bluuebunny/crossref_metadata_2025_split huggingface dataset:
Optimal timing of surgical resection after radiation therapy in locally advanced rectal adenocarcinoma: An analysis of the National Cancer Database (NCDB).
Authors: Huntington Ciara R , Boselli Danielle , Hill Joshua S. , Salo Jonathan C. 
Published: February 2017

510 Background: In treatment of rectal adenocarcinoma, an increased time delay (TD) of 6-12 weeks from the end of radiation therapy to surgery may increase the rate of complete pathologic response (pCR), but the optimal TD with respect to survival has not been established. This study evaluates the impact of TD on overall mortality. Methods: The NCDB was queried for patients with adenocarcinoma of the rectum and no evidence of metastasis at diagnosis, who underwent preoperative chemoradiation followed by radical surgical resection. Standard statistical methods were employed for descriptive statistics and Cox model development. Results: The study included 6805 patients, predominantly Caucasian (87.2%) and males (63.9%) who generally were treated with low anterior resection (57.3%), colonanal reanastomosis (8.4%), or abdominoperineal resection (28.4%), and had median survival of 66.6 months. The effects of age, surgical margins (-/+), comorbidity index, time to discharge after surgery, TMN pathologic staging, surgical volume, and patient income significantly impacted mortality after radiation and surgery (p<0.05 for all values). There was a significant relationship between TD and pCR (p=.0002). At TD less than 30 days, 4.0% of patients achieved pCR, while 9.3% of patients have achieved pCR by 75 days. In TD of greater than 75 days, the rate of pCR decreased. Overall, 6.8% of patients (n=461) achieved pCR. Using a refined cox model, a TD of more than 60 days was associated with 20% greater risk of mortality (95% CI 1.068 – 1.367). This effect became more pronounced with increasing TD; a TD of greater than 75 days was associated with 28% (95% CI 1.06-1.55) increased risk of mortality, while patients with TD less than 60 days saw a survival benefit. Conclusions: Though an interval up to 75 days between radiation and surgery may achieve higher rates of complete pathologic response, delay of more than 60 days from radiation to surgical resection and subsequent systemic chemotherapy decreases overall survival in patients with rectal cancer.
Colon cancer in immigrants from Ethiopia.
Authors: Yarom Nirit , Gorbatsevich Elena , Geva Nir , Evron Ella , Kovel Svetlana , Cyjon Arnold , Sella Avishay 
Published: February 2017

521 Background: During the period 1980-1990, 26,000 African Jews immigrated from Ethiopia to Israel. Reports of the prevalence of cancer in Ethiopia are scarce and difficult to verify. Kaposi sarcoma, liver, prostate, cervical and breast cancer as reported to be the most common cancers. Colon cancer entails less than 7% of all cancers. The aim of this study was to describe and characterize cancer in immigrants from Ethiopia in Israel, in order to tailor screening and treatment approaches to this unique population. Methods: In this retrospective single center study, patients were identified based on the country of birth as registered in the medical records. Clinical data including age at diagnosis, pathology, tumor stage, interval from onset of symptoms to diagnosis and to treatment, response to treatment and survival, were obtained from the clinical charts. Local REB approved the study. Results: Between the years 2003 and 2011, 53 immigrants were treated for cancer in our center. Median survival was 30 months. Patients diagnosed more than 22 years after immigrating to Israel had a better survival (median 79 m) than patients who were diagnosed earlier (median 16 m). The interval from onset of symptoms to diagnosis was found to correlate negatively with stage at diagnosis (R2=0.717). Out of 53 patients 10 had colon cancer (19%). Three patients were diagnosed at stage I or II and 7 at stages III or IV. Median age at diagnosis of patients with colon cancer was 56 (31-81). Median interval from immigration to diagnosis was 22 years (16-31). Median survival (all stages) was 12.5 m and the mean was 33.2 m. Seven patients had well to moderately differentiated adenocarcinoma, two had mixed adeno-neuroendocrine carcinoma and one patient had neuroendocrine tumor. Three out of four patients who were diagnosed with locally advanced, stage IIb-III, refused adjuvant chemotherapy. All those with recurrence consented to palliative treatment. None of the patients offered genetic consultation opted for consultation. Conclusions: Jewish immigrants from Ethiopia to Israel have a high prevalence of colon cancer at younger age and complicated pathology. Further molecular testing and epidemiologic studies should be pursued in order to understand the unique properties of cancers arising in this population.
Prediagnostic plasma adiponectin and survival among patients with colorectal cancer.
Authors: Chong Dawn Q. , Mehta Raaj , Song Mingyang , Kedrin Dmitriy , Meyerhardt Jeffrey A. , Ng Kimmie , Wu Kana , Ogino Shuji , Fuchs Charles S. , Giovannucci Edward L. , Chan Andrew T. 
Published: February 2017

