Pancreatic carcinoma metastasis to a lung carcinoma lesion and pulmonary fibrotic regions, overtaking the stromal microenvironment: A case report.

RATIONALE: Suppression and of cancer metastasis is one of the most important issues in cancer care. Considering the typical clinical course of metastases, cancer cells might prefer certain environments or conditions. However, favorable environments for cancer metastasis have not been clearly identified. We had previously described a case of dual, yet separate, pancreatic and colon cancer, in which the metastatic pancreatic cancer was localized at the invasive portion of the colon cancer. We hypothesized that metastatic pancreatic cancer took over the colon cancer microenvironment. PATIENT CONCERNS: We experienced an another case of double cancer in a 65-year-old man who had lung squamous cell carcinoma and an independent pancreatic adenocarcinoma that metastasized to the liver as well as to the lung cancer lesion and pulmonary fibrotic regions associated with pneumothorax and bronchiolization. INTERVENTIONS: The pneumothorax could not be controlled by conservative treatment. Thus, an emergency surgery with partial resection of the lower lobe of right lung was performed. DIAGNOSES: We found multiple pancreatic cancer metastases in the lung cancer and fibrotic lesions in the surgical specimen. However, we detected no metastasis in normal lung tissues except inside small arteries, although the lung cancer and fibrotic tissue areas were smaller than the normal lung tissue areas in the surgical specimen. OUTCOMES: The patient died 50 days after the surgery. LESSONS: This case may thus provide evidence to strengthen our hypothesis that pancreatic cancer prefers to metastasize to other independent cancer lesions, overtaking the cancer microenvironment constructed by other independent cancers. The lung cancer microenvironment, rich in myofibroblasts and/or cancer-associated fibroblasts, might be suitable for pancreatic carcinoma metastasis. In addition, we propose the hypothesis that compared with normal tissues, noncancerous fibrotic lesions are preferable destinations for cancer metastasis. Furthermore, metastasis of pancreatic carcinoma to lung cancer and fibrotic tissues might be more common, although such cases have not been previously reported.

Intraoperative red cell salvage during obstetric surgery in 50 Japanese women.

OBJECTIVE: To determine the clinical usefulness of intraoperative cell salvage (ICS) in obstetrics. METHODS: A retrospective analysis was performed using data for 50 patients who had received ICS blood during obstetric surgery at 13 Japanese facilities between January 1, 2007 and December 31, 2013. The frequencies of ICS-associated adverse events, allogeneic blood transfusion (ABT), and preoperative autologous donation (PAD) were assessed. RESULTS: Placenta previa was the indication for ICS in 42 (84%) women. The ICS blood was reinfused in all women (median 366 mL; range 80 to at least 3715). No ICS-associated adverse events occurred. The median estimated blood loss (EBL) was 2171 mL (range 574-47 000); 27 (54%) women lost at least 2000 mL. ABT was not used in 33 (66%) women. Among 26 women who lost at least 2000 mL of blood and were included in analyses, 12 (44%) did not receive ABT. EBL was linearly correlated with the total volume of transfused blood (P<0.001). CONCLUSION: ICS caused no adverse events among women at elevated risk of peripartum hemorrhage and might be safe for use in obstetrics.

[Clinicopathological study of small lung cancer (diameter of 2 cm or less) by uptake value of 18F-fluorodeoxyglucose].

18F-fluorodeoxyglucose (FDG)-positron emission tomography (PET) for lung cancer may be a biomarker for malignancy as well as a useful tool for detection of nodal involvement and distant metastasis. The goal of this study was to clarify a relationship between clinicopathological findings and maximum standardized uptake value( SUVmax) obtained by preoperative PET in patients with non-small cell lung cancer in diameter of 2 cm or less. Between January 2008 and April 2011, 124 patients( 54 men and 70 women) with non-small cell lung cancer in diameter of 2 cm or less undergoing lobectomy or segmentectomy were enrolled. The relationship between SUVmax and clinicopathological findings as tumor diameter, histological type, pleural invasion, vascular invasion, lymphatic permeation and nodal involvement were analyzed. Correlation between SUVmax and findings such as vascular invasion and lymphatic permeation showed relatively strong in the patients with adenocarcinoma, on the contrary to the correlation in the patients with non-adenocarcinoma. No tumor showing SUVmax of 2 or less showed vascular invasion and/or lymphatic permeation as well as nodal involvement in any patients with adenocarcinoma. SUVmax of the primary tumor in diameter of 2 cm or less, can be a useful biomarker which indicates a surgical candidate for sublobar pulmonary resection as well as mediastinal nodal dissection, especially in patients with adenocarcinoma.

