[Clinical study of sigmoid volvulus at eleven core hospitals in the Kagawa Prefecture].

We analyzed the clinical features of 157 patients admitted to 11 institutions in the Kagawa Prefecture for volvulus of the sigmoid colon. The following were the background information of the patients:median age, 79.0 years;male-to-female ratio, 102:55;median body mass index, 20.0kg/m2;and the proportion of patients with performance status ≥3, 43.9%. Abdominal bloating and pain were the chief complaints. During hospitalization, endoscopy and endoscopic detorsion were performed 157 and 100 times, respectively. An accidental complication was observed in 3 cases, all of which were intestinal perforations. Surgery, which was indicated for ischemia, was performed in 62 of the 157 cases. Endoscopy is useful in the diagnosis of ischemia, which can be treated following an early diagnosis. Of the 157 patients, 19 died, whereas the rest were discharged. The risk factors for death were age ≥80 years and creatinine kinase level ≥200IU/L.

[A case of hemolysis and acute kidney disease caused by rectal damage due to glycerin enema].

A male patient in his sixties with a long-term history of schizophrenia had been received glycerin enema once or twice a week in a mental hospital. He was emergently transferred to our hospital due to fever, vomiting, hematuria, and dyspnea. Laboratory findings on admission showed an elevation of white blood cells indicating inflammation, hemolysis, and renal dysfunction. Plain CT showed pleural effusion and ascites, elevated levels of perirectal fat, in addition to extraintestinal gas. Based on these findings, he was diagnosed with rectal damage caused by the glycerin enema and associated hemolysis with acute renal failure. He was kept under conditions of nil by mouth and received intravenous antibiotics, diuretic drug, and haptoglobin. Eventually, his condition improved with these conservative therapies. In this case, it is assumed that the hemolysis was caused by the influx of glycerin in the cytoplasm and an increase of osmotic pressure. Care should be taken during glycerin enema, which is widely used in daily practice as well as in home care settings.

The Effects of Percutaneous Endoscopic Gastrostomy on Quality of Life in Patients With Dementia.

BACKGROUND: To examine the effects of percutaneous endoscopic gastrostomy (PEG) on quality of life (QOL) in patients with dementia. METHODS: We retrospectively included 53 Japanese community and tertiary hospitals to investigate the relationship between the newly developed PEG and consecutive dementia patients with swallowing difficulty between Jan 1st 2006 and Dec 31st 2008. We set improvements in 1) the level of independent living, 2) pneumonia, 3) peroral intake as outcome measures of QOL and explored the factors associated with these improvements. RESULTS: Till October 31st 2010, 1,353 patients with Alzheimer's dementia (33.1%), vascular dementia (61.7%), dementia with Lewy body disease (2.0%), Pick disease (0.6%) and others were followed-up for a median of 847 days (mean 805 ± 542 days). A total of 509 deaths were observed (mortality 59%) in full-followed patients. After multivariate adjustments, improvement in the level of independent living was observed in milder dementia, or those who can live independently with someone, compared with advanced dementia, characterized by those who need care by someone: Odds Ratio (OR), 3.90, 95% confidence interval (95%CI), 1.59 - 9.39, P = 0.003. Similarly, improvement of peroral intake was noticed in milder dementia: OR, 2.69, 95%CI, 1.17 - 6.17, P = 0.02. Such significant associations were not observed in improvement of pneumonia. CONCLUSIONS: These results suggest that improvement of QOL after PEG insertion may be expected more in milder dementia than in advanced dementia.

[A case of delayed colonic perforation after metallic stent placement for advanced descending colon cancer during bevacizumab-based chemotherapy].

A 73-year-old man with advanced descending colon cancer and peritoneal metastases underwent a self-expandable metallic stent placement under fluoroscopic guidance on October 2007. The stent placement was successful without early complication. After 6 courses of FOLFOX4 followed by 7 courses of FOLFIRI, he received Bevacizumab-based chemotherapy from August 2008. In April 2009, he was admitted to our hospital with severe abdominal pain due to perforation of descending colon. Although emergent surgery was performed, he developed DIC and died on the 21 postoperative days. This case suggests that metallic stent placement for colorectal cancer cases might increase the risk of bowel perforation during Bevacizumab-based chemotherapy.

Ex vivo large-scale generation of human red blood cells from cord blood CD34+ cells by co-culturing with macrophages.

