Poor response to intensive chemotherapy in de novo acute myeloid leukaemia with trilineage myelodysplasia

Summary. The findings of morphologically dysplastic features in haemopoietic cells in de novo acute myeloid leukaemia (AML) has been named AML with trilineage myelodysplasia (AML/TMDS). We analysed the clinical data, karyotypes, and treatment outcomes of 230 de novo AML patients treated with the Japan Adult Leukaemia Study Group AML-87 protocol. 40 (17%) patients had AML/TMDS. Platelet count was significantly higher ( F =0·006) and bone marrow blasts were fewer ( P =0·01) in the AML/TMDS group than in the AML without TMDS. Abnormal karyotype was shown in 12/30 patients (40%) analysed.
The complete remission (CR) rate for AML/TMDS was significantly lower than AML without TMDS (63% v 81%) ( P =0·01). The overall survival curves showed that the 40 patients with TMDS had a significantly worse survival than the 190 without TMDS ( P =0·0005). AML/TMDS also showed significantly worse disease-free survival (DFS) ( P =0·0001).
Multivariate analysis revealed that the absence of TMDS in AML was the most significant factor in obtaining CR ( P =0·01) and a significant factor in predicting longer DFS ( P =0·04). Our data suggest that AML/TMDS responds poorly to intensive chemotherapy. Further study is required to determine the best treatment strategy for AML/TMDS and the biological differences between AML/TMDS and other types of AML.     

Long-Term Survival after Linac-Based Stereotactic Radiosurgery and Radiotherapy with a Micro-Multileaf Collimator for Brain Metastasis

Background: this study aimed to evaluate the prognostic factors associated with long-term survival after linear accelerator (linac)-based stereotactic radiosurgery (SRS) and fractionated stereotactic radiotherapy (fSRT) with a micro-multileaf collimator for brain metastasis (BM). Methods: This single-center retrospective study included 226 consecutive patients with BM who were treated with linac-based SRS or fSRT with a micro-multileaf collimator between January 2011 and December 2018. Long-term survival (LTS) was defined as survival for more than 2 years after SRS/fSRT. Results: The tumors originated from the lung (n = 189, 83.6%), breast (n = 11, 4.9%), colon (n = 9, 4.0%), stomach (n = 4, 1.8%), kidney (n = 3, 1.3%), esophagus (n = 3, 1.3%), and other regions (n = 7, 3.1%). The median pretreatment Karnofsky performance scale (KPS) score was 90 (range: 40–100). The median follow-up time was 13 (range: 0–120) months. Out of the 226 patients, 72 (31.8%) were categorized in the LTS group. The median survival time was 43 months and 13 months in the LTS group and in the entire cohort, respectively. The 3-year, 4-year, and 5-year survival rate in the LTS group was 59.1%, 49.6%, and 40.7%, respectively. Multivariate regression logistic analysis showed that female sex, a pre-treatment KPS score ≥ 80, and the absence of extracranial metastasis were associated with long-term survival. Conclusions: female sex, a favorable pre-treatment KPS score, and the absence of extracranial metastasis were associated with long-term survival in the current cohort of patients with BM.     

Rupture of the diaphragm and pericardium with cardiac herniation after blunt chest trauma

A 61-year-old man was transferred to our institution because of blunt chest trauma after accidentally falling. A chest roentgenogram (CXR) and computed tomography (CT) revealed bilateral hemopneumothorax and fractures of multiple left ribs, the pelvis, and the left femur. On the second day in hospital, the patient suddenly complained of dyspnea. Emergency CXR and CT revealed elevation of the left diaphragm, suggestive of a traumatic diaphragmatic hernia; emergency surgery was performed. We confirmed rupture of the diaphragm and pericardium with cardiac herniation: the pleural pericardium and diaphragm were torn individually, and the heart and abdominal organs had herniated into the pleural cavity. They were repaired, and there were no cardiopulmonary complications during or after the operation. Pericardiodiaphragmatic rupture with cardiac herniation after multiple blunt traumas is rare. We describe the successful treatment of a diaphragmatic and pericardial rupture with cardiac herniation, with special reference to pericardial injuries.     

