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Background: Immune checkpoint inhibitors (ICIs) sometimes cause immune-related adverse events (irAEs), the timing of occurrence of which is difficult to predict. We created a system to safely manage the patients treated with ICIs who visit hospital during an emergency. Methods: We utilized the Plan-Do-Check-Act (PDCA) cycle method to improve the quality of countermeasures for irAEs in the emergency room. First, an icon showing the patients treated with ICIs was developed for inclusion in electronic medical records. Second, ICI-specified urgent sets of clinical laboratory tests were prepared to cover the spectrum of irAEs. Third, a direct call system to either the attending physician or the chemotherapy team was established. A flow chart for managing irAEs has been prepared since September 2018. We retrospectively analyzed the electronic medical records from September 2018 to December 2020 to determine the effectiveness of the developed system. Results: In the first cycle of PDCA, 24 patients administered ICIs were retrospectively surveyed and seven visited the emergency room. Six cases were examined according to the flow chart, whereas the other patient complaining of grade 2 diarrhea were not examined because of incomplete knowledge regarding ICIs and irAEs. As part of the “Act” step, we reminded the doctors of the flow chart and gave a lecture to the residents on how to manage irAEs. During the second and seventh cycle, no cases were observed without consulting the flow chart. Conclusions: Quality improvement activities for the management of irAEs were conducted using the PDCA cycle methodology. Patients on ICIs are now being continuously monitored to further improve management quality.

BackgroundImmune checkpoint inhibitors (ICIs) sometimes cause immune-related adverse events (irAEs), the timing of occurrence of which is difficult to predict. We created a system to safely manage the patients treated with ICIs who visit hospital during an emergency.MethodsWe utilized the Plan-Do-Check-Act (PDCA) cycle method to improve the quality of countermeasures for irAEs in the emergency room. First, an icon showing the patients treated with ICIs was developed for inclusion in electronic medical records. Second, ICI-specified urgent sets of clinical laboratory tests were prepared to cover the spectrum of irAEs. Third, a direct call system to either the attending physician or the chemotherapy team was established. A flow chart for managing irAEs has been prepared since September 2018. We retrospectively analyzed the electronic medical records from September 2018 to December 2020 to determine the effectiveness of the developed system.ResultsIn the first cycle of PDCA, 24 patients administered ICIs were retrospectively surveyed and seven visited the emergency room. Six cases were examined according to the flow chart, whereas the other patient complaining of grade 2 diarrhea were not examined because of incomplete knowledge regarding ICIs and irAEs. As part of the “Act” step, we reminded the doctors of the flow chart and gave a lecture to the residents on how to manage irAEs. During the second and seventh cycle, no cases were observed without consulting the flow chart.ConclusionsQuality improvement activities for the management of irAEs were conducted using the PDCA cycle methodology. Patients on ICIs are now being continuously monitored to further improve management quality.

Background: Metastatic gastric cancer has a poor prognosis, despite recent therapeutic improvements. The phase 3 SOLAR study confirmed better efficacy of S-1, oxaliplatin, and leucovorin (SOL) than S-1 plus cisplatin in advanced gastric cancer. Lentinan, (1, 3)-glucan purified from Shiitake mushrooms, has been reported to improve the overall survival of cancer patients receiving chemotherapy. We conducted a preliminary study of SOL combined with lentinan during these 4 years. Methods: The clinical study was approved by the ethics committee of Nagoya Memorial Hospital in 2016. After explaining the protocol of this study, patients with recurrent or unresectable gastric cancer were enrolled, if they had the intention to participate. Medical records were retrospectively reviewed to determine the objective response rate (ORR), disease control rate, overall survival, and adverse effects. Results: Twelve patients (age: 59-81 years; sex: 9 men, 3 women) with metastatic gastric cancer (liver: 3, lung: 2, peritoneal: 12, ascites: 9) were treated with SOL in combination with lentinan as the first-line regimen. The cycles ranged from 4 to 15. The ORR and disease control rates were 58.3% (complete response [CR], 1; partial response, 6) and 91.7%, respectively. One patient with CR survived for > 23 months after the initiation of chemotherapy. Concerning adverse events, peripheral neuropathy was the most common event observed in all patients. However, there were no severe side effects, such as febrile neutropenia and diarrhea. Conclusions: SOL combined with lentinan can be a promising option for the treatment of far advanced metastatic gastric cancer.

