Yoshinobu Hata

Clinical characteristics of acute respiratory deterioration in pulmonary fibrosis associated with lung cancer following anti‐cancer therapy

Background and objective:  To clarify the clinical characteristics and risk factors for acute respiratory deterioration following anti‐cancer therapy in patients with pulmonary fibrosis (PF) and lung cancer.

Clinical significance of BIM deletion polymorphism in non-small-cell lung cancer with epidermal growth factor receptor mutation.

Background: Germline alterations in the proapoptotic protein Bcl-2–like 11 (BIM) can have a crucial role in tumor response to treatment. To determine the clinical utility of detecting BIM deletion polymorphism in non–small-cell lung cancer positive for epidermal growth factor receptor (EGFR) mutation, we examined outcomes of patients with and without BIM alterations. Methods: We studied 70 patients with EGFR mutation-positive non–small-cell lung cancer who were treated with an EGFR tyrosine kinase inhibitor between January 2008 and January 2013. BIM deletion was analyzed by polymerase chain reaction in 58 samples of peripheral blood and 24 formalin-fixed paraffin-embedded slides of surgical specimens (20 of lung tissue and four of brain tissue); both blood and tissue specimens were available for 12 patients. We retrospectively analyzed clinical characteristics, response rate, toxicity, and outcomes among patients with and without BIM deletion. Results: BIM deletion was present in 13 of 70 patients (18.6%). There were no significant differences between patients with and without BIM deletion in clinical characteristics, rate of response to EGFR tyrosine kinase inhibitor, or incidence of adverse events. Patients with BIM deletion had significantly shorter progression-free survival (PFS) than those without BIM deletion (median, 227 versus 533 days; p < 0.001). Multivariate Cox regression analysis showed that BIM deletion was an independent indicator of shorter PFS (hazard ratio, 3.99; 95% confidence interval, 1.864–8.547; p < 0.001). Conclusions: Polymerase chain reaction successfully detected BIM deletion in samples of peripheral blood and formalin-fixed paraffin-embedded slides of surgical specimens. BIM deletion was the most important independent prognostic factor in shorter PFS.

Treatment options for patients with large cell neuroendocrine carcinoma of the lung.

Large cell neuroendocrine carcinoma (LCNEC) of the lung is categorized as a variant of large cell carcinomas, and LCNEC tumors display biological behaviors resembling those of small cell lung carcinomas and features of high-grade neuroendocrine tumors. Because patients with LCNEC have a poor prognosis, surgery alone is not sufficient. Multimodality therapies, including adjuvant chemotherapy, appear promising for improved prognosis in patients with LCNEC. In this review article, we discuss treatment options for patients with LCNEC of the lung.

Ciliated Muconodular Papillary Tumor of the Lung: A Newly Defined Low-grade Malignant Tumor with CT Findings Reminiscent of Adenocarcinoma

A ciliated muconodular papillary tumor has been reported to be a peripheral low-grade malignant tumor, consisting of ciliated columnar cells and goblet cells with basaloid cell proliferation. Although ciliated muconodular papillary tumors have not yet been classified according to the World Health Organization classification, they can pose diagnostic and therapeutic problems. Here we report a resected case of ciliated muconodular papillary tumor with computed tomography findings reminiscent of adenocarcinoma, showing a small irregular nodule adjacent to the intersegment pulmonary vein. There was no uptake of F-18 fluorodeoxyglucose positron emission tomography. The patient underwent surgical resection, and a lobectomy was performed because intraoperative needle biopsy suggested neoplastic proliferation. No EGFR mutations were detected. No recurrence was noted during 24-month follow-up after lobectomy.

A clinical study on the influence of hydration volume on the signs of terminally ill cancer patients with abdominal malignancies.

