bluuebunny/crossref_metadata_2025_split huggingface dataset:
Personalized dose monitoring of fluorouracil and metabolites of capecitabine (XELODA) in colorectal cancer patients (PersonaX).
Authors: Nakamura Masato , Makihara Katsuya , Onikubo Toshihide , Nakamura Kumi , Uchibori Kazuya , Azuma Sayaka , Murotani Kenta , Iwamoto Shigeyoshi , Mishima Hideyuki 
Published: February 2017

706 Background: Capecitabin is a prodrug converted into 5-FU via two phases of metabolites, 5' -DFCR and 5' -DFUR. In order to elucidate intra-individual variation of capecitabine, we have investigated pharmacodynamics and kinetics of fluoroprymidine in patients with colon cancer (UMIN000008852). Methods: A dose of 2000mg/m2/day of capecitabin were administered from day 1 to day 14 twice a day every 3 weeks with or without oxaliplatin and bevacizumab. Blood samples were collected on day 8 at 1 hour and 2 hour after morning meal in the first cycle. Concentrations of plasma 5-FU were measured by using ‘My5FU’, and concentrations of 5'-DFCR, 5'-DFUR and unchanged capecitabine were mesured by LC-MS. Results: A total of 34 patients with colorectal cancer were enrolled and evaluated. Although systemic 5FU are low after capecitabine intake, the concentrations of plasma 5FU were successfully measured by ‘My5FU’. Wide variation are shown in plasma 5FU, 5'-DFCR,5'-DFUR and unchanged capecitabine. There was a correlation between unchanged capecitabin and the AUC of their metabolites, 5' -DFCR and 5' -DFUR. The strongest correlation exists in 5FU and 5’DFUR (Spearmann correlation index: 0.82). Median and IQR (Interquartile Range) of 5FU was 175.1 (98.6-304) ug/mL. Conclusions: The monitoring of 5FU concentrations by ‘My5FU’ elucidated intra-individual variation of capecitabine. It will contribute to individual cancer treatment for patients administered capecitabine. The correlation between concentrations of capecitabine metabolites (5-FU, 5'-DFCR, 5'-DFUR,capecitabin) and their efficacy and toxicity are under examination. Clinical trial information: 000008852.
The role of cytoreductive surgery and heated intraperitoneal chemotherapy (CRS/HIPEC) in patients with peritoneal carcinomatosis (PC) of appendiceal origin (AO).
Authors: Sardi Armando , Milovanov Vladimir , Sittig Michelle , Gushchin Vadim 
Published: February 2017

707 Background: Peritoneal carcinomatosis of mucinous appendiceal tumor origin is a rare condition which has poor prognosis if treated with limited surgery or systemic chemotherapy. Several publications show that CRS/HIPEC gives a significant survival benefit for patients with PC of AO. However, many patients do not get appropriate treatment. We show data from our 17-year experience using CRS/HIPEC in PC of AO. Methods: Retrospective analysis of a prospective database of 251 patients with PC of AO was performed. Peritoneal cancer index (PCI), completeness of cytoreduction (CC), lymph node (LN) status, and histopathology data was collected. The impact of each variable evaluated by Hazard ratio analysis. Overall survival (OS) estimated by Kaplan-Meier curves. Results: Mean age 53 years (range 23-81). 251 patients underwent 290 CRS/HIPEC procedures. 31 patients had 2, and 4 patients had 3 CRS/HIPEC. A total of 149 patients (59%) had peritoneal mucinous carcinomatosis (PMCA) and 102 (41%) had disseminated peritoneal adenomucinosis (DPAM) (Ronnett classification). Mean follow-up 4.8 years with a median of 4.7 years. Complete cytoreduction was achieved in 84% (89% DPAM, 80% PMCA; p = 0.047). Mean length of surgery 11.3 hours, mean hospital stay 14 days. No in-hospital or 30-day mortality. 73% had PCI > 20 (78% DPAM; 68% PMCA). LN metastasis in 42% with PMCA. OS from date of HIPEC was 93%, 86%, 81% in DPAM and 90%, 60%, 44% in PMCA for 1, 3, and 5 years, respectively. With CC, the 5-year OS was 84% in DPAM and 49% in PMCA. All PMCA patients with incomplete cytoreduction (n = 30) had PCI ≥ 20 (p < 0.001). Hazard ratios were 2.5 (95% confidence interval [95% CI] 1.3-4.5), 3.1 (95% CI 2.0-4.9), 3.6 (95% CI 2.1-6.2), for PCI < 20, complete cytoreduction, and histopathology (DPAM vs. PMCA), respectively. Hazard ratio (for LN status in patients with PMCA was 3.0 (95% CI 1.8-5.1). Conclusions: Meaningful survival could be achieved in PC of AO even with extensive peritoneal disease (PCI > 20). We consider CRS/HIPEC a standard of care for these patients. CRS/HIPEC should be provided in specialized centers by trained surgeons where complete cytoreduction could be frequently accomplished.
