Hematopoietic Cell Transplantation for Acute Panmyelosis with Myelofibrosis: A Retrospective Study in Japan

Acute panmyelosis with myelofibrosis (APMF) is a rare subtype of acute myeloid leukemia characterized by acute onset of cytopenias and bone marrow fibrosis in the absence of splenomegaly. Because the prognosis of APMF is extremely poor even after chemotherapy, hematopoietic cell transplantation (HCT) has been used to treat APMF. However, the outcome after HCT for APMF remains unclear. To evaluate the outcomes and prognostic factors after HCT as a therapeutic modality for APMF, we retrospectively analyzed the Japanese registration data of 40 APMF patients who received allogeneic and syngeneic HCT between 2005 and 2015. The median age at HCT was 53.5 years (range, 16 to 70). The disease status at HCT was first complete remission (CR1) in 13 patients (33%). The probability of overall survival and the cumulative incidence of relapse at 3 years were 24% and 59%, respectively. Univariate analysis identified that female sex and disease status CR1 at the time of HCT were significantly associated with higher overall survival. Although APMF patients have a poor long-term prognosis even after syngeneic and allogeneic HCT, these data suggested that allogeneic HCT offered a curative option for APMF.     

Pluripotent stem cell models of Blau syndrome reveal an IFN-γ–dependent inflammatory response in macrophages

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Proposal for a morphological classification of intraductal papillary neoplasm of the bile duct (IPN-B)

Purpose

We propose a morphological classification of intraductal papillary neoplasm of the bile duct (IPN-B).

Methods

A retrospective analysis of 16 patients with IPN-B who had undergone surgical resection was conducted. These 16 cases were classified into three types based on the primary lesion’s anatomical location: branch duct type (6 cases), main duct type (5 cases) and mixed type (5 cases). In this paper we have analyzed the characteristics of IPN-B according to our new classification.

Results

All branch duct type IPN-B was located in the left lobe and 5 of them were resected by left hepatectomy without extrahepatic bile duct resection (EBDR). On the other hand, all patients with main duct and mixed type IPN-B underwent EBDR in addition to hepatectomy or pancreatoduodenectomy. Microscopically, 2 of 6 patients with branch duct type IPN-B had no malignant component and, in the remaining 4 patients, cancer invasion was restricted to within the ductal wall. There were no cases of branch duct type IPN-B with lymph node metastasis and superficial intraductal tumor spread. In contrast, all patients with main duct and mixed duct type IPN-B had the malignant component. In all cases, lymph node metastasis was not observed, but superficial intraductal tumor spread was frequently found in extrahepatic bile duct lesions: 3 of main duct type and 3 of mixed type. Four patients with superficial intraductal spread had non-curative resection due to a cancer-positive ductal margin. Most patients with IPN-B obtained a good prognosis, but two patients with a cancer-positive ductal margin developed local recurrence.

Conclusions

Our classification vividly reflects clinical and pathological characteristics of IPN-B and is useful to determine appropriate surgical strategy.     

Poor prognosis of KRAS or BRAF mutant colorectal liver metastasis without microsatellite instability

Background

The discovery of practical biomarkers is important to realize personalized medicine for patients with malignant neoplasias, including colorectal cancer (CRC).

Purpose

The aim of this study was to determine reliable prognostic biomarkers by the analysis of patients with resectable colorectal liver metastases (CRLM).

Methods

Genomic DNA was obtained from the CRLM tissues of a cohort of 126 patients with CRLM with curative hepatic resection. The KRAS/BRAF mutation spectrum and microsatellite instability (MSI) status were successfully analyzed in 100 of the 126 CRLM tissues and these findings were examined in relation to the patients’ clinical outcomes.

