[A Case of Merkel Cell Carcinoma Complicated with Severe Thrombocytopenia Treated with Carboplatin/Etoposide Regimen after Surgery].

Thrombocytopenia is often caused by myelosuppression during chemotherapy. However, when platelet transfusions are required, pathological conditions such as idiopathic thrombocytopenic purpura(ITP)and thrombotic thrombocytopenic purpura( TTP)also occur. We report a case of Merkel cell carcinoma complicated with severe thrombocytopenia treated with carboplatin/etoposide regimen after surgery. The patient's platelet count did not increase in spite of platelet transfusions. However, the platelet count increased after steroid treatment was chosen under the diagnosis of ITP. Subsequent examinations revealed that the patient had HLA antibody, which caused the platelet transfusion refractoriness. When the platelet count does not increase in spite of platelet transfusions during chemotherapy, the possibility that the platelet transfusion refractoriness is due to the presence of HLA antibody should be considered.

[A Pancreatic Cancer Patient in Whom Pegfilgrastim Prophylaxis Did Not Prevent Severe Neutropenia Caused by the FOLFIRINOX Regimen].

Recently, newer agents in regimens such as FOLFIRINOX have shown promising activity, being superior to gemcitabine as a single agent for unresectable pancreatic cancer patients with good performance status. Herein, we report a case of pancreatic cancer treated with the FOLFIRINOX regimen and pegfilgrastim prophylaxis as second-line treatment in a patient who failed this regimen. He previously received gemcitabine/nab-paclitaxel combination chemotherapy as first-line treatment. It was reported that grade 3-4 neutropenia frequently occurred in many patients receiving the FOLFIRINOX regimen. Prophylactic use of pegfilgrastim is recommended for cancer patients who are at high risk of neutropenic events. However, severe neutropenia occurred with the FOLFIRINOX regimen in spite of pegfilgrastim prophylaxis. We emphasize the importance of occasional serious adverse effects with the FOLFIRINOX regimen and pegfilgrastim prophylaxis.

[Two cases of pancreatic cancer treated with FOLFIRINOX regimen and G-CSF prophylaxis at the standard therapeutic dose].

Recently, novel therapeutic regimens, such as FOLFIRINOX, have been demonstrated to show promising anti-cancer activity and to be superior to single-agent gemcitabine for unresectable pancreatic cancer patients with good performance status. In this study, we report 2 cases of pancreatic cancer treated with FOLFIRINOX and G-CSF prophylaxis at the standard therapeutic dose, after treatment with gemcitabine and S-1 chemotherapy failed. It has been reported that grade 3-4 neutropenia frequently occurs in patients treated with the FOLFIRINOX regimen. Furthermore, granulocyte colony-stimulating factor(G-CSF) has not been recommended for helping with neutropenia in pancreatic cancer patients treated with FOLFIRINOX: however, prophylactic use of G-CSF is recommended for cancer patients who are at high risk of neutropenic events. On the other hand, modified FOLFIRINOX(no bolus 5-FU)has demonstrated an improved safety profile with maintained efficacy, and further randomized studies to compare the overall survivals of the modified FOLFIRINOX versus FOLFIRINOX regimen and G-CSF prophylaxis are hence needed in the future.

[A case of Paclitaxel-induced peripheral neuropathy successfully treated with duloxetine].

Here, we report about a 60-year-old woman with metastatic breast cancer who was successfully treated for paclitaxelinduced peripheral neuropathy with duloxetine. She was administered trastuzumab plus paclitaxel(PTX)combination therapy that was ultimately discontinued because of grade 3 peripheral neuropathy detected on day 15, according to the CTCAE (v4.0). She was administered duloxetine on day 90 after the end of the previous therapy because of the peripheral neuropathy. Thereafter, the peripheral neuropathy decreased to grade 1, which enabled PTX administration on her request. Further trials are required to confirm the efficacy of duloxetine.

Bortezomib and dexamethasone for multiple myeloma: higher AST and LDH levels associated with a worse prognosis on overall survival.

