bluuebunny/crossref_metadata_2025_split huggingface dataset:
Correlation of expression of pro-apoptotic proteins bax and bak with lymph node metastasis in colonic adenocarcinoma
Authors: Tracy R. A. , Chuang S. T. , Kim J. , Coppola D. 
Published: August 2020

e15042 Background: Colon cancer has been associated with disturbances in the regulation of apoptosis. Down regulation of Bax and Bak, members of the Bcl-2 family, are associated with tumor metastasis. Here we investigate how these two pro-apoptotic markers correlate with lymph node (LN) metastasis in colonic adenocarcinoma (CA). Methods: Paraffin-embedded sections from 100 cases of CA were constructed in tissue microarrays and subjected to immunohistochemistry (IHC) using the ABC method and antibodies for Bax and Bak. The IHC score is the product of intensity and percentage of positively stained cells, and ranged between 0 and 9. The total scores were divided into categories of “2 or less” and “3 or more.” These were than correlated with LN metastasis. Results: For Bax, 88 tumors were available while Bak was present in 100 tumors. In scoring Bax, 67 tumors had a score of ≤2 and 21 had a score of ≥3. Within the ≤2 category, 23 of 67 (34%) tumors had no LN metastases while 15 of 21 (71%) in the ≥3 category had no metastasis (p= 0.0029). For Bak staining, 23 had a score of ≤2 and 77 had a score of ≥3. Five of 23 (22%) tumors with a score ≤2 had no metastases and 35 of 77 (46%) with score ≥3 had no metastases (p= 0.0427). The LOGISTIC Procedure was used to show that a patient with a ≥3 Bax score has a 4.78 times odds ratio (95% C.I.: 1.64- 13.98) of having no metastases while a patient with a ≥3 Bak score has a 3 times odds ratio (95% C.I.: 1.01- 8.90) of having no metastases. Conclusions: We show correlation of the pro-apoptotic proteins Bax and Bak with decreased lymph node metastasis in CA. The findings suggest a role for these markers in predicting stage and patient survival in colonic adenocarcinoma. No significant financial relationships to disclose.
Characterization of innate responses elicited by neoadjuvant radio-chemotherapy for rectal cancer
Authors: Castiglioni A. , Bencardino K. , Tamburini A. M. , Monno A. , Albarello L. , Staudacher C. , Ronzoni M. , Doglioni C. , Rovere-Querini P. , Manfredi A. 
Published: August 2020

e15044 Background: The neoadjuvant chemo-radiotherapy (CT-RT) has improved the treatment of locally advanced rectal cancer reducing the local recurrence. However a survival benefit has not been reached yet. In order to increase the rate of pathological complete remissions in our Institution we intensified both the CT schedule adding oxaliplatin to 5-FU and the RT program with tomotherapy. The aim of this study was to verify: whether the pattern of innate response elicited by the neoadjuvant CT-RT is heterogeneous among pts and whether this information can be used to identify which pts will benefit from the treatment. Methods: We collected samples of T3N+M0 rectal cancer pts before, during and after neoadjuvant CT-RT (3 cycles of oxaliplatin + 5-FU; 45 Gy). At each time point we characterized circulating monocytes by flow cytometry, infiltrating macrophages by immunoistochemistry (IHC) and selected inflammatatory molecules by ELISA.Results: We recruited so far 25 pts, of whom 10 have reached the surgery with three pathological complete remission and four down staging. No substantial changes were detectable in the number of circulating monocytes. In contrast we observed a clear expansion of CD14/CD86 and CD14/CD163 double positive subsets. This event was transient and apparently causally related to the treatment since it abated at the later time point. Moreover, it correlated with sensitivity to the treatment: 5/7 pts who underwent disease regression had an early and transitory increase of the number of CD14/CD86 and CD14/CD163 positive cells, which was absent or negligible in non responder pts. The IHC study revealed a massive tumoral infiltration by macrophages which displayed clear features of alternative M2 polarization as assessed by expression of the CD163 and 206 scavenger receptors. A subset of pts had elevated PTX3 and low CRP concentration at the onset of treatment. PTX3 concentration abated after the first CT cycle. Conclusions: These data suggest that neoadjuvant CT-RT modulates the cellular components of innate immune responses, that could represent valuable predictive factors. No significant financial relationships to disclose.
Adjuvant chemotherapy for stage II and stage III colon cancer—What is happening in routine practice?
Authors: Ananda S. , Kosmider S. , Lim L. , Barnett F. , Desai J. , Gibbs P. 
Published: August 2020

