bluuebunny/crossref_metadata_2025_split huggingface dataset:
Combined treatment of colorectal cancer cell lines with aspirin and bortezomib
Authors: Voutsadakis I. , Patrikidou A. , Tsapakidis K. , Stathakis N. E. , Papandreou C. N. 
Published: March 2020

14562 Background: The ubiquitin-Proteasome system (UPS) has emerged as an important proteolytic system for the regulation of a wide range of cellular functions. Key determinants of carcinogenesis, are regulated in multiple levels by UPS. Proteasome inhibition by the boronic containing molecule bortezomib is already in use for the treatment of multiple myeloma and is in various phases of investigation for other malignancies. Cox inhibitors such as NSAIDs have been shown to inhibit the growth of colorectal cancer cells in vitro and polyp formation in vivo. Methods: HT-29 and HCT116 colorectal cancer cell lines were treated with aspirin (ASA), bortezomib and their combination. MTT assay was used to evaluate the effect of treatment on cell proliferation compared to controls. Cox activity and proteasome activity were measured with colorimetric methods. The effect of drug treatments on specific proteins expression was assayed by western blotting. Results: Both cell lines are inhibited by ASA and bortezomib and their proliferation is further inhibited by the combination of the two drugs. In HT-29 cells both ASA and bortezomib inhibit proteasome and their combination has additive effect in this inhibition. In contrast in HCT116 cells ASA-mediated inhibition is accompanied by increased proteasome activity while bortezomib-mediated growth inhibition is accompanied as expected by proteasome inhibition. ASA-mediated inhibition is not Cox-mediated since no Cox activity was detected in either cell line. Cell cycle inhibitor p27 expression is induced in HCT116 cells by bortezomib while ASA fails to do so. In HT29 cells p27 is expressed at baseline and does not change significantly by treatments. Conclusion: The combination of ASA and bortezomib inhibited the proliferation of both cell lines more than either drug alone in a Cox-independent way. ASA had opposite effects on proteasome activity in the two lines. p27 induction may mediate at least partially the anti-proliferative effect of bortezomib in HCT116 cells. Further studies are in progress to determine other molecular components of the cellular processes taking place during treatment by the combination of these drugs in order to better understand their mechanism of action and thus explore their potential therapeutic use. No significant financial relationships to disclose.
Predictive value of D-dimer and LDH levels in response to chemotherapy in metastatic colorectal cancer patients
Authors: Er O. , Inanc M. , Ozkan M. , Dogu G. G. , Dikilitas M. , Ozturk A. 
Published: March 2020

14568 Background: Hemostatic activation is known to occur in malignant diseases and this may be associated with tumor progression and angiogenesis. D-dimer levels are elevated in lung, uterine cervix, prostate and colorectal cancer patients. We aimed to evaluate the association and predictive value of LDH and D-Dimer levels with chemotherapy response in metastatic colorectal cancer (MCRC) patients. Patients and Methods: Twenty-five chemotherapy-naive MCRC patients were enrolled into this study. Plasma CEA, CA19–9, D-Dimer and LDH levels were measured before and after 3 cycles of capecitabine + oxaliplatin combination chemotherapy. The comparison between groups were done by Wilcoxon W and Mann-Whitney U tests. Results: Median age was 58 years in 15 female, 10 male patients. All patients received Capecitabine 2,000 mg/m2/day orally on days 1- 14 + Oxaliplatin 130 mg/m2 intravenously on day 1 every 21 days. The chemotherapy response after 3 cycles of treatment were 2 complete response, 7 partial response, 8 stable disease and progressive disease in 8 patients. Plasma CEA, CA19–9, LDH and D-Dimer levels were not significantly different between two groups before chemotherapy (table). Plasma LDH and D-Dimer levels were significantly higher in progressive disease patients than patients with complete, partial or stable response after 3 cycles of chemotherapy, but plasma CEA and CA19–9 were not significantly different between these groups (table). Conclusion: We found that D-dimer and LDH levels dropped in responders while they increased in patients with disease progression. D- Dimer and LDH plasma levels decrease or increase after response and progressive disease, respectively, and can act as a predictive factor of the clinical outcome of the disease. [Table: see text] No significant financial relationships to disclose.
Preventive approach to allergic reaction to oxaliplatin
Authors: Suenaga M. , Mizunuma N. , Chin K. , Kuboki Y. , Shizozaki E. , Yamaguchi T. , Muto T. , Hatake K. 
Published: March 2020

