bluuebunny/crossref_metadata_2025_split huggingface dataset:
Post neoadjuvant chemo-radiation positive anterior circumferential resection margin in carcinoma rectum: Extended resection of rectum versus total pelvic exenteration—Results from a single centre retrospective study.
Authors: Verma Kamlesh , Engineer Reena , Ostwal Vikas S. , Kumar Suman , Arya Supreeta , DeSouza Ashwin , Saklani Avanish 
Published: September 2018

e15156 Background: Positive circumferential resection margin has been shown to be powerful predictor of poor prognosis in rectal CA. Radiologically positive anterior CRM (PACRM) after NACT+RT leads to either resection of involved organ alone ie.Extended resection of rectum (ERR) or Total pelvic exenteration (TPE). Purpose of this study is to compare recurrence rate and survival of patients undergoing ERR or TPE for PACRM after NACT+RT. Methods: Retrospective study of patients operated for rectal CA from January 2013 to December 2014. Results: Out of 237 patients with non-metastatic CA rectum, 51 patients (21.5%) had PACRM. After NACT+RT, 22 patients (43.1%) developed systemic metastases, 7 patients (13.8%) were downsized and underwent extra-mesorectal resection (AR/APR), remaining 22 patients (43.1%) had persistent PACRM. 13 patients with PACRM underwent ERR whereas 9 patients underwent TPE. Median duration of hospital stay in TPE group was 13 days (10 - 26) whereas it was 7 days (5 – 21) in ERR group. Negative pathological CRM was achieved in all TPE and 92.3% of ERR patients. After median follow-up of 31.6 months, 5 patients with TPE (55.6%) and 4 patients with ERR (30.7%) developed systemic recurrence. None of the TPE patient, whereas 3 patients with ERR (23.1%) developed local recurrence. Median D.F.S. was 12.3 months in TPE and 18.9 months in ERR whereas mean O.S. was 36.2 and 32.8 respectively. Conclusions: Due to lack of significant difference in O.S./ D.F.S. and low post-operative complication and duration of hospital stay, ERR can be considered acceptable alternative to TPE.
Long-term experience with oral fluoropyrimidines and oxaliplatin-based long-course chemoradiotherapy in locally advanced rectal cancer patients.
Authors: Diaz Beveridge Robert , Akhoundova Dilara , Bruixola Gema , Mendez Juan Antonio , Medina Maria Eugenia , Garcia Esther , Torres Alba , Navarro Edwin , Melian Marcos , Gimenez Alejandra , Segura Angel , Aparicio Jorge 
Published: September 2018

e15159 Background: Neoadjuvant radiotherapy (RT) previous to surgery (S), both as short-course RT (SCRT) and as long-course RT with 5-FU-based chemotherapy (LCRCT), is used in locally advanced rectal cancer (LARC), with consistent benefits in the local relapse (LR) risk. However, survival benefits have been elusive to find, especially with the use of total mesorectal excision (TME). Concerns about over-treating patients (pts) and long-term side effects have also cast more doubts in a blanket approach of treating all pts with neoadjuvant RT, especially with LCRCT. Methods: Retrospective review of cT3-T4 and/or N+ rectal cancer pts (1999-2014) treated with LCRCT and oral 5-FU and oxaliplatin (65% of pts), followed by TME and 5-FU-based CT. Clinical, radiological and pathological prognostic factors for LR, distant metastases (DM), disease-free survival (DFS) and overall survival (OS) are shown. Results: 203 pts. 98.5% proceeded to S; TME done in 89.7%. Downstaging rate: 70.4% (mainly N staging); pathological complete responses: 14.9%. LR and DM rate was 8.3% and 27%. TNM pathological data (ypTN) were better prognostic factors than tumour regression grades. Prognostic factors (multivariate): circumferential margin (CRM) and perineural invasion. No benefit seen with the addition of oxaliplatin. Compliance to adjuvant CT was poor; < 50% received the full dose. 5- and 10-year DFS and OS: 71.4% and 54.9% and 75.4% and 62.4%. Elderly pts had a worse OS, due to higher unexpected toxicity and lower treatment compliance. Mucinous tumours showed a poor response to LCRCT. Prognostic factors (multivariate) for OS and DFS: older age, CRM invasion, an unsuccessful TME and a heavy lymph node burden. Conclusions: The identification of pts with a low risk of LR where RT could be avoided is based on the premise of an exquisite imaging staging and a surgical team specialized in TME. A free CRM and a successful TME are pivotal for success. Clinical lymph node staging is problematic. The role of adjuvant CT remains undefined, and compliance rates are poor. Neoadjuvant CT is an option, especially if there is a high risk of DM. Better tolerated options, such as SCRT, should be used in elderly or frail pts.
Clinical lymph node staging by imaging in colorectal cancer: A flip of the coin?
Authors: Brouwer Nelleke Pietronella Maria , Stijns Rutger Carel Hubert , Valery Lemmens , Nagtegaal Iris D. , Beets-Tan Regina GH , FÃ¼tterer Jurgen , Verhoeven Rob H.A. , de Wilt Johannes H.W. 
Published: September 2018