Backgrounds: Colorectal cancer is an important contributor to cancer morbidity and mortality. Given that many older adult patients often have concomitant diseases and impairments in organ function, they are at increased risk for chemotherapy toxicity. Therefore, it is important to identify prognostic factors in older patients undergoing chemotherapy. Methods: We performed a retrospective chart review of colorectal cancer patients treated at Nagoya Memorial Hospital between 2012 and 2017 and selected those who received chemotherapy for metastatic colon cancer. Overall survival was calculated from the beginning of chemotherapy until death or the most recent follow-up date. We used the Kaplan-Meier method to plot survival curves and performed a statistical comparison using a log-rank test. In addition, multivariate analysis was performed using stepwise Cox proportional hazards models. Finally, a comprehensive geriatric assessment was conducted for older patients. The chart review was approved by the ethics committee of Nagoya Memorial Hospital. Results: The overall survival of metastatic colon cancer patients was not markedly different between patients aged ≥ 65 years of age (N = 37). Neither lesion site nor the RAS status affected survival, whereas the usage of three kinds of cytotoxic agents prolonged longevity. In a multivariate analysis of patients ≥ 65 years of age, the only independent prognostic factor for survival was the functional capacity, as measured by the Tokyo Metropolitan Institute of Gerontology (TMIG) index of competence. Conclusions: A combination of the comprehensive geriatric assessment and TMIG index was useful for predicting the longevity in patients with metastatic colon cancer ≥ 65 years of age.

Key Clinical Message The association between thrombosis and cancer has been recognized since Trousseau's report in 1865. We present a case of bladder squamous cell carcinoma associated with multiple cerebral infarctions. This patient was diagnosed as having Trousseau's syndrome and received radiotherapy for bladder cancer treatment, along with anticoagulation therapy.

Background Various kinds of immune-related adverse events (irAEs) are caused by the usage of immune checkpoint inhibitors (ICI), which occasionally develop to severe conditions such as colitis and adrenal gland insufficiency. Since we are unable to anticipate when irAEs may occur, it is crucial to be informed of administration history of ICI on urgent visit. Methods We have utilized PDCA cycle Method to improve the quality of countermeasures for irAEs at the emergency room (ER). First, we invented an icon showing the patients treated with ICI on electronic medical records. Second, ICI-specified urgent sets of clinical examination were made to cover the spectrum of irAEs. Third, direct call system to either attending physician or chemotherapy team was established. And then a flow chart to manage irAEs has been prepared since September 2018. Retrospective examination was conducted to check whether the invented system work properly.[Results] Among 19 patients on ICI, four visited ER during these 4 months.Three cases were seen according to the flow chart, while one with grade 2 diarrhea was found not to undertake any examinations at ER, due to the complete lack of knowledge concerning ICI and irAEs.We informed all of the doctors of this flow chart at doctors’ office committee and gave a lecture for the residents about the significance of irAEs and how to manage these patients at ER. Conclusions We are monitoring patients on ICI to check whether their management be performed in safety on urgent visit.

Background Metastatic gastric cancer has a poor prognosis. Overall survival in these patients is approximately 1 years, despite the development of chemotherapeutic and biological agents. The incidence of long-term survivors of metastatic gastric cancer beyond 5 years after the initiation of chemotherapy has been reported to be less than 10%. Methods The characteristics of long-term survivors were compared with those of poor responders to determine the specific factors that regulate chemosensitivity. Those who died within six months after the initiation of chemotherapy were considered as poor responders in this analysis. Medical records were retrospectively reviewed to determine the clinicopathological features of metastatic gastric cancer patients receiving chemotherapy in Nagoya Memorial Hospital. Statistical analyses were carried out by Fisher’s exact test and then a multivariate analysis. Differences with P values less than 0.05 were considered statistically significant. The chart review was approved by ethics committee of Nagoya Memorial Hospital. Results We experienced 8 long-term survivors and 12 poor responders. The analysis showed that number of metastatic sites might be different between 2 groups (P = 0.0144). The objective response rates of long-term survivors and poor responders were 62.5% (CR 4, PR 1) and 0%, respectively. Conclusions We found that tumor burden might be associated with the prognosis of affected patients. Good response to systemic chemotherapy should be essential for prolonged survival of patients with distant metastases.

