Influence of a multidisciplinary cancer board on treatment decisions.

BACKGROUND: To clarify how a multidisciplinary cancer board (CB) influences treatment decisions. METHODS: From March 2010 to June 2011, a total of 475 cases were discussed at our CB and the minutes of the board were reviewed for this study. RESULTS: Of the 475 patients, minor changes in treatment methods were made in 42 patients (9 %) and major changes were made in 28 patients (6 %). Further diagnostic procedures, further publication surveys and reconfirmation of patient's wishes were recommended in 80 patients (17 %). In the 392 patients for whom treatment was recommended, the CB's recommendation was realized in 349 patients (89 %) and was not realized in 20 (5 %) patients. CONCLUSIONS: It is obvious that a CB has a great influence on cancer treatment decisions, but the effectiveness of the CB in our hospital should be verified in the future by analyzing treatment outcomes.

Cisplatin Plus Capecitabine After Adjuvant S-1 in Metastatic Gastric Cancer: A Phase II T-CORE1102 Trial.

BACKGROUND/AIM: This phase II study assessed the efficacy of capecitabine plus cisplatin in patients with advanced gastric cancer refractory to adjuvant S-1. PATIENTS AND METHODS: This single-arm, open-label, multicenter, phase II study was conducted by Tohoku Clinical Oncology Research and Education Society (T-CORE) in Japan. Patients aged ≥20 years with advanced HER2-negative gastric cancer that was refractory to S-1 were enrolled. Patients received 80 mg/m2 cisplatin on day 1 intravenously and 1,000 mg/m2 capecitabine twice daily from day 1 to day 14, in 3-week cycles. The primary endpoint was progression-free survival (PFS). The threshold overall response rate (ORR) was estimated to be 15%. The secondary endpoints were overall survival (OS), time to treatment failure, ORR, and toxicities. RESULTS: In total, 21 patients were enrolled from seven hospitals. The median patient age was 63 years. Nineteen patients received the protocol treatment. Median PFS was 3.7 months [90% confidence interval (CI)=2.7-5.6 months], which did not reach the predefined threshold of 4.0 months. ORR was 5.9% (95%CI=0.0-17.1%). Median OS was 11.9 months (95% CI 6.3-19.4 months). Febrile neutropenia was observed in 5.3% of patients. The most frequently observed grade 3 non-hematologic toxicities were nausea (15.8%) and hyponatremia (15.8%). CONCLUSION: The addition of a fluoropyrimidine to a platinum agent after adjuvant therapy is not suitable for gastric cancer.

[Elental prevented and reduced oral mucositis during chemotherapy in patients esophageal cancer].

Stomatitis is a side effect caused frequently by chemotherapy in patients with esophageal cancer, but a standard treatment for it has not been established. Reactive oxygen species are known to be among the causes of stomatitis induced by chemotherapy or radiotherapy, and some reports suggest that their influences might be reduced by the oral supplementation of glutamine. Elental® is one of the widely-used nutritional supplements, and its pack contains 1, 932 mg of L-glutamine (an especially high amount.). Therefore, we examined the preventive or reducing effects Elental® mey have on oral mucositis. Fifteen patients with esophageal cancer received chemotherapy, six of whom had grade one oral mucositis. All of those six patients entered the investigation, and seven courses of Elental® were administered. After seven courses, all six patients oral mucositis declined from grade 1 to grade 0. This result suggests that Elental® has preventive or reducing effects on oral mucositis.

[A case of advanced esophageal cancer with multiple liver metastases accompanying poorly general conditions and serious liver dysfunctions, successfully treated using concurrent radiotherapy and chemotherapy with low-dose nedaplatin and 5-fluorouracil].

A 64-year-old male visited our hospital complaining of epigastric pain, and was diagnosed as esophageal cancer with multiple liver metastases. Histological examinations revealed squamous cell carcinoma. He had serious liver dysfunctions and his general conditions were severe, expressed as 3 of the performance status. He was treated using radiotherapy and chemotherapy with low-dose nedaplatin and 5-fluorouracil after the fully sufficient informed consent was taken. As for adverse events, Grade 2 of thrombocytopenia was only observed. Liver tumors responded to anticancer drug treatment immediately, and liver functions were almost normalized. The chemotherapy using low-dose nedaplatin and 5-FU combined with the radiotherapy was feasible and effective to patients with poor conditions.

Vimentin-positive and Alpha-fetoprotein-elevated Nuclear Protein of the Testis Midline Carcinoma: A Case Report and Review of the Literature.

