Clinical feasibility of the preoperative C-reactive protein-albumin-lymphocyte index to predict short- and long-term outcomes of patients with gastric cancer.

BACKGROUND: Gastric cancer (GC) is a major leading cause of cancer-related death worldwide. Systemic inflammation and the nutrition-based score are feasible prognostic markers for malignancies. Emerging evidence has also revealed the C-reactive protein-albumin-lymphocyte (CALLY) index to be a prognostic marker for several cancer types. However, its clinical significance to predict surgical and oncologic outcomes of patients with GC remains unclear. METHODS: We assessed the preoperative CALLY index in 426 patients with GC who received gastrectomy. RESULTS: A low preoperative CALLY index was significantly correlated to all well-established clinicopathologic factors for disease development, including an advanced T stage, the presence of venous invasion, lymphatic vessel invasion, lymph node metastasis, distant metastasis, and an advanced TNM stage. A low preoperative CALLY index was also an independent prognostic factor for overall survival (hazard ratio [HR], 2.64; 95 % CI, 1.66-4.2; P < .0001) and disease-free survival (HR, 1.76; 95 % CI, 1.01-3.05; P = .045). In addition, a low preoperative CALLY index was an independent predictive factor for postoperative surgical site infection (odds ratio, 2.64; 95 % CI, 1.42-4.89; P = .002). CONCLUSION: The preoperative CALLY index is valuable for perioperative and oncologic management of patients with GC.

Spinal Dissemination of Pineal Parenchymal Tumors of Intermediate Differentiation Over 10 Years After Initial Treatment: A Case Report.

Pineal parenchymal tumors (PPTs) are rare, accounting for less than 0.3% of all primary central nervous system (CNS) tumors. Pineal parenchymal tumors of intermediate differentiation (PPTID) (WHO grade 2 or 3) show an intermediate prognosis between pineocytoma and pineoblastoma. The clinical course is unknown, and the optimal treatment for PPTID, especially for recurrence, has not been determined. We report a case of PPTID with spinal dissemination over 10 years after treatment and survival for four years. A 56-year-old woman presented with headaches and diplopia. Computerized tomography (CT) and magnetic resonance imaging (MRI) revealed a pineal mass, but leptomeningeal dissemination was not identified on whole-spine MRI. Microsurgical gross total tumor resection (GTR) was performed, and the pathological diagnosis was PPTID (grade 3). In addition, a later study found it to harbor a KBTBD4 mutation. She underwent whole-brain radiation therapy with a focal boost. The patient was unable to continue chemotherapy for severe myelosuppression after the first course of treatment. Eleven years after the surgery, she was unable to walk, and a whole-spine MRI revealed multiple masses at C3-4, T4, and cauda equina. Fluorodeoxyglucose-positron emission tomography (FDG-PET) revealed accumulations of the same lesions. No recurrence was observed in the brain. A biopsy of the caudal portion was performed, and the histopathological findings were the same as those of the initial surgery. Spinal dissemination was refractory to chemotherapy but responded to whole spine radiotherapy with focal boost, and she remained tumor-free for four years. We considered good local control with a combination of GTR and subsequent radiation therapy to contribute to long-term survival. The timing of spinal radiation administration is controversial because of the tendency for late cerebrospinal dissemination. The importance of long-term follow-up of the spine and head is emphasized. In PPTID cases with good local control, withholding spinal radiation until spinal dissemination occurs may become a long-term treatment plan.

Inhibition of BMP signaling pathway induced senescence and calcification in anaplastic meningioma.

