A case of pulmonary squamous cell carcinoma coexisting with pulmonary actinomycosis]

A 71-year-old man was referred to our hospital complaining of cough. Chest radiography revealed a mass opacity in the right upper lung field. A transbronchial biopsy specimen revealed non-specific inflammatory changes. Percutaneous lung aspiration biopsy under ultrasound guidance demonstrated gram-positive rods, suggesting actinomyces. On the diagnosis of pulmonary actinomycosis, the patient was treated with penicillin-G and his symptoms were relieved. In a three-month follow-up, the mass shadow in the right upper lung field was found to have increased in size. Squamous cell lung cancer was diagnosed on the basis of repeated transbronchial tumor biopsies, and right upper lobectomy was performed. Most cases of pulmonary actinomycosis have been diagnosed from post-surgical tumor specimens taken on suspicion of the presence of lung cancer. However, the lung cancer in this case was difficult to diagnose because the lung cancer was co-existent with pulmonary actinomycosis.     

Immunological and molecular analysis of B lymphocytes in low-grade MALT lymphoma of the stomach. Are there any useful markers for predicting outcome after Helicobacter pylori eradication?

Background: Background: Although Helicobacter pylori eradication is effective in treating low-grade gastric mucosa-associated lymphoid tissue (MALT) lymphoma, the condition in some patients deteriorates even after the eradication. Therefore, it is important to predict the disease outcome before starting H. pylori eradication. We investigated the usefulness of flow cytometry, quantifying CD19- and CD20-positive B lymphocytes in MALT lymphoma tissue, for predicting the disease outcome after H. pylori eradication. Methods: Tissue specimens from 14 patients with H. pylori-positive low-grade gastric MALT lymphoma were examined by histology, Southern blotting, and flow cytometry before therapy. Serum levels of soluble interleukin (IL)-2 receptor were also measured. The relationship between the data and the prognosis after H. pylori eradication was analyzed. Results: Remission occurred in 10 of the 14 patients. The condition in the 4 remaining patients deteriorated even after H. pylori eradication. The percentages of CD19- and CD20-positive cells in MALT lymphoma tissue from the patients in remission were both significantly lower than those in the tissue from patients not in remission. Indeed, 4 of the 5 patients in whom both CD19- and CD20-positive cells accounted for more than 50% of the total number of lymphocytes had gastrectomy, whereas all patients in whom both CD19- and CD20-positive cells accounted for less than 50% of the total number of lymphocytes achieved remission. Although immunoglobulin gene rearrangement was present in all patients operated on, there were also 6 patients whose MALT lymphoma was ameliorated in spite of the presence of gene rearrangement. The serum level of soluble IL-2 receptor was in the normal range in all patients tested. Conclusions: Analysis of mature B-cell markers in MALT lymphoma tissue is more useful than the examination of immunoglobulin gene rearrangement or serum levels of soluble IL-2 receptor in predicting the outcome of low-grade gastric MALT lymphoma after H. pylori eradication. Received: January 5, 2001 / Accepted: November 2, 2001     

Left ventricular filling measured by Doppler echocar diography during dynamic exercise in patients with myocardial infarction

Summary To assess left ventricular diastolic properties in response to dynamic exercise, mitral inflow velocity integrals were measured by pulsed-wave Doppler echocardiography in ten patients with myocardial infarction and in ten normal subjects, and simultaneous left ventricular pressure was obtained with micromanometry in the patients. Early filling velocity integrals were maintained in the patients during exercise. Late filling velocity integrals were not augmented during exercise in the patients, but were increased in the normal subjects. In the patients, there was an increase in mitral valve opening pressure, left ventricular end-diastolic pressure, and the time constant of left ventricular isovolumic pressure decay. The lowest diastolic pressure and the number of time constants that had elapsed before the lowest diastolic pressure remained unchanged. These results show that in patients with myocardial infarction, early filling is maintained by an increase in driving pressure during exercise, despite incomplete relaxation. Augmentation of late filling, seen in normal subjects, is impaired in patients with myocardial infarction, probably due to an increase in left ventricular stiffness.     

Successful treatment of chronic granulomatous disease with fludarabine-based reduced-intensity conditioning and unrelated bone marrow transplantation

Allogeneic hematopoietic stem-cell transplantation (HSCT) for chronic granulomatous disease (CGD) with a reduced-intensity conditioning regimen can be expected to lead to less therapy-related mortality and late-onset impairment, whereas it has also been reported to increase the risk of unsustained mixed donor chimerism and late rejection after transplantation. Herein, we report a 4-year-old boy with CGD who was successfully treated with unrelated bone marrow transplantation with a reduced-intensity conditioning regimen (RIC). Fludarabine-based RIC, 4 Gy of total body irradiation, 120 mg/kg of cyclophosphamide, and 125 mg/m² of fludarabine, was adopted for transplantation, followed with 8.9 × 10⁸/kg mononucleated donor cells infused without T-cell depletion. Although hematopoietic engraftment was rapidly obtained by day +17, he developed unstable donor chimerism. After tacrolimus withdrawal, the patient showed grade III acute graft-versus-host disease (GVHD), and subsequently reached full donor chimerism by day +61. Twelve months post-transplant, the patient has remained well with stable and durable engraftment, 100% donor chimerism, and normal superoxide production, without the requirement of donor lymphocyte infusions (DLI).     

