bluuebunny/crossref_metadata_2025_split huggingface dataset:
O-glicosylation alterations of proteins in gastric carcinoma.
Authors: Santos Sousa H. , Bouca-Machado T. , Lima-da-Costa E. , Pinto-de-Sousa J. , Gomes C. , Reis C. A. , David L. , Costa-Maia J. 
Published: February 2017

62 Background: The expression of immature forms of carbohydrates could help to better understand the biological behavior of gastric cancer. Methods: From a universe of 50 patients with gastric or gastroesophageal junction carcinoma submitted to surgical treatment between January and October 2009, in our department, 36 out of 38 carcinomas ressected during this period, were selected for a tumor tissue immunohistochemical study of the simple mucin-type carbohydrate antigens (Tn, STn, T and ST) and the Lewis carbohydrate antigens (SLea and SLex). Several clinico-pathological parameters were evaluated according to the expression pattern of the antigens studied. Results: The ressected gastric carcinomas presented a high incidence of tissue expression of the simple mucin-type and the Lewis carbohydrate antigens, with all cases presenting expression of at least 2 of the antigens and two thirds the expression of 4 or 5. The correlation between the simple mucin-type carbohydrate antigens was high, just as the same as with the Lewis carbohydrate antigens. The analysis of the clinico-pathological profile of gastric carcinomas according to the expression of these antigens revealed the following associations: Tn with venous invasion and perineural invasion; STn with tumor location and macroscopic form; T with age, gender, tumor dimensions and location; ST with macroscopic form and WHO classification; SLea and SLex with the tumor dimensions. Staging of the tumors also revealed associations with the expressions of these antigens: Tn with serosal invasion, lymph node metastases and stage; STn with lymph node ratio; SLea with serosal invasion and lymph node metastases; SLex with depth wall invasion, lymph node metastases and stage. The antigens T e ST did not reveal differences in the expression pattern according to staging. Conclusions: O-glicosylation alterations of proteins are related with gastric carcinoma, not only their incidence is high but they can also be linked with various clinico-pathological characteristics. The knowledge obtained from this study might serve as a starting point for future investigations taking into account the identification of new biomarkers based on glicosylation alterations of proteins. No significant financial relationships to disclose.
Gemcitabine and capecitabine as third-line treatment in patients with metastatic colorectal cancer after failure of irinotecan and oxaliplatin.
Authors: Qiu M. , Bi F. , Liu J. , Li Q. , Yi C. 
Published: February 2017

620 Background: There is no standard chemotherapeutic regimen for patients with advanced colorectal cancer (CRC) progressing after combination regimens including irinotecan and oxaliplatin and having good performance status. 5-FU and gemcitabine are synergistic in preclinical studies of colon cancer cells. And gemcitabine also increases intracellular release of 5-FU from capecitabine. The aim of this study is to evaluate the efficacy and tolerance of the gemcitabine/capecitabine combination as third-line treatment for patients with advanced colorectal cancer. Methods: Between May 2007 and September 2009, the data on 12 patients with metastatic colorectal cancer after failure of irinotecan- and oxaliplatin-containing regimens reviewed retrospectively. The median patient age was 54.0 years (range 37-77). The ECOG performance status was 0, 1 or 2. All patients has 2 or more previous chemotherapy. Patients received GemCap regimen (oral capecitabine 1,000 mg/m2 twice daily on days 1 to 14 plus Gem 1,000 mg/m2 on days 1 and 8 every 3 weeks). Eleven patients were evaluable for the response and all patients were evaluable for toxicity. Results: No partial response was achieved and disease stabilization in 4 (36.4.3%) cases. Median progression-free survival and median overall survival were 9.1 weeks (range 3.0-18.0) and 22.3 weeks (range 10.5- 53.0). Four patients with disease stabilization had longer median progression-free survival than those with disease progression (13 weeks vs. 6.2 weeks). No toxic deaths occurred. Grade 3 toxicities were thrombocytopenia (in 2 patients), neutropenia (in 2 patients) and mucositis (in 1 patient), hand-foot syndrome (in 1 patient) and GI toxicity (in 2 patients). Conclusions: The combination of gemcitabine and capecitabine was found to be a safe palliative regimen for heavily pretreated patients with metastatic CRC. Despite no patients had radiologic response, patients with disease stabilization achieved better progression-free survival. This regimen seems to be potentially effective regimen in the treatment of CRC. No significant financial relationships to disclose.
Impact of FOLFOXIRI plus bevacizumab on resectability and survival in patients with initially unresectable liver metastases from colorectal cancer.
Authors: Shimada M. , Nishioka M. , Hanaoka J. , Mori H. , Ikemoto T. , Imura S. , Morine Y. , Utsunomiya T. 
Published: February 2017