Does the dose of leucovorin (LV) matter with 5-fluorouracil (5FU) in colorectal cancer (CRC)?
Authors: Biagi James Joseph , Coakley Nadia , Earle Craig , Erlichman Charles , Fields Anthony L.A. 
Published: February 2017

708 Background: In June 2015 Cancer Care Ontario convened an expert panel to determine if there is an optimum LV dose in 5FU-LV combinations for the treatment of CRC. This request arose out of observed variation in LV dosages between some cancer centers. The research question was effect of LV dose on overall survival (OS), progression free survival (PFS), disease free survival (DFS), response rate (RR) and adverse events/toxicity, given a constant dose of 5FU. Methods: A systematic search was conducted for guidelines (GL) and comparative trials; eligibility included English language, with > 30 patients, that examined different doses of LV where dose of 5FU was not varied. Assessment of studies for inclusion was completed by 4 reviewers. Results: We identified 5 GL, 0 systematic reviews and 12 trials that defined a LV dose in combination with 5FU. None of the GL informed an optimal dose of LV. RR was assessed in 10 trials; 4 showed trends to higher RR with higher LV dose, but differences were not statistically significant (SS) between arms. PFS or DFS was reported in 6 trials and was similar between arms. Time to recurrence reported in one trial that included bevacizumab (BV) was longer in the high dose LV group that was SS. OS was addressed in 10 studies: no difference found in 7 studies; in one RCT OS was longer with the higher dose LV 55 vs. 45 months (p not reported); in one retrospective study OS was 23 vs. 20 months in favor of high dose LV (p not reported); one study of LV and BV had longer OS vs. lower dose LV at 26 vs. 21 months (SS). Toxicity: higher dose LV was associated with greater toxicity in 3 of 4 studies that reported stomatis, and increased rates of diarrhea in 9 of 11 trials. Meta-analysis was not appropriate as studies were too heterogeneous. Conclusions: There is no convincing evidence to identify an optimum dose of LV to be used in 5-FU/LV combinations. Amongst studies that did show a difference the trend was improved survival in favor of the higher dose. Similarly, differences in toxicities when identified were consistently greater with the higher dose LV. The expert panel concludes that the existing literature provides insufficient data to suggest that chemotherapy protocols should deviate from standard protocol doses.
Leptomeningeal carcinomatosis in colorectal cancer: The Mayo Clinic experience.
