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Background Naldemedine, a novel peripherally-acting mu-opioid receptor antagonist, has improved opioid-induced constipation in randomized controlled trials. The most frequent adverse event of naldemedine is diarrhea, which can cause abdominal pain and often leads to treatment discontinuation. We aimed to identify risk factors and appropriate management strategies for key adverse events including diarrhea associated with naldemedine, since those have not been extensively studied. Methods We conducted a multi-center retrospective cohort study. Eligible patients had cancer, had undergone palliative care at participating centers, had been prescribed regular opioids, and had taken at least one dose of naldemedine between June 2017 and March 2018. The primary endpoint was the incidence of diarrhea according to baseline characteristics. Secondary endpoints included the duration of naldemedine administration, daily defecation counts before and after starting naldemedine, duration and severity of diarrhea as an adverse event of naldemedine, other adverse events, and the incidence of constipation within 7 days after recovery from diarrhea. We defined patients who started naldemedine within three days of starting a regularly prescribed opioid as the early group, and the remainder as the late group. Results Among 103 patients who received naldemedine, 98 fulfilled the eligibility criteria. The median age was 68 years and 48% of the patients were female. Median performance status was 3, and the median oral intake was 50%. The median duration of naldemedine administration and overall survival were 25 and 64 days, respectively. The incidence of diarrhea in the early group (n = 26) was significantly lower than in the late group (n = 72) (3.9% vs. 22.2%, p = 0.02). Daily defecation counts increased after late (median 0.43 to 0.88, p p = 0.34). Constipation after the diarrhea was resolved was common (53%), especially among patients who stopped naldemedine (78%). The diarrhea was improved within three days in 92% of patients who stopped other laxatives. Conclusions The early administration of naldemedine is beneficial because it reduces adverse events including diarrhea. Diarrhea caused by naldemedine can be effectively managed by stopping other laxatives while continuing naldemedine.

It is important for cancer patients to receive end-of-life care at the desired place.To identify issues in selection of place for end-of-life care of cancer patients to realize their optimal survivorship.Between September 2015 and January 2016, a questionnaire consisting of 33 items, including end-of-life care place preferences, was administered to cancer patients who attended three university hospitals in Japan.A total of 971 questionnaires were collected (response rate, 88.4%). Fifty-eight percent of patients preferred to stay at home to receive end-of-life care. In contrast, more than 80% of patients did not know the details of healthcare services. The factors significantly associated with patients' choice for place of end-of-life care at home were "male gender" (odds ratio [OR] = 1.43, p = 0.030), "living in a one-person household" (OR = 0.21, p 0.001), "feeling close to friends" (OR = 0.94, p = 0.049), "thinking that the family is burdened" (OR = 0.55, p 0.001), "thinking that pain is controllable at home" (OR = 1.39, p 0.001), and "thinking that society should establish a system of home palliative care" (OR = 1.93, p 0.001).This study identified six factors influencing the selection of a place for end-of-life care. Most patients have a desire for a social system that allows end-of-life care at home where they can live with their family, but have anxiety about treatment to deal with symptom change, with concern about burden on their family. These issues should be addressed in the future.

Pain is classified as either nociceptive pain, which results from a nociceptor stimulation, or neuropathic pain, which results from a lesion of the neural pathway. Clinically, in many cases, pain consists of a single origin but multiple origins are also possible. In this paper, we outline an assessment and strategy for nociceptive pain in cancer. The onset time, location, feature, strength, and etiology were included as categories for the assessment of pain. Furthermore, we added a psychosocial assessment to the physical assessment, which ensured comprehensive pain evaluation. We performed the investigation according to the WHO method for cancer pain relief. According to the effects and adverse effects, we chose a non-opioid analgesic and an opioid analgesic as medications. However, nonpharmacological therapy, such as radiotherapy and nerve block, is not a concern with the WHO analgesic ladder. It is important that a multi-disciplinary team, which includes physicians, nurses, physiotherapists, and pharmacists, support the patients to manage their pain by themselves through the knowledge of the factors affecting their pain and the medication methods for easing it when it gets worse. Although we cannot ease pain completely, it is important to define the goal of treatment with patients and to examine the strategy for maximum pain relief.