Efficacy of ghrelin as a therapeutic approach for age-related physiological changes

Aging is associated with decreases in food intake and GH secretion, termed the anorexia of aging and somatopause, respectively. The mechanisms underlying these phenomena are not fully understood. Although many approaches have attempted to improve these age-related physiological changes, none have achieved satisfactory results. Ghrelin, a 28-amino-acid acylated peptide, was identified as an endogenous ligand for the GH secretagogue receptor. Ghrelin stimulates GH secretion and food intake in animals and humans. Previous studies have demonstrated that the mean plasma concentrations of ghrelin in normal-weight elderly people were lower than those in younger people. We hypothesized that ghrelin administration might improve the metabolic and physiological changes that accompany the anorexia of aging and somatopause. First, 75-wk-old mice fasted for 72 h, after which they resumed feeding with sc administration of ghrelin (360 microg/kg) twice daily for 4 d. Multiple administrations of ghrelin after a 72-h fast increased food intake and hastened body weight recovery with a high lean body mass ratio. Next, 50-wk-old mice were sc injected with rat ghrelin (40 microg/kg) twice weekly from 50-80 wk of age. Long-term administration of ghrelin kept aged mice with low body weight and low adiposity. These results suggest that ghrelin might be a novel approach for the therapy of age-related metabolic and physiological changes.     

Protocol digest of randomized phase II study of modified FOLFIRINOX versus gemcitabine plus nab-paclitaxel combination therapy for locally advanced pancreatic cancer: Japan clinical oncology group study (JCOG1407)

Gemcitabine is one of the standard treatments for locally advanced pancreatic cancer. Recent studies on metastatic pancreatic cancer have shown that combination chemotherapy with oxaliplatin, irinotecan, fluorouracil, and leucovorin (FOLFIRINOX) and gemcitabine plus nab-paclitaxel (GnP) prolonged the overall survival compared with gemcitabine alone. To select the most promising chemotherapy, a randomized phase II selection design trial was started in July 2016 to compare between modified FOLFIRINOX and GnP for patients with locally advanced pancreatic cancer. A total of 124 patients will be enrolled from 36 Japanese institutions within 2.5 years. The primary endpoint is the proportion of 1-year overall survival, and secondary endpoints are progression-free survival, distant metastasis-free survival, response rate in patients with target lesions, CA19-9 response, adverse events, treatment-related death, early death, grade 4 non-hematological toxicity, and dose intensity. This trial has been registered with the UMIN Clinical Trials Registry [http://www.umin.ac.jp/ctr/index.htm], and the registration number is UMIN000023143.     

Cytotoxic T-Cell Lymphoma Arising in Behçet Disease

The case of a 49-year-old man with peripheral T-cell lymphoma arising in Behçet disease (BD) is reported. A diagnosis of incomplete BD was made, and the patient was treated with immunosuppressive agents for 9 months. A left perirenal mass emerged, and a computed tomography-guided needle biopsy of the tumor revealed the infiltration of small- and medium-sized lymphoma cells.The cells were positive for CD3, CD8, CD45RO, CD43, granzyme B, and T-cell intracellular antigen-1.A diagnosis of non-Hodgkin’s lymphoma (diffuse medium, T-cell) was made.A left orbital mass also appeared. Standard combination chemotherapy diminished the perirenal and orbital lesions.Lymphoma cell infiltration in the esophagus was detected after chemotherapy, and the patient died of massive bleeding from the gastrointestinal tract. Non-Hodgkin’s lymphoma is rarely associated with BD, and only 7 cases have been reported in the literature.We have summarized the published case reports of malignant lymphoma arising in BD.To our knowledge, this case report is the first to describe cytotoxic T-cell lymphoma arising in Behçet disease.     

Adjuvant treatments for resectable hepatocellular carcinoma

Hepatocellular carcinoma often recurs even after curative resection. Although some encouraging data showing improvements in recurrence-free times have been reported with the use of intraarterial 131I-lipiodol infusion, retinoids, interferon, or immunotherapy after hepatectomy, there is no consensus regarding standard adjuvant therapy for resectable hepatocellular carcinoma. A novel target agent, sorafenib, which has recently become a standard of care for advanced disease, may also be promising in an adjuvant setting to prevent early recurrence after curative surgery. In future trials, it will be important to identify appropriate target populations for each type of adjuvant approach; that is, an agent with definitive antitumor activity for high-risk patients, and one that shows chemoprevention for low-risk patients.     

Endosonographic features in patients with non-alcoholic early chronic pancreatitis improved with treatment at one year follow up

Since the prevention of early chronic pancreatitis (ECP) into chronic pancreatitis might be critical for the reduction of pancreatic cancer, we tried to clarify the pathophysiology of ECP patients, focusing on ECP patients without alcoholic chronic pancreatitis. 27 ECP patients without alcoholic chronic pancreatitis and 33 patients with functional dyspepsia with pancreatic enzyme abnormalities (FD-P) were enrolled in this study. Diagnosis of ECP was made when imaging findings showed the presence of more than 2 out of 7 endoscopic ultrasound features. Duodenal degranulated eosinophils and glucagon-like peptide 1 producing cells were estimated by immunostaining. There were no significant differences in characteristics and psychogenic factors between ECP and FD-P patients. Interestingly, endoscopic ultrasound score in ECP patients significantly improved, albeit clinical symptoms in ECP patients showed no improvement at one year follow up. The extent of migration of duodenal degranulated eosinophils in FD-P patients was significantly higher compared to that in ECP patients. The levels of elastase-1 and trypsin in ECP patients with improved endoscopic ultrasound features were significantly reduced by the treatment. Further studies will be needed to clarify whether clinical symptoms and endoscopic ultrasound features in ECP patients without alcoholic chronic pancreatitis were improved in longer follow up study.