Natural compounds containing fungal β-glucans have been used to improve general health for thousands of years in China and Japan. Lentinan, the backbone of β-(1, 3)-glucan with β-(1, 6) branches, is one of the active ingredients purified from Shiitake mushrooms and has been approved as a biological response modifier for the treatment of gastric cancer in Japan. Despite recent advances in chemotherapeutic agents, unresectable or recurrent gastric cancer remains an incurable disease, with survival rates being far from satisfactory. Recent clinical studies have shown that chemo-immunotherapy using lentinan prolongs the survival of patients with advanced gastric cancer, as compared to chemotherapy alone. In addition, trastuzumab, an antibody against HER2/neu growth factor receptor, has been used for the treatment of gastric cancer in combination with cytotoxic chemotherapeutic agents. Lentinan may exert a synergistic action with anti-cancer monoclonal antibodies to activate complement systems through the mechanism of antibody-dependent cellular cytotoxicity and complement dependent cytotoxicity. Because a better understanding of its biological activities should enable us to use lentinan more efficiently in the treatment of gastric cancer, immunological effects provided by β-glucans, a possible mode of action of lentinan, and its clinical application including future potential uses are discussed in the present review.

Gastric cancer is the third leading cause of cancer-related mortality worldwide. Systemic chemotherapy is the main treatment option for advanced gastric cancer when the tumor is inoperable. Despite recent advances in chemotherapeutic agents, the prognosis of unresectable or recurrent gastric cancer remains extremely poor. In Japan, combination therapy including S-1 and cisplatin is the standard first-line treatment for advanced gastric cancer; however, the five-year survival rate remains very low. Lentinan, the backbone of beta-(1,3)-glucan with beta-(1,6) branches, an active ingredient purified from Shiitake mushrooms, has been approved as a biological response modifier for the treatment of gastric cancer. This agent has been used in combination with oral fluoropyrimidines to improve the overall survival of gastric cancer patients. A retrospective chart review on 138 metastatic gastric cancer patients receiving chemotherapy was performed in Nagoya Memorial Hospital from 1 September 2010 to 31 August 2015. 12 patients with liver metastases were treated by lentinan in combination with S-1-based chemotherapy. The rate of objective response was 42% (5/12) and the disease control rate was 83% (10/12) in response to chemo-immunotherapy using lentinan, with a median overall survival of 407 days (95% CI: 207–700 days).

Background: Despite the significant advances in chemotherapy, the prognosis of unresectable gastric cancer is still very poor and the role of immunotherapy remains to be clarified. We examined whether lentinan, a biological response modifier, could enhance the chemotherapeutic effects. Materials and methods: A retrospective cohort study was conducted to evaluate the survival benefits of lentinan among the patients with gastric cancer receiving chemotherapy. To investigate the mechanisms underlying the clinical effects of lentinan, its cytotoxic activity was accessed by cell proliferation assay. The expression of molecules relevant to immune checkpoints were analyzed by real-time PCR using human gastric cancer cell lines; MKN1, MKN45, and NUGC3. Results: The addition of lentinan prolonged the survival of patients with gastric cancer receiving S-1 based chemotherapy. Lentinan reduced the constitutive expression of PD-L1 in all cell lines mainly by suppressing the MAPK pathway. Conclusion: Lentinan at clinical concentrations stimulates tumor-specific adaptive immunity through PD-L1 downregulation, which may enhance chemotherapy-induced tumor clearance and patient survival.

