A 67-year-old man developed a diffuse large B-cell lymphoma, and was simultaneously diagnosed as myelodysplastic syndrome(refractory cytopenia with multilineage dysplasia). Acute lung injury was complicated after the 6th course of rituximab injection, but was recovered by steroid pulse therapy. At that moment, marked leucocytosis was prominent due to the disease progression of myelodysplastic syndrome. Two months later, he relapsed into lymphoma systematically. During salvage chemotherapy without rituximab, the patient deteriorated into lethal respiratory failure. Autopsy findings revealed the diffuse alveolar damage with microscopic evidence of an adenovirus infection. His bone marrow showed the transformation of myelodysplastic syndrome into acute myeloid leukemia. The coincidence of myeloproliferative and lymphoproliferative diseases in the same patient is a rare phenomenon. We should be cautious when acute lung injury occurs during such a condition.

A 60-year-old man with liver cirrhosis caused by hepatitis C, who was receiving warfarin anticoagulation following acute myocardial infarction, was diagnosed with advanced hepatocellular carcinoma and multiple lung metastases, and began treatment with sorafenib 200 mg daily. From the treatment's start to 14 and 63 days later, sorafenib was increased to 400 mg and 600 mg, respectively. After increasing the quantity to 600 mg, he had an increase in PT-INR values and experienced a lower-extremity hemorrhage. For the patient with liver cirrhosis, who is receiving warfarin, PT-INR values might be elevated during the early period of sorafenib treatment dosage as for the increase in quantity. Therefore, when increasing dosage, a frequent measurement of PT-INR and a careful follow-up for PT-INR is necessary.

Vinca alkaloids (VA) are some of the key anti-tumor agents for patients with hematological malignancies, and various adverse events such as paralytic ileus, peripheral neuropathy, and constipation were now recognized as adverse VA effects. Furthermore, azole anti-fungal agents are known to enhance VA toxicity because they delay the metabolism and excretion of VA by inhibiting CYP3A4. However, their clinical relationship has not been clearly described. Therefore, we studied neurotoxicity as a possible adverse event associated with VA in patients treated with azole anti-fungal agents, retrospectively. In our study, 100 patients (479 episodes) who received VA in our department from August 2008 to December 2010 were analyzed. Adverse events attributed to the combined administration of vincristine (VCR) and azole anti-fungal agents were grade 3 paralytic ileuses in 8 patients (8 episodes), grade 3 or 4 constipation in 16 patients (16 episodes), and grade 3 peripheral neuropathy in 10 patients (16 episodes). In addition, we investigated whether temporal discontinuation of azole anti-fungal agents during VA treatment decreases the frequency of these adverse events, and detected that it is likely to help avoid neurotoxicities enhanced by itraconazole, such as severe constipation (p=0. 0308) and paralytic ileus (p=0. 0967). Our findings indicated that we should pay much more attention to these adverse events, and must select patients carefully when we administer azole anti-fungal agents to them while they are being treated with VA.

Nausea and vomiting are major adverse reactions in cancer chemotherapy, and affect quality of life (QOL). We performed a retrospective study that examined the efficacy of aprepitant and palonosetron for chemotherapy-induced nausea and vomiting (CINV) on patients taking cisplatin doublets for lung cancer. The study subjects were 73 patients. A 5-HT(3) group received old-generation 5-HT(3) receptor antagonists and dexamethasone for preventive treatment (32 patients). An A group received old-generation 5-HT(3) receptor antagonists, aprepitant and dexamethasone (22 patients). An A+P group received palonosetron, aprepitant and dexamethasone (19 patients). On acute emesis (occurring within 24 hours after chemotherapy), there was no significant difference in the complete suppression rate of nausea and vomiting among the three groups. However, on delayed onset emesis (occurring between 24 to 120 hours), the complete suppression rate of nausea was significantly higher in the A+P group (57. 9%) than in the 5- HT(3) group (16. 7%) and A group (23. 8%). Significantly better efficacy was seen in the 5-HT(3) group and A group in the complete suppression rate of vomiting, and in the need of rescue medication rates on delayed-onset emesis. The cost of antiemesis was 19, 735 yen for the 5-HT(3) group, 32, 252 yen for the A group and 15, 557 yen for the A+P group. In conclusion, it was suggested that concurrent administration of palonosetron, aprepitant and dexamethasone for CINV on cisplatin doublet in lung cancer is a clinically useful treatment that might reduce the economic burden on patients.

