Brain Alterations and Mini-Mental State Examination in Patients with Progressive Supranuclear Palsy: Voxel-Based Investigations Using 18F-Fluorodeoxyglucose Positron Emission Tomography and Magnetic Resonance Imaging

Background/Aims: The aim of this study was to compare differences in morphological and functional changes in brain regions in individual patients with progressive supranuclear palsy (PSP) and correlate their Mini-Mental State Examination (MMSE) score with anatomy and function using magnetic resonance imaging (MRI) and 18F-fluorodeoxyglucose positron emission tomography (FDG-PET). Methods: Sixteen PSP patients and 20 age-matched healthy volunteers underwent FDG-PET and 3-dimensional MRI. Gray matter, white matter and metabolic activity were compared between patients and normal controls. In addition, possible correlations between the MMSE score and brain function/anatomy were examined. Results: The PSP group had reduced cerebral glucose metabolism, and lower gray and white matter volumes in the frontal lobes and midbrain compared with normal controls. In PSP subjects, the metabolic changes observed in the PET scans were greater than the loss in gray and white matter observed in the MRI scans. The MMSE scores were positively correlated with volume and FDG uptake in the frontal lobe. Conclusion: FDG-PET is a more effective tool in the diagnosis of PSP than MRI. Atrophy and hypometabolism in the frontal lobe are as important as in the basal midbrain for differentiating PSP patients who primarily exhibit cognitive dysfunction from normal controls

The usefulness of preoperative bile cultures for hepatectomy with biliary reconstruction

[Background] Infectious complications can cause lethal liver failure after hepatectomy with biliary reconstruction. This study assessed the increased risk for postoperative infectious complications in patients who underwent hepatectomy with biliary reconstruction and explored the possibility of predicting pathogenic microorganisms causing postoperative infectious complications based on preoperative monitoring of bile cultures. [Methods] This study involved 310 patients who received major hepatectomy with or without biliary reconstruction at our institution between January 2010 and December 2019. The relationship between the microorganisms detected through perioperative monitoring of bile culture and those in the postoperative infectious foci was examined. [Results] Forty-nine patients underwent major hepatectomy with biliary reconstruction, and 261 received hepatectomy without biliary reconstruction. The multivariate analysis revealed hepatectomy with biliary reconstruction to be associated with an increased risk of postoperative infectious complications (odds ratio: 22.9, 95% confidence interval: 5.2–164.3) compared to hepatectomy without biliary reconstruction. In the patients with biliary reconstruction, the concordance rates between the microorganisms detected in the postoperative infectious foci and those in preoperative bile cultures were as follows: incisional surgical site infection (44.4%), organ/space surgical site infection (52.9%), bacteremia (47.1%), and pneumonia (16.7%); the concordance rates were high, and the risk of infection increased over time. [Conclusions] Biliary reconstruction is a significant risk factor for postoperative infectious complications, and preoperative bile cultures may aid in prophylactic and therapeutic antimicrobial agent selection

A transmembrane glycoprotein, gp38, is a novel marker for immature hepatic progenitor cells in fetal mouse livers

Previously, we clarified the surface antigen profiles of hepatic progenitor cells (HPCs) in fetal liver tissue as the CD49f+CD45−Thy1− cell fraction. However, these cells were a heterogeneous cell population containing various stages of differentiation. This study aimed to detect more immature HPCs, using a novel surface antigen, gp38. After the collagenase digestion of fetal livers harvested from E13.5 to E18.5 fetal mice, HPCs were obtained and divided into two subpopulations using flow cytometry: gp38-positive HPCs, and gp38-negative HPCs. Both types of HPCs were characterized by immunocytochemistry and RT-PCR. The proliferative activity was compared by BrdU incorporation and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTS) assay. Furthermore, the comprehensive gene expression was investigated by DNA microarray. Both types of HPCs expressed alpha-fetoprotein. However, the gp38-positive HPCs derived from E13.5 fetal livers did not express albumin or cytokeratin 19, while the gp38-negative HPCs did. DNA microarray revealed that some genes related to the Wnt signal pathway were up-regulated in the gp38-positive HPCs. Furthermore, Wnt3a had a proliferative effect on the gp38-positive HPCs. In conclusion, the gp38-positive HPCs derived from fetal liver tissue until E13.5 could therefore be candidates for hepatic stem cells in the fetal liver

