Treatment results for Stage Ib cervical cancer after stage subdivision by MRI evaluation.

PURPOSE OF INVESTIGATION: The authors analyzed treatment results for cervical cancer after subdividing Stage Ib into Stages Ib1 and Ib2 according to magnetic resonance imaging (MRI) information. MATERIALS AND METHODS: The subjects comprised 40 cases of Stage Ib cervical cancer treated by definitive radiotherapy in Kitasato University hospital and Tokyo University hospital from January 2000 to December 2008. The patients' ages ranged from 28 to 85 years (median: 68 years). The maximum tumor diameter measured with MRI ranged from undetectable to 60 mm (median: 25 mm). The authors classified tumors with the greatest dimension less than 40 mm as Stage Ib1 (29 cases) and those with the greatest dimension more than 40 mm as Ib2 (11 cases). All cases were treated with a combination of external beam irradiation and high-dose-rate intra-cavitary brachytherapy. Chemotherapy was combined with radiotherapy in 11 cases. RESULTS: The follow-up time was from four to 109 months (median: 53 months). At the time of last observation, 37 cases survived, local recurrence was seen in none, and two cases showed distant metastasis. The two- and five-year overall survival rates of all cases were 97.5% and 89.5%, respectively. When a stage was subdivided and examined, the five-year overall survival rate of Stage Ib1 was 100% and that of Stage Ib2 was 50.5% (p = 0.001). CONCLUSION: The authors suggest that the subdivision of stages using image information reflects the prognosis of Stage Ib cervical cancer.

Salvage radiation therapy and chemoradiation therapy for postoperative locoregional recurrence of esophageal cancer.

The purpose of this retrospective study was to assess the efficacy of salvage radiation therapy (RT) or chemoradiation therapy (CRT) for locoregional recurrence (LR) of esophageal cancer after curative surgery. Forty-two patients who received salvage RT or CRT for LR of esophageal cancer after curative surgery between November 2000 and May 2012 were reviewed. The intended RT regimen was 60 Gy in 30 fractions combined with concurrent platinum-based chemotherapy. Median follow-up periods were 17.9 months for all evaluable patients and 28.2 months for patients still alive (19 patients) at analysis time. The 1-, 2-, and 3-year survival rates were 81.2 ± 6.4%, 51.3 ± 8.6%, and 41.1 ± 8.7%, respectively, with a median survival time of 24.3 ± 4.1 months. Out of 41 evaluable patients, 16 patients (39%) were alive beyond 2 years from salvage therapy. However, univariate analyses for overall survival showed no significant prognostic factor. Grade 3 or higher leukocytopenia was observed in 46% of the patients. Salvage RT or CRT for LR after surgery for esophageal cancer was safe and effective. These therapies may offer long-term survival to some patients. RT or CRT should be considered for LR.

Esophageal cancer: definitive chemoradiotherapy for elderly patients.

To investigate the efficacy and toxicity of definitive chemoradiotherapy (CRT) for elderly patients with locally advanced esophageal cancer. Twenty-two patients aged over 75 that performed definitive CRT were retrospectively reviewed. The regimen included concurrent CRT consisting of two cycles of chemotherapy (CTx) of platinum and 5-fluorouracil, and radiation therapy (RT) of 50-50.4 Gy (actual range: 45.4-71.4 Gy), and additional CTx where possible. Both CTx and RT were reduced in dose and field where necessary. The disease-free survival rate and the overall survival rate at 3 years were 33.3% ± 11.4% and 25.9% ± 10.8%. Grade 4 leukocytopenia and thrombocytopenia occurred in three (14%) and four (18%) patients. Treatment-related death was suspected in up to four (18%) patients at the most. Univariate analyses for disease-free survival showed that neither total radiation dose nor number of total cycles of CTx was significant. The pattern of relapse was predominantly more frequent in the intra-RT field than outside the RT field. For elderly patients, adverse events are frequent, and decreased organ reserve may cause treatment-related death. Reduction in CTx dose or RT field, appropriate only for two cycles of CTx, and careful monitoring may help to minimize toxicity. Physicians should not be too afraid of adverse events or be negative about CRT for elderly patients, as long as comorbidities and complications are managed carefully.

Concurrent chemoradiation alone with curative intent for limited-disease small-cell esophageal cancer in nine Japanese patients.