Chemoradiotherapy for head and neck cancer is associated with a high incidence of severe oral mucositis; an adverse, painful event. Oral mucositis also causes nutritional deficiency by making oral feeding difficult. This may lead to prolongation of hospitalization due to complications caused by malnutrition. However, an effective way to prevent oral mucositis completely, remains to be found. In this study, we evaluated the occurrence of oral mucositis, and nutritional conditions such as hypoalbuminemia, reduction of body weight, and length of hospital stay (days) when the mouth was rinsed using rebamipide solution (R solution), or Poraprezinc-alginate sodium solution (P-A solution) (both considered to be effective for oral mucositis). A mouth rinsed with sodium azulene sulfonate (S solution) was used as a control. The mouth was rinsed out six times per day continuously during chemoradiotherapy. In the study, 31 patients were assigned to rinse their mouths using R solution, 11 patients using PA solution, and 15 patients using S solution (reduction rate of body weight in 14 patients). For the evaluation, the criteria for adverse drug reactions CTCAE (v3. 0) were used. Grade 1 and over, oral mucositis occurred in 48% of the R solution group, 36% of the P-A solution group, and 80% of the S solution group, indicating that the P-A solution group significantly prevented the occurrence of oral mucositis as opposed to the S solution group. A reduction in body weight was observed in 81% of the R solution group, 82% of the P-A solution group, and 79% of the S solution group, indicating a similar weight reduction rate among individual solution groups. Hypoalbuminemia equal to grade 2 or higher occurred in 3% of the R solution group, 18% of the P-A solution group, and 29% of the S solution group, indicating that the R group significantly prevented the occurrence of hypoalbuminemia compared to the S solution group. In addition, the length of hospital stays were 44 ± 8. 0 days for the R solution group, 52 ± 18. 8 days for the P-A solution group, and 61 ± 19. 5 days for the S solution group, indicating that the R solution group significantly shortened the length of hospital stay compared to the S solution group. These results suggested that the use of an R or P-A solution may be effective in preventing oral mucositis and impaired nutrition of those undergoing chemoradiotherapy for head and neck cancer.

We describe a 54-year old woman with oxaliplatin-induced autoimmune hemolytic anemia and review the clinical features of similar published cases. The present patient had metastatic colon cancer and was admitted to our hospital with a floating sensation and general malaise on day 4 after undergoing the last of 4 cycles of a 7th round of chemotherapy with XELOX. Laboratory data revealed 4.6g/dl hemoglobin and 8.77 mg/dl creatinine. Direct and indirect Coombs tests of a blood sample for blood transfusion were both positive. We diagnosed immune hemolysis with acute renal failure based on the clinical course and blood samples showing haptoglobin <10mg/dl. We treated her with hemodialysis, plasmapheresis and immune suppression with prednisolone, which improved the anemia and renal failure.

The present study was carried out to examine the chemopreventive effects of 5-fluorouracil (5-FU) and lactoferrin (LF) on goldfish intestinal carcinogenesis induced by 1,2-dimethylhydrazine (DMH). DMH was given to fish by intraperitoneal injection in a dosage of 15 mg/kg body weight once a week for 6 weeks. Eight weeks after the initial DMH injection, fish were randomly divided into 2 groups, control and LF-treated groups. Control fish fed a commercial diet. LF- treated fish fed a commercial diet with bovine lactoferrin (oral administration at 200 mg/kg body weight/day). Ten weeks after the initial DMH injection, each was divided into 2 groups, saline- and 5-FU- treated groups. Physiological saline for freshwater fish (0.75% NaCl solution) in the saline-treated fish and 5-FU dissolved in 0.75% NaCl solution in the 5-FU-treated (75 mg/kg body weight) fish were injected intramuscularly three times every other day, respectively. The mean number of precancer cell foci (PCF) per intestine was 2.7 in DMH treated fish. PCF showed broader distribution in the entire intestine derived from DMH-treated fish. LF-only-treatment has no effect on the number of PCF. Mean number of PCF in 5-FU-only-treated fish decreased in comparison with that of the saline-treated control group, though no statistically significant reduction in PCF was found. But if 5-FU treatment was added to LF pretreatment, a statistically significant reduction in the number of PCF was observed. Pretreatment with LF for 2 weeks also reduced the deleterious side effects of 5-FU.