Objective : Bevacizumab has been increasingly used in combination chemotherapy for the treatment of metastatic or recurrent colorectal cancer. The aim of this report is to underline the possible risks associated with bevacizumab use. Methods : Between July 2005 and March 2013, a total of 130 patients with metastatic colorectal cancer who received oxaliplatin as first-line chemotherapy were divided into 2 groups those treated with bevacizumab (group A) and those without (group B), and compared. The primary endpoint was to clarify the profile of bevacizumab - induced adverse effects. Secondary endpoints examined therapeutic effects, including overall survival (OS). Results : The incidence of major side effects was almost equivalent, except for bleeding, between the 2 groups. With regard to the therapeutic effects, 1 patient in group A showed complete disappearance of multiple lung metastases without any evidence of recurrence. The median OS was 926 days (95% confidence interval [CI], 756 - 1257) in group A and 534 days (95% CI, 421 – 621) in group B ( p < 0.01). Conclusion : The results demonstrate that bevacizumab prolonged survival in these patients although there was an increased risk of clinically significant bleeding.

Background: There have been no well-documented reports detailing the relationship between skeletal metastasis and tumor markers in a large series of patients. The purpose of our study was to assess the relationship between the clinical features of skeletal metastasis and serum tumor markers and to determine whether tumor markers are a useful modality in the differential diagnosis of skeletal metastasis. Methods: We retrospectively reviewed consecutive 458 patients with skeletal metastasis and divided the patients into two groups according to six clinical presenting factors. We assessed whether these groups influenced the level of the tumor markers in univariate and multivariate analysis. Results: Patients with skeletal metastasis of carcinoma had a higher level of markers CEA (P < 0.0001)andCA19-9(P = 0.0008)thanpatientswithprimarybonetumorsandhematological malignancies. Univariate analysis of clinical variables revealed that metastasis on axial skeleton, multiple skeletal metastases and visceral metastasis were associated with the serum CEA and CA19-9 levels. By multivariate analysis, metastasis on axial skeleton, multiple skeletal metastases and visceral metastasis were found to be associated with the serum CEA and CA19-9 levels. At least one of the tumor markers was elevated in 73% of all patients. Conclusions: The higher tumor marker level (CEA, CA19-9) is predictive of metastasis on the axial skeleton, multiple skeletal metastases and visceral metastasis. Tumor markers are useful as a screening test to distinguish skeletal metastases of carcinoma from primary bone tumors or hematological malignancy from primary bone tumor and hematological malignancy.

Prognostic assessment is crucial for the management of AML. Although the use of karyotype analysis for risk-stratification is widely accepted, prognosis of AML remains ambiguous, particularly for patients categorized into the intermediate cytogenetic risk group and additional markers are required for an accurate prediction of outcome. For this study, we used multiplex real-time RT-PCR, which can simultaneously quantify WT1 and 10 distinct fusion gene transcripts, to prospectively evaluate the pre-treatment bone marrow findings of 53 de novo AML patients. Five patients with normal karyotype or insufficient metaphases detected by conventional karyotype analysis proved to have AML1-MTG8, CBFbeta-MYH11 or PML-RARalpha fusion transcripts. WT1 overexpression was observed in 92% of the patients, and the levels were significantly higher in the cytogenetic favorable risk group, especially patients with PML-RARalpha. WT1 levels also correlated with the percentage of blasts in bone marrow, especially in cases of core-binding factor leukemia. There was no association between initial WT1 levels and outcome in terms of event-free survival or overall survival. These results suggest that multiplex real-time RT-PCR is rapid and useful for the precise cytogenetic stratification of AML, and that WT1 levels at presentation correlate with several biologic features of leukemia, but have no prognostic significance.

We report a case of diffuse large B-cell lymphoma involving the thigh skin and tongue in an 85-year-old woman. No systemic symptoms or other lesions were observed at diagnosis. Local radiotherapy was effective, but cutaneous recurrence occurred 6 months after the treatment. The patient died of old age with no macroscopically distinguishable nodal or systemic lesions. A postmortem examination revealed intravascular invasion into the tongue, lung, and lymph nodes around the pancreas. To our knowledge, this is the first report of primary cutaneous diffuse large B-cell lymphoma with tongue involvement.