Authors: Taylor Gretchen E , Karlin Nina J. , Halfdanarson Thorvardur Ragnar , Coppola Kyle , Grothey Axel 
Published: February 2017

710 Background: Leptomeningeal metastasis (LM) has been described as a rare form of metastatic disease progression in colorectal cancer (CRC). There remains a paucity of literature with regards to the course and management of LM in CRC. The aim of this study was to estimate the incidence of LM in CRC patients seen at our institution over a 15-year period, and to describe the clinical course and outcome of these cases. Methods: LM in CRC primary cases between 2000 and 2014 were identified in the Mayo Clinic databases. The charts were retrospectively reviewed. Results: Of 17,095 CRC primaries, we identified 10 patients with LM (0.058%) in this 15-year period. Nine cases were included in the analysis. Four had metastatic disease at the time of their initial CRC diagnosis. One patient also had a lung adenocarcinoma diagnosed during initial staging for the CRC primary. Median overall survival after CRC diagnosis was 25.7 months (range 4.7-74.8). Median time to diagnosis of LM after CRC diagnosis was 25.3 months (range 1-68.1). All patients had MRI findings consistent with LM: 3 patients with spinal LM, 5 patients with intracranial LM, 1 with both. One of three CSF analyses at the time of LM workup was positive for malignant cells; all had elevated protein. Neurologic symptoms correlated with site of the lesions, with headache, cranial nerve palsy, lower extremity weakness, and gait disturbance among the most frequently reported. However, not all patients had neurologic findings, with LM lesions found incidentally in two cases. Seven patients (78%) had palliative radiotherapy (RT) for LM. Three patients continued to receive systemic chemotherapy after diagnosis of LM. No patients underwent intrathecal chemotherapy. Median survival after LM diagnosis was 7 weeks (range 2-39). Conclusions: The diagnosis of LM is an exceedingly rare development in the natural course of CRC. It continues to confer an extremely poor prognosis with limited treatment options. At our institution, most patients had their disease addressed by palliative means, with many receiving RT to control their neurologic symptoms. Based on our series, supportive care remains a sensible approach to the management of LM in CRC.
Predictors of lymph node metastasis and prognosis in early colorectal cancer patients with signet-ring cell and mucinous adenocarcinomas.
Authors: Song Baorong , Yu Yongming , Song Xiao , Li Xinxiang , Dai Xiaoyu , Cai Sanjun , Xu Ye , Cai Guoxiang 
Published: February 2017

717 Background: The local excision of early colorectal cancer is limited by the presence of lymph node metastasis. Signet-ring cell carcinomas and mucinous adenocarcinomas are two relatively infrequent histological subtypes. However, little is known about the predictors of lymph node metastases and prognosis to support the feasibility of local excision in early-stage signet-ring cell and mucinous colorectal adenocarcinomas. Methods: The Surveillance Epidemiology and End Results Database (1988 to 2006) from the National Cancer Institute was used to identify all patients with T1 adenocarcinomas, including conventional adenocarcinoma (AC), mucinous adenocarcinomas (MAC), and signet-ring cell carcinoma (SRC). The prevalence of lymph node metastasis was assessed, and the long-term survival rate in the above three types of colorectal cancer was calculated. Results: Final cohorts of 47,260 patients were eligible for analysis. SRC accounted for 0.3% and MAC accounted for 3.7% of the entire cohort of colorectal adenocarcinomas. Compared to AC, SRC and MAC more frequently presented at a younger age, were located in the proximal colon, and exhibited a higher grade. The incidence of lymph node metastasis in AC, MAC, and SRC was 5.8%, 10.8%, and 15.3%, respectively. Patients with SRC were associated with a worse prognosis, regardless of the tumor location. Patients with MAC of the rectum, but not the colon, were associated with a reduced implication of prognosis. After adjusting for other clinicopathological factors, SRC and MAC of the rectum were independently associated with a high risk of death (HR 2.70, CI 1.77-4.12 and HR 1.65, CI 1.38-1.98 for SRC and MAC, respectively). Histology was not found to be an independent prognostic factor in patients with colon cancer. Conclusions: MAC and SRC are two distinct subtypes of colorectal cancer that require special attention despite their relatively rare prevalence. T1 patients with SRC and patients with MAC of the rectum have higher incidences of lymph node metastasis (LNM), and with these adverse outcomes, local excision is not recommended. Although MAC of the colon has a high rate of LNM, the prognosis of this type is similar to that of AC.