PURPOSE: Meningiomas are the most common type of brain tumors and are generally benign, but malignant atypical meningiomas and anaplastic meningiomas frequently recur with poor prognosis. The metabolism of meningiomas is little known, so few effective treatment options other than surgery and radiation are available, and the targets for treatment of recurrence are not well defined. The Aim of this paper is to find the therapeutic target. METHODS: The effects of bone morphogenetic protein (BMP) signal inhibitor (K02288) and upstream regulator Gremlin2 (GREM2) on meningioma's growth and senescence were examined. In brief, we examined as follows: 1) Proliferation assay by inhibiting BMP signaling. 2) Comprehensive analysis of forced expression GREM2.3) Correlation between GREM2 mRNA expression and proliferation marker in 87 of our clinical samples. 4) Enrichment analysis between GREM2 high/low expressed groups using RNA-seq data (42 cases) from the public database GREIN. 5) Changes in metabolites and senescence markers associated with BMP signal suppression. RESULTS: Inhibitors of BMP receptor (BMPR1A) and forced expression of GREM2 shifted tryptophan metabolism from kynurenine/quinolinic acid production to serotonin production in malignant meningiomas, reduced NAD + /NADH production, decreased gene cluster expression involved in oxidative phosphorylation, and caused decrease in ATP. Finally, malignant meningiomas underwent cellular senescence, decreased proliferation, and eventually formed psammoma bodies. Reanalyzed RNA-seq data of clinical samples obtained from GREIN showed that increased expression of GREM2 decreased the expression of genes involved in oxidative phosphorylation, similar to our experimental results. CONCLUSIONS: The GREM2-BMPR1A-tryptophan metabolic pathway in meningiomas is a potential new therapeutic target.

Targeting cholesterol biosynthesis for AT/RT: comprehensive expression analysis and validation in newly established AT/RT cell line.

Atypical teratoid/rhabdoid (AT/RT) is a rare and highly malignant tumor of the central nervous system (CNS). It is most commonly found in children less than 5 years of age and is associated with inactivation of loss of function of SMARCB1/INI1. An experimental model for AT/RT is necessary to develop new and effective therapies. We established a patient-derived new cell line (MZ611ATRT), which showed loss of BAF-47. MZ611ATRT genetically features somatic heterozygous deletion of SMARCB1 and single nucleotide deletion of the residual allele, exon 5 ([c.541delC]), resulting in a stop codon at codon 954 by frameshift. We assessed the RNA-sequencing data of the other two AT/RT cell lines with forced expression of SMARCB1 available from public databases. We found SMARCB1 overexpression significantly down-regulates the expression of a group of enzymes related to cholesterol biosynthesis. Simvastatin was highly sensitive against MZ611ATRT cells and induced apoptosis (IC50 was 3.098 µM for MZ611ATRT, 41.88uM for U-87 MG, 23.34uM for IOMM-Lee, and 18.12uM for U-251 MG.). Pathways involved in cholesterol biosynthesis may be new targets for adjuvant therapy of AT/RT.

Clinical implications of C-reactive protein-albumin-lymphocyte (CALLY) index in patients with esophageal cancer.

PURPOSE: The C-reactive protein-albumin-lymphocyte (CALLY) index is a novel inflammatory nutritional biomarker. This study aimed to investigate the potential clinical significance and oncological prognostic role of the preoperative CALLY index in patients with esophageal cancer. METHODS: We analyzed the preoperative CALLY index in 146 patients with esophageal cancer. The CALLY index and clinicopathological variables were analyzed by the Mann-Whitney U test, and associations between the CALLY index and survival outcomes were analyzed by Kaplan-Meier analysis and log-rank tests. Univariate and multivariate analyses of prognostic variables were conducted using Cox proportional hazards regression. RESULTS: A lower preoperative CALLY index was significantly correlated with patient age, advanced T stage, presence of lymph node metastasis, neoadjuvant therapy, lymphatic invasion, and advanced stage classification. The preoperative CALLY index decreased significantly in a stage-dependent manner. Patients with esophageal cancer with a low CALLY index had poorer overall survival, disease-free survival than those with a high CALLY index. Multivariate analysis showed that a low CALLY index was an independent prognostic factor for overall survival, disease-free survival and an independent predictor of postoperative surgical site infection. CONCLUSIONS: Preoperative CALLY index is a useful marker to guide the perioperative and postoperative management of patients with esophageal cancer.

Epidemiological Study of Metastatic Brain Tumors in Miyazaki Prefecture: A Regional 10-year Survey in Southern Japan.

