Optimizing antiemetic treatment for chemotherapy-induced nausea and vomiting in Japan: Update summary of the 2015 Japan Society of Clinical Oncology Clinical Practice Guidelines for Antiemesis.

Patients with cancer should appropriately receive antiemetic therapies against chemotherapy-induced nausea and vomiting (CINV). Antiemetic guidelines play an important role in managing CINV. Accordingly, the first Japanese antiemetic guideline published in 2010 by the Japan Society of Clinical Oncology (JSCO) has considerably aided Japanese medical staff in providing antiemetic therapies across chemotherapy clinics. With the yearly advancements in antiemetic therapies, the Japanese antiemetic guidelines require revisions according to published evidence regarding antiemetic management worldwide. A revised version of the first antiemetic guideline that considered several upcoming evidences had been published online in 2014 (version 1.2), in which several updated descriptions were included. The 2015 JSCO clinical practice guideline for antiemesis (version 2.0) (in Japanese) has addressed clinical antiemetic concerns and includes four major revisions regarding (1) changes in emetogenic risk categorization for anti-cancer agents, (2) olanzapine usage as an antiemetic drug, (3) the steroid-sparing method, and (4) adverse drug reactions of antiemetic agents. We herein present an English update summary for the 2015 JSCO clinical practice guideline for antiemesis (version 2.0).

A case of severe acute pancreatitis and ischemic gastropathy caused by acute aortic dissection.

A 49-year-old man presented with chest pain and was given a diagnosis of aortic dissection based on computed tomography (CT) findings. Two days later the dissection reached the origin of the celiac artery and there was poor blood flow from the body to the tail of the pancreas and fundus of the stomach wall. Severe acute pancreatitis developed. Endoscopy showed a near-circumferential gastric ulcer in the gastric cardia and we diagnosed ischemic gastropathy. A fistula between the area of infected pancreatic necrosis and the stomach had formed spontaneously and the necrotic tissue was draining into the stomach. His recovery was uneventful.

[A case of hepatocellular carcinoma diagnosed based on the result of a bone biopsy, in which the primary hepatocellular carcinoma was identified in the liver 14 months after the initial diagnosis].

A 64-year-old man complained of pain in his left humerus. A histopathological examination of biopsy specimens taken from the lesion revealed a hepatocellular carcinoma. No primary hepatic lesion was revealed in a subsequent examination performed at this time. Enhanced computed tomography examination of the abdomen 14 months later, showed a nodular lesion, approximately 15 mm in diameter, therefore a partial hepatectomy was performed. The lesion was histopathologically diagnosed as a moderately-poorly differentiated hepatocellular carcinoma. The inability to identify the primary hepatocellular carcinoma is quite rare, and the present case may be the first report of the discovery of the primary hepatocellular cancer after the diagnosis of a secondary lesion.

Cytologic findings of metastatic hepatocellular carcinoma of the nasal cavity: a report of 2 cases.

BACKGROUND: Hepatocellular carcinoma metastasizing to the nasal cavity is rare, but nasal bleeding caused by it is difficult to treat. The reason is that a large majority of patients have a bleeding tendency due to liver cirrhosis. Accordingly, early and correct diagnosis is essential. CASES: Case 1, a Japanese man in therapy for C type liver cirrhosis and hepatocellular carcinoma, was diagnosed as metastasis to the bones, and then he was admitted. After hospitalization, he complained of nasal obstruction. Fine needle aspiration biopsy from a tumor occupying nasal and maxillary cavities showed overlapped cells and scattered cells having a round to oval nucleus containing one or a few large nucleoli. The characteristics of cells indicated metastasis of hepatocellular carcinoma. In case 2, a Japanese man under treatment for liver cancer visited our hospital with a complaint of nasal obstruction. In fine needle aspiration biopsy from a mass in the right nasal cavity, cohesive clusters and sparse neoplastic cells similar to those observed in the first case were found. CONCLUSION: Aspiration cytology is useful in the diagnosis and treatment of hepatocellular carcinoma metastatic to the nasal cavity. Finding characteristic cells is important in the diagnosis. Clinical information is sure to be a convincing clue.

