bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association of UGT1A1 gene polymorphism with the safety and efficacy of irinotecan monotherapy for advanced gastric cancer.
Authors: Yamaguchi Toshifumi , Iwasa Satoru , Shoji Hirokazu , Honma Yoshitaka , Takashima Atsuo , Kato Ken , Hamaguchi Tetsuya , Boku Narikazu 
Published: March 2017

16 Background: The uridine diphosphate glucuronosyltransferase (UGT) 1A1, which transforms SN-38 into SN-38 glucuronide, is a key enzyme involved in the metabolism of irinotecan. Previous studies showed that UGT1A1 genotype is related to the toxicity of irinotecan-based chemotherapy in metastatic colorectal cancer. The purpose of this study was to investigate the relationship between UGT1A1genotype and safety and efficacy of irinotecan monotherapy in patients with advanced gastric cancer. Methods: We reviewed the data of 208 patients who were tested for UGT1A1 genotype and treated with irinotecan-based chemotherapy for advanced gastric cancer from 2009 to 2014. We evaluated the efficacy and safety of irinotecan monotherapy in the three groups with wild-type (WT), single heterozygosity (SH), and homozygosity/double heterozygosity (Homo-DH) classified by the genotypes for UGT1A1*28 or UGT1A1*6. Results: A total of 117 patients received irinotecan monotherapy: 40 patients in second-line, 74 in third-line, and 3 in forth-line therapy. The UGT1A1genotype was WT in 62 patients (53.0%), SH in 41 (35.0%), and Homo-DH in 14 (12.0%). Patients’ characteristics were similar among the three groups. The initial dose of irinotecan was reduced in 10 patients (16%) with the WT genotype, in 11 (27%) with SH, and in 10 (71%) with Homo-DH. Grade 3-4 neutropenia, diarrhea, and febrile neutropenia occurred in 13/22/64%, 6/5/21%, and 2/7/50% of WT/SH/Homo-DH patients. Median time to treatment failure of second-line and third-line therapies were 2.4/2.8/3.3 months and 2.4/2.3/1.3 months in WT/SH/Homo-DH patients. Median overall survival of second-line and third-line therapy were 7.9/9.9/4.6 months and 6.9/6.3/2.8 months in WT/SH/Homo-DH patients. Conclusions: Patients with UGT1A1 Homo-DH displayed high frequency of grade 3-4 toxicities, although the initial dose of irinotecan was reduced in some patients. UGT1A1 polymorphism may be related to the efficacy of irinotecan monotherapy in second- and third-line treatments for advanced gastric cancer.
Converting borderline-resectable, locally-advanced esophageal carcinoma to resectability with neoadjuvant chemoradiotherapy.
Authors: Horne Zachary D. , Sun Weijing , Gibson Michael K. , Pennathur Arjun , Luketich James D. , Karlovits Brian J , Heron Dwight Earl , Greenberger Joel S. 
Published: March 2017

