Shumpei Uchida

Marked Hematopoiesis Masquerading Multiple Bone Metastasis in a Lung Cancer Patient With Myelodysplastic Syndrome.

We diagnosed a 62-year-old man with lung cancer, well-differentiated squamous cell carcinoma, on the right upper lobe and left lower lobe. He had a history of myelodysplastic syndrome and refractory anemia with ringed sideroblasts diagnosed 5 years earlier. The patients ¹⁸F-FDG PET/CT for the clinical staging of lung cancer revealed accumulations of FDG in multiple bones including the rib bones, which strongly suggested multiple bone metastases. He underwent lobectomies and excision of the right fourth and fifth rib bones. The pathological findings of resected rib bones exhibited hypercellular bone marrow without excess of blasts.

Enteral Malakoplakia Prior to Helicobacter cinaedi Bacteremia

associated infectious pathogens are Klebsiella spp. and Escherichia coli ( 7 ), which colonize the mucosa. In a few cases, a rare opportunistic pathogen leads to the development of a systemic infection, which may occasionally become severe ( 7 ). A defective immune system, such as a cellular immune defect in macrophages, directly contributes to the pathological establishment of malakoplakia ( 8,9 ). In malakoplakia, a functional defect of monocytes or macrophages results in the formation of a well-characterized deposit in macrophages known as a Michaelis–Gutmann body ( 10 ). Moran et al. ( 11 ) reported that characteristic pathological fi ndings, such as Michaelis–Gutmann bodies, had been observed in cases of colonic cancer. Th is suggests that an underlying cancer is one of the diff erential diagnoses for defective immunity when malakoplakia is observed. We treated a 49-year-old man with relapsed and refractory multiple myeloma following autologous stem cell transplantation. Th e patient was admitted to our hospital because of febrile diarrhea. We performed colonoscopy and observed multiple focal white mucosal lesions ( Figure 1 ). Th ese lesions were diagnosed on pathological examination to be malakoplakia ( Figure 2 ). Th ree days aft er the colonoscopy, Helicobacter cinaedi was isolated in the peripheral blood culture, as identifi ed by mass spectrometry. H. cinaedi is a spiral, rod-shaped, fastidious bacteria in the Helicobacteraceae family and is one of the enterohepatic nonHelicobacter pylori Helicobacters ( 12 ). H. cinaedi resides in the gastrointestinal tract and results in bacteremia. In this case, we supposed it was translocated into the blood through the mucosal barrier. Another pathogenicity of H. cinaedi in humans has been recognized as a causative pathogen of cellulitis. Th us, H. cinaedi infections have various clinical manifestations, including bacteremia, cellulitis, gastroenteritis, and meningitis ( 12 ). Th is means that malakoplakia represents a systemic defect in the immune response, characteristically in cancer patients. A unique case report of malakoplakia in a patient with myeloma has been published ( 4 ). Th e authors of that case report speculated that malakoplakia was a predisposing condition, giving evidence of altered cellular immunity REFERENCES 1. Sbahi H , Di Palma JA . Faecal microbiota transplantation: applications and limitations in treating gastrointestinal disorders . BMJ Open Gastroenterol 2016 ; 3 : e000087 . 2. Lee CH , Belanger JE , Kazzam Z et al. Th e outcome and long-term follow-up of 94 patients with recurrent and refractory Clostridium diffi cile infection using single to multiple fecal microbiota transplantation via retention enema . Eur J Clin Microbiol Infect Dis 2014 ; 33 : 1425 – 8 . 3. Chang BW , Pimentel M , Chang C et al. Prevalence of excessive intestinal methane production and its variability with age and gender: a large-scale database analysis . Gastroenterology 2015 ; 148 : S-729 – 30 . 4. Rezaie A , Chang BW , Chua S et al. Accurate identifi cation of excessive methane gas producers by a single fasting measurement of exhaled methane: a large-scale database analysis . Am J Gastroenterol 2015 ; 110 : S759 . 5. Moayeddi P , Surette MG , Kim PT et al. Fecal microbiota transplantation induces remission in patients with active ulcerative colitis in a randomized controlled trial . Gastroenterology 2015 ; 149 : 102 – 9 .