e15046 Background: Randomised studies have defined adjuvant chemotherapy as standard treatment for stage III colon cancer (SIIICC), with multiple options available. For stage II (SII) disease, the selection of patients for adjuvant treatment remains controversial. There remains limited data on clinician decision making regarding adjuvant chemotherapy in routine clinical practice. Methods: A review of patients treated with SII & IIICC at 4 hospitals, utilising data from BioGrid Australia, where clinician choice and rationale were prospectively documented. Results: 372 patients (37%) with SII and 307 (30%) with SIIICC were identified from 1015 CC patients treated from January 2003 till November 2008. Median age was 68 years, 51% were male; 49% female. 66 (25%) of patients with SIIICC were not offered chemotherapy, predominantly due to advanced age or co-morbidity. Since oxaliplatin and capecitabine became widely available in 2005, 66% of treated patients have received oxaliplatin based therapy, 15% bolus 5-FU alone and 19% capecitabine. For SII disease, overall 81 (26%) pts received adjuvant chemotherapy. Age was the dominant influence on treatment choice with 41% aged 70 (p<0.001) receiving treatment. Patients with high risk features were also more likely to receive adjuvant therapy. (p= 0.006 for those with lymphovascular invasion and p= 0.0068 for those with T4 tumours). Dose reductions and completion rates were similar for SII and III disease, and for older and younger patients. Conclusions: Over 25% of patients with SIIICC do not receive adjuvant chemotherapy in routine practice, with physicians basing non-treatment recommendations predominantly on patient age and co-morbidity. Where treatment is used, oxaliplatin-based therapy is the dominant regimen, except in older patients. In SIICC, adjuvant chemotherapy is used in one in four patients, more frequently in younger patients and those with high risk features. No significant financial relationships to disclose.
Long-term overall survival (os) and prognostic factors of patients (pts) with surgery of liver metastases from colorectal cancer origin (lm/crc): Retrospective analysis of a Spanish single institution
Authors: Quispe I. R. , Ramos F. J. , Bilbao I. , Macarulla T. , Cedres S. , Charco R. , Lázaro J. , Moreiras M. , Moreiras M. , Tabernero J. 
Published: August 2020

e15052 Background: Hepatectomy is the only potentially curative treatment for LM/CRC. Long-term survival following liver resection (LR) has improved. The aim of this study was to analyze prognostic factors and OS after LR Methods: A retrospective review of the medical records of pts who underwent LR for LM/CRC from 1997 to 2007 was conducted. Multiple potential prognostic factors for survival were analyzed: synchronic vs. metachronic, post-op chemotherapy (CT) vs. no, lymph node (LN) status of primary tumor, R0 vs. R1–2 resection, gender, location of primary tumor, number and size of metastases, and unilobar vs. bilobar disease. Results: 190 pts (colon 130, rectum 60) underwent LR. Pts’ characteristics: 123 male, 67 female; median age 63 yrs (32–85); 95 pts synchronic, 95 metachronic; 145 pts (76%) received post-op CT; LN status was pN0 in 61 (32%) pts, pN1 in 74 (39%) and pN2 in 52 (27%). A R0 resection was performed in 164 (86%) and R1 in 25 (13%). Post-op mortality was 2.6%.Median OS was 68 months with 5- and 10-year OS of 52% and 31%, and 5- and 10-year disease free survival of 36% and 18%. 5-year OS differed between metachronic and synchronic (64% vs. 39%; p<0.001); LN-status (73% for pN0 vs. 41% for pN1–2; p<0.001); R0/R1–2 surgery (58% for R0 vs. 21% for R1- 2; p=0.002). With a median follow-up of 70 months, 71 (37%) pts remained free of disease, 60 (32%) had new metachronic LM/CRC, 18 (9.5%) had LM/CRC and extrahepatic disease and 36 (19%) had extrahepatic disease alone. Non-significant factors for prognosis were gender, location of primary tumor, number and size of metastases, bilobar disease and adjuvant CT. Conclusions: Pts with LM/CRC who undergo liver resection can achieve long-term OS, our data identifying as prognostic factors: LN status, synchronic/metachronic disease and Type of resection (R0). No significant financial relationships to disclose.
Phase II study of biweekly XELOX (capecitabine and oxaliplatin) as first line chemotherapy in elderly patients with metastatic colorectal cancer
Authors: Grande C. , Quintero G. , Mel J. R. , Huidobro G. , Campos B. , Candamio S. , Méndez J. C. , Salgado M. , Álvarez E. , Casal J. 
Published: August 2020