526 Background: Adiponectin is a hormone secreted by adipose tissue and has been demonstrated to possess anticarcinogenic, anti-inflammatory and insulin-sensitizing effects. Circulating adiponectin has been shown to be inversely associated with the risk of colorectal cancer (CRC) in prospective studies. However, the association of prediagnostic adiponectin with survival among patients with established colorectal cancer is unclear. Methods: We conducted a prospective study of 621 incident colorectal cancer cases from the Nurses’ Health Study and Health Professionals Follow-up Study to evaluate the association between prediagnostic plasma adiponectin and mortality. Plasma adiponectin levels were determined by enzyme-linked immunosorbent assay from ALPCO Diagnostics. The interbatch coefficient of variation from quality control samples randomly interspersed among the case samples was 8.6%. We examined the associations between quartiles of plasma adiponectin and mortality using a Cox proportional hazards model adjusted for established and putative risk factors. All statistical tests were two sided. Results: After a median follow-up of 9 years, there were 267 (43%) total deaths and 130 (21%) CRC deaths in the total study cohort. Compared with patients in the lowest quartile of adiponectin, patients in the highest quartile had a multivariate hazard ratio (HR) for CRC-specific mortality of 2.70 [95% confidence interval (CI), 1.54-4.75; Ptrend = 0.001]. The corresponding multivariate HR for overall mortality was 1.64 (95% CI, 1.14-2.36; Ptrend = 0.007). These associations were reasonably consistent in analyses according to subgroups defined by age, gender, body mass index, stage, grade and site of primary cancer. Similar results were yielded after excluding patients diagnosed within 4 years of blood collection (Ptrend = 0.027). Conclusions: Prediagnostic adiponectin is associated with an increased risk of colorectal cancer- specific and overall mortality. Further studies are needed to elucidate the mechanistic basis for these findings and determine the potential role of adiponectin as a prognostic marker in colorectal cancer.
Japanese D3 lymph node dissection in low rectal cancer with inferior mesenteric lymph node and/or lateral lymph node metastases.
Authors: Ubukata Mamiko , Itabashi Michio , Ogawa Shimpei , Hirosawa Tomoichiro , Bamba Yoshiko , Nakao Sayumi , Kameoka Shingo 
Published: February 2017

530 Background: The current Japanese Classification of Colorectal Carcinoma defines inferior mesenteric lymph nodes (IMLN) and lateral lymph nodes (LLN) as regional lymph nodes in rectal cancer. It states that these lymph nodes should be dissected when performing D3 dissection for rectal cancer. However, there is currently no consensus on the significance of Japanese D3 lymph node dissection in low rectal cancer. A retrospective study involving a large number of patients was conducted. Methods: The subjects were 2,743 patients registered in the multi-institutional registry of the Japanese Society for Cancer of the Colon and Rectum. The data were analyzed for outcomes in R0 cases with IMLN and/or LLN metastasis (IMLN(+)LLN(-) or IMLN(-)LLN(+) or IMLN(+)LLN(+)). Results: In the control group, 67 patients (2.7%) were considered positive for IMLN metastasis, 181 patients (7.4%) for LLN metastasis, and 34 patients (1.4%) for IMLN + LLN metastasis. The outcomes in the R0 cases with IMLN and/or LLN metastasis were 52.8% for 5-year RFS and 63.1% for 5-year OS, which were each better than for R1+R2 cases (5-year RFS 26.2%, p<0.0001; 5-year OS 30.5%, p<0.0001). Including only those with a total of seven or more metastatic lymph nodes, the outcomes in the R0 cases with IMLN and/or LLN metastasis were 53.6% for 5-year RFS and 64.9% for 5-year OS, which did not differ significantly from those for IMLN(-)LLN(-) cases (5-year RFS 54.4%, 5-year OS 55.2%) (RFS: p=0.9718, OS: p=0.4049). Conclusions: We confirmed that cases of IMLN and/or LLN metastasis in low rectal cancer tend to have a large total number of metastatic lymph nodes, but a good outcome can be expected if curative resection can be performed. These results demonstrate the value of radical Japanese D3 lymph node dissection in low rectal cancer with IMLN and/or LLN metastasis.
Controlling the quality of RAS mutation testing by a dichotomous approach: Ring trials and benchmarking mutation frequencies by a RAS monitor.
Authors: Jung Andreas , Dietel Manfred , Gabbert Helmut E , Kloor Matthias , Penzel Roland , Schafer Karl-Ludwig , Schirmacher Peter , Sers Christine , Kirchner Thomas 
Published: February 2017