[Cholangiocarcinoma with bile duct adenoma and hamartoma-like lesion in the bile duct].

A 76-year-old man presented with fever of unknown origin. Diagnostic imaging showed a liver tumor measuring 3cm in maximum dimension. The tumor was subsequently resected, and histopathology showed a moderately differentiated adenocarcinoma. This showed a number of bile ductules with variable amounts of stroma, well circumscribed but not encapsulated, so the lesion was diagnosed as a cholangiocarcinoma. Within the tumor there was also a cholangiolocarcinoma-like lesion. In addition, cystically dilated ductules resembling bile duct hamartoma and bile duct adenoma adjacent to the tumor were found, but with no area of transition among them. In the Glisson's capsule around the tumor, there was also a bile duct hamartoma.

The effect of adjuvant and neoadjuvant chemo(radio)therapy on survival in 1,679 resected pancreatic carcinoma cases in Japan: report of the national survey in the 34th annual meeting of Japanese Society of Pancreatic Surgery.

BACKGROUND: Pancreatic carcinoma causes more than 20,000 deaths every year in Japan. The role of (neo-) adjuvant chemotherapy for pancreatic carcinoma is still controversial. METHODS: At the 34th Annual Meeting of the Japanese Society of Pancreatic Surgery in 2007, questionnaires were distributed regarding the use of (neo-) adjuvant chemo(radio)therapy for pancreatic carcinoma between 2001 and 2005. RESULTS: Sixty of the 146 member institutions responded to the questionnaires. There were a total of 1,846 cases of resected pancreatic carcinoma between 2001 and 2005. The study population had a greater proportion of males, and a mean age of 65.3 years (range 34-90 years). The lesion was located in the head of the pancreas in 1,204 cases (71.7%), in the body in 353 cases (21.0%), and in the tail in 111 cases (6.6%). Overall survival rates were 67.3% at 1 year, 36.0% at 2 years, and 23.9% at 3 years, respectively. Adjuvant chemotherapy (usually involving gemcitabine) was used in 66.0% of cases. The use of adjuvant chemotherapy was found to improve the overall survival rate. Interestingly, adjuvant chemotherapy only improved survival in late-stage (UICC stages IIB, III, and IV) but not early stage (IA, IB, and IIA) patients. Survival was treatment duration-dependent, with patients who received more than 12 months of therapy having a 3-year survival rate of 51.2%. CONCLUSION: This high volume retrospective data indicated the promising effect of gemcitabine-based adjuvant chemotherapy and the rational duration of adjuvant chemotherapy should be determined in the future prospective studies.

[Hemorrhage from varices of an interposed jejunum after choledochojejunostomy successfully treated by transileocolic vein obliteration].

A 72-year-old man was admitted to our hospital with refractory gastrointestinal bleeding. He received extrahepatic bile duct resection, hepaticojejunostomy and pancreatojejunostomy for bile duct stenosis and pancreatic pseudocyst 6 approximately 8years ago. We revealed that the cause of shock state was bleeding from varices of an interposed jejunum and portal vein obstruction as a complication of these operations. He received transileocolic vein obliteration with coils. Refractory gastrointestinal bleeding stopped. We concluded that this obliteration was effective and useful treatment for this complication.

A gram distribution kernel applied to glycan classification and motif extraction.

We propose a novel general-purpose tree kernel and apply it to glycan structure analysis. Our kernel measures the similarity between two labeled trees by counting the number of common q-length substrings (tree q-grams) embedded in the trees for all possible lengths q. We apply our tree kernel using a support vector machine (SVM) to classification and specific feature extraction from glycan structure data. Our results show that our kernel outperforms the layered trimer kernel of Hizukuri et al. which is well tailored to glycan data while we do not adjust our kernel to glycan-specific properties. In addition, we extract specific features from various types of glycan data using our trained SVM. The results show that our kernel is more flexible and capable of finding a wider variety of substructures from glycan data.