A 78-year-old man visited our hospital with a prolapsed hemorrhoid. He was referred to the dermatology unit due to the thickness and redness of the perianal skin. He was diagnosed as having extra mammary Paget's disease by skin biopsy. After a biopsy of the anal polyp was performed to investigate the primary site, he was diagnosed with early anal canal cancer with Pagetoid spread and underwent a radical operation. Abdominoperineal resection with skin(D2 prx D3 lymphadenectomy) was performed with perineal reconstruction using a gracilis muscle graft. Postoperative surveillance without adjuvant therapy was performed because the pathological stage was stage I. Two years and 2 months after surgery, multiple liver metastases were found, and the patient was diagnosed with multiple liver, bone, and lymph node metastases(K-ras and UGT1A1 wild type)on PET. XELOX plus bevacizumab was used as first-line treatment and the liver metastases showed remarkable shrinkage; however, disease progression occurred in the bone. IRIS plus bevacizumab was started as second-line therapy but grade 3 hematotoxicity was observed during the first course. After 4 courses, it was difficult to maintain the therapy due to toxicity and cancer-related pain. The liver metastases had almost disappeared but the patient died 11 months after the initiation of chemotherapy.

We analyzed the effects of the Kampo medicine "Dai-kenchu-to" (DKT) on clinical aspects in colorectal surgery.Total 122 patients who underwent colorectal cancer surgery were divided into a DKT group (n = 53) and a non-DKT group (n = 69). The differences of postoperative course and anti-inflammatory responses between those two groups were analyzed.The 53 out of 59 patients could completely take DKT. In the postoperative course, significant difference was observed in the first flatus day. In the anti-inflammatory effects, differences were observed in the heart rate (HR) of the 3rd POD. In the change between 1st POD and 3rd POD, HR in the DKT group was well controlled compared to the non-DKT group. In the patients who had over 37.5°C of body temperature in 1st POD (n = 53), inflammatory response of the DKT group was reduced compared to the non-DKT group.The DKT might have the favorable influences on postoperative bowel movement and systemic inflammatory reaction, and induce the better postoperative course.

This retrospective report evaluated the safety and efficacy of hepatic arterial infusion chemotherapy (HAIC) for life threatening patients with unresectable hepatic metastases.Seven life threatening patients with hepatic metastases who were treated with HAIC up to September 2011 were retrospectively analyzed. As HAIC regimen, 5-FU (1000mg/m2) was administered weekly via continuous 5-hour infusion using a continuous-infusion device. After improvement of liver dysfunction, cetuximab was administered simultaneously by the same dose of single administration. Treatment was repeated weekly until progression of hepatic lesion or discontinuity by unacceptable toxicity or patients' proposal.In 5 patients with hepatic metastasis related complaints, 3 patients improved after the initiation of HAIC. Three out of 4 patients with PS 2 or 3 were improved by the initiation of HAIC. The median OS was 9.5 months. No severe adverse toxicities and no treatment death related to HAIC were observed. The most severe non-hematologic adverse events were ALP in 3 patients, transaminase and bilirubin in 1 patient with grade 3.HAIC may be considered to perform when the hepatic metastases progress as life threatening status even though those are refractory to standard systemic chemotherapy.

結腸癌手術における閉鎖式持続吸引ドレーンの使用経験について報告する．対象は閉鎖式持続吸引ドレーン（J-VACドレナージシステム）を用いた結腸癌202例．腹腔内合併症に対するドレーンの役割，ドレーン排液量と腹腔内合併症との関連，ドレーン留置の有害事象について検討した．腹腔内合併症に対するドレーンの役割では，縫合不全，腹腔内膿瘍，術後出血のいずれにおいても治療的意義は少なかった．排液量との関連では，腹腔内膿瘍，腸閉塞は4POD以降に排液が多く（後半型），縫合不全，術後出血は3PODまでに排液が多い（前半型）傾向がみられ，合併症により排液パターンが異なった．ドレーン留置に起因する有害事象として，ドレーン部の感染を４例（2.0％）認めたがいずれも軽微で，組織の吸い込みや挫滅，抜去時の組織脱出はなく，本ドレナージシステムは忍容可能であった．本ドレナージシステムは腹腔内合併症に対する予防的あるいは治療的意義は少なく，診断的意義に限られると思われるが，大きな有害事象もなく，排液量に着目することで合併症の早期発見の一助となることが示唆された．