Effects of adjuvant oxaliplatin on anal function in locally advanced rectal cancer treated with preoperative chemoradiotherapy and low anterior resection.
Authors: Arias Fernando , Eito Clara , Viudez Antonio , Asin Gemma , Ibañez Berta , Hernandez Irene , Cambra Koldo , Errasti Marta , Barrado Marta , Campo Maider , Visus Ignacio , Mata Elena , Ciga Miguel 
Published: February 2017

718 Background: The main purpose of the present study was to determine if the addition of adjuvant oxaliplatin (OXA) could have some influence on sphincter function in patients with locally advanced rectal cancer (LARC) treated with preoperative capecitabine/radiotherapy followed by lower anterior resection (LAR). Methods: Those patients with LARC treated at our center with LAR and without two-years loco-regional relapse were retrospectively analyzed independent of the type of adjuvant treatment received. Anal sphincter function was assessed by Wexner´s incontinence score (0 to 20 points, being punctuation inversely proportional to sphincter function). All questionnaires were completed between January 2010 and December 2012. Comparisons of sphincter function measured with the Wexner test between patients with and without OX were conducted with the Mann-Whitney test. Statistical analyses were conducted using IBM SPSS Statistics, version 20. Results: From 2006, 92 consecutive patients were included in our study. Mean time from LAR to fecal function assessment was 58 months (25 to 96 months). Wexner test median values did not differ significantly (p=0.450) between patients with and without adjuvant OXA. The median (IQR) for the group without adjuvant OXA was 6.0 (1.0-11.25), being for group that received adjuvant OXA of 5.0 (1.0-10.0). Conclusions: Based on our findings, OXA could be used as adjuvant treatment in LARC, due to its absent of deleterious influence over the sphincter anal function. Because of the retrospective nature of our study, prospective studies should be warranted in similar scenarios. This study has been supported by a grant of “Mutua Madrileña Fundation.”
Preliminary safety and efficacy of perioperative COI-B (capecitabine, oxaliplatin, irinotecan, and bevacizumab) in patients with borderline resectable or high–recurrence risk colorectal cancer liver metastases (CLM).
Authors: Caporale Marta , Cotsoglou Christian , Berenato Rosa , Scotti Mauro , Di Bartolomeo Maria , Coppa Jorgelina Clara , Milione Massimo , Mennitto Alessia , Flores Reyes Maria , Bossi Ilaria , Consonni Paola Valentina , Brunero Federica , de Braud Filippo , Pietrantonio Filippo , Mazzaferro Vincenzo 
Published: February 2017

719 Background: FOLFOXIRI and bevacizumab achieves high objective response rate (ORR)/R0 resections in pts with unresectable CLM. Bevacizumab increases pathological response, a surrogate endpoint of survival after CLM resection. COI-B regimen is feasible in pts with advanced colorectal cancer. In this phase II study, we aimed at assessing safety and efficacy of perioperative COI-B for pts with borderline resectable or high recurrence risk CLM. Methods: Inclusion criteria: borderline resectability with portal embolization/2-stage hepatectomy, involvement of > 1 hepatic vein or > 4 segments; and/or at least one poor prognostic factor: > 4 metastases; CEA > 200; synchronicity. Limited resectable extraepatic disease and in situ primary allowed. Primary endpoint: TRG1-3 (Rubbia-Brandt et al) according to Simon 2-stage design (first step 22; target 46 pts); secondary endpoints: ORR; R0 resection; safety; progression-free and overall survival. Pts received bi-weekly irinotecan (180 