Trastuzumab is used for patients with metastatic breast cancer of HER2 over expression and adjuvant chemotherapy. Trastuzumab is recognized as a medicine with few adverse effects, although infusion reaction at its first dosage appears in high frequency as a main adverse effect. However, because we realized that there were many patients who appeared to have skin toxicity or nail toxicity, the adverse effects of trastuzumab were investigated retrospectively. Of 51 cases who underwent trastuzumab-containing chemotherapy, 25 cases(49. 0%)had skin toxicity, 14 cases(27. 5%) had nail toxicity, and 12 cases(23. 5%)had both toxicities. Skin toxicity and nail toxicity appeared in 14 of 25 cases(56. 0%) and 6 of 14 cases(42. 9%)respectively, within 6 months after the first medication dosage. Symptoms of skin toxicity were eruptions on the face and body(14 cases; 27. 5%), skin detachment or thinning on hands and feet(9 cases; 17. 6%), itching (8 cases; 15. 7%), skin drying(7 cases; 13. 7%)and so on. On the other hand, symptoms of nail toxicity were softening, thinning, or loss(13 cases; 25. 5%), paronychia(4 cases; 7. 8%), and discoloration(2 cases; 3. 9%). Our present findings suggest that skin toxicity and nail toxicity are highly frequent adverse events for those taking trastuzumab, although the drug is considered to be a molecular target drug with few adverse effects.

Personnel who prepare and administer chemotherapeutic agents have been reported to develop untoward effects. The use of appropriate techniques for preparing these agents is encouraged, and educational training systems that involve the use of a fluorescent or chemiluminescence reagent as placebos have been established to minimize potential exposure to these agents. However, the optimum conditions for the use and visibility of these placebos remain obscure. In this study, our results indicated that the fluorescence intensity of fluorescent reagent decreased when it was used at a concentration greater than 0.01%. Because drops created due to splashes and leaks are extremely small and easily evaporate, it is possible that the fluorescence resulting from such drops readily disappears despite using an anti-evaporation reagent. We also developed a method to evaluate the visibility of the small drop; using this method, we determined the distance at which the drop present on the pin could be seen by the observer. The distance at which the drop was clearly recognized as a pinpoint by using the fluorescence method was almost comparable to that for the chemiluminescence method. In the chemiluminescence method, the drop on the pin was faintly visible as a slightly bright area because of low background when observed at a certain distance that was much greater than that at which the drop was clearly visible; however, such an area was not observed in the fluorescence method. The results of our study will help in the selection of a training method depending on the situation.

Although drug-induced interstitial pneumonitis caused by gefitinib is well recognized in Japan, reports of alveolar hemorrhage caused by gefitinib are very rare. We encountered a case of alveolar hemorrhage thought to be caused by gefitinib. A 74-year-old woman with non-small cell lung cancer (adenocarcinoma; cT4NOM0, stage IIIB) had been receiving gefitinib as second-line therapy from January 2009. However, bloody sputum and nasal bleeding were observed 2 weeks after the initiation of gefitinib therapy. Chest radiography and computed tomography revealed ground-glass opacities predominantly in the lower lung fields. Bronchoscopy was performed, and the bronchoalveolar lavage fluid obtained from the right B8 was bloody. Her symptoms and chest ground-glass opacities improved after the withdrawal of gefitinib. Based on these clinical findings, we diagnosed alveolar hemorrhage caused by gefitinib. If chest radiography or computed tomography findings of gefitinib-treated patients show ground-glass opacities, the possibility of not only interstitial pneumonitis, but also alveolar hemorrhage should be considered in the differential diagnosis.