原発不明未分化腺癌の再燃に対し，サイトケラチン染色を参照して化学療法を施行し，寛解，再燃を繰り返し長期生存している１例を報告する．症例は63歳，女性．盲腸腫瘍が疑われ当科に入院，回盲部嚢胞性腫瘍とDouglas窩に多発する結節性病変を認め，手術（回盲部切除術，大網切除術，子宮全摘出術，両側付属器切除術，低位前方切除術）を施行した．病理組織検査では未分化腺癌で，CK7+/CK20－から卵巣，子宮内膜由来と考えたが，これらの臓器に原発病変はなく，原発不明未分化腺癌と診断した．術後６カ月で腹腔内に再燃し，卵巣癌に準じてTJ療法を施行してCRを得た．その後２回の再燃に対して同療法でいずれもCRが得られ，術後６年近く経過した現在，維持療法は行わず経過観察している．本症例ではTJ療法が奏効したが，CR後から再燃までの間に補助療法や維持療法は行っておらず，このような症例に対する治療方針は今後の検討課題と考えている．

We herein report a case of curative resection, after a response to chemotherapy with mFOLFOX6, for sigmoid colon cancer which had been unresectable due to an invasion of the primary lesion into the aorta. A 58-year-old male patient visited the department of internal medicine of our hospital with chief complaints of lower abdominal pain and a lower abdominal mass. Computed tomography suggested colorectal cancer, and the patient was referred to our department. A diagnosis of sigmoid colon cancer was made, and a laparotomy was performed. However, the cancer was unresectable due to its invasion into the aorta, which led to the implementation of sigmoid-rectal anastomosis. Thereafter, chemotherapy with mFOLFOX6 was initiated, and the tumor shrunk markedly after seven courses of the treatment. The clinical response was rated as partial response. Radical resection of the tumor was considered possible, and another laparotomy was performed. The tumor had shrunk markedly, and a separation of the tumor from the aorta was possible. Therefore, sigmoid colectomy was conducted followed by a D3 lymph node dissection. The overall findings were type 5, pSS, ly0, v0, pN0 (0/26), sH0, sP0, cM0, fStage II, PM0, DM0, RM0, and CurA. In the present study, mFOLFOX6 as neoadjuvant chemotherapy for colon cancer was found to be effective.

患者は67歳の女性, 黄疸と右季肋部痛を主訴に入院した. 精査の結果, Dubin-Johnson症候群 (DJS) に合併した肝細胞癌 (HCC) と診断した. 術前のT. Bil値は3.8mg/dlであったが, 他の肝予備能が保たれていたため肝S5亜区域切除術を施行した. 術後, T. Bil値は5.2mg/dlまで上昇したが漸減し, 第17病日に軽快退院した. 術後13カ月で多発性の肺転移をきたしたがfluorouracil, doxorubicin, cisplatinによるFAP療法を計14コース施行し, 術後5年経過した現在, PRの状態にある. 本邦でDJSにHCCが合併し肝切除が施行された症例は, 今までに8例報告されている. いずれも術前に高ビリルビン血症を伴っていたが肝不全に至らず耐術していた. しかし, 体質性黄疸患者に肝切除を施行する場合, T. Bil値は肝障害度を直接表わす指標でないものの, 高度黄疸下の大量肝切除は黄疸が遷延することがあり注意が必要である.

S状結腸癌同時性卵巣転移によるpseudo-Meigs症候群の1例を経験したので報告する. 症例は32歳の女性. 膨満感, 食欲不振, 体重増加を主訴に当院を受診, 精査加療目的に入院した. 両側胸水, 腹水, 左卵巣腫瘍, 肝腫瘍, S状結腸癌がみられ, 子宮全摘術, 両側付属器摘出術, 骨盤内および大動脈周囲リンパ節郭清術を行い, さらにS状結腸切除術, D3リンパ節郭清を施行した. 病理組織学的に卵巣腫瘍はS状結腸癌の転移と診断した. 術後, 胸水はすみやかに消退し, 経過からS状結腸癌同時性卵巣転移によるpseudo-Meigs症候群と診断した. その後, 肝転移に対し2度の肝部分切除術を施行. 現在無再発で生存中である. 胸腹水をともなう卵巣腫瘍に対しては, 大腸癌卵巣転移による本症候群も疑い精査を行うべきである.