mg/m2) and bevacizumab (5 mg/Kg) day 1, oxaliplatin (85 mg/m2) day 2 and capecitabine (1000 mg/m2/day b.i.d.) days 2–6; 5 cycles pre-operatively (the last without bevacizumab) and 4 post-operatively. Results: We present preliminary data on the first 25 pts. M/F: 13/12, median age 61 years, synchronous disease 19 (76%), multiple nodules 15 (60%), N+ primary tumour 14 (56%), CEA > 200 4 (16%), extrahepatic disease 1, RAS mutation 15 (60%)/BRAF mutation 0. Involvement ≥ 4 hepatic segments 9 (36%) and involvement of > 1 hepatic veins 4 (16%). ORR was 91% (21 out of 23 evaluable, 2 too early), while 1 SD and 1 PD. Surgery performed in 21 pts (4 awaiting) and R0 resection in 18 (86%). TRG1-2 was observed in 6 (29%), TRG3 in 9 (43%), i.e. pathological response 72% (first step reached). Grade ≥ 3 toxicities: neutropenia 2, diarrhea 2, thrombosis 2. Median follow up 13 months, with only 4 relapses and 1 death. Conclusions: COI-B regimen is a feasible neoadjuvant strategy for borderline resectable or high recurrence risk CLM. This is the first trial to select pathological response as primary surrogate endpoint with encouraging results. Clinical trial information: NCT02086656.
Safety and feasibility of laparoscopic surgery for colorectal cancer in elderly patients (YSURG1401 study).
Authors: Atsumi Yosuke , Numata Masakatsu , Aoyama Toru , Hayashi Tsutomu , Yamamoto Naoto , Oshima Takashi , Yukawa Norio , Shiozawa Manabu , Yoshikawa Takaki , Rino Yasushi , Masuda Munetaka 
Published: February 2017

725 Background: The safety and feasibility of laparoscopic surgery (LAP) for colorectal cancer has not yet been fully evaluated in elderly patients. The aim of this study was to compare the short term surgical outcomes of LAP and evaluate the safety and feasibility of LAP in colorectal cancer patients aged > 75 years. Methods: This retrospective study enrolled consecutive patients who underwent laparoscopic surgery for colorectal cancer between April 2013 and March 2014 at Yokohama City University Hospital and its related general hospitals. The patients were categorized into two groups: elderly patients (≧75 years of age: group A) and non-elderly patients ( < 75 years of age: group B). Surgical outcomes and postoperative complications were compared between the two groups. The severity of complications was evaluated using the Clavien–Dindo classification. Results: A total of 237 patients were evaluated in the present study. Eighty-four patients were classified into group A, and 153 into group B. Preoperative clinicopathological outcomes demonstrated no significant differences except for the ASA score. When comparing the surgical outcomes between group A and group B, the rate of conversion to open procedure (3.6 % vs 5.2 %, P = 0.751), median operation time (232 min vs 232 min, P = 0.318), median blood loss (20 ml vs 12 ml, P = 0.353). There was no significant difference in the surgical outcomes. Although the incidence of Japanese D3 dissection was significantly lower in Group A (56 % vs 69.3 %, P = 0.047), the incidences of postoperative surgical complications of grade ≧ Ⅱ were similar between two groups (15.5 % vs 11.8 %, p = 0.427). The length of postoperative hospital stay was also similar (10days vs 10days, p = 0.347). Conclusions: The present study suggested that laparoscopic surgery for colorectal cancer is safe and feasible, regardless of the age of the patient, especially for elderly patients who may be candidates for colorectal cancer surgery.
A pilot study of neoadjuvant chemoradiotherapy for unresectable locally advanced adherent colon cancer: Assessing local tumor response.
