Search

Purpose The purpose of this study was to evaluate factors related to peristomal moisture-associated skin damage (MASD) in patients who underwent ostomy surgery because of colorectal cancer, and their independence in pouching system changes. Findings were used to determine pre- and postsurgical care for these patients. Design Retrospective review of medical records. Subjects and setting The study setting was an 800-bed hospital in metropolitan Tokyo, Japan. The sample comprised 89 patients (median age: 65 years; male vs female: 58 vs 31) who visited a stoma clinic within 8 weeks of ostomy surgery. Fifty-two subjects had ileostomies and 37 had colostomies; data were collected between January 2008 and July 2014. Methods Data were collected from outpatient and inpatient records. Potential relationships between MASD and independence in pouching system changes were evaluated via univariate tests to identify possible associations, followed by logistic regression analysis. Results Patients living with an ileostomy were more likely to experience peristomal MASD than were patients living with a colostomy (odds ratio [OR] = 3.782; 95% confidence interval [CI]: 1.34-10.64; P = .012). Analysis also found that patients with postsurgical chemotherapy were more than 2.5 times more likely to experience peristomal MASD than patients who did not require postoperative chemotherapy (OR = 2.702; 95% CI: 1.02-7.18; P = .046). We also found that patients 65 years or older were significantly more likely to have difficulty in changing their pouching system than were younger patients (OR = 7.193; 95% CI: 2.21-23.41; P = .001), as were those with diabetes mellitus (OR = 11.842; 95% CI: 2.56-54.77; P = .002). Conclusions Patients undergoing ileostomy and those receiving postoperative chemotherapy are more likely to experience peristomal MASD. Older patients (>65 years) and those with diabetes mellitus are less likely to achieve independence. These findings influenced our management of persons undergoing ostomy surgery for management of colorectal cancer in our clinic. We recommend additional research using a larger and more diverse sample to confirm our findings.

A 72‒year‒old man visited our hospital with a chief complaint of epigastralgia. Upper gastrointestinal endoscopy revealed type 3 advanced gastric cancer at the body of the stomach. Following an investigation, he was diagnosed with human epidermal growth factor receptor 2‒positive gastric cancer with invasion to the pancreas as well as the paraaortic lymph node, and multiple liver metastases were also observed. The cancer was judged to be cT4a, N2M1(H1 LYM: No. 16), cStage Ⅳ and thus was considered suitable for chemotherapy. We performed capecitabine plus cisplatin plus trastuzumab therapy. After 3 courses, the primary lesion and swollen lymph nodes decreased in size. After 20 chemotherapy courses, the primary lesion relapsed, so conversion surgery was performed. The patient underwent total gastrectomy, distal pancreatectomy, and partial resection of the liver. We planned to perform adjuvant chemotherapy, but the patient declined it because of anorexia. At 18 months after the operation, recurrence of the tumor was detected at the celiac artery. Chemotherapy was performed as follows: capecitabine plus trastuzumab 10 courses, ramucirumab plus paclitaxel, irinotecan, and nivolumab. However, the patient eventually died 71 months after the first visit.

Trifluridine/tipiracil (TAS-102) is an important chemotherapeutic agent recommended by the Japanese guidelines as third- or fourth-line treatment for colorectal cancer. Some studies have reported that administration of TAS-102 concomitant with bevacizumab prolongs progression-free and overall survival in colorectal cancer. We describe 2 patients treated with a chemotherapeutic regimen comprising TAS-102 concomitant with bevacizumab for recurrent colorectal cancer. No adverse events ≥Grade 3(except for hematotoxicity)were observed in these patients. The patient received several courses of chemotherapy with adjustments of the dose and dosing intervals to prevent neutropenia. Combination therapy using TAS-102 and bevacizumab is a feasible Late-line chemotherapeutic regimen for colorectal cancer.

The patient, a male in his 70s, visited our hospital with a chief complaint of general fatigue and weight loss. Upon a detailed examination, he was diagnosed with sigmoid colon cancer, para-aortic lymph node metastases, and multiple liver metastases, for which he was hospitalized due to a poor performance status(PS). FOLFOX therapy was administered as the symptoms caused by the primary lesion were not recognized and his general condition was considered to be poor and thus he was deemed to be inoperable. After completing 2 courses of the chemotherapy, although his PS improved, laparoscopic sigmoidectomy was carried out with colonic stent placement due to the occurrence of an intestinal obstruction as a result of an enlargement of the primary lesion. Following surgery, 2 courses of FOLFOX therapy and 4 courses of FOLFOX plus bevacizumab therapy were administered and he is alive at 5 months after the operation without progression.

We herein report 2 cases of gastric cancer treated by S-1 and oxaliplatin combination therapy before later undergoing gastrectomy. The pathological results of both cases demonstrated complete response. Case 1 had a giant tumor which was suspected to have invaded the pancreas. Case 2 was associated with extensive lymph node metastasis. Based on the findings of these 2 cases, preoperative chemotherapy with S-1 and oxaliplatin for advanced gastric cancer shows sufficient efficacy.

Currently, chemotherapy against unresectable advanced gastric cancer is progressing with the development new drugs and due to results of several clinical trials. Here, we reported a case of long-term survival of gastric cancer with multiple liver and lymph node metastases. A 68-year-old man was diagnosed with gastric cancer and Virchow lymph node, para-aortic lymph node, and multiple liver metastases at another hospital. He was referred to our hospital from Yamashita Naika Syokakika. We administrated 4 courses of S-1 plus CDDP. The main tumor and all metastatic lesions were significantly reduced. Subsequently, total gastrectomy, partial liver resection, and left neck and para-aortic lymph node resection(conversion surgery)were performed. The cancer cell was remnant at the main tumor and para-gastric lymph node. No cancer cells were detected in another lesion(R0 resection). Postoperatively, only S-1 was administered. However, 28 months after undergoing gastrectomy, liver metastasis occurred. Therefore, S-1 plus oxaliplatin, paclitaxel plus ramucirumab, and CPT-11 plus CDDP were administered. Liver metastases again increased and decreased, respectively. However, 46 months after gastrectomy, liver metastasis recurred and nivolumab was administered. Subsequently, liver metastases disappeared. At 55 months after gastrectomy, rectal resection was performed against rectal cancer and partial liver resection against liver metastases. Cancer cells were not detected in the resected specimens.