536 Background: The PRIME study (Douillard et al. New Engl. J. Med. 2014) demonstrated that testing all coding exons of both KRAS and NRAS proto-oncogenes (all-RAS) predicted response for anti-EGFR targeting antibody panitumumab better than testing only KRAS exon 2 (PFS: 8.9 vs 9.6 mo, OS: 20.2 vs. 26 mo). Thus, the EMA changed the label of this drug for Europe. Now all RAS testing has to be done on a high quality level. Therefore, an improved quality assurance (QA) system was developed. Methods: The German RAS Advisory Board as part of QuIP (Quality initiative Pathology) launched ring-trials to assure quality of RAS mutation detection. 12 test cases of metastatic colorectal cancers (mCRC) containing WT or mutated sequences in one of the three coding exons 2 – 4 of either the KRAS or the NRAS oncogenes. Additionally many QA passed participants supplied the results of all-RAS testing of mCRC for one year resulting in a RAS monitor. Results: In less than half a year an area-wide coverage of quality certified all-RAS testing laboratories was reached. In three ring-trials 89 of 93 (96%) institutions for pathology passed the QA using Sanger-Sequencing (60%), pyrosequencing (25%) or the COBAS system (15%). None of the methods was superior to another as comparable amounts of methods passed or failed the ring trials. As only 12 cases were tested the result is reliable with a lower limit of confidence of only 0.7. Thus, a RAS monitor was introduced as an additional instrument of QA. Here, the results of almost 4000 cases of mCRC tested for all-RAS were collected indicating RAS mutations in 45.7% of investigated cases (KRAS: 41.5%, NRAS: 4.2%). Conclusions: Ring-trials are a versatile tool to establish a network of quality tested diagnostic laboratories in a short time. In parallel data sets for benchmarking the frequencies of RAS mutations were generated region specifically. Thereby quality was brought to a higher level than without the RAS monitor.
Burden of high-risk oral HPV infection in men in the United States and implications for oropharyngeal cancer screening: NHANES (1999-2012).
Authors: Dunn Erin , Moore Kevin J. , Koru-Sengul Tulay 
Published: February 2017

55 Background: In men high-risk human papilloma viruses (HPVs) have been implicated in causing cancer of the penis, anus, and oropharynx. HPV infection, specifically HPV 16, is currently one of the most common causes of oropharyngeal cancer. National population-based surveys provide estimates of population-specific prevalence, trend, and determinants to identify the burden of high-risk HPV in the oropharynx of men. Methods: We calculated HPV infection prevalence by oral testing in the US from 1999-2012 National Health and Nutrition Examination Survey (NHANES) to obtain a representative sample of non-institutionalized civilian population. We provided epidemiology of HPV infection for both females and males with prevalence estimates, unadjusted odds ratio (OR) with 95% confidence interval (95%CI). Analysis was performed by SAS v9.3 with complex sampling design. Results: Among HPV-positive persons, high-risk HPV infection (16, 18, 26, 31, 33, 35, 39, 45, 51, 52, 53, 56, 58, 59, 66, 68, 73, 82) was more prevalent for men (79.4%) than for women (20.6%). Men also had the highest prevalence for each high-risk type tested. Notably, men held 84.9% of the HPV 16 burden, which has the highest risk for orophargyngeal cancer. Mexican-American men had lower odds of high-risk HPV infection than White men (OR=0.47; 95%CI=0.261, 0.86). Further, divorced/separated/widowed men had lower (0.48; 0.26, 0.88) and never married men had greater (1.76; 1.01, 3.07) odds of high-risk HPV compared to men who are married/living with partner. Conclusions: Using a large population-based survey, our results show increased prevalence of high-risk HPV infection in men. Stratification by ethnicity and marital status will increase understanding and awareness of the burden and demographic disparities of potentially oncogenic HPV infections in men and may provide a base for culturally and gender competent oropharyngeal cancer screening programs. Recognizing demographic disparities and behaviors could guide further research into risk factors and conditions that guide the prevalence of HPV infection and oropharyngeal cancer in specific male populations.
Analysis of correlation between oncogene mutation and response to chemotherapy in all RAS wild type metastatic colorectal cancer, using next-generation sequencing technology.
Authors: Higuchi Akio , Kasajima Rika , Shiozawa Manabu , Asari Masahiro , Murakawa Masaaki , Katayama Yusuke , Yamaoku Koichiro , Aoyama Toru , Kanazawa Amane , Morinaga Soichiro , Rino Yasushi , Akaike Makoto , Masuda Munetaka , Miyagi Yohei 
Published: February 2017