14569 Background: Allergic reaction to oxaliplatin is a chronic adverse event in the treatment of cancer. Patients with colorectal cancer were given FOLFOX4, using preventive approaches composed of two steps. Methods: Step I included 40 mg famotidine, 8 mg dexamethasone from the first cycle and 50 mg of diphenhydramine after cycle 4. In step II, for the patients who had a reaction but not a severe one in step I, a 20 mg dose of dexamethasone and four-hour oxaliplatin infusion were administered. Results: Forty-eight patients (15.1%) presented with allergic reaction, divided into group A receiving step I except diphenhydramine and B undergoing all of step I. Significant delay on occurrence was observed in group B. Thirty patients underwent step II. Prevention success (well-prevented) was defined as no reaction in two or more treatments. Allergic reaction appeared again in eleven patients (not well-prevented, 36.7%), but most well-prevented patients got four months longer treatment time with no reaction than not well-prevented patients. Conclusions: In our preventive approach, administration of H-1RA was effective in delaying the occurrence of allergic reaction to oxaliplatin, and increased dose of dexamethasone 20 mg and prolongation of oxaliplatin infusion from 2 to 4 hours was succeeded in continuing the FOLFOX4. No significant financial relationships to disclose.
Colorectal cancer nutritional and quality-of-life parameters predict patients outcomes after radiotherapy: Long-term follow-up from a prospective randomized controlled trial
Authors: Ravasco P. , Monteiro Grillo I. , Camilo M. 
Published: March 2020

14570 Background: Long term data of our published randomized trial of nutritional therapy in colorectal cancer showed that nutritional counseling optimizes pts prognosis. This study aimed to search whether outcomes were affected by individual nutritional & Quality of Life (QoL) parameters after nutrition intervention and radiotherapy (RT). Methods: Data were obtained from the trial pts’ records: G1 (n=37) on individualized nutritional counseling & education (regular foods), G2 (n=37) ad lib+polymeric protein supplements & G3 (n=37) ad lib intake. After RT, current intake (diet history), nutritional status (PG-SGA) & QoL scores (EORTC) were evaluated; their ability to predict survival, disease outcome [loco regional recurrence (LRR), distant metastases] & late RT toxicity (permanent flatulence, abdominal distension, diarrhea) were analyzed after a median follow-up of 3.7 (2.0–5.8) yrs. Results: Energy/protein intakes had decreased in G3 (p<0.01) & increased in G1>G2, p=0.007; wasting only occurred in G3>G2 (p<0.05); QoL scores worsened in G3>G2 (p<0.05) yet improved in G1, p<0.01. On multivariate analyzis of coded time-dependent variables: poorer diet intake, nutritional wasting & worse QoL scores were associated with decreased survival (p<0.002), LRR (p=0.01), distant metastases (p=0.005) & late RT toxicity, p<0.003. Landmark analysis showed that pts with nutritional intake/status & QoL deterioration, had significantly lower survival (hazard ratio [HR]: 8.25; 95% CI 2.74–26.47; p<0.001), worse disease outcome (HR: 8.15; 95% CI 2.22–25.40; p<0.002) & more severe late RT toxicity (HR: 7.15; 95% CI 2.25–16.11; p<0.004). Conclusions: In colorectal cancer after RT, poor diet intake, wasting & deteriorated QoL look as if significant predictors of survival, treatment response & late RT toxicity; such patients are prone to a more aggressive clinical course. No significant financial relationships to disclose.
Institutional experiences with panitumumab monotherapy in metastatic colorectal cancer (mCRC) patients (pts) intolerant to cetuximab
Authors: Langerak A. D. , Mitchell E. , Cheema P. , River G. L. , Shing M. 
Published: March 2020