The patient was a 59-year-old man. He was admitted to our hospital because of increasing anal pain with induration of the perianal region. There were large secondary orifices with mucous discharge on the left side of the perineal resion and buttock. We diagnosed adenocarcinoma on analysis of a biopsy specimen from induration of the perianal region. Pelvic CT and MRI showed that the tumor spreaded within the pelvis, with invasion of the prostate and sacrum. We performed neoadjuvant chemoradiotherapy preoperatively. After chemoradiotherapy, the tumor reduced in size greatly. We performed abdominoperineal resection and massive resection of skin of the perianal region. The defect of the pelvic floor and perianal skin was repaired using skin flap. The surgical margin was tumor free. Neoadjuvant chemoradiotherapy was considered effective for locally advanced carcinoma associated with anal fistula.

Platelet-derived growth factors (PDGFs) are known to be associated with tumor growth and angiogenesis through their activation of the receptor tyrosine kinases, PDGF receptors alpha and beta. Several studies revealed the participation of the PDGF family in colorectal cancer (CRC). However, the role of platelet derived growth factor-C (PDGFC) in CRC is less well studied. This study aimed to determine the correlation between PDGFC expression and the prognosis of patients with CRCs. Tumor samples were obtained from patients with CRC who underwent surgical resection between 2002 and 2006. The mRNA expression of PDGFC was investigated by quantitative reverse transcription-polymerase chain reaction in 85 patients with stage I-IV CRC. PDGFC protein expression was analyzed by immunohistochemistry, and the relationship between PDGFC protein expression and clinicopathologic features was investigated in 245 patients with stage I-III CRC. PDGFC mRNA expression in cancer tissues was significantly higher in patients with distant metastases than in those without metastases (P = 0.016). PDGFC protein overexpression was associated with significantly worse overall and relapse-free survival (P P - 6.081, P

Riverbank collapse often occurs along the Saigon River which flows through Ho Chi Minh City (HCMC). One of the influencing factors is the soft ground which is the riverbank composed of. Our researchabout the ground improvement method using quicklime, rice husks ash so far. Rice straw is newly added to the improved soil in this paper. The Rice straw is expected to improve the failure strain property that is to restrain brittle failure. These mixing materials can be obtained easily and cheaply in Vietnam. A series of unconfined compression tests are carried out to improve the mechanical properties of improved soil. Moreover pH tests are conducted to validate the chemical action of the improved soil and evaluate the effect of improved soil on surrounding environment.

Decorin, a small leucine-rich proteoglycan and important component of the extracellular matrix (ECM), is a natural anticancer agent that modulates several receptors involved in cell growth and survival. Reductions in decorin expression may weaken the ECM and enhance the effectiveness of these receptors and may, consequently, lead to tumor spreading. To determine the contribution of stromal decorin regulation in the development of breast cancer and in tumor invasiveness, immunohistochemistry was used to examine the expression of stromal decorin in 120 breast cancer tissue samples. In patients with invasive breast carcinoma (IBC), stromal decorin expression was highest in normal gland tissue, lower in in situ components and the lowest in invasive components. Stromal decorin expression adjacent to malignant cells in IBC tumors was also significantly weaker compared to that in pure ductal carcinoma in situ (DCIS). These findings indicate that there is a striking difference in the stromal decorin expression around normal glands and around DCIS or IBC tumors. Reduced levels of decorin were associated with more aggressive disease; this finding was consistent with the view that reduced decorin expression may facilitate tumorigenesis, tumor invasion and/or tumor growth. Given these and other reported findings, evaluating stromal decorin expression may be useful in assessing prognosis and malignant potential; therefore, a large-scale study of decorin expression is warranted.

Various guidelines suggest indications for performing additional colectomy with en bloc removal of regional lymph nodes after endoscopic resection for T1 colon cancer. The aim of this study was to evaluate the pathologic outcomes of patients with surgical treatment after endoscopic resection for T1 colorectal cancer. We used data from 275 patients who had undergone curative resection for T1 colorectal cancer at a single institution between 1991 and 2009. We evaluated the rationale for additional surgical treatment after endoscopic resection performed on 68 of the 275 patients and the association between various clinicopathologic features and lymph node metastasis. The 5-year overall survival rate was 96.3 %. Reasons for additional surgical treatment included an endoscopic specimen with a pathologically positive margin (n = 20), lymphovascular invasion (n = 25), and submucosal invasion depth of ≥1,000 μm (n = 23). When endoscopists failed to find macroscopic cancer residue during endoscopic resection, no pathologically residual cancer was found in the resected specimens. Histologic grade was an independent risk factor for lymph node metastasis (p = 0.028). In the absence of lymphovascular invasion, patients with well-differentiated T1 colorectal cancer did not have nodal involvement. Although the outcomes of patients with additional surgical treatment after endoscopic resection for T1 colorectal cancer were satisfactory, excessive and unnecessary treatments may have been performed. Additional surgical treatment after endoscopic resection for T1 colorectal cancer might be unnecessary for patients with well-differentiated adenocarcinoma and no lymphovascular invasion.

Colorectal cancer (CRC) occurs through the accumulation of genetic and epigenetic alterations. The epigenetic abnormalities, in cooperation with genetic alterations, are capable of causing aberrant gene function that results in cancer. In the present study, we examined mutations and methylation status in 164 CRCs to determine whether the combination of genetic and epigenetic alterations may be used to classify CRC patients in relation to their clinicopathological characteristics and outcomes. Mutation analyses for the KRAS and PIK3CA genes were performed using direct sequencing, and the MethyLight method was used to determine the methylation status of BNIP3, p16 and hMLH1. The combination of the KRAS mutation with methylation status did not have any association with clinicopathological characteristics and outcomes. However, patients with the PIK3CA mutation and/or high methylation (2 or 3 methylated genes) had significantly poorer outcomes in disease-specific survival (DSS) compared with those with wild-type PIK3CA and 0 or 1 methylated genes (P=0.0059). Additionally, multivariate analysis revealed that the PIK3CA mutation and/or a high level of methylation predicts a poor DSS independently of clinicopathological characteristics. Our results suggest that a combination of genetic and epigenetic alterations is a potent biomarker for predicting the prognosis of CRC.