[Long-term repeatable chemotherapy for patients with advanced pancreatic cancer].

At present, the advanced pancreatic cancer is known to be one of the most resistant malignancies on chemotherapy. To improve the efficacy of chemotherapy, we shifted the aim of chemotherapy from a tumor regression to long-term survival, and sought for a repeatable regimen with little toxicity. Some of the novel (repeatable) regimens used a combination of 5-FU/S-1, CDDP and paclitaxel performed for 10 patients with advanced pancreatic cancer (4 cases of Stage IVa and 6 cases of Stage IVb). As a result, the survival ratios of one and two years were 85.7% and 22.9%, respectively. The efficacy rate was 50% (5 cases of PR and 5 cases of NC). Hematological adverse reactions over grade 3 were observed in 8 out of 10 cases, although the decrease of platelet count was observed only in 2 cases (grade 3 and 4). The majority of hematological adverse reactions over grade 3 were leukocytepenia and anemia which were easy to control safely. All of non-hematological adverse reactions were observed under grade 2 and did not disrupt the maintenance of chemotherapy.

An HLA-A24-restricted cytotoxic T lymphocyte epitope of a tumor-associated protein, survivin.

To date an increasing number of T-cell epitopes derived from various tumor-associated antigens have been reported, and they proved to play significant roles for tumor rejection both in vivo and in vitro. Survivin was originally identified as a member of the inhibitor of apoptosis protein family. Expression of this gene is developmentally regulated. Although survivin is expressed during normal fetal development, the expression is barely detected in terminally differentiated adult tissues except for testis, thymus, and placenta. In contrast, it is abundantly expressed in a wide variety of malignant tissues. We examined the expression of survivin and the two splicing variants survivin-2B and survivin-DeltaEx3 in various cancer cells, immortalized cells, and normal adult tissues. It was demonstrated that two splicing variants were detected in various types of cancer cells as well as survivin, and their expression was more restricted to cancer cells as compared with survivin expression. To identify HLA-A24-restricted T-cell epitopes from survivin and the variant proteins, three peptides were selected from amino acid sequence of these proteins, based on the HLA-A24-binding motif. Peptide binding assay to HLA-A24 revealed that only one peptide designated as survivin-2B80-88 (AYACNTSTL) was capable of binding to HLA-A24. By stimulating peripheral blood lymphocytes with the peptide-pulsed antigen-presenting cells, CTLs were successfully induced in vitro from five of five HLA-A24-positive cancer patients. The CTLs showed significant cytotoxicity against HLA-A24-positive survivin-2B-positive cancer cells. These data suggest that survivin-2B80-88 may be a potent T-cell epitope eliciting CTL response against a splicing variant survivin-2B, which is specifically expressed in many kinds of cancer cells.

[Early phase II dose-finding study of exemestane in postmenopausal patients with advanced/recurrent breast cancer].

Exemestane was administered orally to postmenopausal women with advanced/recurrent breast cancer at a dose of 10 mg/day or 25 mg/day once daily for more than 8 weeks in order to evaluate the drug's anti-tumor effects and safety in a dose-finding study. The response rate (CR + PR) in the 10 mg and 25 mg group was 25.0% (8/32) and 31.4% (11/35), respectively, demonstrating no significant differences between the two groups, yet a higher efficacy rate was observed in 25 mg group. The efficacy rate in hormone-treatment-resistant patients within the 10 mg and 25 mg groups was 14.3% (3/21) and 26.1% (6/23), respectively, demonstrating more than a 20% response rate in 25 mg group. Incidences of the adverse events of which relevance to the drug could not be excluded were 30.6% (11/36) in the 10 mg group. 13.9% (5/36) in the 25 mg group and 22.2% (16/72) in the total group. The major adverse events were, hot flashes, numbness of the limbs, nausea, headache etc. Abnormal findings in clinical laboratory tests were as follows: ALP increase; GOT increase; GPT increase; gamma-GTP increase; total cholesterol increase; urinary sediment present. Abnormal findings in endocrine function were as follows: aldosterone decrease; testosterone.cortisol.DHEA-S decrease. But discontinuation due to abnormal laboratory findings was not found. No abnormal findings in physical tests were observed. A significant decrease in plasma estrogen concentration at week 4 was observed in both the 10 mg and 25 mg groups compared with baseline. These low levels were maintained throughout the study period. On the basis of these results, the efficacy of exemestane 25 mg/day was verified to be slightly higher than 10 mg/day. In addition the safety profile had no major adverse events to notice. In these patients with advanced/recurrent breast cancer, 25 mg/day was recommended as the most appropriate dose to be used clinically.