Advances in cancer treatment have improved the survival of patients with cancer, with a concomitant increase in the proportion of patients with metastatic brain tumors (MBTs). In this study, we used cancer registries established in Japan after 2016 and available patient data by organ in order to conduct an accurate epidemiological study. To the best of our knowledge, this is the first study to report on the detailed epidemiological data on MBT at the prefectural level in Japan using the Miyazaki Brain Tumor Database and Miyazaki Cancer Registry. This study included 425 new cases of MBTs diagnosed in Miyazaki Prefecture from 2007 to 2016. As per our findings, the most frequent primary tumor in Miyazaki Prefecture was found to be in the lung (49.4%), followed by colon/rectum/anus (9.4%) and breast (8.5%). Among patients with MBTs, 59.1% were males, a number closely similar to that of Japan, as shown in the Japanese Brain Tumor Registry (55.5%). The median age at diagnosis was 68 and 63 years in Miyazaki Prefecture and Japan, respectively. Although more patients were symptomatic in Miyazaki Prefecture than in Japan (88.5% vs. 15.5%), fewer patients opted for surgery (33.6% vs. 61.9%), probably because of their advanced age at diagnosis. As per the findings of this study, the annual incidence rate of new MBTs (i.e., ratio of the number of new cancer registrations to that of new MBT patients in Miyazaki Prefecture) was at 0.41%. The number of tumor sites in MBTs was independent of the total number of cancers per organ. Considering the expansion of cancer registries worldwide, including those on brain tumors, further epidemiological analysis of MBTs is deemed warranted.

Herbal Leaves Can Suppress Oxidation of Perilla Oil.

Perilla oil is a valuable food source of α-linolenic acids. However, its high reactivity with oxygen shortens its shelf-life after opening. This study investigated the antioxidative profiles of 15 plant materials, including herbs, and examined methods to suppress the oxidation of perilla oil using these plant materials. These plant materials had wide ranges of phenolic, carotenoid, and chlorophyll contents. They exhibit radical scavenging activities and suppress lipid peroxidation, which show highly positive correlations with the phenolic contents. Dipping most of the plant materials examined in perilla oil suppressed its oxidation, and the peroxide values of the oil mixtures indicated a negative correlation with the carotenoid and chlorophyll contents of the plant materials. The leaves of Angelica, Astragalus, and Thyme herbs exhibited the same effect as that of ascorbyl palmitate, which was used as a positive control after 8 wk of incubation in the dark. The suppression of lipid peroxidation was found to be related to the herbal contents of carotenoids and chlorophylls, rather than phenols. Hence, herbal leaves can suppress the oxidation of perilla oil in the dark. The oxidation of n-3 polyunsaturated fatty acids could be suppressed effectively by utilizing plant materials with abundant carotenoids and chlorophylls.

Extraction of a metallic susceptor after accidental ingestion of the heated tobaccostick TEREA™: a case report.

BACKGROUND: Tobacco ingestion is widely known to cause nicotine toxicity, which may result in severe symptoms. Two heated tobacco sticks, called TEREA™ and SENTIA™, were launched in 2021 by Philip Morris International (New York, NY, USA), and their ingestion is associated with a risk of bowel injury because they contain a partially pointed metallic susceptor. However, this risk is not well known to the general public or healthcare providers. To increase awareness of this risk, we herein report a case involving extraction of a metallic susceptor after ingestion of the heated tobacco stick TEREA™. CASE PRESENTATION: A 7-month-old girl presented to the emergency department of a nearby hospital because she was suspected to have accidentally swallowed heated tobacco. Although she presented with no symptoms related to nicotine poisoning, abdominal X-ray examination revealed a metal object in her stomach. According to a statement released by the Japan Poison Information Center, the TEREA™ heated tobacco stick contains a metallic susceptor with a rectangular shape and sharp corners. The patient was transferred to our department because of the risk of bowel injury, and upper gastrointestinal endoscopy was performed. No cigarettes were found by endoscopic observation; however, a metallic susceptor was located in the second part of the duodenum. We grasped it with biopsy forceps and carefully removed it using an endoscope with a cap attached to the tip. The post-endoscopic course was uneventful. CONCLUSIONS: Some patients who ingest heated tobacco sticks might be exposed not only to the effects of nicotine but also to physical damage caused by a metallic susceptor. Infants and toddlers especially could swallow these sticks, therefore tobacco companies need to make the problem more public. Clinicians also should alert the problem, and pay attention to this risk in the clinical setting.