621 Background: Prognosis in patients with unresectable liver metastases from colorectal cancer is known to be very poor. However, thanks to progress of chemotherapy including molecular-target agents, “conversion” (from unresectable to resectable) has been sometimes seen. The aim of this preliminary study is to clarify the impact of FOLFOXIRI plus bevacizumab (Bev) on conversion and prognosis in patients with initially unresectable liver metastases from colorectal cancer. Methods: Seven patients with initially unresectable liver metastases from colorectal cancer, who received FOLFOXIRI (LOHP 85mg/m2 D1, CPT-11 150mg/m2 D1, LV 200mg/m2 D1, and 5FU 2,400mg/m2 infusion over 46 hours, D1) plus Bev 5mg/kg bolus every 2 weeks, were included in this study. Resectability, disease-free survival (DFS), and overall survival (OS) after hepatic resection were investigated in detail. In addition, completeness and adverse effects were examined in this regimen. Results: All 7 patients tolerated the regimen well, and no adverse effect of grade 3-4 was observed. Five out of 7 patients (71%) became resectable (conversion), except for 2 with multiple lung metastases and bone metastasis prior to chemotherapy. Our historical conversion rates were, 0% (0/7) in 5FU/LV regimen from 1994 to 2003, 25% (7/27) other regimens such as FOLFIRI and FOLFOX except for FOLFOXIRI plus Bev from 2004. In 5 patients who became resectable, CR was not observed, however, all had PR after 6 cycles of chemotherapy (RR 100%). All 5 patients could undergo curative (R0) hepatic resection, furthermore, all had pathological major response (grade 2). Follow-up period ranged from 8 to 18 months, with a median period of 14 months, and 2 patients relapsed (lung recurrence and peritoneal dissemination), and one died of lung metastases (1.5-year OS and DFS are 80 % and 60%). Conclusions: Our preliminary data suggested the feasibility of this new therapeutic combination in patients with initially unresectable liver metastases from colorectal cancer, and a high conversion rate and better prognosis. [Table: see text]
Maintenance treatment with cetuximab in a series of patients treated with standard chemotherapy and cetuximab in metastatic colorectal cancer.
Authors: Quintero-Aldana G. , Varela S. , Campos B. , Vazquez-Estevez S. , Maseda O. , Santos E. , Iglesias C. , Torres I. , Lancho A. , Mel J. 
Published: February 2017

624 Background: New strategies are needed to improve outcomes and reduced toxicities of currently treatments for patients with advanced colorectal cancer. Nowadays maintaining treatment until disease progression is the standard option for these patients. Cetuximab is a recombinant humanized monoclonal antibody that neutralizes epidermal growth factor receptor and it has shown benefit not only in combination with standard chemotherapy in first- and second-line treatment or as a single agent in progression to standard chemotherapy in KRAS wild-type metastatic colorectal cancer (mCRC). Methods: This data describes patients who received standard chemotherapy with cetuximab every two weeks. For patients with response or stable disease, cetuximab was continued until disease progression or unacceptable toxicity. Results: Twelve patients are reported, nine were male (75%). The median age was 62 years (range, 46 to 78 years). All patients had stage IV, and liver was the most common location (75%). The majority of patients (75%) received FOLFOX VI as a first-line treatment in combination with cetuximab; only two patients were treated with FOLFIRI. Cetuximab was maintained after the first line of treatment in the 75% of patients. The median of cycles of chemotherapy and cetuximab was 12. Best response achieved in this setting was complete response (58.3%, 7/12). Median of monotherapy with cetuximab treatment was 7.5 cycles (range 3 to 12). At the moment of this analysis seven of twelve patients continued with the maintenance. In the rest of patients the treatment was followed until progression (33%, 3/12). No grade 3-4 toxicities were seen during maintenance cetuximab. The most common adverse effect during maintenance was cutaneous toxicity but the majority of patients had minor toxicity (50% grade 1). Conclusions: Cetuximab has significant antitumor activity not only as a single agent or in combination with standard chemotherapy but may also when it is used as maintenance therapy after a complete or partial response to first or second line based chemotherapy in mCRC. Maintenance cetuximab is feasible, safe, and worthy of future study in advanced colorectal cancer. No significant financial relationships to disclose.
Randomized controlled trial comparing Billroth-I and Roux-en-Y reconstruction in distal gastrectomy for gastric cancer.
Authors: Fujita J. , Imamura H. , Takiguchi S. , Fujitani K. , Miyashiro I. , Kobayashi K. , Kimura Y. , Ebisui C. , Matsuyama J. , Doki Y. 
Published: February 2017