BACKGROUND: Bortezomib offers a novel approach to the treatment of multiple myeloma producing rapid control. The aim of this study was to investigate the outcomes of bortezomib and dexamethasone-treated patients with multiple myeloma. METHODS: We conducted a retrospective study of 44 consecutively-treated multiple myeloma patients with bortezomib (1.3 mg/m(2) on days 1, 4, 8, and 11 of a 21-day cycle or 1.3 mg/m(2) intravenously 1, 8, 15, and 22 of every 35-day cycle) and dexamethasone. RESULTS: The median time to progression, progression free survival time, and overall survival time in the treatment groups was 14.9, 14.9, and 38.3 months, respectively. The present study also suggests the possibility that the prognosis of patients with high levels of AST and LDH might be worse. CONCLUSIONS: Our results indicate that the treatment of multiple myeloma with bortezomib and dexamethasone is feasible.

[Effect of dexamethasone on vascular pain caused by the administration of fosaprepitant dimeglumine and epirubicin hydrochloride in patients with primary breast cancer].

Epirubicin hydrochloride injection is indicated as a therapy for patients with primary breast cancer. This drug has been reclassified as a drug with high emetic potential according to the American Society of Clinical Oncology Guidelines for Antiemetics in Oncology. Therefore, patients who receive this agent should also receive fosaprepitant dimeglumine, an anti-emetic agent. However, it has been reported that fosaprepitant induces vascular pain when used in anthracycline-based regimens administered via the peripheral veins. In order to relieve the fosaprepitant and epirubicin-induced vascular pain associated with vasculitis, dexamethasone was administered at the onset of vascular pain. There is a possibility that the fosaprepitant and epirubicin-induced pain may improve owing to the administration of dexamethasone; however, further trials are required to confirm the effect of this method.

[Prospective study of biotin treatment in patients with erythema due to gefitinib or erlotinib].

Gefitinib anderlotinib, which are epidermal growth factor receptor(EGFR)tyrosine kinase inhibitors(TKIs), have been usedfor the treatment of inoperable andrecurrent non-small cell lung cancer(NSCLC)patients. These drugs are known to cause a skin rash, one of the major side effects, at a high frequency. Biotin is a water-soluble vitamin, andit belongs to the vitamin B family. It is well known that biotin deficiency increases the risk of skin dermatitis. We administered biotin to four patients with skin rash, all of whom were treatedwith either gefitinib or erlotinib andwere unable to be treatedby a steroid ointment alone. In all patients, administration of biotin reduced the skin rash. Surprisingly, in 2 patients in whom EGFR-TKI therapy was discontinued because of the skin rash, the administration of biotin allowed for long-term gefitinib or erlotinib treatment. Biotin may be considereduseful for the treatment of skin rash causedby EGFR-TKIs. Further trials may be needed to confirm the value of biotin in this setting.

[A case of paclitaxel-induced peripheral neuropathy successfully treated with pregabalin].

Were port a 51-year-old male left renal pelvic cancer patient with paclitaxel (PTX)-induced peripheral neuropathy, which was successfully treated with pregabalin. From June 2010, a gemcitabine/PTX (GP) regimen was used as third-line treatment. In order to relieve the PTX-induced peripheral neuropathy, pregabalin (75mg/day, at night) was administered from day 6 of the 16th course. Moreover, pregabalin was increased to 150mg/day from day 12 of the course. Sensory neurotoxicity after the administration of pregabalin was decreased from CTCAE (version 4. 0) grade 3 to 1 at day 19 of the course. Therefore, there is a possibility that the PTX -induced peripheral neuropathy may be improved by pregabalin administration. Further trials may be needed to confirm the value of pregabalin.

[A case of neurotoxicity reduced with pregabalin in R-CHOP chemotherapy for diffuse large B-cell lymphoma].