Nuclear protein of the testis (NUT) midline carcinoma (NMC) is a rare malignant tumor expressing NUT with BRD4/3 rearrangements and is sometimes misdiagnosed as germinoma, especially in alpha-fetoprotein (AFP)-elevated cases. A 28-year-old man had a mediastinal tumor with multiple bone metastases and elevated AFP levels. Imaging/laboratory findings led to a pathological diagnosis of extragonadal germinoma. After unsuccessful treatment with etoposide-cisplatin, he was re-diagnosed with sarcoma due to vimentin-positive findings. He was treated with adriamycin-ifosfamide, which resulted in disease-control. A posthumous examination clarified the NUT rearrangement. Even in cases with characteristic findings, such as elevated AFP levels and vimentin positivity, NMC should be considered as a differential diagnosis. We note, however, that adriamycin-ifosfamide has some efficacy in such cases.

Plasma level of granulocyte-colony stimulating factor during granulocyte and monocyte adsorptive apheresis in patients with ulcerative colitis.

BACKGROUND/AIMS: Cytapheresis with extra-corporeal circulation for ulcerative colitis is effective but its mechanisms are still unclear. Granulocytecolony stimulating factor (G-CSF) strongly mobilizes bone marrow-derived cells and serves as antiinflammatory factor. We investigated plasma levels of G-CSF during granulocyte and monocyte adsorptive apheresis (GCAP). METHODOLOGY: Nineteen cases of ulcerative colitis were measured plasma concentration of G-CSF during the first session of GCAP therapy. RESULTS: G-CSF were significantly increased in the column inflow at 30 min compared with the baseline (Wilcoxon test, p < 0.01), and also increased through the column (Wilcoxon test, p < 0.01). The ratio of the increase in the column outflow at 60 min was 1.5-fold compared with the baseline. However, we could not show a significant relation between G-CSF level and clinical efficacy. CONCLUSIONS: This is the first report concerning G-CSF during CAP. G-CSF is increased due to GCAP and appears to be a candidate which should be further investigated.

[A case of primary orbital adenocarcinoma responding to chemoradiation].

Primary orbital adenocarcinoma is very rare. There are not any reports about the treatment of this disease, except for surgery. We experienced a case of primary orbital adenocarcinoma, which we successfully treated by chemoradiation using 5-FU and cisplatin. It is very important to collect and record cases of rare diseases responding to certain chemotherapy regimens.

Rapid Progression of Intracranial Dural Metastases in a Patient with Carcinoma of Unknown Primary Site.

Dural metastases are uncommon in cancer patients, but can have as much of an effect on the lives of patients as brain metastases. Dural metastases are most commonly associated with primary cancers of the breast, prostate, and lung, and it is rare that the primary site of the tumor is unknown. In this study, we encountered a 51-year-old woman who had developed multiple bone tumors, with no known primary cancer lesion. A tumor biopsy of the sacral bone revealed non-keratinizing squamous cell carcinoma; the patient was therefore diagnosed as having multiple bone metastases of an unknown primary cancer. Magnetic resonance imaging revealed cranial metastases and partial thickening of the dura with suspected dura metastases. Platinum-based chemotherapy reduced the bone metastases and the thickened dura. However, as resistance to chemotherapy developed, invasions progressed rapidly and diffusely throughout the dura. This was accompanied by the development of dysarthria, visual impairments, and delirium. The patient died 10 months after being diagnosed with dural metastases. This report provides information on the clinical course and prognosis of patients with dural metastases of unknown primary cancer. Furthermore, it may help to construct a treatment strategy for dural metastases.

A multi center study of granulocyte and monocyte adsorption apheresis therapy for ulcerative colitis-clinical efficacy and production of interleukin-1 receptor antagonist.