Authors: Yu Xin , Xiao WeiWei , Zhang Rong , Zhang LuNing , Qiu Bo , Zeng ZhiFan , Ding Pei-Rong , Pan Zhi-zhong , LI Li-ren , Gao Yuan-Hong 
Published: February 2017

727 Background: To analyze the outcomes of neoadjuvant chemoradiotherapy (neoCRT) in the management of unresectable locally advanced adherent colon cancer (LAACC). Methods: 40 unresectable LAACC patients were identified from Sun Yat-Sen university cancer-center Database from October 2010 to December 2014. Unresectability was determined by multidisciplinary consultation (MDT) according to image examination or confirmed by exploratory laparotomy. NeoCRT followed by surgery and postoperative chemotherapy were given to these patients. There were 27 males and 13 females. Median age was 56 years old. The location of primary tumors were as sigmoid 31, descending colon 3, ascending colon 5, and cecum1, respectively. All the patients were treated with 45-50Gy/25F using 3D-CRT or IMRT, and concomitantly with capecitabine-based chemotherapy every 3 weeks. Surgery was scheduled 6-8 weeks after completion of radiotherapy. Results: A total of 40 patients completed neoCRT and 33 patients (82.5%) received radical resection for the locally diseases, with R0 and R2 resection in 30 and 3 patients, respectively. Seven patients were assessed as unresectable after neoCRT and 3 of them received only colostomy while the other 4 continued chemotherapy. Pathological complete response was documented in 8 patients (20.0%). Multivisceral resection was necessary in 15 patients (36.6%). Among the 33 patients underwent curative surgery, bladder invasion was noticed at diagnosis in 17 patient and bladder function was preserved in all these patients, with full bladder preserving approach in 6 and partial cystectomy in 11 patients. Grade-2 post-operative complications were observed in 4 patients (10.0%) with no 30-day mortality. Median follow-up was 26 months. For all the patients, the 3-year overall survival, local progression-free survival and progression-free survival were 70.8%, 88.2%, 74.5%, respectively. Conclusions: NeoCRT is an effective strategy for the treatment of unresectable LAACC, with high R0 resection rate, satisfactory organ preservation, good local control and acceptable treatment toxicity. NeoCRT in LAACC is worthy of further clinical research.
Inverse correlation between expression and methylation of RPRM, a TP53 dependent G2 arrest mediator candidate, along the gastric precancerous cascade.
Authors: Corvalan Alejandro Hernan , Maturana Maria Jose , Olivares Wilda , Roldan Nicole , Fry Jacqueline 
Published: February 2017

73 Background: Gastric cancer (GC) is one of first cause of cancer death worldwide. Lesions associated with the gastric precancerous cascade include atrophic gastritis (AG), intestinal metaplasia (IM), dysplasia (DY), and early (EGC)/advanced gastric cancer (AGC). Loss of expression due to aberrant methylation of Reprimo (RPRM), TP53 dependent G2 arrest mediator candidate, has been detected in patients with GC. Here we evaluated the methylation of the promoter region of RPRM in the precursor lesions. Methods: Fresh tissue biopsies from AG (N = 8), IM (N = 6), DY (N = 4), EGC (N = 5) and AGC (N = 8) were included. Expression and methylation levels of RPRM were detected by qPCR and MethyLight, respectively. Sequencing of 30 CpG sites of the promoter of RPRM was performed by Bisulfite sequencing. Results: Relative expression levels of the mRNA of RPRM decrease as gastric precancerous cascade progress, being significant in the transitions IM/DY and EGC/ACG. Methylation of the promoter of RPRM was detected in 4/8 AG, 3/6 IM, 4/4 DY, 5/5 EGC and 8/8 AGC. Spearman correlation analysis showed a significant inverse association between methylation and expression (r = -0.99, P < 0.0001). We observed increase of methylation of the CpG site 24 in the transition EGC to AGC. Conclusions: Our results show an inverse correlation between expression and methylation of RPRM along the gastric precancerous cascade. This inverse correlation is determinant in transitions from IM to DY and EGC to AGC. The identification of specific methylation of CpG site 24 associated EGC to AGC may be critical for the regulation of the RPRM expression. Grant Support: CONICYT-Fondap#15130011 and Fondecyt#1151411 from the Government of Chile