We generated red blood cells (RBC) from cord blood (CB) CD34+ cells using a four-phase culture system. We first cultured CB CD34+ cells on telomerase gene-transduced human stromal cells in serum-free medium containing stem cell factor (SCF), Flt-3/Flk-2 ligand, and thrombopoietin to expand CD34+ cells (980-fold) and the total cells (10,400-fold) (first phase). Expanded cells from the first phase were liquid-cultured with SCF, interleukin-3 (IL-3), and erythropoietin (EPO) to expand (113-fold) and differentiate them into erythroblasts (second phase). To obtain macrophages for the next phase, we expanded CD34+ cells from a different donor using the same coculture system. Expanded cells from the first phase were liquid-cultured with granulocyte-macrophage colony stimulating factor, macrophage-colony stimulating factor (M-CSF), IL-3, and SCF to generate monocytes/macrophages (75-fold), which were incubated with type AB serum and M-CSF to fully differentiate them into macrophages. Erythroblasts were then co-cultured with macrophages in the presence of EPO to expand (threefold) and fully differentiate them (61% orthochromatic erythroblasts plus 39% RBC) (third phase). RBC were purified from erythroblasts and debris through a deleukocyting filter to generate 6.0 x 10(12) RBC from 1.0 unit of CB (3.0 transfusable units). Qualitatively, these RBC showed a hemoglobin content, oxygenation of hemoglobin, and in vivo clearance similar to those of adult peripheral RBC. Finally, an almost complete enucleation of orthochromatic erythroblasts (99.4%) was achieved by the cultivation method recently described by Miharada et al. in the absence of macrophages and cytokines (fourth phase). RBC were purified from remnant erythroblasts and debris by passage through a deleukocyting filter to generate 1.76 x 10(13) RBC from 1.0 unit of CB (8.8 transfusable units), the highest yield ever reported. Thus, this method may be useful for generating an alternative RBC supply for transfusions, investigating infectious agents that target erythroid cells, and as a general in vitro hematopoietic model system.

Ex vivo large-scale generation of human platelets from cord blood CD34+ cells.

In the present investigation, we generated platelets (PLTs) from cord blood (CB) CD34(+) cells using a three-phase culture system. We first cultured 500 CB CD34(+) cells on telomerase gene-transduced human stromal cells (hTERT stroma) in serum-free medium supplemented with stem cell factor (SCF), Flt-3/Flk-2 ligand (FL), and thrombopoietin (TPO) for 14 days. We then transferred the cells to hTERT stroma and cultured for another 14 days with fresh medium containing interleukin-11 (IL-11) in addition to the original cytokine cocktail. Subsequently, we cultured the cells in a liquid culture medium containing SCF, FL, TPO, and IL-11 for another 5 days to recover PLT fractions from the supernatant, which were then gel-filtered to purify the PLTs. The calculated yield of PLTs from 1.0 unit of CB (5 x 10(6) CD34(+) cells) was 1.26 x 10(11) - 1.68 x 10(11) PLTs. These numbers of PLTs are equivalent to 2.5-3.4 units of random donor-derived PLTs or 2/5-6/10 of single-apheresis PLTs. The CB-derived PLTs exhibited features quite similar to those from peripheral blood in morphology, as revealed by electron micrographs, and in function, as revealed by fibrinogen/ADP aggregation, with the appearance of P-selectin and activated glycoprotein IIb-IIIa antigens. Thus, this culture system may be applicable for large-scale generation of PLTs for future clinical use.

[Psoriasis vulgaris exacerbated by imatinib therapy in chronic myelogenous leukemia].

Administration of imatinib exacerbated psoriasis vulgaris in a case of chronic myelogenous leukemia (CML). After the cessation of imatinib therapy, the psoriasis was alleviated. Upon readministration of imatinib, the psoriasis worsened despite the improvement of hematological and cytogenetic findings in the CML. Psoriasis is known to be an autoimmune skin disease characterized by Th1 cell-mediated hyperproliferation of keratinocytes, and the type 1 helper T (Th1) cell subset increased with imatinib therapy. Thus, the exacerbation of psoriasis was likely due to the increase in Th1 cells associated with imatinib therapy.

Decrease of Smad4 gene expression in patients with essential thrombocythaemia may cause an escape from suppression of megakaryopoiesis by transforming growth factor-beta1.

Essential thrombocythaemia (ET) is characterized by the abnormal and sustained proliferation of megakaryocytes. The mechanism for this lineage-specific expansion in ET, remains unclear. We have previously reported that transforming growth factor-beta1 (TGF-beta1) is involved in negative feedback regulation of megakaryopoiesis in both healthy volunteers (HV) and patients with idiopathic thrombocytopenic purpura (ITP). The present study found that megakaryocyte colony-forming units (CFU-MK) of ET patients were less sensitive to TGF-beta1 than those of HV. The expression of Smad4 (Sma- and Mad-related protein-4) in CFU-MK of ET patients was reduced in comparison with that of HV. Finally, to confirm that the impaired TGF-beta1 sensitivity was caused by reduced expression of Smad4, we examined Smad4-transfected CFU-MK from ET patients in the presence of TGF-beta1, and verified that the transfectants were indeed as susceptible as CFU-MK from HV to TGF-beta1. Thus it was surmised that one of the mechanisms for impaired sensitivity of CFU-MK to TGF-beta1 is the reduced expression of Smad4.

