Kobe City Medical Center General Research Articles

Clinical Impact of Complex Karyotype, Monosomal Karyotype and Acquisition of Chromosomal Abnormalities in Patients with Myelodysplastic Syndromes

ObjectivesDespite azacitidine prolonging the survival of patients (pts) with myelodysplastic syndromes (MDS), the overall survival (OS) of those with complex karyotype (CK) or monosomal karyotype (MK) remains dismal, and optimal treatments for these pts have not been established. Furthermore, the prognostic impact of acquisition of additional cytogenetic abnormalities (ACA) during the follow-up periods is poorly understood. In this retrospective study, we aimed to evaluate the prognostic impact of CK, MK, and ACA in MDS pts, and determine optimal treatments.MethodsWe collected clinical data on consecutive adult MDS pts who first visited Kobe City Medical Center General Hospital or Kyoto University Hospital between January 2004 and April 2014. Patients were divided into groups based on the number of chromosomal abnormalities (abns) and presence or absence of MK. ACA was defined as any gain in the number of chromosomal abns before treatments. Survival analysis was adjusted using the following variables; sex, age, IPSS-R parameters and MK. A Cox regression model was applied to the results. ACA was fit into the model as a time-dependent covariate.ResultsA total of 299 pts with MDS were identified, five of which were excluded from the study due to a lack of chromosomal information. Median follow-up time was 24.5 months (M). Pts’ characteristics, treatments and incidence of ACA are summarized in Table 1. Among 47 CK pts, 34 (72%) carried MK. Survival analysis revealed that presence of 4 or more chromosomal abns was significantly associated with increased mortality. Among pts with 2–3 chromosomal abns, the presence of MK was a poor prognostic factor, although it had no significant impact on survival in pts with 4 or more abns (Figure 1). Median survival times of pts with 2–3-abns without MK, with 2–3-abns together with MK, and 4 or more abns were 39 M, 12 M (HR 6.6, 95% confident interval, [2.6-17], p < 0.001), and 9 M(HR 5.4, [3.1–9.3], p < 0.001) respectively. Regarding ACA, changes from normal karyotype (NK) to 1 abn (N=15) had no effect on mortality, but changes from NK to 2 or more abns (N=10) led to a significant increase in mortality (HR 9.2 [3.7–24], p < 0.001). Further, changes from 0–3 chromosomal abns without MK to either MK or 4 or more abns were associated with higher mortality (HR 2.7 [1.0–7.1], p = 0.045). Among pts with 2–3-chromosomal abns with MK or those with 4 or more abns at diagnosis (N=45) or during follow-up (N=10), 20 (36%) underwent allogeneic stem cell transplantation (allo-SCT) and only six survived beyond 24 M. Five of these received allo-SCT and were alive at the last follow-up. The other was treated with azacitidine and lived for 33 M.ConclusionThis study revealed that MK or 4 or more chromosomal abns is significantly associated with high mortality. Among NK pts, acquisition of 2 or more abns was associated with a poor outcome. Allo-SCT is the only strategy to increase the chance of long-term survival for pts with MK or 4 or more chromosomal abns, although only a few survivors were identified even after allo-SCT. More data are needed to identify the optimal therapeutic options for this subgroup.Table 1Clinical parameters and treatments received by patientsNumber of abnormalities<3 (N=247) (%)3 (N=10) (%)4<= (N=37) (%)p-valueSex (male/female) (N=195/99)170(69)/77(31)4(40)/6(60)21(57)/16(43)0.04Age =<65 (N=158) >65 (N=136)130(53) 117(47)7(70) 3(30)21(57) 16(43)0.89Bone marrow blast% <=2 (N=123) >2-<5 (N=45) >=5-<=10 (N=50) >10 (N=74) Missing (N=2)112(45) 35(14) 39(16) 59(24) 2(0.81)4(40) 3(30) 2(20) 1(10) 07(19) 7(19) 9(24) 14(38) 00.06Hemoglobin (g/dL) >=10 (N=91) >=8-<10 (N=93) <8 (N=106) Missing (N=4)83(34) 72(29) 88(36) 4(1.6)3(30) 5(50) 2(20) 05(14) 16(43) 16(43) 00.076Platelets (103/ƒÊL) >=100 (N=118) >50-<100 (N=82) <50 (N=90) Missing (N=4)100(40) 68(28) 75(30) 4(1.6)6(60) 1(10) 3(30) 0(0)12(32) 13(35) 12(32) 00.50Neutrophils (/ƒÊL) >=800 (N=183) <800 (N=106) Missing (N=5)160(65) 82(33) 5(2.0)5(50) 5(50) 018(49) 19(51) 00.078Monosomal karyotype (N=39)5(2)3(30)31(79)<0.001ACA (N=37)30(12)1(10)6(16)0.7Initial treatments CC (N=92) azacitidine (±CC) (N=63) Chemo-naïve allo-SCT (N=37) Palliative CT/BSC (N=102)78(32) 43(17) 31(13) 95(38)1(10) 3(30) 3(30) 3(30)13(35) 17(46) 3(8) 4(11)<0.001Allo-SCT (total)79(32)7(70)13(35)0.77 [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