Folic acid in the prevention of neural tube defects: awareness among laywomen and healthcare providers in Japan.

It is known that neural tube defects are folic acid preventable congenital anomalies. We investigated to what extent this information was disseminated among laywomen and healthcare providers. Questionnaire studies were conducted twice, in 2002 and 2007, for four groups of laywomen and seven groups of healthcare providers in Japan regarding awareness, folic acid supplements and healthy diets. Awareness among laywomen was less than 20%, except for families who had experience with spina bifida in 2002, and 5 years later only pregnant women showed a significant increase in awareness. Awareness among healthcare providers varied from 12 to 76%, depending on their profession, and this proportion increased in five of the seven groups in 2007. The majority of laywomen obtained their information from mass media, while the majority of healthcare providers received information through media for professionals. Laywomen who used folate supplements and healthcare providers who recommended them were initially fewer than 25 and 37%, respectively. Five years later, however, pregnant women who used folic acid supplements increased from 9.1 to 43.1%. As awareness among non-pregnant laywomen and some healthcare providers is considerably low, information should be presented repeatedly to these groups. The difficulty in getting women to consume folic acid supplements is an argument for the government to require folic acid fortification of grains so that the prevention of neural tube defects can be maximized.

[Folic acid reduces the risk of neural tube defects: awareness and folate intake among pregnant women in 2006].

Folic acid plays an important role in proliferating cells and tissues of the fetus. A randomized control trial demonstrated in 1991 that 4 mg of folic acid supplements successfully prevented 72% of recurrence of neural tube defects (NTDs) in women who had had afflicted pregnancy. In 2000, the Japanese Government recommended women of childbearing age to take 400 microgram of folate supplements per day from 4 weeks prior to and 12 weeks after conception. A questionnaire study was performed in pregnant women by post on their awareness of the role folic acid plays, their life style, and folate intake by dietary consumption. Thirty-five percent of 1,251 pregnant women were aware of the important role of folic acid in the critical stage of fetal development and 31% actually took the supplement. Information on folic acid was obtained through mass media in 47% of the women, through the internet in 17%, through healthcare providers in 13% and so forth. The food record analysis revealed that the dietary intake of folic acid averaged 341 microg/day that was 60 microg less than what was recommended by the Government and that 33 of 86 women took the supplement. Overall, a half of pregnant women are required to take 400 microg folate supplement per day. It is to be stressed that primary prevention of NTDs by periconceptional intake of folic acid is a major public health opportunity and that prevention is more important than cure in the management of NTDs.

Growth factor treatment and genetic manipulation stimulate neurogenesis and oligodendrogenesis by endogenous neural progenitors in the injured adult spinal cord.

Neurons and oligodendrocytes are highly vulnerable to various insults, and their spontaneous replacement occurs to only a limited extent after damage in the adult spinal cord. The environment of injured tissue is thus thought to restrict the regenerative capacity of endogenous neural stem/progenitor cells; strategies for overcoming such restrictions remain to be developed. Here, we combined growth factor treatment and genetic manipulation to stimulate neurogenesis and oligodendrogenesis by endogenous progenitors in vivo. The recombinant retrovirus pMXIG, which was designed to coexpress green fluorescent proteins (GFPs) and a neurogenic/gliogenic transcription factor, was directly injected into the injured spinal cord parenchyma to manipulate proliferative cells in situ. We found that cells expressing Olig2, Nkx2.2, and NG2 were enriched among virus-infected, GFP-positive (GFP+) cells. Moreover, a fraction of GFP+ cells formed neurospheres and differentiated into neurons, astrocytes, and oligodendrocytes in vitro, demonstrating that GFP retroviruses indeed infected endogenous neural progenitors in vivo. Neuronal differentiation of control virus-infected cells did not occur at a detectable level in the injured spinal cord. We found, however, that direct administration of fibroblast growth factor 2 and epidermal growth factor into lesioned tissue could induce a significant fraction of GFP-labeled cells to express immature neuronal markers. Moreover, retrovirus-mediated overexpression of the basic helix-loop-helix transcription factors Neurogenin2 and Mash1, together with growth factor treatment, enhanced the production and maturation of new neurons and oligodendrocytes, respectively. These results demonstrate that endogenous neural progenitors can be manipulated to replace neurons and oligodendrocytes lost to insults in the injured spinal cord.

Signaling axis in schwann cell proliferation and differentiation.