e15160 Background: Clinical lymph node staging by MRI and CT is important in stratification for neoadjuvant therapy in colorectal cancer. Overstaging may result in unnecessary neoadjuvant therapy, but understaging may refrain patients from adequate preoperative treatment. This study aims to provide insight in current daily practice in clinical lymph node staging in CRC in the Netherlands. Methods: All patients with primary CRC, diagnosed between 2003-2014, who underwent lymph node dissection were selected from the nationwide population-based Netherlands Cancer Registry (n=100,211). Trends in patient- and tumor-characteristics, and lymph node staging were analyzed. For the years 2011-2014, sensitivity, specificity, positive (PPV) and negative predictive value (NPV) were calculated for clinical lymph node staging, with histology as the gold standard. Only patients without preoperative treatment were analyzed. Since prospective studies have shown that 5x5 Gy radiotherapy (RT) followed by total mesorectal excision within 10 days does not lead to nodal downstaging, an additional analysis was performed in this group. Results: The proportion clinically positive lymph nodes increased significantly between 2003-2014; from 7% to 22% for colon cancer and from 7% to 53% for rectal cancer. The proportion histological positive lymph nodes remained fairly stable over time (±35% colon, ±33% rectum). During 2011-2014, clinical lymph node staging was available in the registry in 86% of colon cancer patients, 92% of rectal cancer patients without neoadjuvant treatment and 95% of rectal cancer patients with 5x5 Gy RT. The parameters based on data from this period are presented in table 1. Conclusions: With a sensitivity and PPV of approximately 50%, clinical lymph node staging is about as accurate as flipping a coin. This leads to overtreatment in patients with rectal cancer with neoadjuvant RT. Acceptable specificity and NPV limit the risk of undertreatment. [Table: see text]
Colorectal cancer with mucinous component compared to clinicopathological and molecular features as mucinous adenocarcinoma.
Authors: Yang Liu , Cai Yue , Zhang Jianwei , Hu Huabin , Wenjing Wang , Wu Zehua , Deng Ru , Deng Yanhong 
Published: September 2018