Background/Aims: Increasing negative lymph node count has been reported to be associated with better outcomes in patients with colon cancer. The present study aimed to clarify the clinical significance of the lymph node ratio (LNR) and location of lymph node metastasis (LNM) in patients with stage III right colon cancer. Methods: We enrolled 820 patients who had undergone curative resection due to colon cancer at a single institution between 1991 and 2005. Among them, 197 underwent curative resection for T2–T4 right colon cancer. We evaluated the oncological outcomes according to LNR (quartiles) and distribution of LNM (n1 = LNM adjacent to the colon or along the vascular arcades of the marginal arteries; n2 = LNM along the major vessels; n3 = LNM near the roots of the major vessels). Results: The rates of LNM in T2, T3 and T4 right colon cancer were 11.1, 38.6 and 58.0%, respectively (p < 0.0001). Recurrence rates were 27.3, 37.5 and 57.1% in patients with n1, n2 and n3 LNM, respectively (p < 0.0001). LNR (p < 0.0001) and distribution of LNM (p = 0.046) were independent risk factors for recurrence in patients with stage III right colon cancer. Conclusions: Some patients with extensive LNM benefited from lymph node dissection with high ligation. Those with T3–T4 right colon cancer are suitable candidates for lymph node dissection with high ligation. Adding the concept of LNR and location of LNM to conventional TNM staging could improve the accuracy of evaluating nodal status.

Background Colorectal cancer (CRC) is one of the most frequently occurring cancers in Japan, and thus a wide range of methods have been deployed to study the molecular mechanisms of CRC. In this study, we performed a comprehensive analysis of CRC, incorporating copy number aberration (CRC) and gene expression data. For the last four years, we have been collecting data from CRC cases and organizing the information as an “omics” study by integrating many kinds of analysis into a single comprehensive investigation. In our previous studies, we had experienced difficulty in finding genes related to CRC, as we observed higher noise levels in the expression data than in the data for other cancers. Because chromosomal aberrations are often observed in CRC, here, we have performed a combination of CNA analysis and expression analysis in order to identify some new genes responsible for CRC. This study was performed as part of the Clinical Omics Database Project at Tokyo Medical and Dental University. The purpose of this study was to investigate the mechanism of genetic instability in CRC by this combination of expression analysis and CNA, and to establish a new method for the diagnosis and treatment of CRC. Materials and methods Comprehensive gene expression analysis was performed on 79 CRC cases using an Affymetrix Gene Chip, and comprehensive CNA analysis was performed using an Affymetrix DNA Sty array. To avoid the contamination of cancer tissue with normal cells, laser micro-dissection was performed before DNA/RNA extraction. Data analysis was performed using original software written in the R language. Result We observed a high percentage of CNA in colorectal cancer, including copy number gains at 7, 8q, 13 and 20q, and copy number losses at 8p, 17p and 18. Gene expression analysis provided many candidates for CRC-related genes, but their association with CRC did not reach the level of statistical significance. The combination of CNA and gene expression analysis, together with the clinical information, suggested UGT2B28, LOC440995, CXCL6, SULT1B1, RALBP1, TYMS, RAB12, RNMT, ARHGDIB, S1000A2, ABHD2, OIT3 and ABHD12 as genes that are possibly associated with CRC. Some of these genes have already been reported as being related to CRC. TYMS has been reported as being associated with resistance to the anti-cancer drug 5-fluorouracil, and we observed a copy number increase for this gene. RALBP1, ARHGDIB and S100A2 have been reported as oncogenes, and we observed copy number increases in each. ARHGDIB has been reported as a metastasis-related gene, and our data also showed copy number increases of this gene in cases with metastasis. Conclusion The combination of CNA analysis and gene expression analysis was a more effective method for finding genes associated with the clinicopathological classification of CRC than either analysis alone. Using this combination of methods, we were able to detect genes that have already been associated with CRC. We also identified additional candidate genes that may be new markers or targets for this form of cancer.

Distant metastasis is the major cause of death in colorectal cancer (CRC) patients. To identify genes influencing the prognosis of patients with CRC, we compared gene expression in primary tumors with and without distant metastasis using an oligonucleotide microarray. We also examined the expression of the candidate gene in 100 CRC patients by quantitative real-time reverse transcription PCR and studied the relationship between its expression and the prognosis of patients with CRC. As a result, we identified MUC12 as a candidate gene involved in metastasis processes by microarray analysis. Quantitative real-time reverse transcription PCR showed that MUC12 expression was significantly lower in cancer tissues than in adjacent normal tissues (p < 0.001). In Stages II and III CRC, patients with low expression showed worse disease-free survival (p = 0.020). Multivariate analysis disclosed that MUC12 expression status was an independent prognostic factor in Stages II and III CRC (relative risk, 8.236; 95% confidence interval, 1.702-39.849 p = 0.009). Our study revealed the prognostic value of MUC12 expression in CRC patients. Moreover, our result suggests MUC12 expression is a possible candidate gene for assessing postoperative adjuvant therapy for CRC patients.

Background: This study aimed to validate an easy to use practical classification of peritoneal metastasis arising from colorectal cancer. Patients and Methods: Data from 2,134 consecutive patients who underwent resection for colorectal cancer at a single institution were reviewed. Peritoneal metastasis was classified depending on extent into three groups (P1–P3). The macroscopic radical resection rates and survival of patients with colorectal cancer complicated with peritoneal metastasis were analyzed. Results: Of the 2,134 patients, 116 (5.4%) had peritoneal metastasis. Among them, 20 (17.2%) underwent macroscopic radical resection. Tumor location on the right side was associated with more extensive peritoneal metastasis (p = 0.010). Male gender (p = 0.0027), liver metastasis (p = 0.0021), and P3 peritoneal metastasis were independent risk factors for noncurative resection. The Cox proportional hazards model showed that gender (p = 0.031), operation period (p = 0.031), and macroscopic radical resection for colorectal cancer and peritoneal metastasis (p = 0.031) were independent prognostic factors. Conclusions: Being female with left colon cancer complicated with P1 or P2 peritoneal metastasis is a good indicator for macroscopic radical resection if liver metastasis is absent. The present classification helped to determine surgical indication for patients with colorectal cancer complicated with synchronous peritoneal metastasis in routine clinical practice.