The cytotoxic regimens and bevacizumab (Bev) or anti-EGFR antibody are used for metastatic colorectal cancer (mCRC) that can expect conversion therapy. In this paper, we would present our practical data including the response, survival and toxicity of the capecitabine plus oxaliplatin (CAPEOX) with Bev for mCRC that cannot expect conversion therapy.Nineteen patients with mCRC who were treated with CAPEOX with Bev were enrolled. All the patients had the disseminated hepatic, lung, peritoneal metastases or distant lymph node metastasis assessed as no possibility of R0 resection.The median age was 66 (45-85) years old. Target lesion was liver and lung in 9 patients, peritoneum in 5 patients and distant lymph node in 3 patients. CAPEOX with Bev therapy was administered for a median of 8.0 cycles (range, 4-21 cycles). In the 16 evaluable cases, there were no patient with complete response (CR), 9 patients with partial response (PR), 6 with stable disease (SD), and 1 with progressive disease. The objective response rate (CR plus PR) was 56.3%, and disease control rate (CR, PR plus SD) was 93.8%. The median TTP was 9.3 months and the median OS was 21.1 months. No patients treated with surgery even though the good responses were obtained. No severe hematologic adverse toxicities were observed except only one case with grade 3 platelet decrease. Nonhematologic grade 3 events were observed totally 8 patients including 3 for peripheral neuropathy, 2 for bilirubin, and 1 for nausea/vomiting, amylase and stomatitis.We obtained the quite good results of CAPEOX plus Bev as the first-line treatment practically. This regimen might be useful for mCRC that cannot expect conversion therapy.

Case1: A 63-year-old woman with diarrhea and hematochezia was diagnosed as having rectal cancer invading the pelvis. Six courses of the 5-fluorouracil, leucovorin, and oxaliplatin( mFOLFOX6) plus panitumumab regimen were administered after sigmoid colostomy, following which low anterior resection was performed. Since the 6 courses of mFOLFOX6 were administered postoperatively, no evidence of recurrence has been observed for 18 months. Case2: A 52-year-old man with high fever and abdominal pain was diagnosed as having rectal cancer invading the bladder with a vesicorectal fistula. After transverse colostomy and 6 courses of mFOLFOX6 plus panitumumab, high anterior resection with partial cystectomy was performed. Since the 8 courses of capecitabine plus oxaliplatin (XELOX) were administered postoperatively, no evidence of recurrence has been observed for 12 months. Although no consensus has been reached pertaining to the use of neoadjuvant chemotherapy for the treatment of colorectal cancer, we could, in this study, demonstrate the efficacy of neoadjuvant chemotherapy with panitumumab for the treatment of locally advanced colorectal cancer.

We examined the association of the physical, nutritional, and immune status with adverse events in patients treated with mFOLFOX6 adjuvant chemotherapy after colorectal cancer surgery.This study included 17 patients, 7 male and 10 female. The median age was 62( range, 32-75) years. The median number of treatment cycles was 12 (range, 4-12). Age, performance status( PS), body mass index( BMI),serum albumin level( Alb),Onodera's prognostic nutritional index( PNI), controlling nutritional status( CONUT),Glasgow prognostic score( GPS),the granulocyte/lymphocyte ratio( G/L),neutrophil count, and the total lymphocyte count( TLC) were evaluated with regard to the nutrition and immunity status of the host before chemotherapy. The incidents of toxicity of greater than Grade 2 severity, excluding gastrointestinal events or gastrointestinal toxicities, were analyzed to determine the correlation with host status.Any toxicities and toxicities without digestive symptoms were observed in 11 patients( 64.7%),and the number of incidents was significantly increased in patients with a PNI of45. Gastrointestinal toxicities were observed in 4 patients (23.5%), but there were no significant correlations with any of the factors investigated.Toxicities are observed to a greater extent in patients with a PNI of45 during adjuvant chemotherapy. These findings suggest that nutritional support may be required to safely administer mFOLFOX6 adjuvant chemotherapy.

Cellular schwannoma is rare neoplasma and often situates in deep structures, so that its diagnosis is quite difficult. We herein report a case of a cellular schwannoma variant arisen in an intrapelvic space. A 62 year-old female had a magnetic resource imaging (MRI) examination of the lumber, which indicated a mass in the intrapelvic space behind the rectum. In T1-weighted image, the mass was slight low in intensity with cystic lesions being low. In T2-weighted image, the majority of the mass was low in intensity, whereas diffuse cystic lesions within it high. In computed tomography (CT), the tumor was well-demarcated round mass with heterogeneous low and intermediate attenuation area and punctual calcification. Because the mass was highly suspected as a pelvic mesenchymal neoplasm such as gastrointestinal stromal tumor or sarcoma, operation was performed. At laparotomy, the tumor had a thin capsule without invasion to the rectum or the mesorectum, and was arisen from the left hypogastric nerve. We cut off the left hypogastric nerve to extirpate the tumor. Macroscopically, it was a solid tumor and the color of the cutting surface was yellow-white with cysts. Pathologically, the tumor consisted of compact spindle cells arranged in short bundles or interlacing fascicles with high density. Nuclear palisading and Verocay body formation that is seen in the typical schwannomas were not spotted. Hyalinization, hemorrhage, xanthic change and lipofuscin precipitation were detected. Mitosis and necrosis were not present. Immunohistochemically, S-100β and glial fibrillary acidic protein (GFAP) was positive in tumor cells. Smooth muscle actin (SMA), CD34, CD117 and neurofilament were negative. MIB-1 index was less than 5%. Final diagnosis was obtained as a cellular schwannoma variant.

