bluuebunny/crossref_metadata_2025_split huggingface dataset:
Colorectal cancer survival following adjuvant chemotherapy with weekly i.v. fluorouracil 425 mg/m2 and folinic acid 50mg
Authors: Jameson M. B. , Head M. , Deva S. 
Published: August 2020

e15089 Background: Adjuvant chemotherapy for colorectal cancer (CRC) using fluorouracil (5FU) and folinic acid (FA) has been proven effective and the QUASAR trial showed that a weekly administration schedule was as effective as, and less toxic than, the same daily doses delivered over 5 days every 4 weeks (the “Mayo regimen”). However the 5FU dose used (370 mg/m2) was lower than in some trials and a higher 5FU dose was considered desirable if tolerated. We therefore implemented a weekly regimen using 5FU 425 mg/m2 and DL-folinic acid 50mg in 2001 and retrospectively evaluated its efficacy and tolerability. Methods: Patients with non-metastatic CRC at assessment by medical oncologists in this institution between 2001 and 2004 were included in the analysis. Data was gathered on patient characteristics, duration of adjuvant chemotherapy and survival. Actuarial survival was calculated using the Kaplan-Meier method. Results: 417 patients (pts) were seen: 181 females, 236 males; median age 67 yrs (24–89); 291 with colon cancer, 126 with rectal cancer; 1 stage 1; 100 stage 2, 316 stage 3. Median follow-up was 6.2 years. 210 pts with colon cancer received adjuvant weekly 5FU/FA (32 stage 2, 178 stage 3) as did 58 pts with rectal cancer (50 of whom also received concurrent chemoradiation). 75% of pts with colon cancer received all 30 planned doses and 59% of rectal cancer pts received all 20 planned doses. 3 year survival for all pts treated with this regimen was 83.0% and for the subgroups with colon and rectal cancer it was 82.4% and 84.5% respectively. For stage 2 and 3 colon cancer pts treated with this regimen 3 year survival was 87.9% and 76.0% respectively; for stage III rectal cancer pts it was 84.1%. Conclusions: These outcomes compare favorably on indirect comparison with results from the QUASAR trial (which reported 3 year survival of 70.6%) and suggest that using a higher 5FU dose in this regimen is tolerable and may be advantageous. No significant financial relationships to disclose.
Preoperative transcatheter arterial chemoembolization (TACE) and chemotherapy for hepatic colorectal metastases: Impact on hepatic histology and postoperative outcome
Authors: Lu Q. , Zhao A. , Shen L. 
Published: August 2020

e15090 Background: The objective was to evaluate the effect of preoperative administration of TACE and chemotherapy on hepatic injury and on postoperative outcome in patients with colorectal liver metastases (CRM) Methods: Seventy seven patients underwent hepatic resection for CRM between January 1999 and December 2007 were evaluated. Pathologic review of the non-tumorous liver was performed using established criteria for steatosis, steatohepatitis, and sinusoidal dilation. The effect of two different treatment and hepatotoxicity on postoperative outcome was analyzed. Results: 40 patients (51.9%) received no preoperative treatment, where 27 patients (35.0%) received preoperative chemotherapy, 10 patients (12.9%) performed TACE before resection. The median duration of TACE group was 4.5 months (range, 1–6 months), where the median duration of chemotherapy group was 5 cycles (range, 2–9 cycles). Chemotherapy regimen consisted of oxalipaltin plus FU (29.9%), or irinotecan plus FU (5.2%). On pathologic analysis, 36 patients (46.7%) had steatosis, 24 (31.1%) had sinusoidal dilation, and 8 (10.3%) had steatohepatitis. TACE was associated with steatosis, steatohepatosis and postoperative complication, when compared with no chemotherapy (all p<0.05).Among chemotherapy group,Oxaliplatin was associated with steatohepatitis compared with no preoperative treatment (13.0% v 0%, respectively; p<0.05). Irinotecan was associated with steatohepatitis compared with no preoperative treatment (50% v 0%, respectively; p=0.0006). Patients with preoperative chemotherapy had increased steatohepatitis compared with no treatment group (18.5% v 0%, respectively, p=0.0008), the postoperative morbility rate in preoperative chemotherapy (25.9%) was double that of the no-chemotherapy (12.5%), but this difference was not statistically significant (p=0.20). Preoperative chemotherapy was also not associated with 90-day mortality. Conclusions: Preoperative TACE treatment may cause pathological liver injury, and increase postoperative morbility after hepatic surgery. The standard preoperative chemotherapy regimen with Oxaliplatin or Irinotecan may increase steatohepatis. No significant financial relationships to disclose.
Association of upregulated GATA-4 transcription factor colorectal adenocarcinoma with metastatic and primary tumors
Authors: Marginean E. C. , Torlakovic G. , Neufeld H. , Torlakovic E. 
Published: August 2020