65 Background: In distal subtotal gastrectomy for gastric cancer, Billroth-I (B-I) reconstruction has been performed predominantly in Japan, while increasing number of surgeons chose Roux-en-Y (R-Y) reconstruction recently. To evaluate the safety and superiority of R-Y we conducted a multi-institutional prospective randomized controlled trial. Methods: Gastric cancer patients who underwent distal gastrectomy were randomized to B-I or R-Y intraoperatively. The primary endpoint was the ratio of body weight loss 1 year after surgery, the secondary endpoints were the incidence of delayed gastric emptying (DGE) and postoperative morbidity. Results: Between Aug 2005 and Dec 2008, a total of 332 patients were enrolled and 163 patients were assigned to B-I and 169 patients to R- Y. The patient's characteristics were well balanced between the two groups. The operation time was significantly longer in R-Y than B-I (median 180 min in B-I vs 214 min in R-Y, p < 0.0001). The postoperative morbidity was 14 patients (8.6%) in B-I and 23 (13.6%) in R-Y (p = 0.14), the incidence of DGE was 7 (4.3%) in B-I vs 16 (9.5%) in R-Y (p = 0.06), and the hospital stay after surgery was 14.1days in B-I vs 16.4 days in R-Y (p = 0.02). There was no hospital death in the two groups. The body weight loss at 1 year after surgery compared to preoperation was -5.4kg (-9.1%) in B-I vs -6.2kg (-9.8%) in R-Y (p = 0.11). Conclusions: The advantage of R- Y reconstruction compared to B-I was not proved in terms of postoperative morbidity either the body weight loss 1 year after surgery. No significant financial relationships to disclose.
Comparison of definitive chemoradiotherapy and esophagectomy for stage I esophageal squamous cell carcinoma.
Authors: Yamamoto S. , Ishihara R. , Motoori M. , Kawaguchi Y. , Takeuchi Y. , Higashino K. , Uedou N. , Yano M. , Nakamura S. , Iishi H. 
Published: February 2017

67 Background: Chemoradiotherapy (CRT) of esophageal cancer has been proposed as an alternative to esophagectomy given the favourable survival rate and mild toxicity. However, no comparative study is reported between esophagectomy and CRT in stage I esophageal squamous cell carcinoma. Methods: A total of 54 patients treated by definitive CRT and 116 patients treated by esophagectomy at out institution between February 1995 and August 2008 were included in the analysis. Overall survival and recurrence rates were evaluated. Results: Of 170 patients who had clinical stage I esophageal squamous cell carcinoma and treated by definitive CRT or esophagectomy, 169 patients (99%) were completely followed up. CRT mainly consisted of two cycles of cisplatin and fluorouracil with concurrent radiotherapy of 60 Gy in 30 fractions. Median (range) observation period was 67 (10–171) months in SURG group and 30 (4–77) months in CRT group. In CRT group grade 3 or grade 4 hematological or non-hematological adverse effects were seen in 24 (44.4%) patients. 1-year and 3-year overall survival rates were 97.4% and 85.5% in the SURG group and 98.1% and 88.7% in the CRT group (P = 0.78). By using Cox proportional hazards modelling, overall survival was comparable between the 2 groups after adjusting for age, sex, and size of cancer. Hazard ratio of CRT for overall survival was 0.95 (95% CI: 0.37-2.47). The incidence or local recurrence including metachronous esophageal cancer was significantly higher in the CRT group than the SURG group (P < 0.0001). All recurrences were intramucosal carcinomas and all of them were cured after the salvage treatment mainly using endoscopy. Conclusions: Overall survival rate of CRT was comparable with esophagectomy despite high local recurrence rate. Local recurrent carcinoma is endoscopically treatable in all patients without influence on overall survival. CRT appears to be a reasonable alternative to esophagectomy in patients with stage I esophageal cancer. No significant financial relationships to disclose.
Clinicopathologic features and treatment outcomes of patients (pts) with HER2-positive (pos) adenocarcinomas (ACA) of the esophagus (E) and gastroesophageal junction (GEJ).
Authors: Phillips B. E. , Tubbs R. R. , Rice T. W. , Rybicki L. A. , Plesec T. , Rodriguez C. P. , Videtic G. M. , Saxton J. P. , Ives D. I. , Adelstein D. J. 
Published: February 2017