e15166 Background: CRC can be divided into 3 groups: regular adenocarcinoma (RA), mucinous adenocarcinoma (MA), and adenocarcinoma with mucinous component (MC, mucin formation <50 % ). MA is distinct from RA, however, little is known about MC. We aimed to compare the clinicopathological and genetic features of 3 groups. Methods: A retrospective chort of consecutive CRC patients with available gene status was enrolled. KRAS,NRAS,BRAF,PIK3CA gene, MSI(IHC method) status were analyzed. Results: A total of 1454 patients were enrolled, including 1179 RA, 106 MA and 169 MC. Similar to MA, MC patients were younger, tended in proximal colon, had more advanced T stage ,higher nodal and peritoneal metastasis compared to RA. MSI-H were more occurred in MA and MC than RA (18.9%, 15.1% vs.3.9%). MC and MA had identical mutation frequency.They had higher KRAS (62.1%,62.3% vs.41.4%), BRAF(10.1%,9.4% vs.1.9%) and PIK3CA(21.3%,21.7% vs.9.4%) mutation than RA. Among MA or MC patients, almost 80% had at least one mutation, 17% had double mutation,and the mutation rates between left and right colon was similar, which is distinguish from RA. Conclusions: MC has comparable patholgical and molecular features as MA, which is distinct from RA. We should consider mucinous histology and the genetic features into future clinical practice. [Table: see text]
Association of CD8+/FOXP3+ ratio and PD-L1 expression with survival in pT3N0M0 stage esophageal squamous cell cancer.
Authors: Zhu Yingming , Li Minghuan , Yu Jinming 
Published: September 2018

e15517 Background: Data describing relationships between the tumor immune microenvironment and patient outcome are limited for esophageal squamous cell cancer (ESCC). Methods: The present study investigated the prognostic values of programmed death-ligand 1 (PD-L1) expression and CD8+ or forkhead box protein 3+ (FOXP3+) tumor-infiltrating lymphocytes (TILs) in 133 pathological T3N0M0 stage ESCC patients who underwent radical resection without neoadjuvant or adjuvant therapy. CD8+ and FOXP3+ TIL densities as well as PD-L1 levels in tumor cells and lymphocytes, were assessed through immunohistochemical staining. Results: Patient survival was not associated with CD8+ or FOXP3+ TILs alone, but PD-L1 expression and the CD8+/FOXP3+ ratio were independent predictors of both disease-free and overall survival. PD-L1 expression correlated with age (p = 0.029), tumor length (p < 0.001), tumor differentiation status (p = 0.002) and reduced intratumoral CD8+ TIL density (p < 0.001). Conclusions: Our results suggest pT3N0M0 ESCC clinical outcomes correlate with CD8+ and FOXP3+ TIL densities and PD-L1 levels. Moreover, an intrinsic mechanism for induction of PD-L1 overexpression may be occurring during early tumor oncogenesis. This information may be useful for stratifying patients and guide the application of checkpoint blockade therapy in ESCC.
Bidirectional chemotherapy in gastric cancer (GC) with peritoneal carcinomatosis (PC) combining intravenous chemotherapy with intraperitoneal chemotherapy with low-dose cisplatin and doxorubicin administered as a pressurized aerosol: An open-label, phase II study.
Authors: Khomiakov Vladimir , Ryabov Andrey , Bolotina Larisa V , Utkina Anna , Cheremisov Vadim , Kolobaev Ilya , Ivanov Andrey , Chayka Anna , Sobolev Dmitry 
Published: September 2018

e15532 Background: Up to 40% of GC patients show synchronous PC at time of diagnosis and peritoneal relapse develops in 10–46% of cases after radical surgery. Systemic chemotherapy is standard method of treatment with median survival of several months. Innovative therapeutic approaches are needed to improve survival. Methods:Phase-2, open label prospective clinical trial assessing safety and efficacy of bidirectional chemotherapy for treating of gastric cancer with PC. Treatment protocol for untreated patients included initial staging laparoscopy or laparotomy, 3–4 courses of systemic chemotherapy (XELOX) followed by Pressurized IntraPeritoneal Aerosol Chemotherapy (PIPAC) procedures every 6 weeks until progression of disease or death. Criteria of progression included 50% and more PCI increase or distant metastases. Patients with primary or recurrent GC, who received earlier one or two lines of systemic chemotherapy, didn’t receive 4 XELOX courses before PIPAC. Primary endpoints were overall survival and histological peritoneal regression grading score after rebiopsy. Results:46 patients were included (14 men, 32 women, mean age 53.5 years), 33 patients had primary GC with PM and 13 had peritoneal relapse after surgery. 15 patients had systemic chemotherapy before inclusion to the program. About one half of patients had ascites. Mean PCI was 12.1 (min-max 3-34). Altogether, 89 PIPAC procedures were performed in the 46 patients. Complete and partial pathological response was found in 91% of the 23 patients eligible for tumor response assessment (7 and 14 patients, respectively). Median survival was 14 months and one-year overall survival was 55%. The median survival was better in patients with low PCI in compare with high PCI, but the difference was not significant. Conclusions: Bidirectional chemotherapy combining XELOX with PIPAC with cisplatin and doxorubicin can induce objective tumor regression and is associated with a promising survival in GC with PC.
CWP232291, a Wnt/β-catenin inhibitor, to suppress the growth and development of gastrointestinal cancers.
Authors: Park Jun Won , Um Hyejin , Yang Hanna , Cha Joo Young , Lee Kyoung-June , Kim Hark K. 
Published: September 2018