Granulocyte and monocyte adsorption apheresis (GCAP) is a useful strategy for intractable ulcerative colitis, but its mechanisms of therapy is not fully explained. Previously, depleting activated granulocytes and monocytes (GMs) and modifying product of proinflammatory cytokines had been proposed. In addition, activated GMs are releasing anti-inflammatory cytokines, interleukin-1 receptor antagonist (IL-1ra) that may contribute to the clinical efficacy of GCAP therapy. Hence, to investigate contribution of IL-1ra as well as to confirm clinical efficacy of this therapy based on clinical activity index (CAI), we performed a multicenter study. Twenty-five of 38 (65.8%) patients achieved remission state (CAI < or = 4) and two of 38 (5.3%) revealed clinical improvement. Almost effective cases significantly decreased CAI even at 3rd session of GCAP. Plasma level of IL-1ra from outflow of the GCAP column at 30 min was significantly increased rather than inflow. Median exact elevated level of IL-1ra was 221 pg/ml and median of increasing ratio was 1.6 times. Furthermore, the responsive patients, who well released the IL-1ra at outflow more than 100 pg/ml compared with inflow, tended to show clinical effectiveness. While, the increased ratio of IL-1ra in effective cases did not differ from ineffective cases, and there were no significant relationship with improvement of CAI score. These conflict results suggest that the increase of IL-1ra at outflow is not a direct factor to the clinical improvement, but the induction of clinical improvement is accompanied by the release of IL-1ra. The IL-1ra may be involved in the multiple steps for the improvement induced by GCAP.

Long-term survival after a favorable response to anti-EGFR antibody plus chemotherapy to treat bone marrow metastasis: a case report of KRAS-wildtype rectal cancer.

Bone marrow metastasis is a rare consequence of colorectal cancer that results in a poor prognosis; few reports describe a favorable response to doublet chemotherapy combined with targeted therapy, which is currently the standard treatment. We experienced a case where anti-epidermal growth factor receptor (EGFR) antibody produced a marked anti-tumor response to bone marrow metastasis that led to long-term survival. A 51-year-old man was diagnosed with a primary KRAS-wildtype rectal cancer with multiple metastases, including the bone marrow. Disease control was achieved for 10.8 months following chemotherapy with a modified FOLFOX6 regimen combined with an anti-EGFR antibody. He died of cancer 22.7 and 16.6 months after disease onset and first-line chemotherapy, respectively. This case shows that early tumor shrinkage and deepness of response to the anti-EGFR antibody were observed even in a patient with bone marrow metastasis. Anti-EGFR antibody therapy should therefore be considered even when a patient's medical condition appears to be poor owing to bone marrow metastasis. Moreover, tumors that are likely to be sensitive to chemotherapy, such as RAS-wildtype colorectal cancers, can be considered for anti-EGFR antibody therapy even if the patient is considered unfit for chemotherapy.

Association of visceral fat accumulation and plasma adiponectin with colorectal adenoma: evidence for participation of insulin resistance.

PURPOSE: Colorectal carcinogenesis is thought to be related to abdominal obesity and insulin resistance. To investigate whether visceral fat accumulation contributes to colorectal carcinogenesis, we examined its accumulation and the levels of the adipose tissue-derived hormone adiponectin in Japanese patients with colorectal adenoma. EXPERIMENTAL DESIGN: Fifty-one consecutive Japanese patients ages >/=40 years and with colorectal adenoma were subjected to measurement of visceral fat area by computed tomography scanning and plasma adiponectin concentration. The patients also underwent the 75-g oral glucose tolerance test. Insulin resistance was calculated by the homeostasis metabolic assessment (HOMA-IR) method. The controls were 52 Japanese subjects ages >/=40 years and without colorectal polyp. Cigarette smokers and subjects who consumed alcohol (>/=30 g ethanol/d) were excluded. RESULTS: The patients with colorectal adenoma showed significantly more visceral fat area and significantly less plasma adiponectin concentration in comparison with the controls [odds ratio (OR), 2.19; 95% confidence interval (95% CI), 1.47-3.28; P < 0.001 and OR, 0.24; 95% CI, 0.14-0.41; P < 0.001, respectively] by logistic regression analysis. HOMA-IR index was also associated with colorectal adenoma (OR 2.60; 95% CI, 1.20-5.64; P = 0.040). Visceral fat area and adiponectin were associated with adenoma number (1, 2, >/= 3), the size of the largest adenoma (<10 and >/=10 mm), and adenoma histology (tubular and tubulovillous/villous). CONCLUSIONS: These results suggest an association of visceral fat accumulation and decreased plasma adiponectin concentration with colorectal adenoma in Japanese patients. This study may offer a new insight to understanding the relationship of colorectal carcinogenesis with abdominal obesity and insulin resistance.

The Role of Cancer Boards in the Treatment Decisions Regarding Chemotherapy.