The imaging factor predicting the response to bevacizumab (BV) as concomitant chemotherapy has yet to be determined. This study examined correlation between response to chemotherapy with concomitant BV for hepatic metastasis of colorectal cancer and degree of contrast enhancement (CE) using contrast-enhanced computed tomography (CT). Data were analyzed retrospectively for 35 patients treated with oxaliplatin-based chemotherapy as the first-line chemotherapy. Patient data were divided according to treatment with concomitant BV (BV group: n = 20, non-BV group: n = 15). Using an image control system, the degree of CE was evaluated by the ratio of the contrast-enhanced CT value of hepatic metastatic lesions to plain CT value, whereby patients were classified into the high-CE and low-CE group. After completion of chemotherapy treatment, the degree of enhancement of hepatic metastasis in the BV group was significantly lower than that in the non-BV group (p = 0.03). In the BV group, a significant correlation between higher contrast enhancement and higher tumor shrinkage rate was observed (R 2 = 0.25, p = 0.03), whereas no such correlation was noted in the non-BV group. In the high-CE group (n = 18), the tumor shrinkage rate increased to 29.6 % in the BV group compared with −1.46 % in the non-BV group (p = 0.03), whereas in the low-CE group, no significant difference was noted between patients in the two groups. Pretreatment evaluation of the degree of CE correlated with the response to concomitant chemotherapy with BV.

To investigate differences in clinicopathological features between proximal and distal pT3 colon cancers and to determine whether the depth of the cancer invasion beyond the muscularis propria (DBM) serves as an objective indicator of the depth of tumor invasion in proximal colon cancer and in distal colon cancer.A total of 207 patients who underwent surgery for proximal and distal pT3 colon cancer between 1996 and 2001 were included in the analysis.No differences were noted between proximal and distal cancers in lymph node metastasis, distant metastasis, lymphatic/venous invasion, histological type and curability of surgical resection, although proximal cancer patients were significantly older. High-grade malignancy appeared to be more commonly noted in the proximal colon cancer cases but there was no significant difference in prognosis between proximal and distal cancer patients.Regarding the correlation between DBM and prognosis, there was a significant decrease in the 5-year survival rate in patients with proximal lesions of DBM 3000μm or more, and patients with distal lesions of DBM 5000μm or more. DBM is thus an objective indicator of depth of tumor invasion for both proximal and distal lesions, a prognostic factor and a guide to determining whether postoperative adjuvant chemotherapy is indicated for pT3 colon cancer cases.

We report here the experience of the treatment with cetuximab in our department. Thirteen patients were treated with cetuximab. Median age was 65-year-old including 8 males and 5 females. Six cases were treated with single administration, and seven were with CPT-11. Median number of treatment was 13 times. In evaluable 9 cases, partial response (PR) was obtained in 3 cases and stable disease (SD) and progressive disease (PD) were in 2 and 4 cases, so that the response rate and disease control rate were 33% and 56%, respectively. Median survival after initiation of cetuximab was 219 days. Skin toxicity was observed in 91% including only one case with grade 3. We think that it is important to control skin toxicity for a continuation of cetuximab.

We report a case of multiple lung and liver metastases from colon cancer treated with clinical benefit by hepatic arterial infusion chemotherapy plus cetuximab mono-therapy after a standard chemotherapy was failed. A 61-year-old female who had sigmoid colon cancer with unresectable multiple lung and liver metastases underwent sigmoidectomy. Bevacizumab plus mFOLFOX6 was performed as first-line therapy. Partial response was obtained temporarily. After the first-line therapy failed, bevacizumab plus FOLFIRI as second-line, and cetuximab plus CPT-11 as third-line therapy were performed. Since these regimens did not work, her performance status got worse by cholangitis due to progressive liver metastases and anemia. Hepatic arterial infusion chemotherapy for liver metastases and cetuximab for lung metastases as fourth therapy were chosen because we thought her liver metastases should be critical for the maintenance of her QOL and diagnosis. After that, serum CEA was reduced from 14,715 to 6,940 ng/mL during the 3 month period. And her performance status got better as cholongitis and anemia were improved. Additionally, lung metastases were controlled by cetuximab.