We report on two patients, successfully treated by the combination therapy of gemcitabine and 24-h intravenous infusion of cisplatin, who were initially diagnosed with node-positive advanced urothelial cancer. Each patient had a very good clinical response and underwent curative radical surgery after gemcitabine/cisplatin chemotherapy. A microscopically detailed examination of surgically obtained specimens showed the complete disappearance of malignant cells in the two cases. As a pilot study, we have used the regimen of gemcitabine plus 24-h continuous infusion of cisplatin, instead of bolus injection, for the treatment of 20 patients with node-positive or metastatic urothelial cancer. The clinical response rate in this regimen was 75% (complete response 7/20; 35%, partial response 8/20; 40%). The median overall survival was 665 days. As for the adverse effects, the incidences of severe neutropenia and thrombocytopenia (grade 3-4) were 20% and 15%, which might be less toxic than conventional gemcitabine plus cisplatin therapy. The 24-h infusion of cisplatin combined with gemcitabine can be highly recommended as neoadjuvant chemotherapy for locally advanced urothelial cancer.

CCND1, FGFR3 and c-MAF mRNA expression of tumor samples from 123 multiple myeloma patients were analyzed by global RQ/RT-PCR. CCND1, FGFR3 and c-MAF were positive in 44 (36%), 28 (23%) and 16 (13%) of patients, respectively. In 7 patients, both FGFR3 and c-MAF were positive. The expression of c-MAF was independent unfavorable prognostic factors for overall survival (OS). Autologous stem cell transplantation improved progression-free survival of CCND1-positive patients. Bortezomib, thalidomide or lenalidomide extended OS of FGFR3 and/or c-MAF-positive patients. Thus, CCND1, FGFR3 and c-MAF mRNA expression can predict survival and is useful for planning stratified treatment strategies for myeloma patients.

Aim: To examine the efficacy of oral rinsing against chemotherapy-induced stomatitis. Methods: Consecutive fluoropyrimidine-treated patients with stomach and colorectal cancer were enrolled from April 2009 to March 2011 (n=43; Group 1) and from January 2012 to December 2012 (n=45; Group 2). The incidence and severity of stomatitis were compared between Group 1 patients, who were instructed to gargle with lemonflavored water 6 times daily, and Group 2 patients, who did not receive any specific guidance. Among patients in the gargle group, we determined the rate of gargling compliance as well as quality of life (QOL) scores, and evaluated the impact of rebamipide use on patient outcomes. Results: The incidence of stomatitis was significantly reduced in Group 1 (14.0%) compared to that in Group 2 (33.3%) and its severity in the former group was milder. Among patients using lemon-flavored water, concomitant rebamipide use had no statistically significant impact on stomatitis incidence (with versus without rebamipide, 19.0% versus 9.0%), the rate of gargling compliance (96.4% versus 94.2%), or QOL scores. Conclusions: Oral rinse with lemon-flavored water is useful for the symptomatic control of fluoropyrimidineinduced stomatitis, regardless of the presence or absence of rebamipide.