e15534 Background: CWP232291 (JW Pharmaceutical Corp, Seoul, Korea) is a potent β-catenin inhibitor currently tested in phase I trials for AML and MM. We evaluated the preclinical efficacy of CWP232291 for gastrointestinal cancers using xenograft and genetically-engineered mouse (GEM) models. Methods: For xenograft experiments, we intraperitoneally administered 150 mg/kg of CWP232291 twice a week to 14 heterotopic and 2 orthotopic xenografts of human gastric cancer cell lines formed in NOD/SCID mice. For GEM experiments, we intraperitoneally administered 100 mg/kg of CWP232291 (n = 19) or vehicle (n = 27) twice a week for 17 weeks to 3-week-old Villin-Cre;Smad4 F/F;Trp53F/F GEM mice that spontaneously form intestinal tumors with the β-catenin signaling activation. Results: CWP232291 exhibited in vivo activity in human gastric cancer xenografts. Activity of CWP232291 was more prominent in human gastric cancer cell lines harboring mutations in the β-catenin signaling pathway, such as APC, and in the 5-FU-resistant derivative of SNU-620, than in the other xenografts (P = 0.028, t-test). In the MKN-45 orthotopic xenograft, we noted a decrease in luciferase signal intensity after 4 weeks of CWP232291 treatment. CWP232291 demonstrated synergistic activity with paclitaxel and irinotecan in the SNU-484 heterotopic xenograft. In GEM experiments, CWP232291 treatment significantly suppressed the spontaneous development of intestinal tumors (56.3% vs. 91.3% with vehicle) in Villin-Cre;Smad4 F/F;Trp53F/F mice. Furthermore, CWP232291 treatment significantly reduced the number of mice that develop intestinal adenocarcinomas (37.5% vs. 78.3% with vehicle). Immunohistochemistry revealed CD8 T cell activation within the mouse intestinal tumors. Conclusions: CWP232291 demonstrated significant preclinical efficacy in gastrointestinal tumors, especially in cancers with the β-catenin signaling activation.
Alcohol consumption adjusted by aldehyde dehydrogenase 2 genotype: A potential risk factor for gastric cancer?
Authors: Ye Botian , Li Haojie , Wang Xuefei , He Hongyong , Zhang Heng , Min Lingqiang , Sun Yihong , Liu Fenglin 
Published: September 2018