14579 Background: Two monoclonal antibodies (mAbs) targeting the epidermal growth factor receptor are approved for the treatment (tx) of advanced mCRC - panitumumab (Vectibix™), a fully human mAb, and cetuximab (Erbitux®), a chimeric mAb. Potential for cross-reactivity between these two mAbs with regard to infusion reactions (IR) has not been fully explored. Given the lack of sequence homology between the 2 agents and the fully human nature of panitumumab, it is hypothesized that pts intolerant to cetuximab due to IR could be tolerant to panitumumab. Methods: Single pt tx IND applications to administer panitumumab monotherapy in pts with advanced mCRC were approved by the FDA and local institutions as part of the Panitumumab Compassionate Use program. Eligibility also included previous tx with standard chemotherapy and intolerability to cetuximab, ie. CTCAE v3.0 grade 3 (severe) or grade 4 (life-threatening) IR. Results: Upon informed consent, 4 pts (2M/ 2F) were enrolled in 4 centers. Median (range) age was 62.5 (52, 64) years. 3 pts had colon cancer and 1 pt had rectal cancer. All had surgery and received prior 5-fluorouracil, leucovorin, irinotecan, oxaliplatin, bevacizumab, and cetuximab. One pt had a CTC grade 3 IR and 3 pts had a CTC grade 4 IR to cetuximab. IR symptoms included fever, wheezing, dyspnea, chest/back/abdominal pain, anxiety, hypotension, flushing, tachycardia, and tachypnea. Two IRs occurred within 10 minutes of the first cetuximab infusion. Cetuximab was discontinued and IR symptoms were treated with bronchodilators, diphenhydramine, epinephrine, methylprednisolone, oxygen, intravenous saline, and hospitalization. All pts received panitumumab. Data for pts 1, 2, and 3 are available: pt 1 received 1 infusion of panitumumab at 5 mg/kg Q2W with premedication (diphenhydramine and methylprednisolone); pts 2 and 3 received 7 and 2 panitumumab infusions, respectively, at 6 mg/kg Q2W without premedication. No pt had an IR to panitumumab. Pt 2 had stable disease; pts 1 and 3 died due to disease progression. Conclusions: Panitumumab monotherapy was tolerated without incidence of an IR in these cases of mCRC pts who are intolerant to cetuximab due to a severe or life-threatening IR. Additional data will be presented. No significant financial relationships to disclose.
Additional variables other than AJCC staging show clinical utility for predicting survival in colon cancer
Authors: Wiseman S. M. , Leung S. , Griffith O. , Jones S. , Masoudi H. , Phang T. 
Published: March 2020

14584 Background: The most important predictor of colon cancer patient outcome is disease stage at the time of surgery. However, staging does not accurately predict survival for all patients undergoing a resection with curative intent. The aim of this study was to analyze clinical and pathological characteristics of patients undergoing curative colon cancer, in order to identify characteristics, in addition to stage, predictive of disease outcome. Methods: Between 1997 and 2005 data for 114 patients undergoing curative resection for colon cancer at a tertiary care institution were collected. Clinical and pathological characteristics evaluated were: age, gender, tumor location, tumor size, scheduled vs emergent surgery, pathologic margin status, TNM stage, pathologic grade, number of positive lymph nodes, total number of lymph nodes resected, vascular and lymphatic invasion. Characteristics found to be significant in a Kaplan-Meier univariate survival analysis were included in a multivariate stepwise logistic regression analysis. Patient outcomes studied were overall survival, cancer specific survival, and disease free survival. Results: From the 114 patients examined in this cohort the mean age was 67 years, the male to female ratio was 0.8:1, and the mean follow up time was 2.61 years. Overall survival, cancer specific survival, and disease free survival were calculated to be 83.3%, 91.2% and 84.2%, respectively. Statistically significant variables by univariate analysis were: AJCC stage, number of positive lymph nodes, pathologic N stage, lymphatic and vascular invasion by the primary tumor. Further multivariate analysis revealed that lymphatic invasion was the only significant independent influence for predicting disease recurrence. Conclusions: Clinicopathologic characteristics, in addition to AJCC disease stage, may be of clinical utility in predicting outcome for patients who have undergone curative resection for colon cancer. Further evaluation of these clinicopathologic characteristics should be carried out in a larger colon cancer patient cohort. No significant financial relationships to disclose.
Hand-assisted laparoscopic vs open colectomy in a rural healthcare center
Authors: Osarogiagbon R. U. , Ogbeide O. , George R. 
Published: March 2020