e15093 Background: GATA-4 zinc finger transcription factor is involved in regulation of cellular development, proliferation, and differentiation and is important in embryonic development of gastrointestinal tract. However, GATA-4 is not expressed in normal adult colonic mucosa. Its protein expression in colonic adenocarcinoma has not been systematically evaluated and small number of samples was previously reported as negative. Nuclear factor-B (NF-B) activation was shown to promote the growth of the colon tumors in experimental models and was correlated with tumor angiogenesis and progression in human colorectal cancer. Methods: Forty cases of colorectal adenocarcinoma were evaluated. The benign colonic mucosa and the matching metastatic tumors of the same patients were also included in the study. TMAs which included 139 samples were evaluated by immunohistochemistry and nuclear and cytoplasmic GATA-4 expression was scored (0–3+). NF-B activation was detected as nuclear reactivity for p65. Results: GATA-4 was expressed in 32% of colorectal adenocarcinoma, but not in benign colonic mucosa (p=0.0001, Chi-Square). GATA-4 was also significantly more expressed in metastatic (41%) than in primary (21%) colorectal adenocarcinoma (p<0.0001, Chi-Square). NF-B activation was not present in any of the samples of benign colonic mucosa, but it was detected in 64% adenocarcinomas (p<0.0001, Chi-Square). While there was no difference in NF-B activation between primary vs. metastatic adenocarcinoma, a strong positive association between GATA-4 expression and NF-B activation (p<0.0001, Linear-by- Linear) was found. Conclusions: GATA-4, a developmental transcription factor is not expressed by normal colonic mucosa, but is present in 1/5 of primary tumors that gave rise to distant metastases and in almost 1/2 of their respective metastases. GATA- 4 is also strongly positively associated with NF-B activation previously described to have a role in human cancer progression. GATA-4 may have a role in colorectal adenocarcinoma development and progression and it should be further evaluated in prospective studies as a putative adverse prognostic factor in colorectal adenocarcinoma. No significant financial relationships to disclose.
The role of oophorectomy for colon cancer with ovarian metastasis
Authors: Lee S. , Lee J. , Ahn H. , Park J. , Kim J. , Park K. , Lim H. , Kang W. , Kim B. , Park Y. 
Published: August 2020

e15113 Background: A recent study demonstrated that colorectal cancer with ovarian metastases were less responsive to chemotherapy compared to extraovarian metastases. Hence, the ovary may actually represent a “sanctuary” for metastatic cells from CRC. The aim of the study was to investigate the impact of oophorectomy on survival of colorectal cancer patients with ovarian metastasis. Methods: Between 1996 and 2008, 83 colorectal cancer patients underwent oophorectomy. For the historical control, 47 colorectal cancer patients without oophorectomy were included in the analysis. Survival and its associated factors were analyzed using Kaplan-Meier method, log-rank test and Cox-regression analysis. Results: The median age was younger (48 years) in the oophorectomy group when compared to the historical control (54 years) (P =.012). The proportion of synchronous metastasis was higher in the oophorectomy than the control group (57% vs 30%, respectively; P=.003). After a median follow-up duration of 60.8 months (range, 7.4 - 169.7 months), the median OS was significantly longer in the oophorectomy group (28.1 vs 21.2 months, oophorectomy vs non-oophoreectomy; P=.038). For ovary-specific survival (date of ovarian metastasis diagnosis to death), colorectal cancer patients with oophorectomy showed significantly favorable survival than the control group (20.8 vs 10.9 months, respectively; P<.001). At univariate analyses, no oophorectomy (P=.038), bilaterality of ovarian metastasis (P=0.032), the presence of extraovarian metastasis (P<0.001), elevated CEA (p<0.001), poor performance status (p=0.001), no palliative chemotherapy(p=0.001), no primary disease resection(p=0.005) were identified as significantly poor prognostic factors for overall survival. The no oophorectomy, no chemotherapy, extraovarian metastasis, elevated CEA, poor performance status retained statistical significance at multivariate level. (p=0.003, p=0.004, p=0.005, p=0.015, p=0.029, respectively). Conclusions: Based on this retrospective analysis, the oophorectomy significantly prolonged survival in colorectal cancer patients with ovarian metastases. A potential role of oophorectomy in the management of colorectal cancer should be prospectively studied. No significant financial relationships to disclose.
Use of an in vitro chemoresponse assay to define a subset of colorectal carcinomas responsive to cetuximab
Authors: Rice S. D. , Ervin P. R. , Brower S. L. 
Published: August 2020