A case series of Meckel’s diverticulum: usefulness of double-balloon enteroscopy for diagnosis

BackgroundMeckel’s diverticulum is a congenital anomaly of the gastrointestinal tract. About 98% of affected patients are asymptomatic. Small intestinal examination has become easier since the development of double-balloon enteroscopy. The present case series describes 10 patients with Meckel’s diverticulum in whom double-balloon enteroscopy was useful for diagnosis.Case presentationTen patients (8 men, 2 women) with Meckel’s diverticulum underwent double-balloon enteroscopy at Kobe City Medical Center General Hospital from May 2004 through May 2013. Their median age was 31.5 years (range, 14–83 years). Ten retrograde and two anterograde double-balloon enteroscopy procedures were performed. Double-balloon enteroscopy showed Meckel’s diverticulum in nine patients, but an inverted Meckel’s diverticulum was diagnosed as a lipoma in one patient. Meckel’s diverticulum was detected by iodinated contrast medium during anterograde double-balloon enteroscopy in one of the two patients who underwent this procedure. Meckel’s diverticulum was suspected using capsule endoscopy in one of two patients who underwent this procedure. Abdominal computed tomography was performed in all patients and revealed abnormalities in six, but Meckel’s diverticulum was suspected in only two. Technetium-99 m pertechnetate scintigraphy and a small bowel series were carried out in six patients, revealing Meckel’s diverticulum in one and three patients, respectively. Surgery was performed in eight patients, and endoscopic resection was carried out in one; the remaining patient was transferred to another hospital. Ulcer formation was found in or near Meckel’s diverticulum in eight patients.ConclusionCompared with other modalities, double-balloon enteroscopy is excellent for the diagnosis of Meckel’s diverticulum because direct observation of both Meckel’s diverticulum and ulceration is possible. Double-balloon enteroscopy should be used complementarily to other less invasive examinations when needed to confirm or establish the diagnosis.

Serum IgA level, monocyte count, and international prognostic index are independently associated with overall survival in patients with HTLV-I-negative nodal peripheral T cell lymphoma

Peripheral T cell lymphomas (PTCL) account for 10-15% of non-Hodgkin's lymphomas and are associated with poor prognosis. Although many prognostic factors for PTCL have been proposed, the heterogeneity of PTCL seems to be an obstacle in the establishment of clinically useful prognostic system, such as the International Prognostic Index (IPI) in diffuse large B cell lymphoma. PTCL with nodal manifestation include the HTLV-I-negative histologic subtypes of PTCL not otherwise specified (PTCL-NOS), angioimmunoblastic T cell lymphoma (AITL), and anaplastic large cell lymphoma (ALCL). As PTCL-NOS encompasses a group of similar tumors and mostly shares their clinical pictures, we retrospectively analyzed clinical data from 77 patients diagnosed with ALCL, AITL, and PTCL-NOS at Kobe City Medical Center General Hospital from May 1994 to February 2012 to identify the prognostic factor for nodal PTCL. The median age of patients was 64years, ranging from 23 to 83years. With a median follow-up of 50months, 5-year overall survival (OS) was 43%. Multivariate analysis identified high-risk IPI (hazard ratio (HR), 4.04; P = 0.015), absolute monocyte count > 0.8 × 10(9)/L (HR, 3.44; P = 0.001), and serum concentration of IgA > 410mg/dL (HR, 2.31; P = 0.013) as poor prognostic factors for OS. Thus, we have identified novel prognostic factors of monocyte count and serum IgA level for nodal PTCL. Although conventional prognostic models mainly reflect both tumor characteristics and host factors, the present model indicates the importance of host immune response as the unfavorable prognosis.