Small-cell carcinoma of the esophagus is a rare and aggressive tumor with early widespread dissemination. In this retrospective study, we report clinical outcomes of limited-disease small-cell carcinoma of the esophagus from the analysis of nine patients. Between 2003 and 2006, nine consecutive patients with small-cell carcinoma of the esophagus were treated in our single institution, representing 2.8% of all esophageal malignancies treated with curative concurrent chemoradiation during this period. All the patients received four cycles of etoposide (100 mg/m(2), days 1-3), combined with cisplatin (80 mg/m(2), day 1), plus radiation therapy (50 Gy in daily doses of 2 Gy, 5 days/week). At the time of analysis, the median follow-up time was 10.8 months (range: 4.2-42.8 months) and 21.8 months in five living patients (56%). Of all the nine patients, five patients (56%) had a complete response, and the actuarial 3-year overall survival rate was 55.6%. This regimen resulted in a favorable 3-year survival rate. We conclude that the optimum treatment seems to be the same as for small-cell carcinomas of the lung, that is, a multidrug combination chemotherapy regimen used with concurrent radiation.

Interleukin 1 polymorphisms, lifestyle factors, and Helicobacter pylori infection.

Associations between Helicobacter pylori (HP) infection and lifestyle factors have been reported by several authors, but little is known about the host factors associated with the infection. This study aims to examine the infection rate of HP according to gene polymorphisms of interleukin (IL)-1A, IL-1B, and IL-1RN, and to investigate the interactions with lifestyle factors. Subjects were 241 non-cancer outpatients who had participated in a HP eradication program. Polymorphisms at - 889 (T to C) of IL-1A, at - 31 (C to T; T allele makes a TATA box) and - 511 (C to T) of IL-1B, and at intron 2 (86-bp VNTR (variable number of tandem repeats)) of IL-1RN were genotyped by PCR (polymerase chain reaction), PCR-RFLP (restriction fragment length polymorphism) and PCR-CTPP (PCR with confronting two-pair primers). It was found that IL-1B polymorphisms at - 31 and - 511 were near-completely linked, but in the opposite way to that in Caucasians; - 31C / - 511T and - 31T / - 511C alleles were dominant in the present subjects. The HP infection rate was substantially different among the genotypes of IL-1B C - 31T; 45.2% (19 / 42) for the C / C, 67.7% (90 / 133) for the C / T, and 63.6% (42 / 66) for the T / T. The age-sex adjusted odds ratio (OR) relative to the C / C genotype was 2.32 (95%CI (confidence interval), 1.10 - 4.92) for the T / C genotype and 2.46 (1.06 - 5.74) for the T / T genotype. The OR for the T / T genotype was significantly modified by smoking status; interaction term = 14.6 (1.12 - 190). The polymorphisms of IL-1A and IL-1RN were not associated with the infection rate. The results suggested that the T allele of IL-1B C - 31T is associated with vulnerability to persistent HP infection, and that the vulnerability is modified by smoking.

No association of the 5' promoter region polymorphism of CYP17 with breast cancer risk in Japan.

To examine the association between breast cancer risk and a T-to-C substitution polymorphism at the 5' promoter region of CYP17, a case-control study was conducted at Aichi Cancer Center Hospital in Japan. Subjects were 144 histologically confirmed breast cancer patients diagnosed in the past 4 years and 166 hospital controls without cancer. Allele frequency among controls was 44.9% (95% confidence interval; 39.5 - 50.2) for C allele. Odds ratio (OR) of the polymorphism relative to TT-genotype was 0.97 (0.58 - 1.64) for TC-genotype and 0.81 (0.39 - 1.68) for CC-genotype. Subgroup analyses revealed that the OR was not statistically significant for the subgroups stratified by interval after diagnosis, age at menarche, age at first birth, menopausal status, body mass index, and mother / sisters' history of breast cancer. Consistent with previous studies conducted in other countries, the 5' promoter region polymorphism of CYP17 affected breast cancer risk of Japanese women to a limited extent. Although this is not a large-scale case-control study with population controls, these findings provide enough information to discourage further studies on the association between this polymorphism and breast cancer risk in Japan at large, and suggest that this polymorphism is useless for breast cancer risk estimation.

Virus entry is a major determinant of cell tropism of Edmonston and wild-type strains of measles virus as revealed by vesicular stomatitis virus pseudotypes bearing their envelope proteins.