Results

The cohort of 100 CRLM patients consisted of 46 with synchronous and 54 with metachronous liver metastasis. Overall survival and disease-free survival at 5 years were 57.4 and 24.9 %, respectively. MSI analysis revealed that none of the 100 CRLM specimens showed any evidence of MSI. By KRAS/BRAF mutation analysis, the analyzed CRLM patients were divided into 3 groups; KRAS-mutant (KRAS-Mt; n = 27), BRAF-mutant (BRAF-Mt; n = 3), and wild-types of both genes (Wild-type; n = 70). In the survival analysis, both KRAS-Mt and BRAF-Mt patients showed significantly poorer prognoses compared with Wild-type patients. Furthermore, although the population with the BRAF mutation was small, this mutation had a significant negative impact on disease-free survival.

Conclusions

In this study, all tumors in the cohort of CRLM patients were non-MSI tumors, suggesting MSI cancer in primary CRC would rarely reveal metastatic potential. KRAS and BRAF mutations are suggested to be poor prognostic factors in CRLM. Genetic information has an essential role as a prognostic marker and could contribute to the decisions on treatment strategy for CRLM.     

A fatal case of MAM-2201 poisoning

A 59-year-old man was found dead in his house, where three sachets containing herbal blends were found on a table. The sachet contents were analyzed by gas chromatography–mass spectrometry and found to contain [1-(5-fluoropentyl)-1H-indol-3-yl](4-methyl-1-naphthalenyl)methanone (MAM-2201). The deceased was subjected to forensic autopsy. There were neither external injuries nor endogenous diseases judged by macroscopic and microscopic observations. Liquid chromatography–electrospray ionization–tandem mass spectrometry was used to quantitate the concentrations of MAM-2201 in postmortem samples using deuterated MAM-2201 as internal standard. The MAM-2201 concentrations were: 12.4 ng/ml in whole blood; 18.1 ng/g in the liver; 11.2 ng/g in the kidney; 4.3 ng/g in the brain; and 1,535 ng/g in the adipose tissue. We concluded that the man’s death was caused by acute intoxication with MAM-2201. In addition, we propose that the adipose tissue is the specimen of choice to detect MAM-2201 in the unchanged form. To our knowledge, this is the first report of a fatal MAM-2201 poisoning case. In addition, this report is also the first to describe the distribution of the drug in postmortem human tissues and blood.     

Successful treatment of unresectable advanced hepatoblastoma: Living liver transplantation after surgical removal of lung metastasis

Miyamura T, Yoshida R, Yagi T, Matsukawa H, Chayama K, Ishida T, Washio K, Morishita N, Oda M, Morishima T. Successful treatment of unresectable advanced hepatoblastoma: Living liver transplantation after surgical removal of lung metastasis.
Pediatr Transplantation 2011: 15: E87–E91. © 2010 John Wiley & Sons A/S. Abstract: Hepatoblastoma is a rare malignant tumor of the liver in children. Intensive combination chemotherapy has increased the number of surgically resectable cases and improved prognosis markedly. However, unresectable cases and cases with residual metastasis, including lung metastases, have a poor prognosis. In these refractory cases, treatment strategy has not been established. On the other hand, living liver transplantation has been shown to be effective in cases of advanced hepatoblastoma, but its effectiveness in cases with residual distant metastases after chemotherapy remains unclear. We report one successful case of advanced unresectable hepatoblastoma with multiple lung metastases. Intensive chemotherapy consisting of high‐dose chemotherapy with autologous hematopoietic stem cell transplantation was not effective. We performed living liver transplantation after surgical resection of residual lung metastases, which were histologically viable. After liver transplantation, the level of tumor marker decreased gradually. The patient experienced no severe complications. This case suggested that living liver transplantation could be effective in cases of advanced refractory hepatoblastoma after control of distant metastases.     

Usefulness of dual isotope 123I-IMP and 201Tl SPECT for the diagnosis of primary central nervous system lymphoma and glioblastoma

International Journal of Clinical Oncology - Preoperative differential diagnosis between primary central nervous system lymphoma (PCNSL) and glioblastoma (GBM) is important because these tumors...