Polyclonal Antibodies to DNA Modified with 4-Nitroquinoline 1-Oxide: Application for the Detection of 4-Nitroquinoline 1-Oxide-DNA Adducts in vivo

Antibodies against 4-nitroquinoline 1-oxide (4NQO) adducts were elicited in rabbits immunized with 4NQO-modified DNA complexed with methylated bovine serum albumin. In enzymelinked immunosorbent assay (ELISA), the antibodies could recognize either denatured or native 4NQO-modified DNA, but not unmodified DNA, DNA modified with other carcinogens or free 4NQO derivative. Modification levels as low as 5 μmol of adduct per one mole DNA nucleotide (5 adducts/10⁶ nucleotides) can be easily detected by the competitive ELISA. Indirect immunofluorescence staining by anti 4NQO-DNA antibody indicated that the antibodies bound specifically to the nuclei of normal human skin fibroblast cells treated with 4NQO. The intensity of fluorescence was proportional to the dose of 4NQO used to treat the cells, and the fluorescence positive cells could be detected after treatment with 0.25μ M 4NQO (which resulted in the formation of 10⁴ adducts per cell). Applying the competitive ELISA to the quantitation of DNA-adducts in rats treated with 4NQO, it was confirmed that the sensitivity of immunochemical assays was equivalent to that of isotopic assays. These methods should be helpful in studies on the formation of adducts and their removal in cells and tissues.     

The present state and forthcoming problems in the work of occupational health physicians engaged in the workplace]

The authors conducted a survey in July 2001 to examine the present state and forthcoming problems facing occupational health physicians (OHPs). The establishments investigated were those which employed 1,000 or more workers and had consulted us for the employment of OHPs. The number of establishments chosen was 1,658. A questionnaire was sent to the division chiefs responsible for the health management of the establishments, and those who supervised the OHPs engaged in the establishments were asked to complete the questionnaire. The questionnaire included items about the attributes of the perspective establishments, the work of OHPs and the personnel management system for the OHPs. Four hundred and forty-seven establishments (27.0%) out a total of 1,658 returned eligible responses for further analysis, and the major results were as follows: First, 79.2% of the manufacturing establishments which responded comprised those which employed 1,000 or more workers, even though the percentage of companies which employ 1,000 or more workers throughout Japan is 62.5%. The percentage of the establishments which employed full time OHPs was 64.2% in secondary industries (mining, constructing and manufacturing), and higher than the 40.8% in tertiary industries (other than farming, forestry, fishing and secondary industries). Second, although OHPs properly coped with the obligatory issues regulated by the related laws, the OHPs who routinely consulted with workers about their work-related health problems were few (36.7%). Third, despite the low percentage of the establishments (23.5%) which had recognized OHPs' work to be part of enterprise management, the budget of the health care section was kept unchanged (55.0%). And, in 49.0% of the establishments, the nomination of OHPs was recognized to be necessary irrespective of the presence of the related laws, and OHPs were expected to cope with the work-related health problems of workers (62.9%). On the other hand, the personnel management system for OHPs was insufficient, and the performance rating for OHPs' activity was prepared for only 50.3% of the establishments. In addition, when the subjects were confined to regular OHPs, they were allowed to attend internal training courses for regular employees in only 25.0% of the establishments. Taking the above into account, the activity of OHPs has to be developed more in tertiary industries. OHPs may also be asked to positively cope with workers' work-related health problems. Simultaneously, the personnel management system for OHPs has to be arranged properly.     

Four cases of advanced colorectal cancer successfully treated with irinotecan plus 5-fluorouracil and l-leucovorin combination chemotherapy

We successfully treated four advanced colorectal cancers with irinotecan (CPT-11) plus 5-fluorouracil (5-FU) and l-leucovorin (l-LV) combination chemotherapy. We diagnosed moderately-differentiated adenocarcinoma of the colon in two patients and of the rectum in two patients. We recognized lymph node metastases in one patient and liver metastases in three patients at the time of operation. After excision for a lesion of the colon or the rectum, all patients underwent a 2-week chemotherapy regimen (CPT-11 100 mg/m2/week + 5-FU 500 mg/m2/week + l-LV 10 mg/m2/week). The effect was PR in all patients. The progressive free survival time was 9.5 months and survival time ranged 5-18 months. Grade 3 diarrhea and leukopenia were seen in one patient. All other adverse reactions were mild (grade 1 or 2). CPT-11/5-FU/l-LV combination chemotherapy appears to be effective for advanced and metastatic colorectal cancer.