Although the prognosis of unresectable gastric cancer remains poor (Hohenberger & Gretshel, 2003), recent advances in chemotherapy for this cancer have considerably improved the therapeutic effects. An oral fluoropyrimidine anticancer agent, S-1, developed in Japan, was designed to enhance the anticancer activity of 5-FU via combination with two modulating substances: gimeracil to inhibit dihydropyrimidine dehydrogenase and potassium oxonate to reduce gastrointestinal toxicities (Shirasaka, et al, 1996). The antitumor effects of fluoropyrimidine are known to be enhanced through biochemical modulation of folate metabolism modified by cisplatin (Scanlon, et al, 1986), and combination therapy using S-1 and cisplatin reportedly achieves high response rates (Koizumi, et al, 2008 ; Lenz, et al, 2007). Therefore, in Japan, S-1 with cisplatin is the standard therapy for advanced gastric cancer. However, disease progression is still observed in up to 40% of cases (Iwase, et al, 2005; Koizumi, et al, 2008) and further improvement of treatment is thus necessary. Taxanes have shown encouraging anti-tumor activities against various malignancies, including gastric cancer (Ohtsu, et al, 1998; Sulkes, et al, 1994). Taxane derivatives, docetaxel and paclitaxel, have a unique mechanism of action that differs from those of fluoropyrimidines and platinum compounds. The docetaxel containing combination regimens are associated with severe neutropenia (Yamaguchi, et al, 2006). Just recently, a phase I/ II study of docetaxel combined with S-1 plus cisplatin (DSC triple therapy) was conducted for advanced gastric cancer, and a very high tumor response rate was achieved with febrile neutropenia developing in approximately 20 % of patients (Nakayama, et al, 2008; Sato, et al, 2010). Paclitaxel combined with other drugs reportedly has tolerable toxicity (Kang, et al, 2008). In addition, continuous infusion of cisplatin for 24 hours has

AIM: To examine whether administration of lentinan, purified β-1, 3-glucan, can prolong survival in advanced gastric cancer patients receiving S-1-based chemotherapy. METHODS: Since 2004, 78 patients with metastatic or recurrent gastric cancer have received S-1-based chemotherapy as first-line treatment. Survival, side effects, and the ratio of granulocytes/lymphocytes (G/L ratio) were compared between 2 groups of patients who received chemo-immunotherapy using lentinan and chemotherapy alone. RESULTS: Median overall survival was significantly lon ger in the former group than in the latter group [689 d (95% CI: 431-2339 d) vs 565 d (95% CI: 323-662 d), P = 0.0406]. In addition, the G/L ratio in patients who received lentinan was maintained around or below 2, which was significantly lower than that in patients who received chemotherapy alone (P < 0.001). CONCLUSION: Chemo-immunotherapy with lentinan offers a significant advantage over S-1-based chemo therapy alone in terms of survival in patients with advanced gastric cancer.

Bone marrow transplantation (BMT) is performed as curative therapy for acute lymphoblastic leukemia (ALL). In most patients, BMT is performed at the time of remission which implies that the number of leukemic cells is less than 5% of all hematopoietic cells, namely, 0 to 10(10) leukemia cells in the body. Thus, some patients may well undergo BMT despite the fact that no leukemic cells are left in the body. In this respect, more accurate diagnosis of complete remission status would be to the patients' benefit. To detect minimal residual disease (MRD) not found by light-microscopy, further strategies are required after achieving hematological remission. Cytogenetic methods, Southern blot analysis and conventional immunological techniques can all provide accurate diagnosis, however, the sensitivity of these techniques for the detection of MRD is just as low as that of the light microscopy. Recently, polymerase chain reaction (PCR) has become available for the detection of low levels of chimeric bcr-abl transcripts in Philadelphia chromosome positive (Ph1) ALL patients. With this assay, investigators have reported MRD in patients after chemotherapy or BMT. Most patients who achieve hematological remission after conventional chemotherapy still have bcr-abl transcript detectable by PCR, confirming the general concept that this particular leukemia needs BMT in order to cure the disease. Some patients who had MRD prior to BMT continued disease free survival > 1 year after BMT with a negative PCR result and in these patients, MRD seems to have been eradicated by the BMT procedure.(ABSTRACT TRUNCATED AT 250 WORDS)

We prospectively analyzed the adverse effects and outcomes of 15 patients with stage IV gastric cancer who underwent palliative gastrectomy from December, 2002 to May, 2008 and subsequently received combination therapy of S-1 and 4-h infusion of cisplatin. The National Cancer Institute common toxicity criteria (version 3. 0) were applied to evaluate the adverse effects of this therapy, and the Kaplan-Meier method was used to plot the survival curve. The side effects most frequently observed were anorexia (grade 3; 33%), although one case of grade 4 who was easily fatigued was noted during the first course and could not receive further courses of this therapy. The 2-year survival rate was 33% and median survival time was 31 months. It has been suggested that 24-h infusion of cisplatin combined with oral S-1 after reduction surgery might improve survival in patients with stage IV gastric cancer.