e15541 Background: The role of aldehyde dehydrogenase 2 (ALDH 2) in alcohol metabolism has been ascertained, yet the association between ALDH2 genotype and the carcinogenesis of gastric cancer remains controversy. Methods: We retrospectively collected data of 292 subjects hospitalized in Zhongshan Hospital in Shanghai during March 2016 to September 2016. All subjects were divided into case group (identified with gastric cancer by postoperative pathology) and control group. Distribution of aldehyde dehydrogenase 2 genotype, drinking status along with other clinical variables were compared. Logistic regression model included age, gender, smoking and drinking status, family history and ALDH2 genotype. Adjusted odds ratios (ORs) were calculated. Results: There was a significant elevation of alchohol consumption in case group (P = 0.033). Subjects with ALDH2 *1/*2 and *2/*2 genotype showed less inclination for drinking than ALDH2 *1/*1 (P < 0.001). The risk for gastric cancer showed no differences among subjects with ALDH2 genotype adjusted drinking status [OR 1.121, 95% confidence interval (CI) 0.555-2.263 in Never/rare drinkers; OR 3.380, 95% CI 0.232-49.240 in Light drinkers and OR 2.416, 95% CI 0.326-14.151). Further analysis indicated that high body weight index (BMI) and heavy smoking were individual risk factors for gastric cancer among Light/heavy dringkers with ALDH2 *1/*2 or *2/*2 genotype (OR 84.736, P = 0.021 for BMI and OR 3.904, P = 0.037 for smoking). Conclusions: A dose-response relationship between alchohol consumption and risk for gastric cancer was observed in primary analysis. However ALDH2 genotype failed to modify the alchohol consumption. Our findings suggested that there might be other pathways to further explain the mechanisim of the role of alchohol consumption in carcinogenisis of gastric cancer.
Clinical observation of nab-paclitaxel plus S-1 as first-line chemotherapy for advanced gastric cancer.
Authors: Hu Yi , Sun Danyang 
Published: September 2018

e15554 Background: Gastric cancer is the third leading cause of death in the world with poor prognosis. Until recently, no standard treatment was available for patients with advanced gastric cancer in the first-line setting. Nab-paclitaxel and S-1 were both proved to have antitumor activity in many solid tumors including gastric cancer. We aimed to evaluate the efficacy and tolerance of nab-paclitaxel in combination with S-1. Methods: Patients with unresectable or recurrent gastric cancer received combination therapy of nab-paclitaxel plus S-1 every 3 weeks as one cycle. Nab-paclitaxel was administered at total dose of 260mg/ m2 on day 1 and 5 or on day 1 and 8. S-1 was given orally twice a day for 14 days, the doses were assigned according to body surface area. S-1 alone was administered as maintenance therapy after 6 to 8 cycles of combination therapy until disease progression. Results: Among the 33 patients enrolled, 28 patients (84.8%) had KPS 90, one third of patients were recurrent after gastrectomy. They received an average of 5.7 cycles of combination treatment. The median PFS was 6.6 months (95%CI, 5.557-7.716 months). The overall response rate was 51.5%, with one CR, 16 PR, 16 SD, and no PD. The median overall survival time was not obtained at the time of analysis. In safety profile, the highest incidence rate of grade 3 and grade 4 adverse events was neutropenia (12.1%). Conclusions: The combination of nab-paclitaxel plus S-1 was well tolerated and presented antitumor efficacy which may be a new therapeutic option for patients with advanced gastric cancer.
Metastatic stomach cancer: Real world scenario from a developing country.
Authors: Ganguly Sandip , Biswas Bivas , Ghosh Joydeep , E Prasad , Banerjee Sudeep , Mallath Mohandas K. , Chatterjee Suvadip , Dabkara Deepak 
Published: September 2018