Biological heterogeneity of the peptide-binding motif of the 70-kDa heat shock protein by surface plasmon resonance analysis.

70-kDa heat shock protein family is a molecular chaperone that binds to a variety of client proteins and peptides in the cytoplasm. Several studies have revealed binding motifs between 70-kDa heat shock protein family and cytoplasmic proteins by conventional techniques such as phage display library screening. However, little is known about the binding motif based on kinetic parameters determined by surface plasmon resonance analysis. We investigated the major inducible cytosolic 70-kDa heat shock protein (Hsp70)-binding motif with the human leukocyte antigen B*2702-derived peptide Bw4 (RENLRIALRY) by using a Biacore system based on surface plasmon resonance analysis. The K(D) value of Hsp70-Bw4 interaction was 1.8 x 10(-6) m. Analyses with truncated Bw4 variant peptides showed the binding motif of Hsp70 to be seven residues, LRIALRY. To further study the characteristics of this motif, 126 peptides derived from Bw4, each with single amino acid substitution, were synthesized and analyzed for Hsp70 binding affinity. Interestingly, the Hsp70 binding affinity was abrogated when the residues were substituted for by acidic (Asp and Glu) ones at any position. In contrast, if the substitute residue was aromatic (Trp, Tyr, and Phe) or an Arg residue at any position, Hsp70 binding affinity was maintained. Thus, this study presents a new binding motif between Hsp70 and peptides derived from the natural protein human leukocyte antigen B*2702 and may also elucidate some characteristics of the Hsp70 binding characteristic, enhancing our understanding of Hsp70-binding determinants that may influence diverse cellular and physiological processes.

A survey of the timing and approach to the surgical management of patients with acute cholecystitis in Japanese hospitals.

BACKGROUND/PURPOSE: Despite the fact that there is evidence advocating early laparoscopic cholecystectomy for acute cholecystitis (AC), the practice of this treatment has not been investigated sufficiently. This study was designed to assess the current practice of laparoscopic cholecystectomy for AC among Japanese general surgeons. METHODS: A postal questionnaire was sent to the 291 councillors of the Japanese Society of Abdominal Emergency Medicine in order to ascertain their current management of patients with AC. RESULTS: The response rate was 72.5%. A policy of early cholecystectomy for AC was adopted by 41.7% of the responding surgeons. However, almost the same percentage of surgeons routinely managed their patients conservatively, and opted for delayed cholecystectomy at a later date. The adoption of laparoscopic cholecystectomy was made by 79.1% of surgeons. Laparoscopic cholecystectomy for patients with AC who had percutaneous transhepatic gallbladder drainage (PTGBD) was adopted by 73.9% of the surgeons. Of the surgeons opting for laparoscopic cholecystectomy, 37.3% performed intraoperative cholangiography laparoscopically for all patients with AC. CONCLUSIONS: Although early cholecystectomy for patients with AC was not adopted by the majority of the surgeons who responded, laparoscopic cholecystectomy was a common procedure for early and delayed cholecystectomy. Despite evidence that strongly supports the use of early cholecystectomy, the use of this treatment remains suboptimal in Japan.