A subcentimeter duodenal neuroendocrine neoplasm with a liver metastasis upgraded to G3: a case report

BACKGROUND: Although duodenal neuroendocrine neoplasms (DuNENs) usually have indolent phenotypes, some DuNENs exhibit aggressive clinical manifestations. Tumor size > 1 cm, lymph node metastasis, and high grade have been associated with poor prognosis. However, preoperative risk evaluation is often difficult, because Ki-67 index on biopsy is frequently underestimated due to the intratumor heterogeneity. Here, we present a case of a subcentimeter DuNEN with a low Ki-67 index on endoscopic biopsy, who developed lymph node metastasis and high-grade liver metastasis. CASE PRESENTATION: The patient was a 52-year-old female who presented an epigastric pain. Esophagogastroduodenoscopy revealed a duodenal submucosal lesion with a size of 8 mm. The endoscopic biopsy showed DuNEN with a Ki-67 index of 3.3% (G2 categorized by the World Health Organization 2019 classification). We performed an open partial duodenectomy with adjacent lymph node dissection. Pathological examination of the resected specimens revealed a Ki-67 index of 13.5% (G2) in the "hot spot" and lymph node metastasis. A hepatic low-density area detected on preoperative contrast-enhanced computed tomography appeared to be a liver metastasis on postoperative gadoxetic acid-enhanced magnetic resonance imaging. Subsequently, we performed a laparoscopic partial hepatectomy. Pathological examination of the liver specimen showed a metastatic neuroendocrine tumor with a Ki-67 index of 27.5% (NET-G3). The patient has been alive for 14 months since the hepatectomy. CONCLUSIONS: This case shows the possibility of high malignant potential of DuNEN even if the primary lesion is < 1 cm and has a low Ki-67 index on biopsy

RVS for small lesion in hepatectomy

Background : Systemic chemotherapy can drastically downsize metastatic liver tumors and these small liver lesions could sometimes be difficult for surgeons to detect during hepatectomy. We assessed the usefulness of intraoperative real-time virtual sonography (RVS) with contrast-enhanced ultrasonography (CEUS) using ‘Sonazoid’ contrast agent (RVS-CEUS). Methods : We performed the intraoperative RVS-CEUS technique on 10 tumor lesions in six cases, which were scheduled for hepatic resection of < 10 mm in diameter in our liver metastases series. These lesions were preoperatively diagnosed by contrast enhanced-computed tomography (CE-CT) or Gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (EOB-MRI). We assessed the detectability of a tumor with RVS-CEUS during surgery and compared it with that of preoperative CE-CT or EOB-MRI. Results : Detectability of RVS-CEUS for 10 small lesions was 90% (n = 9/10) and that of other preoperative modalities were 50% (n = 5/10, CE-CT) and 100% (n = 10/10, EOB-MRI). Minimum tumor size detected was 3.0 mm in diameter, and maximum depth of detection with RVS-CEUS was 43.5 mm ; these results could be an advantage when compared with other intraoperative diagnostic modalities. Conclusion : Intraoperative RVS-CEUS was useful for detecting small metastatic liver lesions after chemotherapy and could be an effective intraoperative diagnostic technique for hepatic resection of a size < 10 mm

The Feature of Solitary Small Nodular Type of Hepatic Epithelioid Hemangioendothelioma