Objective The influence of cancer boards with respect to the treatment decisions regarding chemotherapy remains to be elucidated. In the present study, we investigated the cases that presented at our institutional cancer boards, to assess the effect of cancer boards on the treatment decisions regarding chemotherapy. Methods Data from the cancer boards at Yamagata University Hospital, Yamagata, Japan, were collected. Along with data from the clinical records, the details of the discussions and the chosen plan of treatment of the cancer boards were analyzed. Results From February 2010 to February 2014, 1,541 cases were discussed at our cancer boards. Of these, 811 cases (52.6%) involved discussions about chemotherapy. Of those 811 cases, recommendations were made to alter the treatment plans for 189 cases (23.3%). The reasons for discouraging chemotherapy varied; however, 29/45 (64.4%) cases involved discouragement for the following reasons: old age, a comorbid condition, the physical (performance) status, or insufficient evidence to administer chemotherapy. Eighty-six patients were referred to the medical oncology department through the cancer boards. Conclusion Our results showed that cancer boards have a great influence on the treatment decisions regarding chemotherapy and the prompt referral of cases to medical oncologists as necessary. In terms of future research, we will evaluate the effect of cancer boards on the prognosis and outcomes of cases using the institutional cancer registry.

Significance of rapid turnover proteins in protein-losing gastroenteropathy.

BACKGROUND/AIMS: We investigated the significance of rapid turnover proteins (retinal-binding protein, pre-albumin and transferrin) in protein-losing gastroenteropathy. METHODOLOGY: We evaluated the levels of these proteins in 12 patients with protein-losing gastroenteropathy. RESULTS: The protein-losing gastroenteropathy patients showed very low level of total serum protein of 4.3 +/- 0.7 g/dL, albumin 2.1 +/- 0.4 g/dL, and IgG 682 +/- 232 mg/dL. However, retinal-binding protein was 4.4 +/- 1.9 mg/dL (normal range; 2.5-8.0 mg/dL), pre-albumin 29.3 +/- 7.9 mg/dL (21-43 mg/dL) and transferrin 226 +/- 62 mg/dL (205-370 mg/dL). The levels of rapid turnover proteins, particularly retinal-binding protein and pre-albumin were almost preserved within the normal range, despite hypoproteinemia. CONCLUSIONS: If there is a patient with severe hypoproteinemia and preserved levels of rapid turnover proteins, protein-losing gastroenteropathy should be suspected and we get a strong proof to do the following examinations such as a fecal clearance of alpha-1 antitrypsin.

Personalization of chemotherapy for metastatic pancreatic cancer.

Erlotinib is an approved drug for the treatment of advanced pancreatic cancer; however, its survival benefit is small and its cost is high, and the decision to use the drug may often be personalized according to the patient's background. A 72-year-old Asian man in good general condition chose gemcitabine monotherapy over combination therapy with gemcitabine plus erlotinib because the survival benefit of the latter was small. The cost of the drug did not appear to affect this decision. This report details the process of decision making with respect to whether a patient receives targeted therapy, and suggests that the use of molecular-targeted drugs must be personalized from many perspectives, including the patient's social situation.

Status of radiotherapy in a multidisciplinary cancer board.

Multidisciplinary cancer boards (CBs) for making cancer treatment decisions have become popular in many countries; however, the status of radiotherapy in CBs and the influence of CBs on radiotherapy decisions have not been studied. To clarify these issues, we reviewed the minutes of our CBs from February 2010 to March 2012, and we classified planned treatments discussed at the CBs into five categories and analyzed decisions concerning radiotherapy in each category. The fraction of cases for which radiotherapy was recommended was 536/757 (71%). These cases included 478 cases (63%) for which radiation therapy was planned and four cases (0.5%) for which radiation therapy was unexpectedly recommended. On the other hand, radiation therapy was canceled in 21 cases (4%) for which radiation therapy had been planned. This study showed that radiotherapy was discussed in many cases at CBs and that CBs have a great influence on decisions concerning radiotherapy.

Genetic diversity of the Helicobacter pylori sialic acid-binding adhesin (sabA) gene.

A putative virulence factor, SabA, a sialic acid-binding adhesin, has recently been characterized in Helicobacter pylori from European isolates. However, little genetic information is available for sabA genes in strains isolated from Japanese patients. Here, we investigated the presence of the sabA gene in 23 H. pylori clinical isolates using polymerase chain reaction detection. It was found that 91.3% of H. pylori isolates examined contain the sabA gene. Sequence comparison and phylogenetic analysis based on the deduced amino acid sequence of sabA in nine H. pylori isolates from Japanese patients and three H. pylori strains from Western individuals suggested that sabA is genetically diverse and the clustering of the strains based on SabA is related to their geographical origin. It needs to be further assessed whether the genetic diversity of sabA is associated with the clinical outcomes of H. pylori infection.