盲腸癌による穿通で広範な腹壁膿瘍を呈し，癌による穿通部以外にも複数の箇所で腹壁膿瘍と腸管に交通を認めた症例を経験したので報告する．症例は74歳の男性で，食思不振・腹痛で当院を受診された．腹部CTにて広範な腹壁膿瘍を認めるとともに，盲腸壁の肥厚を認めた．大腸癌による腹壁膿瘍が疑われたが，まず膿瘍ドレナージを施行し，全身状態の改善を図った．後日，結腸右半切除術を施行した．腹壁膿瘍が非常に広範であったこと，また入院時より患者の全身状態が不良なこともあり腹壁は合併切除しなかった．病理組織学的検索では盲腸の中分化腺癌で，pSI，pN2，ly2，v2，fStage IIIbであった．腹壁膿瘍を治療する場合，その原因として大腸癌も念頭におく必要があると考えられた．また，その診断にはCTが有用である一方，膿瘍ドレナージにおける細胞診の有用性は低いと考えられた．

The p53/MDM2/p14ARF pathway is one of the major signaling cascades involved in the regulation of apoptosis. Although many tumors have been reported to show disruption of the p53/MDM2/p14ARF pathway, few studies have examined p53, MDM2, and p14ARF simultaneously in colorectal carcinoma. The present study was undertaken to clarify whether correlations exist among MDM2, p53, and p14ARF in colorectal cancer.We determined the presence of mutations in the p53 gene, MDM2 expression, and methylation status of the p14ARF in 97 primary colorectal carcinoma specimens. Associations with survival and clinicopathologic factors were investigated.At least one abnormality of these three molecules was found in 82 (84 percent) tumors. We observed a significant inverse association between MDM2 expression and tumor invasion (P = 0.01). Furthermore, the presence of liver metastasis was also significantly associated with low MDM2 expression (P = 0.02).The results suggest that disruption of the p53/MDM2/p14ARF pathway may frequently participate in colonic carcinogenesis and that MDM2 expression status may be a factor in the prediction of potential invasion and liver metastasis of colorectal carcinomas.

The PI3K-AKT pathway is activated in a variety of human cancers, resulting in disturbance of cell growth, proliferation and survival. Among the factors affecting the pathway, the K-Ras mutation and PIK3CA mutation are the most common oncogenic alterations in colorectal cancer. We hypothesized that these two mutations are important in activation of the PI3K pathway and colorectal carcinogenesis. In this study, we aimed to examine the influence of PIK3CA mutation and K-Ras mutation on AKT activation, and to clarify whether PIK3CA mutation, K-Ras mutation and p-AKT expression may be used as parameters for predicting prognosis in colorectal cancer. Tissue samples from 158 colorectal cancer patients who underwent surgical resection were examined. The sequences of exon 1 of K-Ras and exons 9 and 20 of PIK3CA were determined by direct sequencing using genomic DNA extracted from paraffin-embedded blocks. Activation status of AKT was evaluated by immunohistochemical staining using phospho-specific AKT antibody (Ser473). Correlation between these factors and clinicopathologic findings/patient survival were examined. As a result, PIK3CA mutation was significantly associated with shorter relapse-free survival (RFS) in stage II/III patients (p = 0.0216) and shorter disease-specific survival in all patients (p = 0.0357). In the multivariate analysis, PIK3CA mutation was the only independent and significant prognostic factor for RFS in stage II/III patients (p = 0.0433, HR 2.478). This study revealed the prognostic value of PIK3CA mutation in colorectal cancer patients. Patients with PIK3CA mutation should be followed up carefully. Moreover, our result suggests that inhibition of PIK3CA mutant may be a new molecular target therapy.

Gastric cancer is the second most common cause of cancer deaths worldwide. The identification of molecular genetic parameters that are associated with response to chemotherapy and prognosis is of utmost interest. We examined methylation of the apoptosis-related genes, TMS1 and DAPK, in 81 primary gastric cancers using methylation-specific PCR and compared their methylation status with clinicopathological findings. Aberrant methylation of TMS1 and DAPK genes was detected in 26 (32.1%) tumors and in 18 (22.2%) tumors, respectively. The overall survival of patients with both methylated genes was significantly shorter compared with those with only one methylated gene or no methylated genes (p = 0.0003). Neither gene methylation had any relation to other clinicopathological findings. Next, we examined 43 patients treated by 5-fluorouracil-based chemotherapy, who had distant metastasis or recurrence after radical resection, to determine the relation between chemosensitivity and methylation. The response rate was lower in patients with either methylation than without (TMS1: 22.2% vs. 48.0%; DAPK: 21.4% vs. 44.8%). Overall survival tended to be shorter in the patients with both methylations compared with either or no methylations (p = 0.0806). The time to progression of patients with methylation of TMS1 or DAPK was significantly shorter than patients without methylation (TMS1: p = 0.0123; DAPK: p = 0.0464). Furthermore, the time to progression of patients with both methylated genes was significantly shorter than patients with one methylation or no methylation (p = 0.0082). In conclusion, TMS1 and DAPK methylation might predict the prognosis and response to chemotherapy in gastric cancer.