Double inferior vena cava, an uncommon but relevant anatomical anomaly in surgery for lower rectal cancer: a report of two cases.

BACKGROUND: Double inferior vena cava (DIVC) is rare and usually detected incidentally. DIVC may be associated with several anatomical variants of the retroperitoneal and pelvic veins. These variants can pose a clinical problem during colorectal surgery. We present two patients with lower rectal cancer who also had a DIVC. CASE PRESENTATION: Case 1 was a 72-year-old man with advanced lower rectal cancer (T3N0M0) who underwent robot-assisted low anterior resection after neoadjuvant therapy. A DIVC was detected on preoperative computed tomography (CT). During the operation, a presacral vein was injured while mobilizing the rectum and hemostasis could not be achieved. We converted to open surgery and packed the pelvic cavity for hemostasis. Retrospective analysis suggested the injured vein arose from an interiliac vein of the presacral pelvic venous plexus. Case 2 was a 50-year-old woman with lower rectal cancer (T3N0M0), immune thrombocytopenic purpura, and a DIVC. Although preoperative three-dimensional CT angiography showed no obvious pelvic vein abnormalities, a short course of preoperative radiotherapy was delivered to avoid lateral pelvic lymph node dissection. Chemotherapy was deferred owing to her thrombocytopenic disease. Laparoscopic abdominoperineal resection was performed meticulously to minimize bleeding and achieve rapid hemostasis. No intraoperative complications occurred. CONCLUSION: DIVC is often accompanied by venous malformations that may pose a problem when mobilizing the mesorectum from the retroperitoneum. Preoperative assessment of pelvic vessel anatomy using three-dimensional CT is essential in patients with a DIVC who undergo rectal surgery.

Novel Strategy Involving High-Dose Chemotherapy with Stem Cell Rescue Followed by Intrathecal Topotecan Maintenance Therapy without Whole-Brain Irradiation for Atypical Teratoid/Rhabdoid Tumors.

Atypical teratoid/rhabdoid tumor (AT/RT) is a rare aggressive central nervous system tumor that typically affects children under three years old and has poor survival with a high risk for neurologic deficits. The primary purpose of this study was to successfully treat the disease and delay or avoid whole-brain radiotherapy for children with AT/RT. A retrospective analysis was performed for six children diagnosed with AT/RT and treated with multimodal treatment at a single institute between 2014 and 2020. Furthermore, germline SMARCB1 aberrations and MGMT methylation status of the tumors were analyzed. One patient who did not receive a modified IRS-III regimen replaced with ifosphamide, carboplatin, and etoposide (ICE) in induction chemotherapy was excluded from this analysis. Five patients who received ICE therapy were under three years old. After a surgical approach, they received intensive chemotherapy and high-dose chemotherapy with autologous peripheral blood stem cell transplantation (HDCT/autoPBSCT) followed by intrathecal topotecan maintenance therapy. Three patients underwent single HDCT/autoPBSCT, and the other two received sequential treatment. Two patients with germline SMARCB1 aberrations and metastases died of progressive AT/RT or therapy-related malignancy, while 3 with localized tumors without germline SMARCB1 aberrations remained alive. One survivor received local radiotherapy only, while the other two did not undergo radiotherapy. All three surviving patients were able to avoid whole-brain radiotherapy. Our results suggest that AT/RT patients with localized tumors without germline SMARCB1 aberrations can be rescued with multimodal therapy, including induction therapy containing ICE followed by HDCT/autoPBSCT and intrathecal topotecan maintenance therapy without radiotherapy. Further large-scale studies are necessary to confirm this hypothesis.

Spontaneous malignant transformation of trigeminal schwannoma: consideration of responsible gene alterations for tumorigenesis-a case report.