Recent progress in molecular biology has markedly expanded our knowledge of the molecular mechanism behind the proliferation and differentiation processes of Schwann cells, the myelin-forming cells in peripheral nervous systems. Intracellular signaling molecules participate in integrating various stimuli from cytokines and other humoral factors and control the transcriptional activities of the genes that regulate mitosis or differentiation. This article provides an overview of the roles played by the intracellular pathways regulating Schwann cell functions. In Schwann cell proliferation, cyclic adenosine monophosphate signals and mitogen-activated protein kinase pathways play pivotal roles and may also interact with each other. Regarding differentiation, myelin formation is regulated by various cytokines and extracellular matrix molecules. Specifically, platelet-derived growth factor, neuregulin, and insulin-like growth factor-I all are classified as ligands for receptor-type tyrosine kinase and activate common intracellular signaling cascades, mitogen-activated protein kinase pathways, and phosphatidylinositol-3-kinase pathways. The balance of activities between these two pathways appears crucial in regulating Schwann cell differentiation, in which phosphatidylinositol-3-kinase pathways promote myelin formation. Analysis of these signaling molecules in Schwann cells will enable us not only to understand their physiological development but also to innovate new approaches to treat disorders related to myelination.

Opposing extracellular signal-regulated kinase and Akt pathways control Schwann cell myelination.

Schwann cells are the myelinating glia of the peripheral nervous system, and their development is regulated by various growth factors, such as neuregulin, platelet-derived growth factor (PDGF), and insulin-like growth factor-I (IGF-I). However, the mechanism of intracellular signaling pathways following these ligand stimuli in Schwann cell differentiation remains elusive. Here, we demonstrate that in cultured Schwann cells, neuregulin and PDGF suppressed the expression of myelin-associated protein markers, whereas IGF-I promoted it. Although these ligands activated common downstream signaling pathways [i.e., extracellular signal-regulated kinase (Erk) and phosphatidylinositol-3-kinase (PI3K)-Akt pathways], the profiles of activation varied among ligands. To elucidate the function of these pathways and the mechanisms underlying Schwann cell differentiation, we used adenoviral vectors to selectively activate or inactivate these pathways. We found that the selective activation of Erk pathways suppressed Schwann cell differentiation, whereas that of PI3K pathways promoted it. Furthermore, lithium chloride, a modulator of glycogen synthase kinase-3beta (GSK-3beta) promoted Schwann cell differentiation, suggesting the involvement of GSK-3beta as a downstream molecule of PI3K-Akt pathways. Selective activation of PI3K pathways in Schwann cells by gene transfer also demonstrated increased myelination in in vitro Schwann cell-DRG neuron cocultures and in vivo allogenic nerve graft experiments. We conclude that signals mediated by PI3K-Akt are crucial for initiation of myelination and that the effects of growth factors are primarily dependent on the balance between Erk and PI3K-Akt activation. Our results also propose the possibility of augmenting Schwann cell functions by modulating intracellular signals in light of future cell therapies.

Surgical considerations for pulmonary actinomycosis.

BACKGROUND: Diagnosis and treatment of pulmonary actinomycosis is difficult without surgical intervention. METHODS: Thirteen patients (10 men, 3 women; mean age, 62 years) underwent pulmonary resection and were given a pathologic diagnosis of pulmonary actinomycosis at our institution between 1976 and 2001. To clarify when pulmonary actinomycosis should be suspected in patients and the role of surgical intervention, we reviewed preoperative clinical characteristics, computed tomography findings, surgical indication, operative procedure, postoperative clinical course, and outcome. RESULTS: Ten patients (77%) had poor oral hygiene. Twelve patients (92%) were symptomatic, and 10 patients (77%) had hemoptysis. The mean interval between radiographic identification of the abnormality and surgical intervention was 8 months (interquartile range, 3.25 to 8 months). Computed tomography findings in all cases included radiologic opacity with air bronchogram or a low attenuation area. Lung cancer was diagnosed initially because of computed tomography findings of spiculation or pleural indentation, and operation was required in 8 patients (62%). The others were diagnosed with chronic pneumonia, and surgical intervention became necessary because of recurrent hemoptysis or prolonged illness. Six patients underwent lobectomy; the others underwent partial resection or segmentectomy. Neither complication nor recurrence has occurred. CONCLUSIONS: When patients, particularly those with poor oral hygiene, show radiologic opacity with an air bronchogram or low attenuation area on the computed tomography scan, pulmonary actinomycosis should be considered and penicillin should be administered as diagnostic therapy. Surgical intervention may be necessary when frequent hemoptysis has no resolution or lung neoplasm cannot be ruled out.