We reported two cases of colorectal cancer patients with EGFR-positive unresectable synchronous liver metastasis effectively treated by cetuximab after the progression of the prior chemotherapy. Case 1: A 49-year-old female with unresectable synchronous liver metastasis from colon cancer received cetuximab monotherapy as fifth-line therapy. Then, abdominal CT showed shrinkage of the liver metastasis (PR) and the performance status was improved from 3 to 0 as upper abdominal pain reduced. Case 2: A 67-year-old female with unresectable liver metastasis from colon cancer received cetuximab with CPT-11 combined therapy as fourth-line therapy. After that, liver metastasis also decreased (PR), and upper abdominal pain and PS were improved from 2 to 0. These two cases of KRAS status on cancer tissue also showed wild-type, and in these cases cetuximab proved effective.

We herein report a case of successful treatment with OK-432 administration into lymphatic cyst formed after resection of rectal cancer. A 61-year-old male patient underwent a very low anterior resection with D3 lymphadenectomy for locally advanced rectal cancer. Four months after the surgery, he arrived at our department with lower abdominal fullness. He was diagnosed as having bilateral intra-pelvic abscess by CT scan, and underwent a tube-drainage. After drainage, abscess lesions were shrunk, but a serous discharge remained. Because we diagnosed lymphatic cysts caused by the delayed lymphatic discharge after lymphadenectomy, an administration of OK-432 into cysts was performed. After administration, the discharge was decreased, and then fistula was closed.

Phase I study of combination therapy with peptide vaccine and anti-cancer drug for colorectal cancer has been performed in our hospital. The purpose of this study was to evaluate the safety and immune response of different dose of RNF43-721 emulsified with Montanide ISA 51 in combination with S-1/CPT-11 chemotherapy. The study design was a dose escalation of peptide (0.5, 1.0, 3.0 mg) with three patients' cohort. Nine patients were enrolled. All patients were treated with peptide subcutaneously every week and two courses with S-1/CPT-11 chemotherapy. Vaccinations were well tolerated without any major adverse events. Immunological reactions are not analyzed yet. We herein report a case who has been evaluated to be long SD with this intervention for para-aortic LN metastasis from sigmoid colon cancer.

Bevacizumab, a humanized monoclonal antibody to VEGF for advanced recurrent colorectal cancer, has been known for complications of gastrointestinal perforation, hemorrhage, thromboembolism and proteinuria, as adverse effects. These findings must be taken care as well as adverse drug reactions (ADR) caused by combination chemotherapy. We here in present a clinical experience in treatment with bevacizumab for unresectable colorectal cancer. Six patients treated with bevacizumab for over two courses until April 2008 were analyzed for this study. PR was obtained in one case with mFOLFOX6. Even though, grade 3 neutropenia was observed in only one case with FOLFIRI, the other cases had grade 2 or less in ADR. In addition, there were no any specific ADRs related with bevacizumab, so we concluded that combination chemotherapy for advanced recurrent colorectal cancer with bevacizumab was well-tolerated.

S-1 is a novel oral anticancer drug, composed of tegafur (FT), gimestat (CDHP) and otastat potassium (Oxo), based on the biochemical modulation of 5-fluorouracil (5-FU). S-1 plus irinotecan (CPT-11) for advanced colorectal cancer as expected showed equally good results as these with CPT-11 plus infusional 5-FU/LV (FOLFIRI regimen). A case of unresectable lymph node metastasis from colon cancer successfully treated with S-1 plus CPT-11 is reported here. A 65-year-old man had metastasis to the lymph nodes in the left supra clavicular region and the superior mesenteric artery. S-1 plus CPT-11 was chosen for the treatment. After 2 courses, since grade 2 toxicity for dysgeusia was observed, S-1 administration was shortened. After 3 courses of the revised regimen, the enlarged lymph nodes disappeared on conventional CT and fluorine-18 fluorodeoxyglucose positron emission tomography with CT (FDG-PET/CT) and the case was assessed as a complete response (CR). Because CR was continued by an additional four courses of treatment, the regimen was changed to a single administration of S-1. Although eighteen months have passed since the induction of CR by S-1 plus CPT-11 therapy, no symptoms or findings of relapse have been observed.