C(H)OP refractory chronic lymphocytic leukemia patients in whom salvage chemotherapy chosen by evaluating multiple chemotherapeutic drug-resistant factors was remarkably effective.

It is well known that the expression of anticancer drug-resistant factors is elevated in patients with primary refractory or relapsed chronic lymphocytic leukemia (CLL) who have been treated with chemotherapy. We report here two C(H)OP refractory patients with CLL in whom salvage chemotherapy chosen by evaluating anticancer drug-resistant factors (glutathione-S-transferase-Pi [GST-Pi], glycoprotein [GP]-170, multidrug resistance-associated protein [MRP], and lung resistance protein [LRP]) was remarkably effective. A 71-year-old male patient was refractory to induction therapy with cyclophosphamide, vincristine, and prednisone (COP), and his leukemic cells at diagnosis displayed overexpression of GST-Pi and GP-170. A 74-year-old female patient's condition had been stable; she had received ten courses of COP over 9 years. However, because systemic lymphadenopathies recurred, she was treated with chemotherapy consisting of cyclophosphamide, adriamycin, vincristine, and prednisone (CHOP) or dexamethasone, etoposide, ifosphamide, and carboplatin (DeVIC). However, she did not respond at all, and her leukemic cells at recurrence displayed overexpression of GST-Pi. Therefore, we chose for these patients a salvage therapy consisting of dexamethasone and high-dose cytosine arabinoside (Ara C), to which neither GST-Pi nor GP-170 show any drug resistance. In both patients, this salvage therapy proved effective.

Interaction between leukemic-cell VLA-4 and stromal fibronectin is a decisive factor for minimal residual disease of acute myelogenous leukemia.

Bone-marrow minimal residual disease (MRD) causes relapse after chemotherapy in patients with acute myelogenous leukemia (AML). We postulate that the drug resistance is induced by the attachment of very late antigen (VLA)-4 on leukemic cells to fibronectin on bone-marrow stromal cells. We found that VLA-4-positive cells acquired resistance to anoikis (loss of anchorage) or drug-induced apoptosis through the phosphatidylinositol-3-kinase (PI-3K)/AKT/Bcl-2 signaling pathway, which is activated by the interaction of VLA-4 and fibronectin. This resistance was negated by VLA-4-specific antibodies. In a mouse model of MRD, we achieved a 100% survival rate by combining VLA-4-specific antibodies and cytosine arabinoside (AraC), whereas AraC alone prolonged survival only slightly. In addition, overall survival at 5 years was 100% for 10 VLA-4-negative patients and 44.4% for 15 VLA-4-positive patients. Thus, the interaction between VLA-4 on leukemic cells and fibronectin on stromal cells may be crucial in bone marrow MRD and AML prognosis.

[Treatment of chronic myelogenous leukemia with imatinib mesylate resulting in hematological remission and marked regression of myelofibrosis].

We treated two chronic phase chronic myelogenous leukemia patients with imatinib mesylate. Hematological complete remission and significant regression of bone marrow fibrosis were observed in both patients. The large amount of TGF-beta produced by increased bone marrow megakaryocytes might have caused the myelofibrosis, and it was revealed that imatinib mesylate brought about regression of the myelofibrosis by reducing the number of megakaryocytes in both patients.

A patient with paroxysmal nocturnal haemoglobinuria in whom granulocyte colony-stimulating factor administration resulted in improvement of recurrent enterocolitis and its associated haemolytic attacks.

We report an elderly patient with paroxysmal nocturnal haemoglobinuria (PNH), having recurrent enterocolitis and haemolytic attacks associated with cellular immunodeficiency. On admission, the patient had normal neutrophil count and function but a decreased T-cell count, decreased mitogenic reactions, and a negative tuberculin test. Granulocyte colony-stimulating factor (G-CSF) was administered, resulting in an increased T-cell count, normalization of T-cell function, increased blood levels of helper T cell (Th)1 and Th2 cytokines and improvement in the enterocolitis and haemolytic attacks. This suggests that G-CSF may be useful in the treatment of elderly PNH patients with cellular immunodeficiency.

[Successful treatment with G-CSF and corticosteroid of adult idiopathic autoimmune neutropenia presenting as recurrent enterocolitis].

A 63-year-old woman had previously been admitted to another hospital due to fever, abdominal pain and diarrhea. She was treated with fasting, antibiotics and G-CSF administration because of the coexistence of neutropenia, and the symptoms improved. However, discontinuation of G-CSF administration resulted in a recurrence of the neutropenia accompanied with enterocolitis. After admission to our hospital, a diagnosis for idiopathic AIN was performed as she tested positive in both granulocyte immunofluorescence and granulocyte agglutination tests. Administration of corticosteroid following G-CSF resulted in a continuous increase in the neutrophil count and the disappearance of anti-neutrophil autoantibodies.