BACKGROUND Current discrepancies in the practice of artificial hydration therapy for terminally ill cancer patients have the potential to cause serious clinical problems. PURPOSE The studys purpose was to explore the influence of hydration volume on the sings during the last three weeks of life in terminally ill cancer patients. METHODS This was a prospective, observational study of 75 consecutive terminally ill patients with abdominal malignancies during the last four years. Primary responsible physicians evaluated the severity of membranous dehydration (calculated on the basis of three physical findings), peripheral edema (calculated on the basis of seven physical findings), ascites and pleural effusion (rated as physically undetectable to symptomatic), bronchial secretion, and hyperactive delirium. RESULTS Patients were classified into two groups: the hydration group (n=32), receiving 1000 mL or more of artificial hydration per day, one and three weeks before death, and the nonhydration group (n=43). The percentage of patients with deterioration in dehydration score in the final three weeks was significantly higher in the nonhydration group than in the hydration group (35% versus 13%, p=0.027), while the percentages of patients whose symptom scores for edema, ascites, and bronchial secretion increased were significantly higher in the hydration group than in the nonhydration group (57% versus 33%, p=0.040; 34% versus 14%, p=0.037; 41% versus 19%, p=0.036, respectively). There were no significant differences in the degree of pleural effusion or the prevalence of hyperactive delirium between these groups. CONCLUSIONS The potential benefits of artificial hydration therapy should be balanced with the risk of worsening fluid retention signs.

Primary pulmonary myxoid sarcoma with EWSR1‐CREB1 fusion, resembling extraskeletal myxoid chondrosarcoma: Case report with a review of Literature

Reported herein is an extremely rare case of primary pulmonary myxoid sarcoma (PPMS). A 31‐year‐old man presented with a 2.7 cm‐sized pulmonary tumor surrounded by capsule‐like fibrosis. The patient has been free of disease for 5.8 years after surgery. This tumor focally showed endobronchial features, and consisted of reticular cords of oval, short spindle, or polygonal cells with swollen vesicular nuclei accompanied by an abundant myxoid stroma, closely resembling extraskeletal myxoid chondrosarcoma. Tumor cells were diffusely positive for vimentin and focally positive for epithelial membrane antigen, but were negative for cytokeratin, TTF‐1, Napsin A, S‐100 protein, CD34, desmin, smooth‐muscle actin, CD10, p63, calponin, h‐caldesmon, c‐kit, HMB‐45, synaptophysin, or glial fibrillary acid protein. Our reverse transcription‐polymerase chain reaction using the formalin‐fixed, paraffin‐embedded tumor tissues detected EWSR1‐CREB1 fusion transcript, but could not demonstrate EWSR1‐ATF1 fusion or EWSR1/TAF15/TFG‐NR4A3 fusion. These findings indicate that the current tumor is an additional case of PPMS with EESR1‐CREB1 fusion, recently reported by Thway et al. Some cases of PPMS can behave in an indolent manner.

Laminin and procollagen-III-peptide as a serum marker for hepatic fibrosis in congenital biliary atresia

The extracellular matrix (ECM) is a complex of macromolecules that includes collagens, proteoglycans, and complex glycoproteins. In fibrotic liver tissue there is an increase in all of these matrix components, and they increase in serum in the patients with alcoholic hepatitis or liver cirrhosis. These ECM components have been used as a serum marker of hepatic fibrosis. Prolonged obstruction of bile flow results in morphologic and biochemical changes and the development of secondary biliary cirrhosis. In congenital biliary atresia (CBA) there is a close correlation between the degree of the hepatic fibrosis and bile flow after the operation. We estimated that, in CBA, ECM increased in serum, and it would reflect the degree of the hepatic fibrosis. To clarify this we examined the serum procollagen-III-peptide (P-III-P) and laminin in CBA patients. P-III-P was elevated in all preoperative patients but in two of the three postoperative patients whose jaundice disappeared P-III-P was in the normal range. In the all 3 patients whose jaundice continued, P-III-P was in normal range. Serum laminin was elevated in 12 preoperative patients with CBA, but there is no correlation between day of diagnosis and level of laminin. Mean concentration in CBA without jaundice after operation was 3.18 U/mL, 3.226 U/mL in CBA with jaundice and 3.3 U/mL in infantile hepatitis. There were no significant differences among three groups. With the elevation of serum alanine aminotransferase, aspartate aminotransferase, and total bilirubin, serum laminin level was also increased.(ABSTRACT TRUNCATED AT 250 WORDS)