A40 -year-old woman visited our hospital with adenocaricinoma of the sigmoid colon with multiple liver metastases and ovarian metastasis. Because of a stenosis of the primary tumor, she underwent a colostomy before chemotherapy. 5-fluorouracil and irinotecan and leucovorin(FOLFIRI)was selected as first-line chemotherapy. At the start of chemotherapy, just after the end of irinotecan and leucovorin administration, the patient developed dysarthria. There were no neurological abnormalities or hematological abnormalities. The treatment was temporarily discontinued, and the dysarthria completely disappeared within 90 minutes. 5-fluorouracil was administered after the disappearance of dysarthria. Within 60 minutes of the administration of irinotecan and leucovorin at the second chemotherapy treatment, the patient developed dysarthria again. The patient had no neurological or hematological abnormalities. Magnetic resonance imaging(MRI)showed no abnormalities. The treatment was stopped and dysarthria disappeared within 60 minutes as it did the first time. At each time, no treatment for dysarthria was performed. This patient refused to continue irinotecan because of dysarthria. Therefore, chemotherapy without irinotecan was continued for the third time onward. In the previous literature, 8 cases of dysarthria caused by irinotecan were reported as a rare toxicity. In all cases, dysarthria was temporary and reversible. Because the mechanism of dysarthria is unclear, specific treatment and precaution for dysarthria is not recommended. Since dysarthria is reversible, however, irinotecan might be continued until progression.

For clinical treatment of cancer patients, surgical operation, chemotherapy, radiotherapy, immunotherapy and palliative care are available. Among these therapies, the main radical treatments such as surgical operation, chemotherapy and radiotherapy provide patients with anti-cancer-effects, but also cause unwanted invasive influences to normal tissues. Nutritional support is essential for cancer patients because it helps reduce these invasive influences and promotes recovery of damaged non-cancer tissues. Nutritional support for cancer patients receiving any anti-cancer therapies helps decrease the degree of invasion to non-cancer tissues and healthy body functions, helps with the promotion of reproduction and recovery of injured tissues and functions, normalizes metabolic disturbances by anti-cancer therapies, improves malnutrition based by side effects of invasive treatments, promotes immune-function using immune-nutrients, and offers nutritional care for patients at the terminal stage by assisting in metabolic conditioning for patients with cancer cachexia.

We report a case of intraocular lymphoma that developed macular edema and cotton wool spots after treatment with intravitreal methotrexate.

The Hepatitis B virus (HBV) reactivation is defined as proliferation of HBV and hepatitis flare after medication of anti-cancer drugs and/or immunosuppressant drugs in inactive HBV carriers or patients with past illness by HBV infection. In January 2009, the guideline for prevention of immunosuppressive or chemotherapy-induced reactivation of HBV infection was established by Japanese study groups of the Ministry of Health, Labour and Welfare. We then surveyed and analyzed order numbers of the tests of HBV DNA and anti-HBc, the rate of positive results and the department of the doctors who ordered those tests, the patient ages and clinical profiles and the purpose of the tests, from 2008 to 2009 before and after announcement of the guideline. The total numbers of tests of HBV DNA were 942 in 2008 and 1350 in 2009, and those of anti-HBc were 430 in 2008 and 904 in 2009. The percentage of the orders for anti-HBc from doctors in department of gastroenterology and medicine was 71.4% in 2008 and decreased to 53.4% in 2009, instead those of hematology and oncology, pulmonary surgery and gynecology increased remarkably. The positive rates of anti-HBc increased among the patients over age 40, especially it was more than 40% over age 50. The number of the tests for the follow-up after immunosuppressive or chemotherapy increased over 4 folds. This report made clear the actual situation of screenings for the HBV reactivation by analyses of the bases in the orders and the results of the virus tests in our hospital.