From July, 2007 to June, 2008, we prospectively investigated the influence of Hange-shashin-to on the therapeutic and adverse effects of chemotherapy and the changes in quality of life(QOL)scores of the patients with metastatic gastric and colorectal cancer. Twenty patients receiving S-1/Irinotecan (CPT-11) therapy were randomly allocated into group A (with Hange-shashin-to) and B (without Hange-shashin-to). While the anti-tumor effects did not differ significantly between these two groups, severe side effects of more than grade 3 occurred less frequently in group A. Our results suggested that the decrease in QOL scores on day 15 might be alleviated in group A, compared to group B. Therefore, Hange-shashin-to can be one of the useful supportive medicines in the combination therapy of S-1/CPT- 11.

Two unresectable advanced gastric cancer cases with peritoneal metastases were successfully treated by the combination therapy of S-1 and paclitaxel. S-1 (1.25m(2): 80 mg/day, 1.25m(2)-1.50m(2):120 mg/day) was administered orally for 14 consecutive days followed by 14 days rest and a 2-hour infusion of paclitaxel (50 mg/m(2)) was administered on day 1 and 15 of each course. Treatment was repeated every 4 weeks unless disease progression or severe adverse effects were observed. Case 1: 65-year-old male (performance status: PS 3) with type 1 gastric cancer with malignant ascites. Case 2: 66-year-old male (PS3) with peritoneal metastases whose primary gastric lesion was surgically resected. Partial response was obtained in the former and complete response in the latter. Combination therapy of S-1 and paclitaxel can be highly recommended for patients with inoperable gastric cancer with poor PS.

We report on two patients, successfully treated by the combination therapy of S-1 and 24-h infusion of cisplatin (CDDP), who were initially diagnosed with unresectable stage 4 advanced gastric cancer. Each patient had a very good clinical response and underwent curative gastrectomy after completion of 14 and 10 courses of S-1/CDDP chemotherapy, respectively. A microscopically detailed examination of surgically obtained specimens showed the complete disappearance of malignant cells in the two cases. S-1/CDDP combination therapy can, therefore, be highly active in incurable advanced gastric carcinoma.

A 67-year-old man with multiple liver metastases of colonic cancer was treated with combination therapy of S-1 and irinotecan (CPT-11): S-1 (120 mg/day) administered orally for 14 consecutive days followed by 14 days rest. CPT-11 (100 mg/m(2)) was given as a 2-hour infusion on day 1 and 15. The patient complained of high fever and subsequent exertional dyspnea in the middle of the second course of S-1/CPT-11 therapy. He was hospitalized with severe hypoxemia. CT scan showed extensive ground glass and consolidative changes in bilateral lungs. Steroid pulse therapy with oxygen therapy remarkably improved his symptoms, and abnormal findings on CT scan also resolved. Drug-induced pneumonia needs to be considered in the differential diagnosis when patients treated with S-1/CPT-11 combination therapy present high fever and dyspnea.

A 56-year-old woman with multiple lung metastases and lymphangiosis carcinomatosa due to recurrent rectal cancer was treated with chemotherapy of modified FOLFOX6 (mFOLFOX6) regimen: l-leucovorin (l-LV 200 mg/m(2)) and oxaliplatin (L-OHP 85 mg/m(2)) were given as a 2-hour infusion followed by bolus injection of 5-FU 400 mg/m(2) and a 46- hour infusion 5-FU 2,400 mg/m(2) every two weeks. Since partial response was achieved and dyspnea was remarkably improved, she was discharged without oxygen therapy after 5 courses.