Anticancer drugs may frequently induce host immunosuppression and symptomatic toxicities. Once symptomatic toxicity occurs, the patient's quality-of-life (QOL) is reduced. Since little is known of the relationship between host immunity and the toxicity of chemotherapy, the host immunity before and after chemotherapy was compared to assess whether it is related to symptomatic toxicity during chemotherapy.Fourteen patients with colorectal cancer underwent leucovorin /5-fluorouracil (LV/5-FU) treatment, or S-1/irinotecan (CPT-11). Host immunity (cytokine production of peripheral blood mononuclear cell (PBMC), serum soluble interleukin-2 receptor (sIL-2R) levels and phenotypic analyses of PBMC were measured before and after the first chemotherapy.An increase of sIL-2R, CD4+CD25+ T-cells and the CD4/8 ratio in patients with symptomatic adverse reactions were found. These changes in the first chemotherapy were significantly different (p = 0.0211, p = 0.0087, p = 0.0234).The current study indicated that there are some parameters correlated with toxicity during chemotherapy which effect QOL. In such patients, negative influences on host immunity, such as an increase of sIL-2R and regulatory T-cells, and a decrease of cytotoxic T-cells could occur.

A 72-year-old woman, who had the carcinoma of cecum with unresectable multiple liver metastases, underwent ileocecal resection and insertion of hepatic arterial infusion catheter. Hepatic arterial infusion (HAI) chemotherapy using Leucovorin. 5-FU caused to decrease liver metastases after an initiation of HAI. However, the metastatic nodule at the right lobe of lung was found. Then systemic chemotherapy with CPT-11 CDDP was performed alternately with HAI chemotherapy. After the initiation of revised regimen, all metastatic lesions were shrunk. We here in present the case of extra- and intra-hepatic metastasis successfully treated with alternative chemotherapy with hepatic arterial infusion and systemic intravenous infusion after responding to hepatic metastasis from colon cancer by hepatic arterial infusion.

The aim was to assess the practical efficacy of low-dose chemotherapy in patients with intrapelvic recurrence of rectal cancer without radiotherapy.The records of 13 patients treated with low-dose chemotherapy for intrapelvic recurrence of rectal cancer between 1996 and 2003 were retrospectively reviewed. The patients had received low-dose leucovorin and 5-fluorouracil (LV/5-FU) as first-line and low-dose irinotecan and cisplatin regimen (CPT-11/CDDP) as second-line therapy without radiotherapy.With the LV/5-FU treatment, no patients showed a complete response (CR), two patients showed a partial response (PR), three patients had stable disease (SD), and eight patients experienced progressive disease (PD), giving a response rate (RR) of 15.4% and a disease control rate (DCR) of 38.5%. With the CPT-1/CDDP treatment, no patients showed CR or PR, three patients had SD, and ten patients had PD, which results in a DCR of 23.1%. The progression-free survival (PFS) of LV/5-FU and CPT-11/CDDP were 4.7 months and 4.7 months respectively. The median survival time (MST) of all the patients was 17.3 months. There were no patients who experienced grade 3 or 4 of any adverse reaction during the course of these regimens.The results suggest that low-dose chemotherapy for intrapelvic recurrence of rectal cancer without radiotherapy could be acceptable. For patients who refused radiotherapy in order to avoid adverse effects, these low-dose low toxicity chemotherapy regimens might be recommended.

To assess the practical efficacy of low-dose leucovorin plus 5-fluorouracil (LV/5-FU) in elderly patients with metastatic colorectal cancer.The records of 20 patients treated with LV/5-FU for unresectable metastatic disease from colorectal cancer from 1999 to 2004 were retrospectively reviewed. The patients received LV/5-FU as first-line, and low-dose CPT-11 and CDDP regimen (CPT-11/CDDP) as second-line therapy.In the treatment of LV/5-FU, no patients had CR, 3 patients had PR, 4 patients had SD and 13 patients had PD, which results in a response rate (RR) of 15% and in a disease control rate (DCR) of 35%. MST of all patients was 18.4 months. There was one patient who experienced grade 3 or 4 adverse reactions during the course of these regimens.Low-dose LV/5-FU chemotherapy in elderly patients with metastatic colorectal cancer could be acceptable in order to avoid adverse effects and to obtain quite a favorable survival time.