Treatment for cancer may cause gonadal dysfunction and bone loss (cancer treatment-induced bone loss ; CTIBL) . Especially, endocrine therapies for breast cancer or prostate cancer carry a significant risk of CTIBL. Therapy-induced premature menopause in premenopausal breast cancer patients, aromatase inhibitor in postmenopausal breast cancer patients, and LHRH agonist with or without anti-androgen in prostate cancer patients may cause bone loss of 5% or more. RANKL (receptor activator of nuclear factor-κB ligand) antibody (denosumab) is effective for prevention of CTIBL and it may prevent CTIBL-induced fracture. During cancer treatment with gonadal dysfunction, bone mineral density should be carefully followed to avoid QOL impairment due to osoteoporosis.

Bevacizumab is a monoclonal antibody that targets vascular endothelial growth factor (VEGF) for treatment of metastatic colorectal cancer. Recently, much evidence has suggested that bevacizumab-induced hypertension might be predictive of the effect of bevacizumab. The aim of our study is to retrospectively assess the relationship between the onset of hypertension and the activity of bevacizumab in Japanese metastatic colorectal cancer patients. Between July 2007 and December 2010, 36 patients (median age 66 years; 36-81 years) with metastatic colorectal cancer were assigned to receive bevacizumab in combination with either mFOLFOX6 (5-FU, levofolinate and oxaliplatin) or FOLFIRI (5-FU, levofolinate and irinotecan) at the Tokushima University Hospital. A patient who had increase by >20 mmHg in diastolic blood pressure or had increase to >150/100 mmHg or received antihypertensive treatment was defined as hypertensive. The objective response rate (ORR), disease control rate (DCR) and progression-free survival (PFS) were compared between the hypertensive group (n=10) and non-hypertensive group (n=26). ORR and DCR were 60.0% and 100%, respectively, in the hypertensive group and ORR and DCR were 23.1% and 80.8%, respectively, in the non-hypertensive group. These differences were statistically significant (p<0.05). The median PFS tended to be longer in the hypertensive group (65.0 weeks) than in the non-hypertensive group (40.0 weeks). Our data suggested that bevacizumab-induced hypertension may be predictive of the effect of bevacizumab in Japanese metastatic colorectal cancer patients.

We retrospectively examined the results of antiemetic therapy with granisetron and dexamethasone; with granisetron, dexamethasone and aprepitant; and with palonosetron, dexamethasone and aprepitant, in patients who received chemotherapy with cisplatin at 50 mg/m2 or more for the first time. Vomiting was dramatically reduced by the concomitant administration of aprepitant. There was no difference in this effect when palonosetron was used instead of granisetron as a serotonin receptor antagonist. There was also no significant difference in the percentage of patients without nausea among the 3 groups. The results of this study indicate that vomiting in patients receiving chemotherapy can be controlled using aprepitant in combination with two other drugs.

Glomerular filtration rate (GFR) is an important factor when considering carboplatin dosage adjustment. The Japanese equation for estimating GFR (eGFR) was recommended as a guideline for evaluating GFR in 2009 by The Japanese Society of Nephrology. However, benefits in the field of cancer chemotherapy with the use of eGFR have not yet been shown. To clarify the clinical benefits of eGFR, we investigated the renal function of 100 patients with gynecologic cancer who were treated with carboplatin from 2003 through 2009, and the carboplatin dosage was calculated by the Calvert formula in which eGFR was substituted for GFR. To predict the clinical benefit on the basis of carboplatin dosage using eGFR, we retrospectively divided the patients into two groups so that carboplatin dosage was within dosage in using eGFR and one was not. We compared response rates and adverse effects of the two groups. Renal function using eGFR was lower than renal function calculated by using the other formulae. Carboplatin dosage using eGFR was significantly lower than the dosage calculated with the other formulae (p<0.01). Moreover, the patients group actually, administered the dosage calculated by eGFR showed less side effects than the group of patients not treated this way, but the efficacy did not change. Thus, using eGFR in planning carboplatin dosage suggested clinical application to patients with Japanese gynecologic cancer.