553 Background: Targeted therapies of monoclonal antibodies have changed the treatment of metastatic colorectal cancer (mCRC). A target therapy with chemotherapy regimen for mCRC was decided by KRAS mutation status (KRAS exon2 [codon12, codon13]). Currently, there are many reports suggesting that in addition to analysis of KRAS mutation status, the evaluation of EGFR gene copy number, levels of EGFR ligands, BRAF, NRAS, PIK3CA mutations could be helpful to have a more accurate selection of patients who may have a benefit from anti-EGFR targeted drugs. Methods: Mutation status of 50 oncogenes were analysed in 35 mCRC patients with all RAS wild type, using next-generation sequencing technology. The response for chemotherapy was classified response group (R group) and non-response group (N group) by RECIST. The relation between mutation status of 50 oncogenes and the response for chemotherapy was assessed. Results: There were 25 oncogene mutations in the 50 genes. Driver mutation associated with oncogenic mutation deeply were 5 oncogenes, which were PIK3CA, AKT1, BRAF, PDGFRA and TP53. Only BRAF mutation was significantly associated with poor chemo response in the 5 oncogenes. A case which had two driver mutations was only in the N group. One of the two driver mutations was tumor suppressor gene, TP53. Conclusions: BRAF mutation and the number of driver mutations are key predictors of chemosensitivity in the mCRC cases with all RAS wild type.
An observational study of a team management approach for first-line XELOX therapy in patients with advanced/recurrent colorectal cancer: The SMILE study (the study of metastatic colorectal cancer to investigate impact of learning effect).
Authors: Nakamura Michio , Matsuoka HIroshi , Shibata Yoshihisa , Munemoto Yoshinori , Okuda Hiroyuki , Uchida Hiroshi , Ogata Yutaka , Nishimura Genichi , Shiroiwa Takeru , Kishimoto Junji , Maeda Kotaro 
Published: February 2017

554 Background: Although oral chemotherapies such as XELOX are widely favored for convenience and flexibility, these have several disadvantages such as drug non-compliance and delayed discovery of adverse events. So we designed a multicenter, prospective, observational study to evaluate the efficacy of supportive interventions in first-line XELOX for colorectal cancer (CRC) patients (pts). Methods: CRC pts undergoing first-line XELOX (+Bevacizumab) therapy practicing one or more of supportive interventions as follows: 1) a telephone follow-up (TF), 2) instruction on dosage and administration by a pharmacist, 3) skin care instruction by a nurse, and 4) pts education by a doctor were eligible. The objective was to evaluate the incident rate of grade 2 or worse hand-foot syndrome (HFS), QoL, safety, and efficacy. QoL was assessed at baseline, 2, 4, 5 and 8 cycles after the treatment started, using the Hospital Anxiety and Depression Scale (HADS) and the Mental adjustment to cancer scale (MAC). Results: From April 2011 to September 2012, 80 pts were enrolled from 14 institutes. The characteristics were as follows: male/female: 46/34, age median: 63 (36-75), and supportive intervention 1)/2)/3)/4): 36/68/73/78. The incidence of grade 2 or worse HFS during 6 months were 11.1% (n=4) for those received TF (n=36), and 20.5% (n=9) for those received other intervention except TF (n=44). Relative dose intensity (RDI) was 75.7% (TF+/-: 77.7/74.3%) in oxaliplatin and 77.5% (TF+/-: 80.2/75.3%) in capecitabine, respectively. Although a tendency of the QoL score improvement about anxiety, fighting spirit and helplessness in a TF group was observed during the periods from start of therapy to 4 courses, there were no significant differences compared to other interventions except TF. Conclusions: We confirmed that HFS incidence was mitigated in a TF group. In regard to QoL, although we could not show the statistical differences due to some limitations of this study such as small sample size and non-randomized, it was indicated that TS had the potential to improve several QoL about anxiety, fighting spirit, and helplessness. Clinical trial information: UMIN000007185.
Muscle volume loss after the induction of first-line chemotherapy as a novel prognostic factor in metastatic colorectal cancer patients.
Authors: Yoshikawa Yusuke , Okabayashi Koji , Hasegawa Hirotoshi , Tsuruta Masashi , Seishima Ryo , Takahashi Hidena , Yamada Toru , Matsui Shimpei , Kondo Takayuki , Shimada Takehiro , Matsuda Mutsuhito , Yahagi Masashi , Asada Yusuke , Sugiura Kiyoaki , Suzuki Yoshiyuki , Tajima Yuki , Nakadai Junpei , Kitagawa Yuko 
Published: February 2017