e15053 Background: Analysis of efficacy and toxicity of biweekly XELOX as first line monotherapy in elderly patients (pts) with metastatic colorectal cancer (MCRC), based in results of W. Scheithauer (J Clin Oncol 2003; 21: 1307). Methods: From March/06 to November/08, 28 chemonaïve elderly pts (>75 years old) with MCRC, PS: 0–2, and adequate renal, hepatic and bone marrow functions, were included in a phase II study of: oxaliplatin 85 mg/ m2/ day 1 plus capecitabine 2000/ m2/ in 2 divided doses/ days 1–7 every 2 weeks. Treatment was continued until 12 cycles, tumour progression or innaceptable toxicity. Response evaluation every 6 cycles and toxicity every cycle was performed. At present 28 pts for toxicity and 24 pts for response are evaluable. Results: Median age: 78.2 years (range: 73.5–79.5). Male/Female: 14/14. Rectal/Colon: 9/19. Metastatic sites 1/2/>2: 15/6/6. Liver 78.6%, Lung 32.1%, Local tumour 7.1%, Retroperitoneum 14.2%, Peritoneum 10.7%. and Bones 7.1 %. Previous adjuvant with 5-FU regimens to 4 pts. Comorbidity grade by Charlson index 0–1/2/>2: 60.8%/ 28.6% / 10.7%, respectively. Median number of cycles for oxaliplatin and capecitabine were 8 (5.25–12) and 8 (5.25–11.75). Response rate: 2 pts complete response (8.3%), 8 pts partial response (33.3%),10 pts stable disease (41.7 %) and 4 pts progression (16.7%). The main CTC toxicity was Asthenia G2+3 in 6 (21.5%), Nausea and emesis G2 in 7 (25%), Diarrhea G2+3 in 7 (25%) and Hand-foot syndrome G1+2 in 5 pts (17.8%). No G4 toxicity or toxic deaths were observed. Median time to progression was 8.6 months.Median overall survival will be given updated at the congress. Conclusions: Preliminary results suggest that bi-weekly XELOX is an effective first line treatment for MCRC in elderly pts with an acceptable toxicity profile (especial surveillance of diarrhea is necessary) and protocol cumpliment. Combination with bevacizumab should be considered. No significant financial relationships to disclose.
Extent of resection for curable colorectal cancer in young patients: A 27-year experience at a tertiary care centre
Authors: Al-sukhni E. , Ridgway P. F. , O’Connor B. , McLeod R. S. , Swallow C. J. 
Published: August 2020

e15059 Background: Patients diagnosed with colorectal cancer (CRC) under the age of 50 have an increased lifetime risk of developing metachronous primary tumours. Some familial GI cancer experts have recommended that younger patients with curable CRC undergo definitive subtotal colectomy at initial presentation. We sought to determine the compliance with these recommendations at our institution, the factors predictive of subtotal/total colectomy, and the influence of resection extent on survival. Methods: A case- control study utilised a prospective CRC database at Mount Sinai Hospital, Toronto. All patients under 50 who underwent initial resection of CRC with curative intent from 1979–2007 were included. Patients 50 or over were identified as controls. Type of resection was classified as complete (total/subtotal colectomy, proctocolectomy) or segmental. Results: From the database of over 1400 CRC cases, 201 patients were under age 50. 1182 controls were identified. The young patients had significantly higher rates of identifiable risk factors for CRC (IBD, FAP/HNPCC, family history of cancer) and were significantly more likely to undergo complete resection (23.38% vs 6.01%, OR 4.78). Interestingly, rectum was the primary site in 54.73% of young patients. Factors contributing to complete resection were site of disease (colon), IBD, and family history of CRC (Table). Four patients (2.6%) who underwent segmental resection developed metachronous disease at a median of 66.38 months post resection. No significant change in practice was noted over time. Conclusions: The majority of young patients with curable CRC underwent segmental resection only. Factors predictive of a complete resection included IBD, family history of CRC, and colonic primary site. Overall survival was not influenced by extent of resection. The authors support this pragmatic approach while more sophisticated estimates of tumor biology are being developed to guide the decision for more extensive prophylactic resection. [Table: see text] No significant financial relationships to disclose.
Regulation of expression of cd133, a colon cancer stem cell marker and other stemness genes/pathways, by celecoxib: Clues from clinical observations
Authors: Deng Y. , Wang L. , Tian Q. , Miller C. , Lin T. , Chien A. J. , Ulrich C. M. , Grady W. M. , Blau C. A. , Lin E. H. 
Published: August 2020