The Edmonston strain of measles virus (MV) that utilizes the human CD46 as the cellular receptor produced cytopathic effects (CPE) in all of the primate cell lines examined. In contrast, the wild-type MV strains isolated in a marmoset B-cell line B95a (the KA and Ichinose strains) replicated and produced CPE in some but not all of the primate lymphoid cell lines. To determine the mechanism underlying this difference in cell tropism, we used a recently developed recombinant vesicular stomatitis virus (VSV) containing as a reporter the green fluorescent protein gene in lieu of the VSV G protein gene (VSVDeltaG*). MV glycoproteins were efficiently incorporated into VSVDeltaG*, producing the VSV pseudotypes. VSVDeltaG* complemented with VSV G protein efficiently infected all of the cell lines tested. The VSV pseudotype bearing the Edmonston hemagglutinin (H) and fusion (F) protein (VSVDeltaG*-EdHF) infected all cell lines in which the Edmonston strain caused CPE, including the rodent cell lines to which the human CD46 gene was stably transfected. The pseudotype bearing the wild-type KA H protein and Edmonston F protein (VSVDeltaG*-KAHF) infected all lymphoid cell lines in which the wild-type MV strains caused CPE as efficiently as VSVDeltaG*-EdHF, but it did not infect any of the cell lines resistant to infection with the KA strain. The results indicate that the difference in cell tropism between these MV strains was largely determined by virus entry, in which the H proteins of respective MV strains play a decisive role.

Dermatomyositis associated with invasive thymoma.

We report a case of dermatomyositis (DM) associated with invasive thymoma in a 22-year-old woman who was admitted to our hospital complaining of dyspnea which required ventilation support. The reddened elevated scaly eruptions were prominent over the extensor surfaces. Chest X-ray and computed tomography showed mediastinal masses, which were diagnosed as mixed type thymoma. Muscle and skin biopsy specimens were compatible with DM. She was treated with methylprednisolone pulse therapy followed by extended removal of the anterior mediastinal tumor and subsequent radiotherapy. She has had a good clinical course without recurrence of thymoma or DM for more than 3 years. The role of thymoma in the development of DM is discussed.

Tea polyphenol intake and changes in serum pepsinogen levels.

Following a phase I study, a phase II study was conducted to evaluate the effects of two different doses of tea polyphenols on serum pepsinogen levels. Subjects were patients aged 40 to 69 years who had undergone gastroscopy between 1995 and 1997 at Aichi Cancer Center Hospital, and had been found to have no disease requiring medication. Those with pepsinogen I < 70 ng/ml and pepsinogen I/II ratio < 6 were included in this study. Capsules containing 100 mg of tea polyphenols were administered for 1 year: 1 capsule per day for 101 patients (42 males and 59 females), and 6 capsules (equivalent to 10 cups) per day for 83 patients (30 males and 53 females). The enrollment of the 1 capsule group preceded that of the 6 capsule group, in which re-participation was allowed. Blood samples were obtained 1 year after participation from 86 participants of the 1 capsule group and 77 participants (43 new participants and 34 re-participants) of the 6 capsule group. The compliance in polyphenol capsule intake ranged from 11.4 to 105.7% (87.6% on average) of the scheduled amount for the 1 capsule group and 3.2 to 112.3% (77.8% on average) for the 6 capsule group. No serious polyphenol-related adverse effects were reported. The difference in pepsinogen I between before and after 1 year intake of the polyphenol was 3.1 ng/ml for the 43 participants of the 6 capsule group, but 3.5 ng/ml for the 1 capsule group. The mean pepsinogen I/II ratio for the 43 participants increased from 2.37 by 0.08. This increase was not larger than that for the 1 capsule group (from 2.61 by 0.11). Among 34 participants in both interventions, no significant increase in pepsinogen I and I/II ratio for the 6 capsule intervention was observed. This result suggests that additional polyphenol intake for 1 year in Japanese does not improve pepsinogen levels, which are considered to reflect stomach atrophy, a high-risk condition for stomach cancer.

Identification of a novel bovine serum protein which is involved in human T-cell leukemia virus type I (HTLV-I)-induced syncytium formation.