Malignant peripheral nerve sheath tumors (MPNSTs) arising from the trigeminal nerves are extremely rare (only 45 cases, including the present case, have been published) and have been reported to develop de novo from the peripheral nerve sheath and are not transformed from a schwannoma or neurofibroma. Here, we report a case of MPNSTs of the trigeminal nerve caused by the malignant transformation of a trigeminal schwannoma, with a particular focus on genetic considerations. After undergoing a near-total resection of a histologically typical benign schwannoma, the patient presented with regrowth of the tumor 10 years after the primary excision. Histopathologic and immunochemical examinations confirmed the recurrent tumor to be an MPNST. Comprehensive genomic analyses (FoundationOne panel-based gene assay) showed that only the recurrent MPNST sample, not the initial diagnosis of schwannoma, harbored genetic mutations, including NF1-p.R2637* and TP53-p.Y234H, candidate gene mutations associated with malignant transformation. Moreover, the results of reverse transcription polymerase chain reaction showed that the fusion of SH3PXD2A and HTRA1, which has been reported as one of the responsible genetic aberrations of schwannoma, was detected in the recurrent tumor. Taken together, we could illustrate the accumulation process of gene abnormalities for developing MPNSTs from normal cells via schwannomas.

Robot-assisted laparoscopic abdominoperineal resection for anal canal cancer associated with Crohn's disease: A case report.

A 37-year-old man with Crohn's disease (CD) and a history of abdominal surgery was diagnosed with anal canal cancer. Robot-assisted laparoscopic abdominoperineal resection was performed and the patient was discharged without any postoperative complications. Recently, minimally invasive surgery for CD patients has grown in popularity. However, there have been few studies of robotic surgery for CD patients with anal canal cancer. To the best of our knowledge, we present the first report of a patient with CD-associated anal canal cancer who underwent robot-assisted laparoscopic abdominoperineal resection.

Clinicopathologic analysis of pineal parenchymal tumors of intermediate differentiation: a multi-institutional cohort study by the Kyushu Neuro-Oncology Study Group.

PURPOSE: Pineal parenchymal tumors of intermediate differentiation (PPTIDs), which were recognized in the 2007 World Health Organization (WHO) classification, are rare, accounting for less than 1% of all central nervous system tumors. This rarity and novelty complicate the diagnosis and treatments of PPTID. We therefore aimed to evaluate the clinicopathological significance of this tumor. METHODS: At 11 institutions participating in the Kyushu Neuro-Oncology Study Group, data for patients diagnosed with PPTID were collected. Central pathology review and KBTBD4 mutation analysis were applied to attain the diagnostically accurate cohort. RESULTS: PPTID was officially diagnosed in 28 patients: 11 (39%) with WHO grade 2 and 17 (61%) with WHO grade 3 tumors. Median age was 49 years, and the male:female ratio was 1:2.1. Surgery was attempted in all 28 patients, and gross total resection (GTR) was achieved in 46% (13/28). Adjuvant radiotherapy and chemotherapy were administered to, respectively, 82% (23/28) and 46% (13/28). The 5-year progression-free survival (PFS) and overall survival rates were 64.9% and 70.4% respectively. Female sex (p = 0.018) and GTR (p < 0.01) were found to be independent prognostic factors for PFS and female sex (p = 0.019) was that for OS. Initial and second recurrences were most often leptomeningeal (67% and 100% respectively). 80% (20/25) of patients harbored a KBTBD4 mutation. CONCLUSIONS: Female sex and GTR were independent prognostic factors in our patients with PPTID. Leptomeningeal recurrence was observed to be particularly characteristic of this tumor. The rate of KBTBD4 mutation observed in our cohort was acceptable and this could prove the accuracy of our PPTID cohort.

[Development of New Sublingual Formulation for Transmucosal Delivery of Peptides].

Since oral bioavailability of peptides is extremely low, self-injectable and intranasal formulations have been developed; however, these treatments have problems such as storage and discomfort. The sublingual route is considered suitable for peptide absorption because there is less peptidase and it is not subject to hepatic first-pass effects. In this study, we attempted to develop a new jelly formulation for sublingual delivery of peptides. Gelatins with molecular weights of 20000 and 100000 were used as the jelly base. The gelatin was dissolved in water with a small amount of glycerin and air-dried for at least 1 d to form a thin jelly formulation. A mixed base of locust bean gum and carrageenan was used as the outer layer of the two-layer jelly. Jelly formulations with various compositions were prepared, and we evaluated the dissolution time of the jelly formulations and urinary excretion. It was found that the dissolution time of the jelly became slower as the amount of gelatin and the molecular weight increased. Using cefazolin as a model drug, urinary excretion after sublingual administration was measured, and it was found that urinary excretion tended to increase when using a two-layer jelly covered with a mixed base of locust bean gum and carrageenan compared to oral administration of an aqueous solution. Our findings suggest that sublingual drug absorption could be improved by allowing the drug eluted from the jelly formulation to remain in sublingual region for a longer time.