Bendamustine and G-CSF support

We read the manuscript by Cerchione C et al. with particular interest [1]. The use of peg-filgrastim in patients treated with bendamustine in terms of the timing of filgrastim/pegfilgrastim is concerning. Prolonged neutropenia is sometimes anticipated during bendamustine chemotherapy. Cerchione C et al. reported the clinical benefits of peg-filgrastim as the primary prophylaxis for neutropenia [1]. This manuscript reported reduced neutropenic episodes and reduced febrile neutropenia (with or without documented infection) in patients treated with peg-filgrastim compared to those in the control group who were treated with filgrastim. This finding was hypothesized to reduce overall chemotherapy disruptions. We can acknowledge the importance of relative dose intensity (RDI) in the treatment of malignant lymphoma, which is supported by significant evidence. RDI is associated with a higher remission rate and better survival [2]. However, the relationship between RDI and survival in patients receiving bendamustine treatment and R-CHOP has not yet been fully revealed. In addition, grade 3–4 neutropenia occurred in only 44% of patients in a phase II study conducted by Czuczman MS et al. [3]. Grade 3–4 febrile neutropenia was observed in 6.1% of patients in another phase II study [4]. Thus, we might consider using peg-filgrastim in a Bsecondary-prophylaxis^ manner, according to the risk assessment of the NCCN Clinical Practice Guidelines (NCCN guidelines®) for myeloid growth factors. Here, we report the case of an 82-year-old male diagnosed with advanced mantle cell lymphoma and treated with rituximab–bendamustine (RB) therapy. He repeatedly received six courses of RB treatment until achieving complete remission. He did not initially receive G-CSF support during the chemotherapy. However, in his third course of RB therapy, prolonged neutropenia delayed the following course of chemotherapy (Fig. 1). He then received a single dose of each filgrastim and peg-filgrastim during the following chemotherapy course. Thereafter, his treatment course was not affected by chemotherapy disruption owing to the prolonged neutropenia after the fourth course of RB. Additionally, RDI was maintained throughout the following chemotherapy courses. Our case did not require G-CSF/peg-G-CSF support during the first two courses of RB. The first onset of grade 3 neutropenia was observed after the third course of chemotherapy. This suggests that primary prophylaxis with G-CSF/peg-G-CSF is not necessary for all the cases, even in those of elderly patients. Therefore, a secondary prophylactic use of peg-G-CSF seems more reasonable for the chemotherapy-induced neutropenia caused by bendmustine. However, the NCCN guidelines® for myeloid growth factors (Version 2.2017 revised on October 13, 2017) do not evaluate the use of G-CSF for bendamustine-containing regimens. Our case suggests that bendamustine causes prolonged neutropenia during the following course rather than during the initial course. The prevalence of severe neutropenia (grade 3– 4) complicated with febrile neutropenia was estimated to be < 10% according to several clinical studies [4] (up to 8.23% based on Japanese post-marketing surveillance data). This frequency of febrile neutropenia does not require routine prophylaxis of G-CSF/peg-G-CSF (NCCN guidelines). Further investigation to evaluate the efficacy of the primary or secondary prophylactic setting of G-CSF is warranted for the RB regimen. * Osamu Imataki oima@med.kagawa–u.ac.jp

Pure erythroid leukemia in a polymyositis patient treated with azathioprine

Acute erythroid leukemia, also known as acute myeloid leukemia-M6, may be associated with previous chemotherapy or immunosuppressive therapy. For 10 years, a 69-year-old Japanese female patient with pure erythroid leukemia (or acute myeloid leukemia-M6b) was treated for polymyositis with 50–100 mg/day azathioprine. She complained of dyspnea with low-grade fever and was diagnosed as having pure erythroid leukemia. Chromosomal analysis revealed a complex karyotype abnormality, with the deletion of 5q, -6, -7 and addition of 11q13. No morphological myelodysplastic changes were observed in her bone marrow cells. In this study, azathioprine accumulation was considered to be associated with the patient’s leukemogenesis.