Oxaliplatin (L-OHP) has been established as a key drug for advanced colorectal cancer, and combination therapy with 5-FU/Leucovorin (LV)(FOLFOX regimen) is commonly used in Europe and the US. A phase I study of modified (m) FOLFOX 6 therapy was conducted to determine the recommended dose (RD) of 5-FU infused for 46 hours. Inclusion criteria were unresectable advanced colorectal cancer,measurable lesions, performance status (PS; ECOG) 0-2, age 20-75 years, and adequate organ functions. L-OHP and l-LV was administered over 2 hours and followed by bolus injection and continuous infusion of 5-FU for 46 hours every 2 weeks. Two cycles of mFOLFOX 6 therapy were performed. Doses of L-OHP, l-LV, and bolus injection of 5-FU were fixed at 85 mg/m(2), 200 mg/m(2), and 400 mg/m(2), respectively. The dose of continuous infused 5-FU was escalated from 1,600 mg/m(2), (level 1), 2,000 mg/m(2), (level 2), 2,400 mg/m(2), (level 3), and 2,800 mg/m(2), (level 4). RD was determined in a dose escalation manner, and safety was evaluated according to NCI-CTC Ver 2.0. A total of 13 patients were enrolled. Male/female=7/6, PS 0/1/2=2/4/7, mean age 64 years (range 55-75). Thrombocytopenia was not observed, and grade 2 of neutropenia and peripheral neuropathy was observed in 4 and 6 out of 13 patients. No dose-limiting toxicity (DLT) was observed at level 1 (n=3), 2 (n=4), and 3 (n=4), but at level 4 (n=2), 2 patients experienced DLT; grade 3 easy fatigue and anorexia required treatment delay over 7 days. Level 3 was therefore determined as RD. A phase II study is ongoing to evaluate the efficacy of mFOLFOX 6 therapy.

Three cases with unresectable advanced gastric cancer with liver metastases were successfully treated by the combination therapy of TS-1 and cisplatin( CDDP). TS-1 (1.25 m2: 80 mg/day, 1.25 m2-1.50 m2: 100 mg/day,or =1.50 m2: 120 mg/day) was administered orally for 14 consecutive days followed by 14 days rest,and a 24-h infusion of CDDP (70 mg/m2) was administered on day 8 of each course. Treatment was repeated every 4 weeks unless disease progression was observed. Partial response was obtained in all of the following three advanced gastric cancer cases with liver metastases. Case 1: 67-year-old male with Borrmann type I gastric cancer with multiple liver metastases. Case 2: 55-year-old female with multiple liver and lymph node metastases whose primary gastric lesion was surgically resected. Case 3: 53-year-old-male with Borrmann type III gastric cancer with liver and lymph node metastases. TS-1/CDDP therapy can be highly recommended for the treatment of advanced gastric cancer with liver metastases.

Background: Cancer patients often suffer from mucosal stomatitis during chemotherapy. Since our institute does not have Department of Dentistry, community-based cooperation with dentists should be warranted to maintain the oral health in cancer patients. Therefore, we have developed the system of regional cooperation of oral care with local dentists since April, 2013. Methods: This cooperation was initiated with lecture on oral care in cancer patients by late Dr. Youjiro Ohta (Sizuoka Cancer Center), which enabled us to discuss in concrete manner how to communicate between dental clinics and our institute. At first questionnaire survey was conducted for local dentists (n = 74), aiming at examining their will to participate in this cooperation, skill levels, consultation hours, and accommodations such as the presence of stairway and parking lots. Secondly, trainings on cancer treatment were performed, which contained general remarks on chemotherapy and Aichi-method of dental-medical cooperation, case study of oral care in the patients with hematological malignancy receiving stem cell transplantation, and molecular targeting therapy. Results: Our survey showed that 86% of local dentists (64/ 74) have some interests in the regional cooperation of oral care in cancer patients. Based on this survey, three levels of training were organized by the cooperation between the oral care project members in our hospital and board of directors of Tenpaku-ku dental association. Initial exchange of patients' information was conducted using FAX and 20 patients receiving chemotherapy entered Aichi-method cooperation of oral care from September, 2013. Early and preventive oral intervention by dentists was realized and the levels of self care were much improved, which could reduce the incidence and severity of oral complications. Conclusions: Good cooperation between physicians and dentists is very important to continue chemotherapy maintaining the quality of life in cancer patients.