Antioxidative Activities of Plants and Fungi Used as Herbal Medicines.

Plants and fungi classified as herbs are utilized for the maintenance of health in humans. In this study, to evaluate the beneficial effects of herbs, we investigated the phenolic content and antioxidative activity of 20 samples. Some herbs, including Cistanche herb, had high phenol levels and exhibited high activities for radical-scavenging and suppression of lipid peroxidation. Phenolic contents and antioxidative activities showed a high positive correlation. In contrast, some herbal medicines with low phenolic content exhibited high suppressive effects on lipid peroxidation, and it was thought that carotenoids contributed to their suppression. The results of this study are expected to support the clarification of the mechanism of herbal medicines in promoting wellness.

[Stage â £ Gastric Cancer with Long Term Survival by Conversion Surgery-A Case Report].

A 78-year-old man presenting with a chief complaint of discomfort was found to have advanced gastric cancer invading pancreatic body, and with the metastasis of paraaortic lymph node(No. 16). After 3 courses of the S-1 plus oxaliplatin regimen, CT scan showed the disappearance of invasion to pancreatic body, and the No. 16 lymph node. Then total gastrectomy(D2+No. 19+No. 16a1+No. 16a2), Roux-en-Y reconstruction and cholecystectomy were undergoing. Histological assessment for treatment response showed Grade 1a, and we finally diagnosed gastric cancer: MU, Post, type 2, 30×20 mm, tub1>por1, ypT3, ypN1, ycM0, ypStage ⅡB. The postoperative course was uneventful, and the patient was discharged from the hospital on postoperative day 19. S-1 as adjuvant chemotherapy was performed for 12 months, and no recurrence was recognized for 5 years and 9 months after operation.

Fatigue in patients with cancer receiving outpatient chemotherapy: a prospective two-center study.

BACKGROUND: Cancer-related fatigue (CRF) is one of the most common symptoms in patients with cancer. However, CRF has not been sufficiently evaluated as it involves various factors. In this study, we evaluated fatigue in patients with cancer receiving chemotherapy in an outpatient setting. METHODS: Patients with cancer receiving chemotherapy at the outpatient treatment center of Fukui University Hospital and Saitama Medical University Medical Center Outpatient Chemotherapy Center were included. The survey period was from March 2020 to June 2020. The frequency of occurrence, time, degree, and related factors were examined. All patients were asked to fill out the Edmonton Symptom Assessment System Revised Japanese version (ESAS-r-J) questionnaire, which is a self-administered rating scale, and patients with ESAS-r-J "Tiredness" scores of ≥ 3 were evaluated for factors related to tiredness, such as age, sex, weight, and laboratory parameters. RESULTS: A total of 608 patients were enrolled in this study. Fatigue after chemotherapy occurred in 71.0% of patients. ESAS-r-J "Tiredness" scores of ≥ 3 were observed in 20.4% of patients. The factors related to CRF were low hemoglobin level and high C-reactive protein level. CONCLUSIONS: Twenty percent of patients receiving cancer chemotherapy on an outpatient basis had moderate or severe CRF. Patients with anemia and inflammation are at increased risk of developing fatigue after cancer chemotherapy.

Epigenetic upregulation of Schlafen11 renders WNT- and SHH-activated medulloblastomas sensitive to cisplatin.