e15127 Background: Cetuximab (Erbitux) is a chimeric monoclonal antibody that binds to the extracellular domain of the epidermal growth factor receptor. This interaction interferes with ligand binding and activation of the receptor blocking the downstream signaling of EGFR and impairing cell growth and proliferation. Cetuximab also has been shown to mediate antibody dependent cellular cytotoxicity. Thus, a singular approach to drug mechanism likely would not capture the true effects of cetuximab. Cetuximab is FDA-approved to treat head and neck cancer and colorectal carcinomas and is being evaluated for use in non-small cell lung and endometrial cancer. Due to the low population response rate of cetuximab, an integrated biomarker that can identify patients with an increased likelihood for response would be of great clinical utility. The current study describes an in vitro chemoresponse assay to predict response of primary cultures of human colorectal tumor specimens to cetuximab. Methods: The chemoresponse assay (ChemoFx) was developed using four different immortalized carcinoma cell lines (NCI-H292, NCI-H522, NCI-H1666, Calu3). The chemoresponse assay was also performed on 54 first passage primary cultures of human colorectal tumor specimens. Cell lines and specimens were treated with a 10 dose concentration range of cetuximab for 72 hours, stained with a nuclear dye, and remaining post-treatment live cells were counted. Resulting dose-response curves were analyzed. Results: Two of the examined cell lines showed response to cetuximab treatment; EC50 values for NCI-H292 and NCI-H1666 were 825nM and 13nM, respectively. NCI-H522 and Calu3 were deemed non-responsive to cetuximab. Dose-response curves of the 54 primary colorectal cultures revealed that 8% of the cultures tested were responsive to cetuximab, 22% had an intermediate response, and 70% were deemed non-responsive. These results are consistent with a reported clinical response rate of 11% for cetuximab in colorectal carcinoma patients. Conclusions: Initial results demonstrate that in vitro chemoresponse testing may be useful in predicting patient response to cetuximab. This could increase the efficacy of the current chemotherapy decision-making process for oncologists and their patients. No significant financial relationships to disclose.
New “sutureless” technique of ileostomy and colostomy
Authors: Phadke M. V. , Stocks L. H. , Phadke Y. G. 
Published: August 2020

e15132 Purpose: Purpose is to prevent infection and subsequent complications following construction of either an Ileostomy or a colostomy in an elective or emergency operation. Technique is based on delayed-primary wound healing and established principles of basic sciences. Methods: Discovered by serendipity in 1986 during an Ileostomy, procedure was used for all stomata. Stomal (proximal) end of bowel (small/large) was left obstructed with staples and brought out at proposed site of stoma. Mesenteric corner was brought above skin opening. A cone was formed by lifting anti-mesenteric corner of bowel as apex of the stoma by pulling anti-mesenteric surface of bowel. Length of the stoma was determined by thickness of the abdominal wall. Serosa was sutured circumferentially to a round opening in rectus sheath starting below the mesenteric corner leaving an arc to accommodate the mesenteric vessels. This neutralized pulling effect of peristalsis on mesenteric corner of stoma and protects mesentery under skin reducing the chances of thrombosis of mesenteric vessels. Stoma was covered in OR using an appliance with transparent pouch. Obstructed stoma prevented immediate contamination of stomal and main wounds by feces. Postoperatively, serosal surface was covered by angiogenesis, making the stomal wound refractory to infection. When peristalsis returned, bulging stoma was opened using electro-cautery as a bedside procedure. Mucosal cuff protrudes and everts on angiogenesis over a single layer of serosa. Cuff progresses with peristalsis and grafts over a bed of granulation tissue. Margins of cuff adhere with dermis of skin opening completing self-maturation of stoma. Absence of sutures reduced tissue trauma and eliminated foreign body reaction resulting in better wound healing. This new scientific technique was named “DELAYED-PRIMARY SELF-MATURATION (DPSM)”. Results: 63 Colostomies and 17 Ileostomies were performed using DPSM. Infection in stomal and/or main wound was prevented. Subsequent complications were prevented. Conclusions: DPSM prevents infection and complications associated with Ileostomy and Colostomy operations. It is technically easier and more scientific than a conventional stoma. This technique is recommended for all cases requiring end/loop, temporary/permanent types of intestinal stomas. No significant financial relationships to disclose.
Safety profile of first-line bevacizumab and chemotherapy in patients with unresected primary colorectal cancer and synchronous metastases
Authors: Mello C. , Oliveira T. B. , Paiva T. F. , Silva M. J. , Sanches S. M. , Cruz M. R. , Nicolau U. R. , Fanelli M. F. 
Published: August 2020