e15065 Background: CD133 identifies intestinal stem cells and colon CSC, the putative culprit of cancer initiation, progression and resistance. Elevated CD133 levels at protein & mRNA levels predict poor outcomes in patients (pts) with colon cancer. Given that celecoxib reduces colon polyp and only maintenance capecitabine plus celecoxib lead to paradoxically high complete remission (CR) in colon cancer pts who had no resection or positive margin resection of metastases (ASCO 2007), we hypothesized that celecoxib could modulate CD133 and other stemness genes/signaling pathways. Methods: we studied the effects of celecoxib versus 5-FU on CD133, Wnt and other stemness genes/pathways using flow cytometry, immunoflurorescence, real time RT-PCR, western blot, TOP-Flash for Wnt, limiting dilution assay, and Affymetrix in colon cancer cell lines and primary colon cancer spheres. Results: Celecoxib or 5FU inhibited the growth of COX-2+ HT29 or COX-2- DLD1 that express CD133 at 80% and 30% respectively. Only celecoxib down-regulated CD133 expression at the mRNA, and protein levels in a dose and time dependent manner. This effect could not be rescued with PGE2 and may be due to Wnt inhibition. Microarray showed 4 folds down-regulation of CD133 and other stemness genes e.g. CD24, ABC transporters, and LGR4/5, findings of colon cancer sphere under differentiation. Celecoxib affected several key stem cells signaling pathway, restored RB and promote cell cycle progression (P < 0.05). In contrast, 5FU affected G2M transition but had no effects on stemness genes/pathways (p < 0.05). Celecoxib resulted in 6–10 folds reduction in colony size and number with 5.6–36 folds down-regulation of CD133 mRNA in primary colon cancer spheres. Pts with confirmed radiographic CR who had received >6 months of maintenance capecitabine and celecoxib reached 5-year survival > 90% comparable to pts who achieved pathological CR (12/19). Conclusions: Targeting colon CSC with capecitabine and celecoxib may lead to durable CR and survival and deserves further investigation. No significant financial relationships to disclose.
Safety of bevacizumab when given perioperatively for colorectal cancer with liver metastases: McGill University pilot study
Authors: Kavan P. , Bouganim N. , Eid M. , Metrakos P. , Chaudhury P. , Batist G. 
Published: August 2020

e15083 Background: Bevacizumab (BV) increases responses and survival rates when used with chemotherapy in metastatic colorectal cancer (CRC). Current practice is to give peri-operative chemotherapy for resectable CRC liver metasases (LM). The safety and efficacy of chemo-BV in this setting is unknown. Post-operative complications have been reported in patients (pts) who underwent surgery while receiving BV. The goals were to determine safety of perioperative BV. Methods: In a prospective pilot study, patients with resectable LM from October 2005 to 2008 that received BV perioperatively along with chemotherapy. Of a total of 60 pts, 34 had oxaliplatin-based CTX, 22 CPT-11 (FOLFIRI) and 4 IROX. All but seven pts received BV pre and postoperatively. The average age was 55 years. All patients underwent liver surgery 6–8weeks post last dose of BV. Univariate Cox regression models were used to evaluate the association of patient and tumour characteristics, therapy and postoperative complications. Results: Postoperative complications developed in a total of 24 pts (40%). 12 pts (35%) who received Oxaliplatin CTX + BV, 9 pts (40%) with CPT 11 CTX + BV and 3 pts (75%) with Oxaliplatin + CPT-11 CTX +BV. The average time from BV discontinuation to surgery was 49 days. No significant associations were identified between BV and CTX regimen or timing and postoperative complications. Wound healing complication were most frequent with 8 pts (13%), DVT diagnosed in 6 pts (10%), protracted pancytopenia 4 pts (7%), sepsis 1pt, infections 2pts, MI 1pt, acute cardiomyopathy 1pt, and billiary leak 1pt. No bowel perforations or sudden deaths were reported. These side effects apart from thromboembolic events are comparable to previously reported post-operative complications. Conclusions: Neither the use of BV with CTX nor timing of BV administration were associated with a non acceptable increase in complication rates as compared to previously published by EORTC intergroup. Our data confirm that the combination of BV with neoadjuvant chemotherapy is feasible and safe in patients CRC LM. A higher incidence of thromboembolic events was seen. To determine the optimal timing and drug combination prospective randomized trials are urgently required. [Table: see text]
Systematic review of histamine type 2 receptor antagonists as an adjunct to curative surgical resection in gastrointestinal malignancies
Authors: Deva S. , Jameson M. B. 
Published: August 2020