14587 Background: Complete surgical resection is a key component of curative therapy for colon cancer. Accurate pathologic staging requires examination of a sufficient number of lymph nodes in the resection specimen. Open colectomy (OC) is the traditional surgical technique, newer minimally-invasive laparoscopic techniques allow equivalent-quality cancer resection while reducing post-operative morbidity, but require longer operating time. Hand-assisted laparoscopic colectomy (HALC) may yield the benefits of laparoscopic colectomy while reducing operating time. The benefits of laparoscopic surgery reported in tertiary healthcare centers may not be achievable in non-tertiary care centers. We compared the operative experience of patients undergoing HALC to those who had OC at a rural veterans Hospital. Methods: Study design: Retrospective case-control study of consecutive patients undergoing HALC for colon cancer from April 2000 to September 2004 compared to patients who had OC. Patients with rectal and stage IV colon cancer were excluded. Reported variables were compared by the non-parametric Mann-Whitney U-test, all p-values are two-tailed. Results: Data is reported as HALC vs. OC. N= 39 in HALC cohort vs. 55 in OC. Median age: 72.1 vs 70.3 yrs (p 0.46). Location of tumors: right colon 62% vs 56%, left colon 2.5 vs 11%, sigmoid colon 36% vs 33. Stage: 0, 23% vs 11%; I 23% vs 23%; II 31% vs 36%; III 23% vs 31%. Median operating room time was 139 vs 137 minutes (p 0.94). 4 of 39 (10%) HALC procedures were converted to OC. Number of lymph nodes in resection specimen 12 vs 9 (p=0.043). Duration of hospitalization: 6 days vs 10 days (p=0.007). 5% of HALC patients were transfused vs 13% of OC patients. There were 3 cases of serious post-operative infection in the HALC group vs 9 in the OC cohort, 0 cases of wound dehiscence vs 3, 0 perioperative deaths vs 3. Overall, 8% of HALC patients developed severe post-operative surgical complications vs 22% of OC patients (p<0.05). Conclusions: HALC is technically feasible in the non-tertiary care setting, with equivalent duration of surgery to OC, but significantly shorter duration of hospitalization. The quality of surgical resection, pathologic staging and rates of peri-operative morbidity and mortality are similar or slightly better with HALC. No significant financial relationships to disclose.
Repeat hepatic resection and chemotherapy for recurrent colorectal liver metastases
Authors: Ferrari D. , Opocher E. , Santambrogio R. , Pisani A. , Barabino M. , Codecà C. , Scalzone R. , Marussi D. , Luciani A. , Foa P. 
Published: March 2020

14590 Background: An aggressive surgical approach combined with chemotherapy (CHT) is the best way to prolong survival in patients with colorectal cancer and synchronous resectable metastatic disease. Reintervention followed by systemic CHT is often a safe and effective procedure for fit patients with metastatic liver recurrence. Methods: Patients with resectable metastatic liver disease who underwent at least two surgical operations were included in the study. At diagnosis they had a median number of 6 measurable liver metastases (range 1–16), and median sum of largest diameters of lesions was 35 mm (range 10–70) from CT scan. Hepatic resection was followed each time by systemic CHT. Radiofrequency (RF) was added as needed to reach a curative intent . The aim of our study was to evaluate DFS and OS combining surgery, RF and CHT in this high-risk group. Results: Between November 2003 and July 2006 13 patients (median age 52 yrs, range 36–73; PS 0) with metastatic colorectal cancer underwent surgery on primary tumour and liver metastases followed by adjuvant CHT consisting of FOLFOX4 (oxaliplatin 85 mg/m2 and LV5FU) or FOLFIRI (irinotecan 180 mg/m2 and LV5FU) for 6 months. Free margins were obtained in 12 patients (92.3%). The second relapse was treated by liver surgery and systemic CHT (either FOLFIRI or FOLFIRI + Cetuximab in EGFR expressing tumours). Eight patients were offered concomitant radiofrequency (RF) for smaller lesions. Five patients (38.5%) underwent a third operation + RF followed by third-line CHT consisting of capecitabine alone or associated to oxaliplatin. After second and third hepatectomy there was no intraoperative or early postoperative mortality. With a median follow-up of 24 months (range 6–37) 6 patients are free of disease and all patients are still alive. Two-year DFS and OS are 46.2% and 100% respectively. Conclusions: Patients with metastatic colorectal cancer should be treated aggressively by surgery and CHT. In a small group of fit patients operated at least two times we obtained excellent 2-year DFS and OS. The benefit of adding adjuvant CHT as second-line or even third-line treatment seems to be justified by good long-term results. Our promising data from a single institution prompt further evaluation for aggressive surgery associated to CHT and new target molecules. No significant financial relationships to disclose.
XELOX causes less disabling peripheral neuropathy than FOLFOX 4 for Chinese colorectal cancer patients
Authors: Yau T. , Chan P. , Tsang J. , Liang R. , Epstein R. 
Published: March 2020