e15133 Background: The role of palliative resection of the primary tumour in patients who present with metastatic colorectal cancer (mCRC) is unclear. Most recently bevacizumab has been used as first line treatment for mCRC showing improvement in survival with a slight increase in the risk of bleeding and rarely gastrointestinal (GI) perforation. These side effects would cause concern in patients with unresected colorectal cancers (CRC). Methods: Retrospective analysis of twelve patients treated straightaway by chemotherapy (CT) and bevacizumab without primary tumour resection, between January 2007 and August 2008. The aim of the study was to evaluate the rate of complications related to the unresected colorectal tumour and to determine the safety of bevacizumab use in this situation. All of these patients had none or minimal symptoms related to the primary tumour. Results: Mean age 54.6 years (range 28–75), 5 males and 7 females, all patients ECOG 0. The sites of the primary lesion were the rectum in 8 patients (66.6%), the left sigmoid colon in 3 (25%), and the transverse colon in 1 (8.3%). Eight patients (66.6%) presented with rectal bleeding at diagnosis (mild). The mean interval between diagnosis and start of CT was 40,8 days (range 6–125). The total number of bevacizumab cycles was 151 (mean 12,5 cycles, range 4–37). First line CT was FOLFOX-6 in 66% and FOLFIRI in 33% of patients. Only 3 patients (25%) developed low GI bleeding, all grade 1, without bevacizumab interruption. None of them developed intestinal perforation or obstruction. Two patients (16.6%) developed grade 1 epistaxis and 1 (8.3%) grade 2 hypertension. No other complications were observed in a mean follow up of 9.3 months. Conclusions: Our data show that upfront chemotherapy with bevacizumab in patients with unresected primary CRC and synchronous metastases is safe. No major complications related to the primary tumour were observed. Although our data comes from a limited number of patients there is a lack of prospective controlled trials in the literature on this topic. Therefore, in select cases, a non-operative management of asymptomatic or minimal symptomatic mCRC could be advised, even with the use of anti-angiogenic therapy. No significant financial relationships to disclose.
Preoperative concomitant chemoradiotherapy with capecitabine in locally advanced rectal carcinoma
Authors: Larbaoui B. 
Published: August 2020

e15134 Background: Preoperative concomitant chemoradiotherapy has shown to improve local control and sphincter preservation with decreased acute toxicity compared with postoperative treatment in locally advanced rectal carcinoma. The primary endpoint of this phase II trial was pathologic tumor response. Secondary endpoint was sphincter preservation and toxicity. Methods: Inclusion criteria: rectal adenocarcinoma <12 cms from anal verge, clinical stage T3–4, adequate renal, hematological and liver function. Planned sample for this trial was 40 patients. Treatment schedule: Pelvic radiotherapy (45 Gy : 2 Gy /day ) and chemotherapy: Capecitabine 850 mg/m2 b.i.d p.o: day 1 to 14 (2weeks of treatment followed by 1 week rest period (cycle repeated every 3 weeks). Surgery with TME was performed after the end of the second cycle of chemotherapy. Adjuvant chemotherapy with 5FULV2 was administered after surgery Results: 15 patients have been recruited between January and October 2007: 12 males/3 females. Median age 40 years (range 22–70). Clinical stage (determined by CT or RMI): T3: 70% and T4: 30%. Tumor location (from anal verge): < 6 cm in 8pts, >6 cm in 7pts. Surgery (performed in 14 patients) consisted of low anterior resection in 7pts and abdominal-perineal resection in 8pts. Tumor down staging was observed in 9pts (60%), including 5pts with complete pathological response (33.3%). Main adverse effects (NCI-CTC): diarrhea G3–4: 15.2%, nausea/vomiting G3–4: 13%, Anemia G3- 4: 8.5%, neutropenia G3–4: 12.5%. Conclusions: Preliminary results show that preoperative concomitant chemoradiotherapy with Capecitabine is an effective regimen with an acceptable safety profile for locally advanced rectal cancer, leading to a high probability of tumor downstaging. No significant financial relationships to disclose.
Rectal prognostic index (RPI) to predict outcome of patients with locally advanced rectal cancer (LARC) treated with preoperative chemo-radiation (preop-CRT)
Authors: Piperdi M. , Velagapudi V. , Ayata G. , Simons J. , Tseng J. F. , Piperdi B. 
Published: August 2020