Background The potential of expression profiling using microarray analysis as a tool to predict the prognosis for different types of cancer has been realized. This study aimed to identify a novel biomarker for colorectal cancer (CRC). Methods The expression profiles of cancer cells in 152 patients with stage I-III CRC were examined using microarray analysis. High expression in CRC cells, especially in patients with distant recurrences, was a prerequisite to select candidate genes. Thus, we identified seventeen candidate genes, and selected Traf2- and Nck-interacting kinase (TNIK), which was known to be associated with progression in CRC through Wnt signaling pathways. We analyzed the protein expression of TNIK using immunohistochemistry (IHC) and investigated the relationship between protein expression and patient characteristics in 220 stage I-III CRC patients. Results Relapse-free survival was significantly worse in the TNIK high expression group than in the TNIK low expression group in stage II (p = 0.028) and stage III (p = 0.006) patients. In multivariate analysis, high TNIK expression was identified as a significant independent risk factor of distant recurrence in stage III patients. Conclusion This study is the first to demonstrate the prognostic significance of intratumoral TNIK protein expression in clinical tissue samples of CRC, in that high expression of TNIK protein in primary tumors was associated with distant recurrence in stage II and III CRC patients. This TNIK IHC study might contribute to practical decision-making in the treatment of these patients. Electronic supplementary material The online version of this article (doi:10.1186/s12885-015-1783-y) contains supplementary material, which is available to authorized users.

A 66-year-old man underwent a sigmoidectomy for advanced sigmoid colon cancer. The pathological examination revealed that the tumor was T3, N0, M0, and KRAS wild type. Fifteen months after surgery, the patient was hospitalized with stenosis of the anastomosis due to recurrent disease that had disseminated to the peritoneum, and which was unresectable. After transverse colostomy, the patient received 8 courses of mFOLFOX6+panitumumab (Pmab), and 39 courses of infusional 5-fluorouracil (5-FU) + Leucovorin (LV)+ Pmab. A partial remission (PR) was maintained for 27 months. The utility of maintenance therapy with an anti-epidermal growth factor receptor (EGFR) antibody-based regime has not previously been demonstrated. In this case, a long PR was achieved using infusional 5-FU+LV+Pmab, suggesting that this is a useful maintenance therapy following mFOLFOX6 + Pmab. However, the side effects resulting from Pmab treatment reduced the patient's quality of life (QOL). We suggest that Pmab maintenance therapy can be established by controlling the side effects of the anti-EGFR antibody.

We reviewed the clinical records of 3 patients with anal squamous cell carcinoma treated with chemoradiotherapy (CRT). Case 1: The patient was diagnosed with StageI (T1N0M0) and treated with cisplatin (CDDP)+5-FU+radiation. Chemotherapy was discontinued after the second course because of adverse effects. She achieved partial response(PR), and underwent a salvage surgery. Seven months after the surgery, she died from other comorbidities. Case 2: The patient was diagnosed with Stage I (T1N0M0) and treated with CDDP+5-FU+radiation. Chemotherapy was discontinued after the second course because of adverse effects. He achieved PR, and underwent a salvage surgery. Three years and 7 months after the surgery, he died from other comorbidities. Case 3: The patient was diagnosed with Stage IIIB (T4N1M0) and treated with MMC+S-1+radiation. Chemotherapy was discontinued after the first course because of adverse effects. She achieved complete response (CR) and is still surviving without cancer recurrence. We conclude that CRT is an effective treatment for anal squamous cell carcinoma.

Aberrant promoter hypermethylation is an epigenetic change that silences the expression of crucial genes, resulting in inactivation of the apoptotic pathway in various cancers. This hypermethylation can be restored by the demethylating agent 5-aza-2'-deoxycytidine (DAC). DAC might increase the tumor sensitivity to chemotherapy through demethylation and restoration of gene expression. We investigated the effect of combined therapy with DAC and irinotecan (CPT-11) on the human colon cancer cell line HCT-15.Human colon cancer cell line HCT-15 was treated with DAC and/or CPT-11 both in vitro and in vivo. The changes in mRNA expression of several apoptosis-related genes were investigated by reverse transcriptase-polymerase chain reaction (PCR). Promoter methylation was detected by methylation-specific PCR and combined bisulfite restriction analysis. Suppression of tumor growth was observed during the treatment with DAC and/or CPT-11 and apoptosis in the tumors was investigated by TUNEL (terminal deoxynucleotidyl transferase dUTP nick-end labeling) assay.Promoter methylation of p14ARF, p16 INK4a, BNIP3, and XAF1 was confirmed, and DAC restored mRNA expression of these genes. Demethylation and restoration of gene expression was observed with low-dose DAC, and demethylation status was sustained for several weeks. Combined therapy with DAC and CPT-11 produced marked suppression in tumor growth compared with DAC or CPT-11 alone, both in vitro and in vivo.Pretreatment with low-dose DAC may have the potential to be used as a "biosensitizer" of DNA-damaging agents such as CPT-11 when the apoptotic pathway is inactivated as a result of aberrant promoter methylation in the cancer.

Several lines of experimental evidence indicated that over-expression of vascular endothelial growth factor-C and cyclooxygenase-2 genes promotes angiogenesis and lymphangiogenesis, both of which are essential for the growth and spreading of tumor cells. This study was designed to evaluate the coexpression of vascular endothelial growth factor-C and cyclooxygenase-2 in human colorectal carcinoma to determine their relationships and correlations with lymph node metastasis and prognosis.Tissue samples of primary tumors and metastatic lymph nodes from 150 patients undergoing intentionally curative surgical resections for colorectal adenocarcinoma were immunohistochemically examined for vascular endothelial growth factor-C, cyclooxygenase-2, and CD34 expressions. Then, we analyzed their relationships and correlations with clinicopathologic findings and patients' survival time.The positivity rate of vascular endothelial growth factor-C and cyclooxygenase-2 in the primary tumor was 68 and 72.7 percent, respectively, and in the metastatic lymph nodes was 93.3 and 80 percent, respectively. A significant correlation was found between the expression scores of vascular endothelial growth factor-C and cyclooxygenase-2 (P0.0001), and both also were correlated to microvessels density and several clinicopathologic parameters, including primary tumor size, lymph node metastasis, lymphatic invasion, and TNM stage. Patients with vascular endothelial growth factor-C-positive and/or cyclooxygenase-2-positive tumors had a significant shorter survival time than those with negative tumors did. However, in a multivariate analysis, only cyclooxygenase-2 expression was recognized as an independent prognostic factor (P = 0.0412; relative risk ratio, 3.067; 95 percent confidence interval, 1.046-8.994).These data show that in human colorectal carcinoma, vascular endothelial growth factor-C and cyclooxygenase-2 are coexpressed and significantly associated with lymph node metastasis and prognosis.