14592 Background: Infusional 5-FU plus leucovorin and oxaliplatin (FOLFOX4) is an efficacious treatment for colorectal cancer patients in both the adjuvant and metastatic settings. However, around 10% of FOLFOX4 patients will develop with disabling grade 3–4 neuropathy. Recent phase II studies have demonstrated that oral capecitabine in combination with oxaliplatin (XELOX) is as least as effective as FOLFOX4 for colorectal cancer. In this study, we assessed the toxicities of XELOX in Chinese colorectal cancer patients. Methods: Patients who received XELOX at Queen Mary Hospital, Hong Kong between November 2004 and November, 2006 were analyzed. Toxicities were graded by the National Cancer Institute common toxicity system. Results: Thirty-five patients received XELOX on an outpatient basis during the study period: Twenty-four as adjuvant therapy and 11 as treatment for metastatic disease. The most common side effect was grade 1–2 peripheral neuropathy which occurred in 77% of patients. No grade 3–4 neuropathy was reported. Grade 1–2 diarrhea and palmar-plantar erythrodysesthesia (PPE) also occurred in 40 % and 37 % of patients, respectively. The commonest grade 3 toxicities was diarrhea which occurred in 17% of the patients followed by 9% of patients experienced grade 3 PPE. No grade 4 toxicities were reported in our patient’s cohort. Overall, only one (3%) patient had neutropenic sepsis and 36% of patients required 20% reduction in drug dosage. No treatment related death was reported. Conclusions: Our study suggests that XELOX is a well-tolerated and convenient treatment regime. Although mild neuropathy is common in patients receiving XELOX, it causes far less disabling neuropathy than FOLFOX4 in Chinese metastatic colorectal cancer patients. No significant financial relationships to disclose.
Colon cancer epidemiology in United Arab Emirates
Authors: Maarraoui A. M. , Uttamchandani A. , Abdulatif H. , Attia N. M. , Gausia Q. U. , Rubina M. H. , Daud N. 
Published: March 2020

14597 Background: Mafraq Hospital is the largest tertiary hospital in United Arab Emirates (UAE). The exact charecterstics of colon cancer in this country are not yet documented. Methods: This is a retrospective study of colo-rectal cancer. Files of all patients with the diagnosis of colo-rectal cancer between 1/99 and 12/05 at the department of Oncology at Mafraq Hospital were reviewed. Intent to treat analysis was used. Total of 176 patients were seen. The youngest was age 18 and the oldest was 79 Results: Mean age of patients at initial presentation was 48.5. Gender was as follows: males 121 patients (68.7%) and females 55 patients (31.3%). Mean male age at initial presentation was 49.5, and mean female age was 46.4. UAE Citizens represented 34 patients (19.3%) of cohort and non-citizens 137 patients (80.7%). Cancer stages were as follows: stage I: 7 patients (4.7%), stage II: 41 patients (27.5%), stage III: 48 patients (32.2%), stage IV: 53 patients (35.6%). 27 patient elected to do staging work-up and further care elsewhere. Conclusions: 1- Colon cancer screening is needed in order to diagnose cancer at earlier stages. 2- As our patients are younger than patients in the West. Colon cancer screening should be done at an earlier age. No significant financial relationships to disclose.