Anemia and hypogammaglobulinemia caused by Ménétrier’s disease

was performed. Histopathological examination did not reveal any malignancy. H. pylori was detected in the stomach. Cytomegalovirus (CMV) infection was not detected in the gastric mucosa. His immunoglobulin levels decreased to 543 mg/dL (normal range 870–1700 mg/dL). In addition, he exhibited mild hypoproteinemia, his total protein level was 6.4 g/dL, and serum albumin level was 4.1 g/dL. Anti-CMV antibody was negative. Therefore, Ménétrier’s disease was diagnosed. Protein-losing gastroenteropathy was confirmed by 99mTc-human serum albumin scintigraphy (Fig. 2), and stool was examined for α-1-antitrypsin. The daily volume of fecal α1-antitrypsin was 36.4 mg/day, and the clearance of fecal α1-antitrypsin was 29.1 ml/day (normal range 0–22 ml/day) [1]. Ménétrier’s disease is categorized as a protein-losing gastroenteropathy, and its pathogenesis is hypothesized to be associated with epidermal growth factor receptor. Eradication therapy was administered for H. pylori infection, and anemia did not recur. Therefore, Ménétrier’s disease should be recognized as a cause of anemia in adolescents and young adults. A 13-year-old boy with anemia, identified during a health check-up at his junior high school, visited his primary physician clinic. His first laboratory results indicated a hemoglobin (Hb) level of 9.8 g/dL. After 2 months, a subsequent consultation with his primary physician showed that his Hb had decreased to 7.1 g/dL. Next, he presented at our hospital. His blood results revealed microcytic hypochromic anemia. Reticulocyte count was elevated to 29.23 × 104/μL (normal range 3 × 104–9 × 104/μL). Serum iron level was 526 μg/ dL (80–140 μg/mL), serum ferritin level was 137.8 ng/ mL (39–765 ng/mL), vitamin B12 level was 503 pg/mL (233–914 pg/mL), folate level was 5.4 ng/mL (3.6–129 ng/ mL), serum zinc level was 84 μg/dL (64–111 μg/dL), and serum copper level was 97 μg/dL (78–130 μg/dL). In addition, his erythropoietin level had increased to 43.9 mIU/mL (4.2–23.7). Although the patient did not report any episode of enteral bleeding, we suspected this based on his laboratory results. Gastroendoscopy revealed a fibrous mucoid coagulation in the stomach with enlarged gastric folds (Fig. 1). Atrophic mucosa suggested a Helicobacter pylori infection, and a biopsy of the hyperplastic mucosal lesion

Paradoxical thrombosis in idiopathic thrombocytopenic purpura.

a platelet count of 17.0 × 10/μL and rhabdomyolysis, showing creatinine kinase elevation to 6798 U/L (normal range 40–200 U/L). After recovery of the platelet count, he underwent catheter intervention that restored the blood flow (day 83) (Fig. 1c). Thromboembolism in the setting of thrombocytopenia is a hematological conundrum. The treatment of thromboembolism in thrombocytopenic patients is problematic due to its paradoxical pathophysiology. In ITP patients, both venous thromboembolism and arterial thrombus are more prevalent in patients with more comorbidities [1]. This risk is similar both before and after treatment. These apparently contradictory conditions can be understood based on the classical rule for thrombus formation, as hypothesized by Virchow’s triad: (1) hypercoagulopathy occurs with low platelet numbers and excessive platelet turnover; (2) endothelial cell injury occurs when platelet numbers are decreased; and (3) disturbed blood flow is caused by a precedent condition, for instance arteriosclerosis, as was seen in the present case. Our patient did not have glucose intolerance and hyperlipidemia, but had a smoking history (40 cigarettes/day × 48 years) as a risk factor for thromboembolism. The determinant risk posed by co-existing vascular conditions can be evaluated before the treatment, for A 77-year-old male patient was referred to our hospital with frailty, accompanied with muscle weakness and gait disturbance, and bilateral lower leg resting pain. Blood tests showed severe thrombocytopenia without remarkable coagulopathy, and cranial CT revealed multiple focal hemorrhages (Fig. 1a), which suggested a potential cause for the gait disturbance. At the onset of intracranial hemorrhage, the patient’s platelet count was 0.3 × 10/μL. Diagnostic testing for thrombocytopenia was performed by examining bone marrow aspirate. We diagnosed idiopathic thrombocytopenic purpura (ITP) based on the unrepressed proliferation of megakaryocytes in the hyperplastic bone marrow (day 0). His presentation was not consistent with any other possible differential diagnosis. We did not observe any immunological abnormalities in the blood tests, including anti-cardiolipin antibody and lupus anticoagulant (antiCL–β2GP1 complex). Soon after the diagnosis of ITP, the patient was treated with prednisolone at 1.0 mg/kg/day. His platelet count immediately recovered from 0.2 × 10 to 13.8 × 10/μL 10 days after corticosteroid treatment. Seventeen days after prednisolone treatment for ITP, the pain in the patient’s right leg was exacerbated, and ischemia and cyanosis were observed (day 17). CT angiography revealed arterial sclerosis obliterans in the right leg (Fig. 1b), with