Purpose: We investigated whether a 5-fluorouracil (5-FU)-resistant tumor could regain chemosensitivity after the administration of 5-aza-2′-deoxycytidine (DAC) as a demethylating agent. Methods: Human colorectal cancer cells (SW48) are characterized by the hypermethylation of proapoptotic genes. They were transplanted into 20 athymic BALB/c nu/nu mice which were randomly placed into 4 groups (1 = control; 2 = 5-FU alone; 3 = DAC alone; 4 = DAC followed by 5-FU). We evaluated the synergistic effect of DAC and 5-FU on the growth of these xenografts. Reactivation of proapoptotic genes in these cells was analyzed by methylation-specific PCR. Gene expression was determined by a quantitative reverse-transcription PCR assay. Results: Compared with the control group, relative tumor volumes were statistically significantly decreased only in group 4 mice (p = 0.006). In groups 3 and 4, p14, p16 and death-associated protein kinase (DAPK) promoter regions were demethylated and p14 gene expression was gradually increased after DAC administration. Conclusion: DAC could be a useful medicine that breaks the silencing of various genes and recovers some expressions. By pretreating with DAC at a nontoxic level, we confirmed the restoration of 5-FU chemosensitivity and apoptosis induction. The combination of demethylating agents and several cytotoxic drugs has potential in clinical practice.

人々の清潔志向を背景に, 腋臭を中心とした体臭のデオドラントニーズは年々高まっている。われわれは, 官能評価および機器分析を用いてヒトの腋臭について研究した結果, 新たな臭気原因成分としてビニルケトン類 (1-octen-3-one, cis-1,5-octadien-3-one) を発見した。これらビニルケトン類のにおい閾値は非常に低く強烈な金属臭を有し, 腋臭に大きく寄与していることが示唆された。これら臭気は, 人体代謝物中の不飽和脂肪酸と鉄が接触して生成する酸化物であることをモデル実験によりつきとめ, におい発生のメカニズムを解明した。また, 植物抽出エキスの抗酸化作用により, ビニルケトン類の生成を抑制する方法をin vitro系にて検討し, 『クワエキス』に優れた生成抑制効果を見出した。

An anastomotic leak is one of the major complications following colorectal surgery. Standard treatments for anastomotic leak are total parenteral nutrition or temporary ileostomy. The over-the-scope-clipping (OTSC) system was originally developed to treat intestinal perforation or to close the tissue after natural orifice transluminal endoscopic surgery. Two cases of successful management of an anastomotic leak after colorectal surgery using the OTSC system are reported. One patient avoided a temporary ileostomy. In the other, hospitalization was shortened by the use of the OTSC system. The OTSC system can be a potential option in the management of anastomotic leaks after colorectal surgery.

The accurate preoperative diagnosis of depth of tumor invasion and nodal status in distal rectal cancer is important because neoadjuvant chemotherapy or lateral pelvic lymph node dissection is indicated for patients with T3-T4 tumor or nodal involvement. This study aimed to determine the optimal cutoff value for predicting lymph node metastasis in patients with distal rectal cancer using multidetector row computed tomography (MDCT).The study investigated 77 patients who had undergone surgery for distal rectal cancer at a single institution between 2008 and 2011. Diagnostic performance for depth of tumor invasion and mesorectal and lateral pelvic lymph node metastases was evaluated. The optimal cutoff value was determined by receiver operating characteristic curve analysis.For predicting mesorectal and lateral pelvic lymph node metastasis, MDCT had a sensitivity of 0.36 and 0.89 and a specificity of 0.78 and 0.97, respectively. The optimal cutoff values of major and minor axes lengths for predicting mesorectal lymph node metastasis were 6.5 mm and 5.7 mm, respectively. The areas under the curve (AUCs) were 0.82 and 0.88, respectively. For predicting lateral lymph node metastasis, the optimal cutoff values were 9 mm for the major axis and 6 mm for the minor axis. Both AUCs were 1.Using MDCT, the optimal cutoff value of minor axis length for predicting mesorectal and lateral pelvic lymph node metastases in patients with distal rectal cancer was 6 mm. The accuracy of MDCT was satisfactory for predicting lateral pelvic lymph node metastasis.

A 62-year-old man presented to a hospital with left buttock pain, and sacral neoplasia was suspected. He was referred to our hospital. Colonoscopy( CS) and bone biopsy showed rectal cancer with metastasis to the sacrum. There was no bleeding or ileus associated with the primary lesion, and the sacral metastasis was unresectable; therefore, we decided to provide palliative care for pain relief. Radiation therapy( 40 Gy) was performed on the sacral metastasis and included the primary lesion, and zoledronate was administered concomitantly. Both CS and computed tomography (CT) showed tumor regression of both the primary and metastatic lesions, and the patient's carcinomatous pain was alleviated. Irinotecan, 5- fluorouracil, and Leucovorin (FOLFIRI)+cetuximab was administered to reduce the progression of the primary lesion. After 3 months, CT showed significant tumor regression of both the primary and metastatic lesions. The sacral metastasis was no longer evident on the CT images, and positron emission tomography( PET)-CT did not show fluorodeoxyglucose (FDG) accumulation. The primary lesion had shrunk and become flat, but biopsy indicated residual lesion. Although clinically the frequency of bone metastasis of colon cancer has been reported to be 8.6 to 10.7%, single metastasis is not often seen. In this report, we present a case of advanced rectal cancer with bone metastasis, which was successfully treated with chemo-radiation therapy.

A 58-year-old woman had a very large advanced rectal cancer( with wild-type K-RAS expression). Abdominal computed tomography( CT) revealed a space-occupying lesion in the pelvis and an enlarged lymph node. We established a diagnosis of unresectable rectal cancer and subsequently performed transverse colostomy. The patient received 6 courses of Leucovorin, fluorouracil, and oxaliplatin( mFOLFOX6) plus panitumumab( Pmab), 2 courses of simplified Leucovorin plus 5-fluorouraci(l sLV5-FU) plus Pmab, and 1 course of Pmab. The size of the primary tumor decreased remarkably after chemotherapy. Low anterior resection was performed. The pathological stage was T4a, N0, M1, Stage IVa. The results from this case suggest that mFOLFOX6 plus Pmab preoperative chemotherapy is a useful regimen for the treatment of locally advanced K-RAS wild-type rectal cancer.