BACKGROUND: Intensive chemotherapeutic regimens with craniospinal irradiation have greatly improved survival in medulloblastoma patients. However, survival markedly differs among molecular subgroups and their biomarkers are unknown. Through unbiased screening, we found Schlafen family member 11 (SLFN11), which is known to improve response to DNA damaging agents in various cancers, to be one of the top prognostic markers in medulloblastomas. Hence, we explored the expression and functions of SLFN11 in medulloblastoma. METHODS: SLFN11 expression for each subgroup was assessed by immunohistochemistry in 98 medulloblastoma patient samples and by analyzing transcriptomic databases. We genetically or epigenetically modulated SLFN11 expression in medulloblastoma cell lines and determined cytotoxic response to the DNA damaging agents cisplatin and topoisomerase I inhibitor SN-38 in vitro and in vivo. RESULTS: High SLFN11 expressing cases exhibited significantly longer survival than low expressing cases. SLFN11 was highly expressed in the WNT-activated subgroup and in a proportion of the SHH-activated subgroup. While WNT activation was not a direct cause of the high expression of SLFN11, a specific hypomethylation locus on the SLFN11 promoter was significantly correlated with high SLFN11 expression. Overexpression or deletion of SLFN11 made medulloblastoma cells sensitive and resistant to cisplatin and SN-38, respectively. Pharmacological upregulation of SLFN11 by the brain-penetrant histone deacetylase-inhibitor RG2833 markedly increased sensitivity to cisplatin and SN-38 in SLFN11-negative medulloblastoma cells. Intracranial xenograft studies also showed marked sensitivity to cisplatin by SLFN11-overexpression in medulloblastoma cells. CONCLUSIONS: High SLFN11 expression is one factor which renders favorable outcomes in WNT-activated and a subset of SHH-activated medulloblastoma possibly through enhancing response to cisplatin.

Combined assessment of muscle quality and quantity predicts oncological outcome in patients with esophageal cancer.

BACKGROUND: Sarcopenia consists of two dysregulation patterns of body composition, myopenia and myosteatosis. The aim of this study is to compare the preoperative status of various body composition indexes including our newly developed modified intramuscular adipose tissue content (mIMAC) to investigate these clinical values in esophageal cancer patients. METHOD: We assessed preoperative psoas muscle mass index (PMI), IMAC, and mIMAC in 150 esophageal cancer patients. RESULTS: Preoperative high IMAC and low mIMAC status were significantly associated with older age. Preoperative decreased mIMAC was significantly associated with advanced T classification and the presence of distant metastasis and low preoperative mIMAC was an independent prognostic factor for poor overall survival and disease-free survival in esophageal cancer patients. Combined assessment of preoperative mIMAC with PMI could help stratify risk for oncological outcomes. Finally, preoperative PMI and mIMAC were positively correlated with various nutritional factors in esophageal cancer patients. CONCLUSION: Combined assessment between preoperative PMI and mIMAC could stratify risk for oncological outcomes, and preoperative mIMAC might be surrogate marker for aging and nutritional status in esophageal cancer patients.

PBRM1 and BAP1: novel genetic mutations in malignant transformation of craniopharyngioma-a case report.

Malignant craniopharyngioma is especially rare, so the causes and genetic mutations associated with the malignant transformation have not been explained in detail. We investigated the molecular genetic characteristics of malignant transformation in craniopharyngioma. A 53-year-old man with a history of adamantinomatous craniopharyngioma presented with complaints of subcutaneous swelling. Magnetic resonance imaging showed a less enhanced intradural supra-sellar lesion and a heterogeneously well-enhanced extradural invasive lesion infiltrating the dura mater, brain, frontal bone, and subcutaneous tissue. Histopathological examination of the recurrent tumor revealed typical findings of both craniopharyngioma (intradural supra-sellar lesion) and malignant transformation, such as marked nuclear atypia with mitosis (invasive extradural lesion), which were not present in the primary tumor. A genetic panel test with the Oncopanel system was performed to investigate the genetic mutations responsible for the malignant transformation. Four genetic mutations were identified: CTNNB1 c.C98T, TP53 p.C135fs*35(PLS = 3 UPD/LOH), PBRM1 p.R1000*(PLS = 3 UPD/LOH), and BAP1 p.L650fs*5(PLS = 3 UPD/LOH). Sanger sequencing showed CTNNB1 in both the intradural supra-sellar and extradural invasive lesions, but TP53, PBRM1, and BAP1 only in the extradural invasive lesion. The genetic mutations of PBRM1 and BAP1 may be genetic factors in the malignant transformation of adamantinomatous craniopharyngioma.