By immunizing rats with cocultured HTLV-I-positive ILT8M2 and HTLV-I-negative MOLT-4-cells, we isolated a monoclonal antibody (mAb), designated as mAb R21, which enhances the syncytium formation induced by coculturing ILT8M2 cells with MOLT-4 cells. The antigen recognized by mAb R21 was found on the surface of all T-cell, fibroblastoid, and epithelial cells lines, and a part of B-cell and myelomonocytoid cell lines. MAb R21 reacted with an approximately 17-kDa protein from ILT8M2 and MOLT-4 cell lysates in both nonreducing and reducing conditions by immunoblotting. Immunoprecipitation experiments using surface-labeled cells revealed that a 17-kDa protein is present on the surface of both ILT8M2 and MOLT-4 cells. Since the enhancing activity by mAb R21 of syncytium formation was observed only in the presence of a factor contained in fetal calf serum (FCS) which seems to bind to mAb R21, we purified this serum factor from FCS using a mAb R21-coupled Sepharose 4B column. The purified protein, designated as R21 protein, was revealed to be O-glycosylated but not N-glycosylated protein of approximately 17 kDa. The partial amino acid sequence of this protein indicates that R21 protein is a novel bovine serum protein which has approximately 90% amino acid homology with bovine platelet factor 4, a member of CXC chemokine family. These results indicate that the R21 protein on the surface of cells and/or in FCS may play an important role in the process of HTLV-I-induced syncytium formation by as yet unknown mechanism.

Host range of human T-cell leukemia virus type I analyzed by a cell fusion-dependent reporter gene activation assay.

We constructed a sensitive and quantitative assay system to examine human T-cell leukemia virus type I (HTLV-I) envelope (env) glycoprotein-mediated cell fusion in which T7 RNA polymerase in donor cells coexpressing env glycoproteins activates a reporter gene in recipient cells upon cell fusion. An efficient expression of HTLV-I env glycoproteins (gp46 and gp21) was observed in 293T cells transfected with an expression plasmid by both immunoblot and immunofluorescence analyses. The cells expressing env glycoproteins also exhibited self-fusion. By cocultivating the donor cells with recipient cells transfected with a reporter plasmid possessing the luciferase gene under the T7 promoter, the expression of luciferase was observed upon cell fusion. The activation of the luciferase gene was inhibited by either anti-env neutralizing antibody or synthetic peptide corresponding to env gp21, thus indicating the cell fusion to be specifically mediated by the HTLV-I env glycoproteins expressed in the donor cells. A broad range of cell lines exhibited susceptibility to HTLV-I env-mediated cell fusion by this assay. This newly established assay system may thus provide an efficient way both to study the fusion mechanisms mediated by HTLV-I env glycoproteins and to identify the HTLV-I receptor(s).

Hemophagocytic syndrome associated with fulminant ulcerative colitis and presumed acute pancreatitis.

We herein report a case of hemophagocytic syndrome that developed in a 25-yr-old man with fulminant ulcerative colitis and presumed acute pancreatitis. Physical examination on admission showed a chronically ill, delirious patient with an upper abdominal mass. Peripheral blood showed progressive pancytopenia and bone marrow aspirate smears revealed hypocellular bone marrow with an increase of histiocytes showing prominent hemophagocytosis. Plain abdominal radiography revealed toxic megacolon. Both ultrasound and computed tomography showed the enlargement of the pancreas, thus indicating presumed acute pancreatitis. No apparent neoplasms or viral or bacterial infections, which are normally reported to be the cause of hemophagocytic syndrome, were detected. The patient was successfully treated with high doses of prednisolone and gamma-globulin.

Patients' views on residual blood use for research purposes.

In order to document patients' views on residual blood use for research purposes, a questionnaire survey was conducted at Aichi Cancer Center Hospital in October 1997. Subjects were patients who had undergone blood tests at a central blood sampling room in the morning during the week of the study enrollment. The questionnaire was handed out and collected at a waiting area in front of the blood sampling room. Of the 583 patients to whom we tried to hand out the questionnaire, 558 participated (258 males, 294 females, and 6 of sex unknown) and 25 refused. Those who regarded research to improve health care as important were 76.7% of those sampled. Only 28 patients (5.0%) answered that they would not permit the use of their residual blood for research purposes. Although logistic analysis did not detect significant factors influencing the giving of permission, the percentage who would not permit the use of their residual blood for research purposes was significantly higher in cancer outpatients (6.7%) than in inpatients (1.0%). It seems desirable for hospitals to establish an open policy concerning residual blood use for research purposes.

[Comparative trial of granisetron alone and granisetron plus methylprednisolone for prevention of nausea and vomiting during cancer chemotherapy].