When performing R-CHOP(rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone)for diffuse large B-cell lymphoma(DLBCL), neurotoxicity of vincristine(VCR)is the serious dose-limiting factor.Pregabalin is one of the first-line treatments for painful diabetic peripheral neuropathy in many countries, and we have administered it to relieve the neurotoxicity associated with adverse effects of VCR in a DLBCL patient treated with the R-CHOP regimen.A 49-year-old man with kidney DLBCL had surgery performed.Afterward, the R-CHOP regimen was introduced.In order to relieve the neurotoxicity of VCR, pregabalin was used from day 8 in the second course.The severity of sensory neurotoxicity after the administration of pregabalin was improved from CTCAE(v4.0)grade 3 to grade 1.Therefore, there is a possibility that VCR-induced neurotoxicity is relieved by pregabalin.Further trials are needed to confirm the value of pregabalin.

Nausea and vomiting caused by candida esophagitis in an elderly frail patient.

An elderly frail lady with features of malnutrition was investigated by endoscopy because of nausea and vomiting. Candida esophagitis was found, and there was symptomatic and endoscopic resolution after treatment with amphotericin B.

Rare presentation of annular and polypoid heterotopic gastric mucosa in duodenum.

In this case, Esophagogastroduodenoscopy showed an approximately 25-mm diameter annular and polypoid mucosa at the opposite side of Pylorus ring in first part of duodenum. The biopsy specimens were diagnosed with the heterotopic gastric mucosa (HGM) pathologically. This is a rare presentation of annular and polypoid HGM in duodenum. This may indicate the needs for other documents as well as analysis regarding the mechanism for the development of HGM in duodenum.

Transperineal prostate brachytherapy, using I-125 seed with or without adjuvant androgen deprivation, in patients with intermediate-risk prostate cancer: study protocol for a phase III, multicenter, randomized, controlled trial.

BACKGROUND: The optimal protocol for 125I-transperineal prostatic brachytherapy (TPPB) in intermediate-risk prostate cancer (PCa) patients remains controversial. Data on the efficacy of combining androgen-deprivation therapy (ADT) with 125I-TPPB in this group remain limited and consequently the guidelines of the American Brachytherapy Society (ABS) provide no firm recommendations. METHODS/DESIGN: Seed and Hormone for Intermediate-risk Prostate Cancer (SHIP) 0804 is a phase III, multicenter, randomized, controlled study that will investigate the impact of adjuvant ADT following neoadjuvant ADT and 125I-TPPB. Prior to the end of March, 2011, a total of 420 patients with intermediate-risk, localized PCa will be enrolled and randomized to one of two treatment arms. These patients will be recruited from 20 institutions, all of which have broad experience of 125I-TPPB. Pathological slides will be centrally reviewed to confirm patient eligibility. The patients will initially undergo 3-month ADT prior to 125I-TPPB. Those randomly assigned to adjuvant therapy will subsequently undergo 9 months of adjuvant ADT. All participants will be assessed at baseline and at the following intervals: every 3 months for the first 24 months following 125I-TPPB, every 6 months during the 24- to 60-month post-125I-TPPB interval, annually between 60 and 84 months post-125I-TPPB, and on the 10th anniversary of treatment.The primary endpoint is biochemical progression-free survival (BPFS). Secondary endpoints are overall survival (OS), clinical progression-free survival, disease-specific survival, salvage therapy non-adaptive interval, acceptability (assessed using the international prostate symptom score [IPSS]), quality of life (QOL) evaluation, and adverse events. In the correlative study (SHIP36B), we also evaluate biopsy results at 36 months following treatment to examine the relationship between the results and the eventual recurrence after completion of radiotherapy. DISCUSSION: These two multicenter trials (SHIP0804 & SHIP36B) are expected to provide crucial data regarding the efficacy, acceptability and safety of adjuvant ADT. SHIP36B will also provide important information about the prognostic implications of PSA levels in intermediate-risk PCa patients treated with 125I-TPPB. TRIAL REGISTRATION: NCT00664456, NCT00898326, JUSMH-BRI-GU05-01, JUSMH-TRIGU0709.