Neuroendocrine carcinoma (NEC) of the anal canal is a comparatively rare tumor with a poor prognosis. We report herein a case of NEC of the anal canal with multiple bone metastases that was successfully treated with combined therapy. A 63-year-old man was referred to our hospital with the chief complaint of anal and back pain. A tumor was found in the anal canal, and pathologic examination revealed it to be NEC( Ki-67 expression50%); fluorodeoxyglucose( FDG) positron emission tomography (PET)-computed tomography (CT) showed multiple bone metastases. Initially, a l-leucovorin/5- fluorouraci(l 5-FU)/oxaliplatin( L-OHP)(: mFOLFOX6)/bevacizumab( Bmab) regimen and octreotide were administered to treat the unresectable and advanced NEC. Strontium-89 and zoledronate were used to treat pain related to the bone metastases. After 3 months, the tumor and bone metastases became difficult to identify. The patient experienced grade 2 neurotoxicity after 5 months, and thus, we stopped L-OHP administration. After 10 months, we reintroduced L-OHP because of additional progression of the bone metastases.

A 62-year-old woman was diagnosed as having rectal cancer and underwent low anterior resection. The final pathological diagnosis was RS, type 3, circ, modmucpor,pSE, ly1, v1, pN2, sH0, sP0, cM0, fStage IIIb, with KRAS mutation. Adjuvant chemotherapy with tegafur-uracil( UFT) plus Leucovorin( LV) was administered for 6 months. Ten months after surgery, right internal iliac and common iliac lymph node metastasis and peritoneal dissemination were diagnosed. In October 2009, capecitabine plus oxaliplatin (CapeOX) plus bevacizumab (Bmab) therapy was initiated. In May 2010, diagnostic imaging revealed a complete response after 42 months. In the present report, we describe the case of a patient with rectal cancer who experienced postoperative recurrence and achieved long-term complete response with CapeOX plus Bmab therapy. We also include a brief review of the literature.

p14(ARF), generated through an alternative splicing process that replaces the first exon, 1alpha, of p16(INK4a) with exon 1beta, located >15 kb upstream of exon 1alpha, has been shown to function as a growth suppressor. We examined 11 gastric cancer cell lines for mRNA expression, homozygous deletion, mutation, and promoter methylation of the p14(ARF) gene. No mRNA expression was detected in 5 of the 7 diffuse-type cell lines. All intestinal cell lines displayed normal levels of expression except for one with a low level of expression. Of the 5 cell lines without expression, 3 (MKN45, NUGC-2, and NUGC-4) and 1 (KATO III) displayed homozygous deletion and methylation of the p14(ARF) gene, respectively. No mutation was found in the whole coding region of the p14(ARF) gene in 8 cell lines without homozygous deletion. Our results indicate that the p14(ARF) gene is more frequently inactivated by homozygous deletion or methylation in diffuse-type gastric cancer cell lines (5/7, 71.4%) than in intestinal ones (0/4, P = 0.022). When we also analyzed 62 primary gastric cancers for the methylation status of the p14(ARF) promoter region, the methylation frequency tended to be higher in diffuse-type gastric cancers (15/33, 45.5%) than in intestinal ones (7/28, 25%). Thus, p14(ARF) alterations might be involved in diffuse-type gastric carcinogenesis.

Microsatellite instability (MSI), which is recognized as an important mechanism in tumorigenesis, has been reported in familial gastric cancers (FGC). However, genetic defects responsible for this phenotype, that is, mutations in mismatch-repair genes such as hMLH1 and hMSH2, have not been detected in most FGC cases. Earlier studies have shown that the promoter region of the hMLH1 gene was methylated in some sporadic colorectal and endometrial cancers. To determine how FGC acquire MSI, we examined the MSI status, hMLH1-protein expression and methylation status of the hMLH1-promoter region in FGC cases. Out of 9 cancers, 6 from 8 FGC kindreds showed MSI at one or more loci; no germline mutations in the hMLH1 or hMSH2 genes were detected; 4 cancers exhibiting MSI displayed aberrant hMLH1 expression: complete loss in one, decreased level in another, and partially staining pattern in the remaining 2. Methylation in the hMLH1-promoter region was found in these 4 cases. In contrast, the cancers displaying hMLH1-protein expression were not methylated in the hMLH1-promoter region. Our data show a significant association between the absence of hMLH1 expression and methylation of its promoter in FGC cases with MSI. This suggests that the mechanism of inactivation of hMLH1 is epigenetic and that there are other genes responsible for FGC. Int. J. Cancer 85:50–53, 2000. © 2000 Wiley-Liss, Inc.

A 52-year-old man underwent ileocecal resection for cecal cancer, followed by left hepatectomy and S6 partial resection for liver metastasis. A month later, abdominal computed tomography revealed metastases in the mediastinal lymph nodes, para-aortic lymph nodes, and left adrenal gland. After 4 courses of the capecitabine plus oxaliplatin(CapeOX) regimen and 4 courses of CapeOX plus bevacizumab, a complete response was observed regarding the lymph nodes metastasis. Then, left adrenalectomy was performed for the residual left adrenal metastasis. CapeOX plus bevacizumab was administered as a postoperative chemotherapy for 8 courses, Capecitabine was started due to adverse reactions, such as peripheral neuropathy (grade 2) and a gastric ulcer. After the gastric ulcer healed, capecitabine plus bevacizumab was administered for 5 courses. The patient has had no recurrence for almost 2 years since the resection of the adrenal metastasis.