The Role of Pharmacy Residents as Preceptors on Clinical Training

Long-term clinical training programs started as part of a 6-year pharmacy course in May 2010. In order to provide training approaches more appropriately and efficiently, it is necessary for teaching facilities to develop effective training systems and curriculums. In Kobe City Medical Center General Hospital, a pharmacy residency system was instituted in 2009, and, based on this, a preceptorship program for clinical training was adopted. In this study, the influence of pharmacy residents as preceptors on clinical training was evaluated based on training reports submitted by 26 students, consisting of a total of 1238 pages; residents' comments were observed in 31.3% of them. Changes in students' awareness were also noted; in the course of training, they became more aware of the responsibility and role of pharmacists, and such awareness appeared to provide a basis for their future goals. Further, although most of the residents' comments were initially made for encouragement, concrete advice gradually increased with time. Residents' commitment to clinical training as preceptors may have facilitated students' understanding of the significance of training, while promoting their own development.

IMPACT OF ELEVATED CORONARY WEDGE PRESSURE ON LONG-TERM CARDIOVASCULAR EVENTS AFTER PRIMARY CORONARY INTERVENTION FOR ACUTE MYOCARDIAL INFARCTION

Abstract Category: 3. Intravascular DiagnosticsPresentation Number: 2520-28Authors: Koichi Tamita, Atsushi Yamamuro, Shuichiro Kaji, Yutaka Furukawa, Junichi Yoshikawa, Nihinomiya Watanabe Cardiovascular Center, Nishinomiya, Japan, Kobe City Medical Center General Hospital, Kobe, Japan Background: Recent studies have shown that the coronary wedge pressure (CWP) is not unlikely to reflect collateral function but to increase with the severity of microvascular dysfunction in patients with acute myocardial infarction (AMI). The aim of this prospective study was to examine whether an elevated CWP may predict the long-term cardiovascular events in patients with AMI.Methods: The study population consisted of 53 consecutive patients with a first anterior AMI successfully treated with primary coronary intervention (PCI). We examined the ratio of mean CWP to mean aortic pressure (CWP/Pa) during a balloon inflation using a pressure guidewire. According to previous reports, we defined an elevated CWP as a CWP/Pa >0.24. Patients were divided into two groups: those without an elevated CWP (n=35; group 1) and those with an elevated CWP (n=18; group 2). We evaluated the association between an elevated CWP and the long-term major adverse cardiovascular event (MACE) rates.Results: The median follow-up period was 5.5 years. The Kaplan-Meier survival curves showed that group 2 was poorer than group 1 in prognosis (p=0.0026). Risk-adjusted data by multivariate analysis showed that an elevated CWP was one of the strongest predictors for long-term MACE (hazard ratio: 3.81; 95% confidence interval, 1.25-11.63; p=0.0189).Conclusion: Among patients with a firtst anterior AMI, an elevated CWP during PCI was associated with increased long-term MACE rates.