Ameloblastin is a cell adhesion molecule required for maintaining the differentiation state of ameloblasts.

Tooth morphogenesis results from reciprocal interactions between oral epithelium and ectomesenchyme culminating in the formation of mineralized tissues, enamel, and dentin. During this process, epithelial cells differentiate into enamel-secreting ameloblasts. Ameloblastin, an enamel matrix protein, is expressed by differentiating ameloblasts. Here, we report the creation of ameloblastin-null mice, which developed severe enamel hypoplasia. In mutant tooth, the dental epithelium differentiated into enamel-secreting ameloblasts, but the cells were detached from the matrix and subsequently lost cell polarity, resumed proliferation, and formed multicell layers. Expression of Msx2, p27, and p75 were deregulated in mutant ameloblasts, the phenotypes of which were reversed to undifferentiated epithelium. We found that recombinant ameloblastin adhered specifically to ameloblasts and inhibited cell proliferation. The mutant mice developed an odontogenic tumor of dental epithelium origin. Thus, ameloblastin is a cell adhesion molecule essential for amelogenesis, and it plays a role in maintaining the differentiation state of secretory stage ameloblasts by binding to ameloblasts and inhibiting proliferation.

Gene expression profiling in rat liver after VMH lesioning.

It has been reported that ventromedial hypothalamic (VMH) lesions induce hepatic cell proliferation and apoptosis and metabolic changes in the body. In the present study, we identified genes of which expression profiles showed significant modulation in rat liver after VMH lesions. Total RNA was extracted, and differences in the gene expression profiles between rats at day 3 after VMH lesioning and sham-VMH lesioned rats were investigated using DNA microarray analysis. The results revealed that VMH lesions regulated the genes that were involved in various types of metabolisms and cell proliferations in the liver. Real-time PCR also confirmed that gene expressions of ELOVL6 and SPC24 were upregulated, and that of SERPINA7 was downregulated. VMH lesions may change the expressions of multiple metabolism genes and cell proliferation-related genes in rat liver.

[Report of a case effectively treated by appropriate therapy for severe anticipatory nausea and vomiting due to FOLFOX or FOLFIRI].

To date, the standard treatments for severe anticipatory nausea and vomiting is not well established. 5-HT3 antagonist is one of the effective drugs to reduce chemotherapy-induced nausea and vomiting, but had no effect on these symptoms for this patient. The patient could be successfully administered standard chemotherapy(FOLFOX or FOLFIRI, q2w)without adverse reactions by appropriate treatments in the form of increased doses of dexamethasone and normal dose administration of prochlorperazine. This report suggests a possibility that FOLFOX or FOLFIRI may be successfully treated by appropriate treatments for severe chemotherapy-induced vomiting colon cancer patients, and that this observation may lead to the improved prognosis of these patients.

Nodal Merkel Cell Carcinoma in Head and Neck Lesions with an Unknown Primary: A Case Report in Light of the Literature.

Merkel cell carcinoma (MCC) is a rare but aggressive neuroendocrine skin cancer. To diagnose nodal MCC with an unknown primary disease is challenging, and it has to be separated from other nodal metastatic neoplasms. We report a unique case of nodal MCC in head and neck lesions with an unknown primary. A 70-year-old woman was admitted to our department with a right submandibular mass. Fine needle aspiration biopsy was performed and indicated malignancy. F-18-fluorodeoxyglucose positron emission tomography (PET) demonstrated abnormal accumulation in the right submandibular lymph node, right palatine tonsil, and right thyroid gland. For diagnostics and treatment, bilateral selective neck lymph node dissection, right tonsillectomy, and right thyroidectomy were performed. Histopathological examination revealed that most parts of the submandibular lymph node were occupied by diffuse sheets of tumor cells. Contrary to our expectation, malignant cells were not detected in the right palatine tonsil and right thyroid. Immunohistochemistry demonstrated a marked positive reaction for AE1/AE3, chromogranin A, synaptophysin, cytokeratin 20 (CK20) and CD56 and a negative reaction for vimentin, leucocyte common antigen (LCA), thyroid transcription factor-1 (TTF1) and cytokeratin 7 (CK7) in the tumor cells. Immunostaining of Merkel cell polyomavirus-large T antigen (MCPyV-LT) showed a positive reaction and MCPyV-positive MCCs were assessed by PCR analysis, demonstrating that viral copy number was 12.8 copies per cell. These histological findings confirmed the diagnosis of Merkel cell carcinoma of the lymph node. In cases of tumors in the lymph node with a neuroendocrine appearance in head and neck lesions, it is necessary to eliminate the possibility of metastasis from MCC.