Methionine PET Might Be Reliable for the Detection of Low M-Protein–Producing Myelomas

C-methionine (MET) positron emission tomography (PET) is more sensitive than F-fluorodeoxyglucose (FDG)-PET for detecting myeloma lesion. Many clinical studies support this evidence mainly for multiple myeloma cases of IgG or IgA subtypes. However, this is not confirmed for low monoclonal protein-producing myelomas, such as IgD, IgE, and nonsecretory type. We encountered a 71-year-old man with IgD λ-type myeloma. In this patient, FDG-PET did not reveal any abnormal uptake lesions, whereas MET-PET revealed diffuse bone marrow uptake that relieved after initial chemotherapy. We speculate that the determinants for high serological activity of protein metabolism are transporter system activity or proliferation index.

Strain-specific transmission in an outbreak of ESBL-producing Enterobacteriaceae in the hemato-oncology care unit: a cohort study

BackgroundExtended-spectrum β-lactamase (ESBL)-producing bacteria are resistant to several types of antibiotics excluding carbapenems. A transmissibility of ESBL-producing Enterobacteriaceae would be depending on each bacterial property, however, that has not been elucidated in clinical setting. In this study, we attempted to identify the source of an outbreak of ESBL-producing bacteria in a medical oncology and immunology care unit.MethodsAn ESBL-producing Enterobacteriaceae (ESBL-E) outbreak observed between July 2012 and August 2012 in Kagawa University Hospital was surveyed using various molecular microbiology techniques. We used Pulsed-field gel electrophoresis (PFGE), PCR-based ESBL gene typing, and direct sequence of ESBL gene as molecular microbiology typing method to distinguish each strain.ResultsThe typical prevalence of ESBL-E isolation in the unit was 7.0 per month (1.7 per week). The prevalence of ESBL-E isolation during the target research period was 20.0 per month (5.0 per week). In total, 19 isolates (11 K. pneumoniae and 8 E. coli) were obtained from clinical samples, including four control strains (two each of both bacteria), that were physically different from those obtained from other inpatient units in our hospital. Pulsed-field gel electrophoresis (PFGE) for K. pneumoniae (digested by XbaI) produced similar patterns excluding one control strain. PCR classification of the ESBL gene for K. pneumoniae revealed that all strains other than the control strain carried SHV and CTX-M-9. This result was reconfirmed by direct DNA sequencing. Although the outbreak of K. pneumoniae was considered to be “clonal,” PFGE and PCR classification of the ESBL genes for E. coli uncovered at least six different “non-clonal” strains possessing individual ESBL gene patterns. According to the result of an antibiogram, the pattern of antimicrobial susceptibility was more variable for K. pneumoniae than for E. coli.ConclusionsTyping by PFGE and ESBL gene PCR analysis is practical for discriminating various organisms. In our cohort, two outbreaks were concomitantly spread with different transmission strategies, namely clonal and non-clonal, in the same unit. This might represent clinical evidence that transmissibility differs according to the type of strain. We speculated that patient-to-patient transmission of ESBL-E occurred according to the properties of each individual strain.