A crossover clinical trial between granisetron alone and granisetron combined with methylprednisolone (MPL) was undertaken for the prevention of nausea and vomiting during chemotherapy, including cisplatin, in 12 patients with advanced primary and metastatic lung cancer. The antiemetic effect was obtained in 91.7% (11/12 cases) of patients receiving granisetron alone compared to 100% (12/12 cases) of patients receiving the combination of granisetron plus MPL. Complete control of anorexia was achieved in 91.6% (11/12 cases) of patients receiving the combination compared to 58.3% (7/12 cases) of patients receiving granisetron alone. Moreover there was a significant improvement of delayed clinical symptoms including nausea, vomiting, and anorexia in the patients receiving the combination of granisetron plus MPL. Our data suggest that the antiemetic effect of the combination of granisetron plus MPL is superior to granisetron alone in patients receiving cancer chemotherapy.

[Evaluation of cardiotoxicity in new anthracycline analog ME 2303. ME 2303 Study Group].

ME 2303 is a new anthracycline analog which differs from adriamycin in the sugar moiety. ME 2303 displays a higher antitumor activity against L 1210 and P 388 Leukemia than adriamycin. To evaluate the cardiotoxicity of ME 2303, ECG tracings (21 patients) and Holter ECGs (9 patients) were recorded before and after the administration of ME 2303 for various malignancies (mean dose 123.8 mg/m2), and some of the electrocardiographic parameters were analyzed. Control ECGs were normal in 17 patients, in 4 patients minor ECG findings like sinus tachycardia (2 patients), low voltage (1 patient) and flattening of the T wave (1 patient) were observed. After treatment, no relevant ECG changes were observed except one case who showed a flat T in pretreatment ECG. In this patient developed ST-T changes were seen after treatment. The basic rhythm was sinus rhythm in all of the cases, and the heart rate showed no significant changes. ME 2303 had no effects on the specialized conduction system. With regard to arrhythmia, no increase in number and severity was observed. In Holter ECG no development of ST-T changes was seen after treatment.

[Cardiotoxicity and pulmonary toxicity of chemotherapy].

Recently, the quality of life of a cancer patient has been extensively discussed. Especially, side effects of chemotherapy are major problems of cancer patients. Cardiotoxicity of adriamycin and pulmonary toxicity of bleomycin are not common side effects of chemotherapy, but they can be devastating, particularly, when they occur in a patient who has been cured of cancer. Therefore, we tried to demonstrate the efficacy of cardiac or pulmonary monitoring in early detection of the toxicity. In conclusion, now non-invasive and invasive standard methods of monitoring have yet to be convincingly established, because most methods are either of no predictive value or too sensitive. Moreover, to date an effective prophylaxis of cardiotoxicity or pulmonary toxicity is still lacking. Exact evaluation of risk factors and thorough cardiac or pulmonary monitoring are necessary in patients under chemotherapy.

[Therapeutic effect of recombinant interferon alpha on Takatsuki disease].

A case of Takatsuki disease, 57-year-old male associated with monoclonal IgA, lambda-type immunoglobulin was treated with recombinant alpha-interferon daily by intramuscular injection with an initial dose of 3 X 10(6) U/day. Four weeks later, gynecomastia was improved and breast pain disappeared. Increases of cholesterol from 84 mg/dl to 135 mg/dl and cholinesterase from 0.24 delta pH to 0.48 delta pH were observed, 8 weeks later. Though, there was no reduction in serum M protein, no decrease in the number of bone marrow tumor cell and no restoration of muscle atrophy and polyneuropathy. No predominant side effect was observed. We conclude that rIFN alpha has a some potential role in the treatment of Takatsuki disease and additional chemotherapy should be considered. Significance of the therapy against Takatsuki disease was discussed.

[Clinical study of acute cardiotoxicity of anti-cancer agents-- analysis using Holter ECG monitoring].

To investigate the features of acute cardiotoxicity caused by the anticancer agents, adriamycin (ADM), THP-adriamycin (THP), epirubicin (epi-ADM) and mitoxantrone (MIX), Holter electrocardiograms were recorded before and after administration of these drugs and some of the electrocardiographic parameters were analyzed. The heart rate tended to increase after ADM administration, but other agents had no effect. The basic rhythm was sinus rhythm in many cases except for only one case in which intermittent atrial fibrillation developed after ADM administration. These agents had no effects on the specialized conduction system. With regard to supraventricular premature beats, no increase in preexisting supraventricular premature beats was observed, but there was a slight tendency for the fresh appearance of supraventricular extrasystoles after administration of these agents. On the other hand, ventricular premature beats tended to increase in number and severity after ADM therapy. The other three agents induced no significant increase in ventricular extrasystoles. Development of ST-T changes was seen after the administration of ADM and THP, but epi-ADM and MIX produced no significant changes. In conclusion, epi-ADM and MIX were less cardiotoxic than ADM and THP.