e15139 Background: Preop-CRT followed by surgical resection is the standard for LARC. LARC patients (pts) treated with preop-CRT have 60–70% 5-year survival. Several pathologic features including T stage (yT), lymph node (N) ratio (# of positive N (Np) / # of N examined (Ne)) and tumor regression grade (TRG) have been shown to be independent prognostic markers. We developed a prognostic score to determine pts with low risk of recurrence after preop-CRT. Methods: Our sample set consists of 20 pts treated on in house trial of preop-CRT with paclitaxel. All pts had R0 resections and received 4 months of 5-FU based adjuvant chemotherapy. All pathology slides were independently reviewed by GI pathologist. RPI scale of -4 to 14 was developed based on the formula: RPI = T (1–4) + (Np/Ne x 10) - TRG (0–4). The low, intermediate and high risk for recurrence were predefined as RPI (≤1), (>1 and <5), (≥5). Results: Between 1999–2003, 20 pts were treated on the trial and had R0 resection. The data is summarized in table 1 . The 5yr disease-free (DFS) and overall survival (OS) rate of all pts were 62 and 77%. Two pts (10%) achieved complete pathological response. Low, intermediate and high risk RPI was noted in 50, 35, and 15 % of pts. The 5yr DFS and OS for low, intermediate and high risk groups were 75, 42, 33 % and 86, 71 and 33% respectively.Conclusions: RPI can accurately predict a subset of pts with low risk of recurrence after preop-CRT. Majority of pts in this cohort have low risk RPI and have a favorable outcome (5yr survival rate of 86%). RPI could be very helpful in designing future trials tailoring adjuvant chemotherapy based on risk of recurrence. We are validating this data with a larger, independent group of LARC patients from our cancer registry (N=30) and this data will be available for presentation. Since RPI only requires the final pathology after CRT, it should be readily reproducible in future prospective studies across different institutions. [Table: see text] No significant financial relationships to disclose.
Inter- and intra-criteria reproducibility of RECIST ver 1.1 and modified EASL (European Association for the Study of the Liver) tumor response criteria to transarterial chemoembolization (TACE) for hepatocellular carcinoma (HCC): From the dataset of JIVROSG (Japan Interventional Radiology in Oncology Study Group) 0401
Authors: Sato Y. , Watanabe H. , Sone M. , Onaya H. , Sakamoto N. , Osuga K. , Takahashi M. , Yamamoto S. , Arai Y. 
Published: August 2020

e15501 Background: In spite of systemic response evaluation criteria, RECIST is widely used for evaluating the tumor response (TR) in local therapy. As a result, there are double standard criteria (RECIST ver 1.1 and modified EASL) in the evaluation for TR of HCC treated by TACE. Tumor size is evaluated by measurement of the entire lesion including necrotic part in RECIST ver 1.1 (EJC 2009;45:228), whereas the only contrast-enhanced part on radiological images is measured when the modified EASL are used (JNCI 2008;100:698). Both criteria adopt the unidimensional measurement. Methods: This is a study of the radiological findings of patients who underwent TACE for multiple HCCs in the JIVORSG 0401 study. The subjects were 65 lesions in 21 patients treated by pan- hepatic TACE using cisplatin and gelatin particles without mixing iodized-oil. Five radiologists measured independently each lesion twice, therefore 130 measurements were performed per radiologist according to the 2 criteria (RECIST ver 1.1 and modified EASL). To compare the inter- and intra- criteria reproducibility of TR for each lesion, CR rate, response rate, proportion of agreement, and the kappa statistics for response categories were calculated. Results: Results are shown in the table. CR rate and response rate obtained using the modified EASL were higher than those obtained using RECIST ver 1.1. The inter-criteria reproducibility between RECIST ver 1.1 and modified EASL were poor. The intra-criteria reproducibility of RECIST ver 1.1 indicated substantial agreement, while that of modified EASL indicated almost perfect agreement. Conclusions: For a precise interpretation of the tumor response in clinical trials of TACE for HCCs, appropriate attention must be paid to the criteria employed for the evaluation. [Table: see text] No significant financial relationships to disclose.