Decreased levels of plasma adiponectin associated with increased risk of colorectal cancer.

AIM: To investigate the association between adiponectin levels and risk of colorectal adenoma and cancer (early and advanced). METHODS: A cross-sectional study in a cohort of hospital-based patients was conducted between January 2004 and March 2006 at Yamagata University Hospital. Male subjects, who had colorectal tumors detected by endoscopic examination, were enrolled according to inclusion and exclusion criteria. Based on the T factor of the TNM system, intraepithelial carcinoma and submucosally invasive carcinoma were defined as early cancer, and invasion into the muscularis propria or deeper was defined as advanced cancer. The plasma levels of glucose, insulin, total cholesterol, triglyceride, high sensitivity C-reactive protein, insulin like growth factor (IGF)-1, IGF binding protein-3, adiponectin, leptin, and resistin were measured. Each factor level was designated low or high, and the risk of adenoma or cancer was estimated by univariate and multivariate logistic regression analysis. RESULTS: We enrolled 124 male subjects (47 with adenoma, 34 with early cancer, 17 with advanced cancer, and 26 without tumors as controls). In patients with adenoma, high triglyceride and low adiponectin were associated with a significant increase in the odds ratio (OR) by univariate analysis. Only a low adiponectin level was related to increased adenoma risk, with an adjusted OR for low level (< 11 microg/mL) to high (>or=11 microg/mL) of 5.762 (95% confidence interval (CI): 1.683-19.739, P = 0.005). In the patients with early cancer, high body mass index, high triglyceride, and low adiponectin were associated with a significant increase in OR in univariate analysis. In multivariate analysis, only low adiponectin was significantly associated with early cancer, with an adjusted OR of 4.495 (95% CI: 1.090-18.528, P = 0.038). However, in patients with advanced cancer, low adiponectin was not recognized as a significant risk factor for advanced cancer. CONCLUSION: A decreased level of adiponectin is strongly associated with an increased risk of colorectal adenoma and early cancer. These data call for further investigation, including a controlled prospective study.

Increased plasma levels of 8-hydroxydeoxyguanosine are associated with development of colorectal tumors.

Increased oxidative stress is generally thought to be associated with tumorigenesis. In this cross-sectional study, we evaluated plasma 8-hydroxydeoxyguanosine (8-OHdG) levels in patients with colorectal adenoma and cancer, as a surrogate marker of oxidative damage to deoxyribonucleic acid (DNA). We collected blood samples from 58 patients with adenoma, 32 with early cancer, 25 with advanced cancer, and 36 without polyps or cancer (as controls), and measured plasma levels of 8-OHdG by enzyme-linked immunosorbent assay. Univariate analysis by logistic regression showed that an increased level of 8-OHdG was a significant risk for adenoma [odds ratio (OR) 1.393, 95% confidence interval (CI) 1.008-1.926, p = 0.045]. In patients with early cancer, univariate analysis revealed significant differences for age, body mass index (BMI), systolic blood pressure, and 8-OHdG level. Subsequent multivariate analysis revealed that 8-OHdG [OR 1.627, 95% CI 1.079-2.453, p = 0.020] and BMI [OR 1.283, 95% CI 1.038-1.585, p = 0.021] were significant risk factors for early cancer. However, 8-OHdG was not a significant risk factor for advanced cancer. Our results suggest that an increased plasma level of 8-OHdG is associated with development of colorectal adenoma and cancer.

Osteonecrosis of the lateral femoral condyle in a patient with ulcerative colitis: report of a case.

Osteonecrosis is a major complication in patients with ulcerative colitis (UC). It appears most commonly in the femoral head, but sometimes occurs in the proximal humerus or femoral condyle. A 27-year-old Japanese woman presented with severe pain in the left knee in 2006. Osteonecrosis was found in the left lateral femoral condyle, and osteochondral autografting was performed. Ten and a half years prior to this episode, at the age of 17 years, she had been diagnosed as having UC, and after 18 months of medication, she had undergone total colectomy. A total prednisolone dose of 3020 mg had been administered before the operation, but the true pathogenesis-i.e. idiopathic or steroid-associated osteonecrosis-had not been determined at that time. The osteonecrosis occurred long after prednisolone therapy had been discontinued, and the total dose of prednisolone was not considered to be unusually high. In this case, osteochondral autografting was ultimately required for treatment of the osteonecrosis. However, conservative therapy is indicated for early-stage cases and should result in a good course. We report this case to draw attention to this relatively rare complication of UC and to facilitate early detection of similar lesions.