558 Background: Muscle volume loss (MVL) is observed in end-stage cancer patients as cachexia. However, the impact of MVL on tumor response and survival still remains unclear during chemotherapy in metastatic colorectal cancer (mCRC) patients. The aim of this study is to evaluate correlation between MVL and oncologic outcomes in mCRC patients. Methods: A total of 91 mCRC patients who received first-line chemotherapy were identified in our prospective registry between February 2007 and April 2013. Skeletal muscle index at the level of L3 vertebra (SMI) was calculated by muscle volume normalized by stature at the time of the induction of first-line chemotherapy (bSMI) and first evaluation of tumor response (fSMI). Patients whose SMI decreased more than 10% were classified as MVL group. The impact of these variables on oncologic outcomes (overall survival [OS], progression free survival [PFS], and tumor response rate [RR]) were analyzed. Results: Mean bSMI and fSMI were 35.0 (SD: 7.11) cm2/m2, and 34.2 (SD: 6.85) cm2/ m2, respectively. Eighteen patients were classified into the MVL group. The patients in MVL group significantly responded to the chemotherapy (RR of MVL: 11.1% vs. RR of non-MVL: 49.3%, p < 0.01). There was no significant difference in terms of high grade adverse effect between MVL and non-MVL group. Patients in MVL group had a significant shorter median PFS (MVL: 5.5 [2.5 - 10.1] months vs. non-MVL: 12.8 (3.8-80.5) months, p < 0.01) and median OS (MVL: 13.9 [6.2-61.2] months vs. non-MVL: 29.3 (8.2-94.0) months, p < 0.01). Multivariate analysis demonstrated that patients with MVL had significantly worse prognostic factor (OS: HR 3.51 [1.99-6.21], p < 0.01 and PFS: HR 8.27 [2.91-23.5], p < 0.01. Conclusions: The findings of this study suggested that MVL after the induction of the first line chemotherapy could be a novel predictive factor for chemotherapy response and prognosis. Further investigation should be required to clarify the mechanistic background.
Relation between carcinoembryonic antigen (CEA) production in colorectal cancer (CRC) tissue and serum CEA levels: Comparison between the time of recurrence and initial diagnosis.
Authors: Saito Gota , Sadahiro Sotaro , Okada Kazutake , Tanaka Akira , Suzuki Toshiyuki , Kamijo Akemi 
Published: February 2017

561 Background: Because serum CEA often becomes positive before the diagnosis of recurrence, CEA is widely used for postoperative surveillance. Serum CEA is negative at initial diagnosis as well as at recurrence in some patients. We examined the relation between serum CEA levels and tissue CEA staining status both at initial surgery and at recurrence. Methods: Between 1998 to 2012, 1,306 patients (pts) with colon cancer (CC) underwent curative resection. Serum CEA levels were measured at initial surgery and at recurrence and immunohistochemical staining for CEA in primary and metastatic lesions was performed in 46 pts. Serum CEA levels of 10ng/mL or more were regarded as positive. Results: Serum CEA were positive in 17 pts (37%) at initial surgery and in 20 (43%) at recurrence. CEA staining was positive in primary lesions in 24 pts (52%) and metastatic lesions in 33 (72%). The positive rate was higher in metastatic lesions (p=0.053). Among pts in whom serum CEA was positive at initial surgery, CEA staining in primary lesion was positive in 12 pts (71%) and negative in 5 (29%). Among pts in whom serum CEA was negative, CEA staining in primary lesion was positive in 12 pts (41%) and negative in 17 (59%). Serum CEA at initial surgery was not related to CEA staining in primary lesion(p=0.0722). Among pts positive for serum CEA at recurrence, CEA staining in metastatic lesions was positive in 19 pts(95%) and negative in 1(5%). Among pts negative for CEA at recurrence, CEA staining in metastatic lesions was positive in 14 pts (54%) and negative in 12 (46%). Serum CEA at recurrence was significantly related to CEA staining in metastatic lesions (p=0.0026). Among 33 pts in whom CEA staining was positive at recurrence, serum CEA was negative in 14 (42%). Conclusions: In pts with recurrence of CC, there was no relation between the staining CEA status and serum CEA level at initial diagnosis. In contrast, these variables were significantly related at recurrence. However, 42% of pts with positive staining for CEA in metastatic lesions had negative serum CEA levels. Our findings suggest that factors besides the production of CEA by cancer cells are related to serum CEA levels.