71 Background: HER2 is overexpressed in 21% of gastric and 33% of GEJ ACA, and pts with advanced HER2pos disease survive longer after chemotherapy and trastuzumab than after chemotherapy alone. This retrospective analysis was undertaken to better define the clinicopathologic features and treatment outcomes in pts with HER2pos ACA of the E and GEJ. Methods: Between 11/99 and 7/06, 156 pts with T3 or N1 or M1a ACA of the E or GEJ were entered on one of two Cleveland Clinic trials. Induction chemoradiation, with 96 hour infusions of cisplatin (20 mg/m2/d) and fluorouracil (1,000 mg/m2/d) beginning on day 1 of radiation (30 Gy at 1.5 Gy bid), was followed by surgery and identical post-operative chemoradiation. 76 pts also received 2 years of oral gefitinib. Pathology was tested for HER2 by immunohistochemistry using PATHWAY anti-HER-2/neu 4B5 rabbit monoclonal primary antibody (Ventana, Tucson AZ) and in situ hybridization with the inform HER2 dual ISH DNA probe cocktail assay (Ventana, Tucson AZ). Baseline characteristics and outcomes after treatment of the HER2pos and negative (neg) pts were compared. Results: Of the 156 pts, 136 pts had either initial biopsy or resection specimen available. HER2 was deemed pos if either was pos. Discordance between biopsy and resection was found in only 6/65 pts (9%). 32 pts (24%) were HER2pos; 27% of 82 pts with GEJ, and 19% of 54 pts with E tumors (p=0.31). There was no statistical difference between HER2pos and neg pts in age, gender, race, stage, or pathological response. The only difference was that HER2neg tumors were more likely poorly differentiated (p<0.001). Locoregional control, distant metastatic control, freedom from recurrence and overall survival were statistically the same in both the entire cohort, and in the gefitinib-treated subset. Conclusions: Except for tumor differentiation, HER2pos and neg pts with ACA of the E and GEJ do not differ in clinicopathologic characteristics and treatment outcomes. Given the demonstrated benefit of trastuzumab in HER2pos gastric cancer and the similar incidence of HER2 overexpression in the E and GEJ, further evaluation of HER2 directed therapy in this disease seems indicated. No significant financial relationships to disclose.
Outcomes after complete pathologic response (pCR) to neoadjuvant treatment for gastric and gastroesophageal junction (GEJ) adenocarcinoma.
Authors: Fields R. C. , Strong V. E. , Gonen M. , Brennan M. F. , Coit D. G. , Shah M. A. 
Published: February 2017

75 Background: pCR is rare following neoadjuvant chemotherapy (NAChemo) ± radiation therapy (RT) for locally advanced gastric/GEJ adenocarcinoma. Recurrence and survival after pCR are not well characterized. Methods: A retrospective review of a prospective database identified patients with pCR after NAChemo ± RT for gastric/GEJ adenocarcinoma. Recurrence, overall survival (OS), recurrence free survival (RFS), and disease specific survival (DSS) were analyzed. Results: From 1985 – 2010, 2,676 patients underwent resection for gastric/GEJ adenocarcinoma, and 714 (27%) received NAChemo ± RT. There were 102 (14%) patients with a pCR. 60 patients (8%) had adequate pre-operative staging and follow-up and comprised the study group: 47 (78%) GEJ and 13 (22%) gastric tumors. 51 (85%) received neoadjuvant RT. With 46 month median follow-up, 14 patients (23%; 12 GEJ, 2 gastric) developed a recurrence (Table); 13 of 14 (93%) occurred within 2 years of follow-up with a median time to recurrence of 13.5 months. 5 (42%) recurred in the CNS. Median time to death after recurrence was 11.5 months. 5-year OS, RFS, and DSS were 56%, 70%, and 65%, respectively. Conclusions: pCR occurs in less than 15% of cases after neoadjuvant therapy for gastric and GEJ adenocarcinoma. Despite a pCR, there is a significant risk of recurrence and cancer-specific death during follow-up. As CNS recurrence is more prevalent in this group of patients, whole brain imaging should be considered. [Table: see text] No significant financial relationships to disclose.
Room for improvement? The adoption of multimodal esophageal cancer care in the United States.
Authors: Merkow R. P. , Bilimoria K. Y. , McCarter M. , Stewart A. , Chow W. B. , Williams R. , Ko C. Y. , Bentrem D. J. 
Published: February 2017