The reversal of recurrence hazard rate between ER positive and negative breast cancer patients with axillary lymph node dissection (pathological stage I-III) 3 years after surgery.

BACKGROUND: Prognostic factors are defined as biological or clinical measurement associated with overall survival and/or disease-free survival. Previous studies have shown that patients with estrogen receptor (ER) positive cancers have a better prognosis than patients whose cancers do not have these receptors. METHODS: This study investigated the assessment of variables in defining prognosis of 742 breast cancer women with pathological stage (pTNM) I-III diagnosed between 1980 and 2005 at the Kyoto University Hospital in Japan, by age, clinical stage (cTNM), pTNM, the numbers of positive lymph nodes (pN), and ER status. RESULTS: Multivariate analysis demonstrated that pTNM and ER status were the independent prognostic factors for overall survival, and that pTNM and pN were the independent prognostic factors for disease-free survival. For the 0- to 2-year interval, the hazard of recurrence was higher for the ER-negative patients than the ER-positive patients, and beyond 3 years the hazard was higher for ER-positive patients. CONCLUSION: The present study confirmed the previous reports which showed favorable prognosis of the patients with lesser pTNM or positive ER status. A reversal of recurrence hazard rate between ER positive and negative breast cancer patients beyond 3 years after operation was detected. The fact may indicate the importance of long term adjuvant hormone therapy for ER positive cancer patients.

Changes of neuron-specific and apoptosis gene expression levels after ventromedial hypothalamic lesions in rat intestine.

The intestinal epithelium is continuously renewed through a balance between cell proliferation and apoptosis. We identified genes of which expression profiles showed significant modulation, and we investigated the cellular mechanisms of this gene regulation in rat intestine after ventromedial hypothalamic (VMH) lesions. Total RNA was extracted, and differences in the gene expression profiles between rats at day 3 after VMH lesioning and in sham-VMH lesioned rats were investigated using DNA microarray analysis and real-time polymerase chain reaction (PCR) methods. DNA microarray analysis revealed that VMH lesions regulated the genes that were involved in functions predominantly related to neuronal development, cell proliferation and apoptosis. Real-time PCR also confirmed that gene expressions of Efnb1 were downregulated. Meanwhile, expression of Casp3 was similar. It is noted that the signaling networks of many gene families, including neuron-specific genes and apoptosis genes in the intestine were changed after VMH lesioning. VMH lesions may suppress mainly the caspase independent type II pathway for apoptosis and induce cell proliferation in the intestine.

[A case of left urothelial carcinoma with multiple bone metastasis, liver metastasis and right adrenal metastasis successfully treated with combination chemotherapy of gemcitabine and carboplatin].

The patient was a 53-year-old male. He had been admitted to another hospital with a complaint of left sciatica. He was referred to our hospital for further examination and therapy. He was diagnosed as left urothelial carcinoma with multiple bone metastasis, liver metastasis and right adrenal metastasis. He was treated with combination chemotherapy of gemcitabine and carboplatin (1,000 mg/m2 day 1 and AUC 2 day 1, respectively) biweekly. After the ninth course, a significant tumor reduction was obtained, and has been maintained. He has been treated on an outpatient basis because of no grade 3 or severer adverse reactions. We report an effective case of biweekly chemotherapy with gemcitabine and carboplatin in the treatment of advanced urothelial carcinoma.