A 48-year-old man with respiratory discomfort was diagnosed with rectal cancer with carcinomatous lymphangiosis, together with lung and sternum metastasis. As the patient's performance status(PS) was 2, mFOLFOX6+bevacizumab (Bmab)therapy with a 20% reduction in the dose was started. Three courses of this treatment resulted in improved respiratory function, and his PS dropped to 1. A chest computed tomography(CT) scan taken after four courses of this treatment indicated that pleural effusion had almost disappeared, and that the shadow on the lung had also reduced. However, after 20 courses of this treatment the disease had progressed. The regimen was changed to irinotecan (CPT-11)+Bmab administration. All of these chemotherapeutic treatments were administered on an outpatient basis. Sixteen months after the diagnosis of rectal cancer, the patient died. In recent years, combination chemotherapy for unresectable colorectal cancer has become recognized as a standard regimen, though adverse effects frequently occur. Thus, intensive chemotherapy is not always recommended for patients with poor PS. In this report, we presented a case of pulmonary metastases from rectal cancer, carcinomatous lymphangiosis, and sternum metastasis that was successfully treated with mFOLFOX6+Bmab.

We report a case of sigmoid colon cancer, successfully treated by a multidisciplinary strategy for local recurrence and distant metastases. This 60-year-old male patient underwent sigmoidectomy for sigmoid colon cancer. Three years after the operation, local recurrence with invasion to the left ureter was found, and we performed colectomy and left nephroureterectomy. One year after the resection, a second relapse lesion was discovered, which was considered unresectable, and was treated instead with radiation therapy(total 50 Gy). One year after the radiation therapy, five pulmonary metastases each of 12 mm in diameter were found in both lungs. He had renal dysfunction due to nephrectomy. Several regimens of chemotherapy [irinotecan (CPT-11), capecitabine+oxaliplatin (CapeOx) and CPT-11+panitumumab] were performed. He is still alive 7.5 years after the initial surgery and 4.5 years after the first recurrence.

Background A number of patients undergo percutaneous endoscopic gastrostomy (PEG) under various conditions. Open colectomy is usually performed for colon cancer in patients with PEG because the safety of the laparoscopic approach for such patients has not been established. However, if the laparoscopic approach is possible in patients with PEG, it will be less invasive and more helpful in rehabilitation into society. Case presentation We describe the case of a 64-year-old male with a T1 adenocarcinoma of the ascending colon 2 years after surgery for nasal cancer and PEG for dysphagia. The patient did not have any distant metastases or malignant tumors on preoperative computed tomography and positron-emission tomography. He underwent laparoscopic-assisted colectomy (LAC) with lymph node dissection. No complications developed during or after the surgery. Conclusions LAC could be a potential option for the treatment of colon cancer in patients who have undergone PEG. To our knowledge, this is the first recorded case of an ascending colon cancer treated with LAC under the condition of gastrostoma.

We identified a novel prognostic biomarker for the distant metastasis of colorectal cancer (CRC) using comprehensive combined copy number and gene expression analyses. Expression of mRNA in CRC tissue was profiled in 115 patients using an Affymetrix Gene Chip, and copy number profiles were generated for 122 patients using an Affymetrix 250K Sty array. Genes showing both upregulated expression and copy number gains in cases involving distant CRC metastasis were extracted as candidate biomarkers. Expression of the candidate gene mRNA was validated in 86 patients using quantitative reverse transcription polymerase chain reaction assays. Expression of the protein encoded by the candidate gene was assessed using immunohistochemical staining of tissue from 269 patients. The relationship between protein expression and clinicopathologic features was also examined. Following combined copy number and gene expression analyses, three genes linked to distant metastasis of CRC were extracted as candidate biomarkers. The expression of NUCKS1, reportedly overexpressed in several cancers other than CRC, was significantly higher in CRC tissue than in normal tissue. Overexpression of the NUCKS1 protein in CRC cells was found to be associated with significantly worse overall survival and relapse-free survival, indicating that NUCKS1 is an independent risk factor for CRC recurrence. The overexpression of NUCKS1 in cancer cells could be used as a CRC prognostic marker and might also be a target for treatment of this disease.

Unearthing of silenced genes in colorectal cancer (CRC).Oligonucleotide microarray was used in order to find changes in gene expression in five CRC cell lines before and after 5-aza-2'-Deoxycitidine treatment. Up-regulated genes were integrated with expression profile of matched colorectal tissue samples. Methylation-specific polymerase chain reaction and Real-time quantitative reverse transcription polymerase chain reaction were used to further analyze candidates using 15 CRC cell lines and 23 paired samples.After applying study selection criteria for 68 genes obtained from integrated arrays, we identified 16 genes; apoptosis-stimulating of p53 protein 1(ASPP1) and Scavenger receptor class A, member 5 (SCARA5) were selected for further analysis. Methylation was only identified for SCARA5 in 20% of the cell lines and in 17% of tumor the samples. Down expression of SCARA5 was observed in CRC cell lines and in tumor samples compared to normal (p0.001 and p=0.001, respectively).Genome-wide screening identifies genes potentially affected by methylation in CRC. SCARA5 may have a role in tumorigenesis in CRC.

Identification of methylation-silenced genes in colorectal cancer (CRC) is of great importance. We employed oligonucleotide microarrays to identify differences in global gene expression of five CRC cell lines (HCT116, RKO, Colo320, SW480 and HT29) that were analyzed before and after treatment with 5-aza-2'-deoxycitidine. Selected candidates were subjected to methylation-specific PCR and real-time quantitative reverse transcription-PCR using 15 CRC cell lines and 23 paired tumor and normal samples from CRC patients. After 5-aza-2'-deoxy- citidine treatment, 139 genes were re-expressed in all 5 CRC cell lines collectively with a fold change of more than 1.5 in at least one cell line. These genes include known methylated and silenced genes in CRC. After applying study selection criteria we identified 20 candidates. The GADD45B and THSD1 genes were selected for further analysis. Among 15 colon cancer cell lines, methylation was only identified in THSD1 (27%). THSD1 methy- lation was subsequently investigated in 23 colorectal tumors and methylation was detected in 9% of the analyzed samples; the observed promoter hypermethylation was cancer-specific. THSD1 mRNA down-regulation was observed in tumor tissues. This genome-wide screening led to the identification of genes putatively affected by methylation in CRC. The THSD1 gene may play a role in the tumorigenesis of CRC.