78 Background: Consensus guidelines recommend neoadjuvant chemo- or chemoradiation therapy as the preferred treatment for locally advanced esophageal adenocarcinoma; however, it is unknown if this recommendation has been widely adopted in the U.S. Our objective was to examine esophageal cancer multimodal therapy and identify factors associated with the use of neoadjuvant therapy. Methods: From the National Cancer Data Base, patients with middle third, lower third and GE junction (GEJ) adenocarcinomas were identified. Patients who were clinical stage I-III and underwent surgical resection were included. Separate logistic regression models were developed to identify predictors of neoadjuvant therapy utilization and outcomes. Results: From 1998 to 2007, 8,051 patients underwent surgical resection for esophageal cancer: 16.3% stage I, 45.0% stage II and 38.7% stage III. For stage II/III tumors, neoadjuvant use increased (49.0% to 77.8%, p<0.001). After adjustment, factors associated with underuse of neoadjuvant therapy in stage II/III patients were older age, Black or Hispanic ethnicity, more severe comorbidities, tumor location (GEJ and middle vs. lower third), tumor size ≥ 2cm, stage II (vs. III) and geographic region. Stage II/III patients not receiving neoadjuvant had an over two fold increased risk of positive lymph nodes (OR 2.14. 95% CI 1.79 – 2.55, p<0.001). In addition, the positive surgical margin rate increased almost three fold (OR 2.80 95% CI 2.17-3.62, p<0.001) but 30-day postoperative mortality risk was not significantly affected (OR 1.50 95% CI 0.94-2.39; p=0.090). For stage I patients, neoadjuvant therapy decreased over time (38.0% to 11.4%, p<0.001). The overuse of neoadjuvant therapy was associated with higher tumor grade, larger tumor size, and low surgical case volume (all p<0.05). Conclusions: The adoption of neoadjuvant therapy has increased in the past decade; however, opportunity exists to improve guideline treatment for locally advanced esophageal cancer. Registry-based feedback to individual hospitals, such as benchmark comparison tools, could help institutions provide care in concordance with national guidelines. No significant financial relationships to disclose.
Randomized phase II study of nimotuzumab, an anti-EGFR antibody, plus irinotecan in patients with 5-fluorouracil–based regimen-refractory advanced or recurrent gastric cancer in Korea and Japan: Preliminary results.
Authors: Kim Y. H. , Sasaki Y. , Lee K. H. , Rha S. Y. , Park S. , Boku N. , Komatsu Y. , Kim T. , Kim S. , Sakata Y. 
Published: February 2017

87 Background: Nimotuzumab is a humanized IgG1 anti-EGFR monoclonal antibody. In previous studies, nimotuzumab has demonstrated efficacy associated with an absence of severe skin toxicity, commonly caused by other EGFR-targeting therapies. Methods: This is a Korea and Japan collaborative, multi-center, randomized, open-label study of nimotuzumab (400 mg, IV q1 week) plus irinotecan (150 mg/m2 IV q2 weeks) (N+I) versus irinotecan (I) in patients with advanced or metastatic gastric cancer refractory to 5-fluorouracil-based regimen. The primary endpoint was PFS with an external review and the secondary endpoints included safety, ORR, OS, PK, and a biomarker. Results: Eighty-two eligible patients (ECOG PS 0-1, one prior regimen) were treated with N+I (n = 40) or I (n = 42). Baseline characteristics were balanced between both arms. Archival tumor tissues collected from 48 patients (N+I arm: 26, I arm: 22) were analyzed for EGFR and K-ras. EGFR status, 0/1+/2+/3+, examined by immunohistochemistry was 44%/25%/13%/17%, respectively. Two patients in N+I arm had a K-ras mutation in codon 12 or 13. The efficacy analysis was conducted 6 months after completion of randomization with median follow-up period of 197 days. Median PFS was 73.0 days in N+I arm compared with 85.0 days in I arm (HR 0.860; 95% CI, 0.516, 1.435). MST was 293.0 days in N+I arm compared with 227.0 days in I arm (HR 0.717; 95% CI, 0.420, 1.224). In the sub-analysis, the hazard ratio in PFS for patients with EGFR +1/2+/3+ was 0.463 (95%CI, 0.177, 1.212) and that of EGFR 2+/3+ was 0.341 (95% CI, 0.080, 1.457) and the hazard ratio in OS was 0.584 (95% CI, 0.242, 1.409) and 0.295 (95% CI, 0.077, 1.129), respectively. The incidence of adverse events was similar between both arms. No adverse events of grade 3 skin rash or grade 3 infusion-related reaction were reported. Conclusions: These results didn't demonstrate clear benefit at this sample size. However, EGFR-positive patients treated nimotuzumab showed a potential improvement of PFS and OS. This study supports the selection of gastric cancer patients by molecular status for future study of nimotuzumab. [Table: see text]