S-1 is a novel oral anticancer drug, composed of tegafur (FT), gimestat (CDHP) and otastat potassium (Oxo) in a molar ratio of 1:0.4:1. S-1 plus irinotecan (CPT-11) administered for advanced colorectal cancer could be expected to show as equally good results as the infusional 5-fluorouracil/leucovorin (5-FU/LV) with CPT-11 (FOLFIRI) regimen. When toxicity is too severe preventing patients from receiving an intensive chemotherapeutic regimen, survival benefit might be forfeited. A pilot study of low-dose S-1 plus CPT-11 therapy with constant doses without consideration of body surface area (BSA) was therefore performed.Twenty-two patients were enrolled in this study. S-1 was given orally at 40 mg b.i.d. for 21 consecutive days followed by a 14-day rest period. CPT-11 was administered as a 90-minute intravenous infusion at a dose of 80 mg on days 1 and 15. Courses of treatment were repeated every 35 days.The median age was 62.5 years (26-74). The median cycles were 8.5 (3-20). The overall response rate was 45.5% (complete response (CR), 1; partial response (PR), 9). Median progression-free survival (PFS) and median overall survival time (MST) were 9.0 and 20.2 months respectively. No grade 3 or 4 toxicities were observed. Eight patients (36.4%) did not have any sign or symptom of toxicity throughout all the treatment courses. The response, survival and toxicity were not significantly different according to BSA.These results suggest that simplified low-dose S-1 plus CPT-11 treatment might be of considerable advantage as first-line chemotherapy for patients with advanced colorectal cancer who would like to avoid toxicity.

Human X-box binding protein 1 (XBP-1) is a transcription factor essential for hepatocyte growth, as well as for plasma cell differentiation. Recently, overexpression of XBP-1 has been reported in breast cancer including non-invasive carcinomas, and was suggested to play an important role in breast carcinogenesis. To investigate the involvement of XBP-1 in colorectal tumorigenecity, the expression of XBP-1 was examined in four colon cancer cell lines, six colorectal polyps and five colorectal carcinomas.The study population consisted of eleven patients who had undergone resection for colorectal cancer or adenoma from 2000 to 2002. Four colon cancer cell lines, DLD1, SW480, HCT15 and WiDr, were also analyzed for expression of XBP-1. Reverse transcription-polymerase chain reaction was performed using eleven primary colon tumors. XBP-1 expression was then investigated using an immunohistochemical method for archived paraffin-embedded sections.The XBP-1 gene was overexpressed in four cases out of five primary colorectal carcinomas and in four cases out of six colorectal adenomas. Also all four cancer cell lines expressed XBP-1 mRNA. Immunohistochemical staining demonstrated that XBP-1 protein was strongly stained in the cytoplasms of cancer cells, whereas it was unreactive in the normal colon epithelial cells and stromal cells.These data indicate that increased expression of XBP-1 gene may play some role in human colon carcinogenesis through impairment of cell differentiation regulation.

Administration of cimetidine after curative surgery can improve prognosis of patients with colorectal cancer. In this study, we analyzed whether cimetidine can influence the survival of patients with a recurrent disease after colorectal surgery. The subjects were 29 patients with recurrent disease: 14 patients were administered with cimetidine and 15 patients were not. In the cimetidine administered group, seven cases were recurrent in the liver, 5 cases in a local site and 1 case in the lymph node, whereas 7 cases were recurrent in the liver, 4 cases in a local site and 3 cases in the lung for the non-cimetidine administered group. There were no significant differences for both groups in terms of patient's survival after recurrence. Although it was not significant, the patient's survival after curative resection of recurrent disease for the cimetidine administered group was better than the non cimetidine administered group. Although the results did not show cimetidine could influence the overall survival of the patients after recurrence, it might be possible to improve the survival of the patients after resection of the recurrent disease.

e14105 Background: The addition of bevacizumab (Bev) to chemotherapy is associated with improved survival by anti-angiogenic mechanism in colorectal cancer (CRC). Therefore, the antitumor effect of...

3067 Background: RNF43 is a cancer testis antigen expressed in colorectal cancer (CRC) but not in normal organs. RNF43–721 induces HLA A24 restricted cytotoxic T lymphocytes (CTL) against RNF43 expressed target. S-1/CPT-11 chemotherapy (CT) is reported to be obtained the similar result to FOLFOX or FOLFIRI as first-line for advanced CRC. We plan phase I study to evaluate the safety of different doses of RNF43–721 emulsified with Montanide ISA51 in combination with S-1/CPT-11 CT expecting synergistic effect. Methods: Inclusion criteria as follows: HLA A24 positive, pathological CRC, life expectancy > 3 months, WBC>3000/mm3, Hb>10mg/dl, Plt>75000/mm3, creatinine No significant financial relationships to disclose.