Histopathological Implications of Aspergillus Infection in Lung

This paper opens with a discussion on the significance of invasive fungal infections in advanced contemporary medicine, with an emphasis on the intractability of disease management and the difficulties of diagnosis. This is followed by a discussion concerning classification, histopathological features, and pathophysiology. While it has been largely accepted that Aspergillus species is recognized by cellular receptors and attacked by neutrophils, the radiological and macroscopic findings linking infection with neutropenia remain unconfirmed. In an effort to gain a better understanding of the pathophysiology and pathogenesis of invasive aspergillosis, we wish to emphasize the utility of radiological and histopathological examinations since these can provide detailed information on the extremely complex interaction between the causative microbes and tissue responses. A review of noninvasive or semi-invasive aspergillosis is also provided, with particular emphasis on chronic necrotizing pulmonary aspergillosis, which is recognized as a transition form of simple pulmonary aspergilloma and invasive pulmonary aspergillosis, although few findings have been reported in this area.

Pathophysiological implication of reversed CT halo sign in invasive pulmonary mucormycosis: a rare case report

BackgroundIt has been accepted that reversed halo sign (RHS) appeared on a computed tomography (CT) image in immunocompromised patients indicates an invasive fungal infection, but its pathophysiology remains obscure as to what this image implies. Therefore, the present report describes detailed radiological and histopathological findings of a case of invasive pulmonary mucormycosis (IPM) presenting RHS with comparison to those from a lesion of discrete nodule caused by invasive pulmonary aspergillosis (IPA), and discusses the pathophysiological implications of this characteristic image.Case presentationRHS had been clinically noted at the time of recovering of bone marrow function of a 64-year-old Japanese man who had chemotherapy for his acute lymphoblastic leukemia. Histological examination of the surgically removed lung revealed a lesion of IPM. This was composed of coagulation necrosis of septa at the center of lesion with preservation of air content which was encompassed outer rim comprising triplet structure; liquefaction, consolidation, and organization from the inner to the outer layer. In addition, Micro-CT examination confirmed reticular structure and monotonous high density at the central coagulation necrosis preserving air content and surrounding consolidation, and organization lesion of the IPM lesion.ConclusionOur investigations suggest that RHS might be understood as a kind of immune reconstitution syndrome and be the initial and prior status of air crescent sign.Virtual SlidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/3480054198968132

Immunotargeting Chemotherapy for AFP-Producing Pediatric Liver Cancer Using the Conjugates of Anti-AFP Antibody and Anti-Tumor Agents

The effect of immunotargeting chemotherapy for hepatoblastoma (HB) and hepatocellular carcinoma (HCC) following the application of adriamycin (ADM) or cis-platinum conjugated with anti-alpha-fetoprotein (AFP) antibody was evaluated experimentally and clinically. The conjugate was made from mouse monoclonal antihuman AFP antibody linked to ADM or CDDP, with a weight ratio of 2.5:1 via a dextran bridge. Experimentally, AFP-producing human HCC transplanted subsequently on nude mice was used. A mixture of the antibody and ADM or CDDP was prepared with the same ratio. Each drug was injected intraperitoneally, three times at the total dose of 14.4 mg/kg as ADM and one time at the dose of 8 mg/kg as CDDP. Tumor growth was inhibited significantly in the conjugate group compared with the other mixture group, the ADM or CDDP group, and the control group. Clinically, the conjugates were administered intraarterially in 4 cases (2 HBs and 2 HCCs) and intravenously in one case (1 HB). ADM and CDDP conjugated with anti-AFP antibody were used in 2 cases and 3 cases, respectively. Antitumor effects from the viewpoint of volume suppression rate showed partial response in 2 cases and no change in 3 cases. The immunotargeting chemotherapy using anti-AFP monoclonal antibodies may be a promising method for treatment of malignant epithelial liver cancer in children.