Hepatic epithelioid hemangioendothelioma (HEHE) is a rare tumor. Preoperative diagnosis of HEHE is difficult because it does not manifest specific symptoms or tumor markers. We report a resected case of small and solitary HEHE. The patient, a 74-year-old man, had undergone surgical resection for left renal cell carcinoma 20 years ago. During follow-up, a tumor approximately 1.3 cm in diameter was detected by computed tomography (CT) at liver segment VIII. It showed isodensity in the arterial phase, low density in the portal venous phase, and homogeneous enhancement in the late phase on CT and magnetic resonance imaging (MRI). We performed hepatic resection of the right hepatic vein drainage area. A pathological diagnosis of HEHE was made. Although small and solitary HEHE is rare, an enhancement pattern in each phase on CT and MRI, using contrast media, can yield clues for the diagnosis of HEHE

Conversion to complete resection with mFOLFOX6 with bevacizumab or cetuximab based on K‐RAS status for unresectable colorectal liver metastasis (BECK study): Long‐term results of survival

[Background/Purpose]To investigate the long‐term outcome and entire treatment course of patients with technically unresectable CRLM who underwent conversion hepatectomy and to examine factors associated with conversion to hepatectomy. [Methods]Recurrence and survival data with long‐term follow‐up were analyzed in the cohort of a multi‐institutional phase II trial for technically unresectable colorectal liver metastases (the BECK study). [Results]A total of 22/12 patients with K‐RAS wild‐type/mutant tumors were treated with mFOLFOX6 + cetuximab/bevacizumab. The conversion R0/1 hepatectomy rate was significantly higher in left‐sided primary tumors than in right‐sided tumors (75.0% vs 30.0%, P = .022). The median follow‐up was 72.6 months. The 5‐year overall survival (OS) rate in the entire cohort was 48.1%. In patients who underwent R0/1 hepatectomy (n = 21), the 5‐year RFS rate and OS rate were 19.1% and 66.3%, respectively. At the final follow‐up, seven patients had no evidence of disease, five were alive with disease, and 20 had died from their original cancer. All 16 patients who achieved 5‐year survival underwent conversion hepatectomy, and 11 of them underwent further resection for other recurrences (median: 2, range: 1‐4). [Conclusions]Conversion hepatectomy achieved a similar long‐term survival to the results of previous studies in initially resectable patients, although many of them experienced several post‐hepatectomy recurrences. Left‐sided primary was found to be the predictor for conversion hepatectomy

SOX9 is a novel cancer stem cell marker surrogated by osteopontin in human hepatocellular carcinoma

The current lack of cancer stem cell (CSC) markers that are easily evaluated by blood samples prevents the establishment of new therapeutic strategies in hepatocellular carcinoma (HCC). Herein, we examined whether sex determining region Y-box 9 (SOX9) represents a new CSC marker, and whether osteopontin (OPN) can be used as a surrogate marker of SOX9 in HCC. In HCC cell lines transfected with a SOX9 promoter-driven enhanced green fluorescence protein gene, FACS-isolated SOX9+ cells were capable of self-renewal and differentiation into SOX9-cells, and displayed high proliferation capacity in vitro. Xenotransplantation experiments revealed that SOX9+ cells reproduced, differentiated into SOX9-cells, and generated tumors at a high frequency in vivo. Moreover, SOX9+ cells were found to be involved in epithelial-mesenchymal transition (EMT) and activation of TGFb/Smad signaling. Gain/loss of function experiments showed that SOX9 regulates Wnt/beta-catenin signaling, including cyclin D1 and OPN. Immunohistochemistry of 166 HCC surgical specimens and serum OPN measurements showed that compared to SOX9-patients, SOX9+ patients had significantly poorer recurrence-free survival, stronger venous invasion, and higher serum OPN levels. In conclusion, SOX9 is a novel HCCCSC marker regulating the Wnt/beta-catenin pathway and its downstream target, OPN. OPN is a useful surrogate marker of SOX9 in HCC