [5-35] days vs suprapubic: 8 [7-32]). CONCLUSIONS: Postoperative pain is comparable between umbilical and suprapubic incision in patients who underwent laparoscopic left lateral segmentectomy. In terms of postoperative pain, either a transumbilical incision or a suprapubic incision can be selected for specimen extraction.

A Simple Rapid Method for Measuring Liver Steatosis Using Bioelectrical Impedance.

BACKGROUND/AIM: Easy measurement of liver steatosis without pathological diagnosis may help improve donor surgery efficiency and increase the chances of organ donations. We analyzed the correlations between bioelectrical impedance (BI) in human livers, liver fat content, and pathological findings. MATERIALS AND METHODS: Sixteen tumor-free liver specimens resected during elective oncological surgery were analyzed. All samples were stored in ice chilled saline before BI measurement. The BI measurement was performed using a device with the tetrapolar circuit method in which the current and voltage electrodes are independent. Liver cholesterol and triglyceride levels were investigated from the same specimen using the Soxhlet extraction method. Pathological findings were examined by counting the number of hepatocytes with fatty changes per high-power field. RESULTS: The median liver steatosis percentage was 0.4%. The liver steatosis percentage was significantly correlated with the intrahepatic triglyceride content (r=0.82, p<0.001). Linear regression of the measurements and predicted values yielded an r2 of 0.63 between the BI at 100 kHz and liver steatosis, indicating reasonable agreement (p<0.001). CONCLUSION: BI analysis is a simple, non-invasive method that can be easily applied to evaluate liver steatosis.

Giant fibroadenoma of the breast: A rare case in a mature woman.

INTRODUCTION: Fibroadenomas are common benign lesions of the breast that are usually found young patients. Giant fibroadenomas are uncommon benign lesions, defined as fibroadenomas of >5 cm in size, which are usually found in patients of less than 20 years of age. PRESENTATION OF CASE: A 39-year-old premenopausal woman presented with a right breast tumor that had rapidly increased in size and which showed ulceration and bleeding. Needle biopsy showed mixed connective tissue and an epithelial tumor without a leaf-like pattern, but indeterminate. Total mastectomy and skin grafting were performed. Histopathology confirmed the diagnosis of giant fibroadenoma. DISCUSSION: In comparison to all previous reports on patients with giant fibroadenoma, this patient was relatively old and the etiology was unknown. Although rare, an appropriate therapeutic strategy should be decided according to the results of a histopathological examination. CONCLUSION: Early treatment could allow breast preserving surgery and patients should be recommended to undergo reexamination with awareness of progression.