e15569 Background: Data on epidemiology and outcome in metastatic stomach carcinoma patients from resource poor country is scarce. We aimed to evaluate clinical features and treatment outcome in patients treated at our center. Methods: This is a single institutional review of metastatic stomach carcinoma patients treated between May’2011 and October’2016. Patients with past history of adjuvant treatment were also included when they developed metastasis. Progression-free survival (PFS) was calculated from date of diagnosis of metastasis to date of disease progression. Patients who received at least one cycle of chemotherapy were included for a modified intent-to-treat survival analysis. Results: Total 143 patients were diagnosed with metastatic stomach carcinoma with median age of 56 years (range: 29-86) and male:female ratio of 92:51. Twenty-five (17%) patients received prior adjuvant therapy before developing metastasis. Commonest symptoms were abdominal pain in 112 (78%), weight loss in 72 (50%) and gastric outlet obstruction in 33 (24%) patients. Primary sites were proximal stomach in 44 (30%), body in 81 (57%) and distal stomach-pyloric region in 18 (13%) patients. Site of metastasis was peritoneum in 86 (60%), liver in 62 (43%), lung & pleura in 22 (15%), ovary in 14 (10%), and bone in 12 (8%) patients, and 104 (75%) patients had > 1 site of metastasis. Seventy-one (50%) patients were eligible for survival analysis. Common chemotherapy regimens were capecitabine-cisplatin in 27 (38%) and EOX in 22 (31%) patients. Survival status couldn’t be assessed in 29 (41%) patients who lost to follow-up. After a median follow-up 9.7 months (range: 0.5-37.7), median PFS was 7.9 months (range: 0.5 – 23.9) and median OS was 12.2 months (range: 0.5-37.7). ECOG performance status (PS) ≥2 and presence of linitis plastica showed a trend towards inferior PFS (p = 0.052 and 0.053, respectively) only in univariate analysis. Female sex and ECOG PS≥2 predicted inferior OS in both univariate and multivariate analysis (p = 0.012, 0.02 and 0.03 & 0.05, respectively). Conclusions: Platinum based doublet chemotherapy was used in majority of patients. Overall outcome was comparable to that of the available literature. Female sex and ECOG PS≥2 predicted inferior outcome.
A phase II study of induction chemotherapy with docetaxcel, cisplatin, and S-1 (DCS) for gastric cancer with peritoneal metastasis (KUGC06): Early results.
Authors: Okabe Hiroshi , Hata Hiroaki , Ueda Shugo , Hosogi Hisahiro , Ota Shuichi , Kinjo Yousuke , Hoshino Nobuaki , Hisamori Shigeo , Tsunoda Shigeru , Obama Kazutaka , Sakai Yoshiharu 
Published: September 2018

e15574 Background: Although the prognosis of gastric cancer with peritoneal metastasis is extremely poor, we previously showed the significant efficacy of S-1 plus cisplatin for limited peritoneal dissemination, and favorable outcome following curative resection. We conducted a phase II study to evaluate the safety and efficacy of induction chemotherapy with docetaxel, cisplatin, and S-1 (DCS) triplet regimen for patients (pts) with gastric cancer with peritoneal metastasis. Methods: The key eligibility criteria were gastric cancer with peritoneal metastasis or positive peritoneal cytology, without any other distant metastases, age between 20 and 75 years old, PS 0 or 1, capable of oral administration, and adequate hematologic, hepatic, and renal function. Pts received three 28-day cycles of DCS (cisplatin of 60 mg/m2, docetaxel of 40mg/m2 on day 1, and S-1 of 80 mg/m2 from day 1 to 14). Following evaluation for resectability, pts received D2 gastrectomy if R0 was possible. Primary endpoint was R0 resection rate. Secondary endpoints were clinical response of peritoneal metastasis, overall response, pathological response, adverse events, progression free survival, and overall survival. Sample size was determined to have 80% power for detecting 20% improvement of R0 resection rate over 45% baseline at one-sided alpha of 0.1. Results: Between June 2011 and April 2015, 30 pts were enrolled. All pts started DCS and were included in the analysis. Three cycles of DCS (80%) were completed in 24 pts (80%). The most frequent grade 3/4 toxicity was neutropenia (60%). Complete response of peritoneal metastasis was observed in 16 pts (53%), 21 pts underwent surgery, and 14 pts achieved R0 resection (47%; 95%CI, 28-66%). When the extent of peritoneal metastasis was classified as P0CY1, P1, P2, and P3 according to the Japanese classification, R0 resection rate for each group was 63%, 60%, 46%, or 0%, respectively. Conclusions: Induction chemotherapy with DCS is safe, and could achieve R0 resection in some patients with limited peritoneal metastasis or positive peritoneal cytology. However, the efficacy seems to be similar to the conventional S-1 plus cisplatin. Clinical trial information: UMIN000004932.