e15085 Background: H2RAs have induced regression in a number of malignancies. The mechanisms that may contribute to this effect include inhibition of T-suppressor lymphocytes, increased tumor infiltrating lymphocytes and blockade of histamine-induced tumor proliferation and angiogenesis. Unique to cimetidine is its ability to inhibit vascular endothelial expression of the cell adhesion molecule E-selectin, to which many GI tumor cells adhere via carbohydrate antigen ligands. The optimal use of H2RAs in cancer patients could therefore be as adjuvant therapy rather than for metastatic disease. Methods: This systematic review examines the impact of H2RAs on the overall survival of patients when used as an adjunct to curative surgical resection for a GI malignancy. Using a sensitive search strategy, randomized controlled trials were identified in relevant databases. Criteria for study selection included: patients with colorectal or gastric cancer surgically resected with curative intent; H2RAs used i) at any dose, ii) for any length of time, iii) with any other treatment modality and iv) in the pre-, peri- or post-operative period. The results were stratified for both the type of malignancy and the H2RA used and analyzed by meta-analysis using Cochrane Collaboration software. Results: Of 350 trials identified, 8 were eligible for inclusion and had sufficient data for analysis, including a total of 1461 patients. Meta-analysis revealed a risk ratio for mortality of 0.86 (95% CI 0.76–0.99, p = 0.03) for patients randomised to H2RAs. Trials of colorectal cancer patients where cimetidine was the H2RA being evaluated demonstrated a significant survival advantage, risk ratio 0.53 (95% CI 0.33–0.84, p = 0.007). All other subgroups demonstrated a non-significant trend favouring H2RAs. Conclusions: H2RAs, and cimetidine in particular, appear to confer a survival benefit when given as an adjunct to curative surgical resection of GI cancers. The trial designs were heterogeneous and further large studies are warranted. No significant financial relationships to disclose.
Phase II study of biweekly cetuximab (C) and irinotecan (I) as a second-line regimen for metastatic colorectal cancer (mCRC)
Authors: Carneiro B. A. , Bahary N. , Lembersky B. , Fakih M. , Krishnamurthi S. S. , Lancaster S. , Pinkerton R. , Crandall T. , Potter D. , Ramanathan R. K. 
Published: August 2020

e15088 Background: I + C is a standard second line mCRC regimen. Our study investigated the efficacy and safety of a biweekly I + C combination in patients (pts) with mCRC. Methods: mCRC pts who failed 1st line fluoropyrimidine/oxaliplatin regimens and had not received I or C, were eligible for this open label phase II trial with response rate (RR) as the primary end-point and planned sample size of 31 patients to achieve a 25% RR with 80% power. C 500 mg/m2 IV was administered on d1 followed by I 180 mg/m2 IV over 60 minutes biweekly. Results: Pt. characteristics (n=32): Male (n=17), female (n=15), Median age 59.9; ECOG PS ≤1 (31 pt), PS=2 (1). Median number of cycles 3 (range 1–21), 17pts received ≤ 3 cycles. Chemotherapy doses were reduced/delayed in 20 pts. Initial I dose was reduced to 150mg/m2 in 12 pts due to previous radiation (6 pts), age ≥ 70 years (5 pts), or PS 2 (1 pt). Grade 3 or 4 adverse events: acneiform rash (n=6), diarrhea (n=5), and neutropenia (n=4); possible grade 5 (respiratory failure). One PR was seen, 12 pts had stable and 13 pts PD; 6 pts were not evaluable for response. Median OS 11.1 mos (95% CI 6.0–15.1) and TTP 2.4 mos (95% CI 1.4-NA). Among the 23 pts tested, 9 pts had KRAS, and 2 pts BRAF mutations. There was a trend towards higher OS and TTP among pts with wild type (wt) KRAS (OS 11.9 vs 9.96mo, p=0.66; TTP 5.97 vs 3.11mo, p=0.288) and BRAF (OS 12 vs 4.6mo, p=0.17; TTP 4.56 vs 1.86mo, p=0.239). Conclusions: The lower RR than previously reported was likely caused by the small sample size and possibly those factors leading to initial I dose reductions. In addition 90% of patients had prior therapy with FOLFOX/bevacizumab. The OS and TTP are consistent with those reported previously (Martin et al Brit J Cancer 2008, Pfeiffer P et al Ann Oncol 2008), supporting biweekly I + C as a convenient second-line regimen in mCRC. [Table: see text]