Introduction of Kobe City Medical Center General Hospital

Introduction of Kobe City Medical Center General Hospital

SMA ダブルディスク法を用いたスクリーニング検査が陰性のVIM-1型メタロ―β―ラクタマーゼ産生&lt;i&gt;Pseudomonas aeruginosa&lt;/i&gt;による アウトブレイク

VIM-1 metallo-beta-lactamase (MBL) producing Pseudomonas aeruginosa was isolated from 35 Kobe City Medical Center General Hospital patients from September 2007 to July 2008. All but one were highly resistant to all beta-lactams, aminoglycoside, and fluoroquinolone, and one susceptible to amikacin. Strains negative to a disk diffusion screening test using sodium mercaptoacetate for detecting MBL numbered 35. PCR for MBL indicated all strains were positive for bla(VIWM-1). These strains were indistinguishable by pulsed-field gel electrophoresis, indicating an outbreak of infections caused by VIM-1 MBL producing Pseudomonas aeruginosa. After intervention to control contact, the outbreak was controlled.

Refractory de novo myeloid sarcoma: a case report and therapeutic strategy based on bone marrow minimal residual disease

Myeloid sarcoma (MS), which usually develops concurrently with acute myeloid leukemia (AML), is an extramedullary tumor that consists of immature myeloid cells. Clinically, the incidence of MS in AML is 3–5% [1, 2], and the association of MS is linked to a poor prognosis [3]. De novo MS is characterized by leukemic tumor formation without the involvement of bone marrow and peripheral blood. Patients receiving radiotherapy or incorrect chemotherapy develop AML at a median time of 7 and 12 months, respectively, and show an extremely poor prognosis after leukemic transformation [4]. Thus, systemic chemotherapy effective against AML, which lowers the rate of leukemic transformation from 71 to 41%, is essential for the treatment of de novo MS [5]. A 17-year-old male was referred to our hospital in April 2007, because of small tumors in the left neck and supraclavicular fossa. A CT scan showed several separated tumors in the neck and mediastinum, one being 4 9 2 cm in the superior mediastinum and the others around 1.5 cm. The histologic picture of a biopsied left supraclavicular lymph node demonstrated that the normal architecture had been destroyed and completely replaced by middle-sized immature myeloid cells (Fig. 1), which expressed T-cell markers including CD2 and CD7 in addition to CD13, CD33, CD38, CD43, cytoplasmic myeloperoxidase, and HLA-DR on flow cytometry. Chromosomal analysis of the specimen revealed an abnormal karyotype of 46,XY,i(17)(q10) in 5 of 7 dividing cells. Blood and marrow cells did not contain abnormal cells as evaluated by flow cytometry and G-banding. A diagnosis of de novo MS was made. After 2 courses of intensive chemotherapy effective against AML, a complete remission (CR) of MS was achieved as evaluated by CT scan. Two months after the initial therapy, however, we detected a small population of myeloblasts (0.05% of all nucleated cells), which aberrantly expressed CD2 and CD7 in the bone marrow on flow cytometry, regardless of the disappearance of MS tumors. Thus, we regarded CD2/CD13 myeloblasts as MRD in the bone marrow. Subsequently, 3 courses of consolidation therapy including high-dose cytarabine were performed; however, MRD in the bone marrow persisted (0.05– 0.20%). Although we planned allogeneic HSCT, overt AML rapidly developed during the recovery phase after the third consolidation chemotherapy. The leukemia was highly refractory to any treatment including the regimens for acute lymphoblastic leukemia after December 2007. Chromosomal analysis of the bone marrow cells showed an abnormal karyotype of 46,XY,t(1;11)(p10;q10),add(4) (q21),i(17)(q10) in 8 of 20 dividing cells in addition to that D. Inoue (&) Y. Nagai T. Kimura S. Shimoji M. Mori K. Togami S. Tabata M. Kurata A. Matsushita K. Nagai T. Takahashi Department of Hematology and Clinical Immunology, Kobe City Medical Center General Hospital, 4-6 Minatojima nakamachi, Chuo-ku, Kobe 650-0046, Japan e-mail: daichi@kcgh.gr.jp

Gynecologic chemotherapy at the ambulatory therapy center in Kobe City Medical Center General Hospital

Gynecologic chemotherapy at the ambulatory therapy center in Kobe City Medical Center General Hospital