160 Background: Treatment of T3-4/N+ esophageal cancer is challenging. Outcomes are suboptimal and patterns of care are not well defined for borderline-resectable esophageal cancer (BREC). We present our institutional experience using preoperative chemoradiotherapy (CRT) in the management of BREC. Methods: We identified 67 patients with T3-4/N+ BREC who were treated with concurrent CRT between 2009 and 2014. Survival was calculated with Kaplan-Meier curves and cohort comparisons were made with log-rank test and Cox regression. Results: We treated 67 patients (81% males, median age 61 years, and KPS of 80), primarily with T3N2 disease. Median follow-up was 16 months. The most common CRT regimen was 58.8Gy in 28 fractions with carboplatin and paclitaxel. Median survival was 16.5 months. Forty two (62.7%) patients underwent minimally invasive Ivor-Lewis esophagectomy within 100 days of CRT. Resected patients had a median survival of 30.6 vs. 6.4 months without surgery (p<.001). Pathologic complete response and pN0 was 30.0% and 59.5%, respectively. Acute grade 3+ toxicity was seen in 34.3% and late grade 3+ toxicity in 49.3%. Three patients (4.5%) died during CRT or before surgery. Predictors of overall survival (OS) on univariate analysis included age, KPS, male gender, absence of radiographic progression and surgical resection (all p<.05). Surgery remained significant on multivariate analysis (HR 0.215 [95%CI .114-.408, p<.001]). For resected patients, survival was predicted by positive margins, pathologic N stage, and number of positive nodes (all p<.05). The only predictor of OS on multivariate analysis was pathologic N stage, with actuarial 1- and 2-year OS for pN0 vs. pN+ of 96.2%/73.1% vs 53.3%/40.0% (p=.001). pN+ patients receiving adjuvant chemotherapy (53.3%) had improved survival of 26.7 vs 8.3 months without (p=.023). Conclusions: Preoperative CRT enabled a significant proportion of patients with BREC to proceed with a potentially curative resection. Further investigation with careful patient selection is warranted in incorporating a trimodality strategy to optimize outcomes and better define a treatment algorithm for this complex cohort of patients.
Trends in utilization of chemotherapy and radiation for resectable gastric adenocarcinoma: An NCDB analysis.
Authors: Motz Benjamin Mitchell , Lorimer Patrick Daniel , Walsh Kendall K , Perry I'sis N , Han Yimei , White Richard L. , Salo Jonathan C. , Hill Joshua S. 
Published: March 2017

163 Background: Locally advanced gastric adenocarcinoma (GACa) is optimally treated with a combination of surgery, chemotherapy (CHEMO) and radiation (RT). Utilization of therapies can vary with institutional practices. Methods: The NCDB was queried for pts with GACa who had RO resection (2006-2012). Pts with metastatic disease, incomplete pathologic staging, and incomplete CHEMO or RT sequencing data were excluded. Pts were divided into groups by treatment regimen: G1: perioperative CHEMO; G2: adjuvant CHEMO±RT; G3: neoadjuvant CHEMORT; G4: other adjunctive regimens; G5: surgery only. Pts who received neoadjuvant therapy were staged using clinical TNM; those who did not or had incomplete clinical staging were staged using pathologic TNM. 3 subsets were created: LOCAL: T0-2N0, LOCALLY ADV: T3-4N0, REGIONAL: N+. Chi-square, univariate, multivariable with stepwise selection, and Cochran-Armitage time trend analyses were performed. Results: N = 12946: G1 = 1099, G2 = 4771, G3 = 180, G4 = 244 and G5 = 6652. The percentage of pts receiving adjunctive therapy was determined for each subset: LOCAL = 17.2%, LOCALLY ADV = 59.8%, and REGIONAL = 66.0%. Use of adjunctive therapy increased from 2006: 44% to 2012: 53% (p < 0.01). Use of perioperative CHEMO increased from 2006: 4% to 2012: 18% (p < 0.01). Factors affecting use of adjunctive therapy on multivariable analysis are: age (p < 0.01), race (p < 0.01), income (p < 0.01), insurance (p < 0.01), comorbidity score (p < 0.01), and facility volume (p = 0.01). Conclusions: Though utilization of adjunctive therapy is increasing, a large proportion of pts with resectable GACa do not receive recommended adjunctive therapy. This study highlights disparities in utilization of optimal multimodality care. National efforts to expand access to care are necessary to improve outcomes in resectable GACa. [Table: see text]
Comparative outcomes of minimally invasive and robotic-assisted esophagectomy.
Authors: Meredith Kenneth L , Huston Jamie , Shridhar Ravi 
Published: March 2017

167 Background: Minimally invasive esophagectomy(MIE) has demonstrated superior outcomes compared to open approaches. The myriad of techniques has precluded the recommendation of a standard approach. The addition of robotics has potential to further improve outcomes. We sought to compare the outcomes of existing techniques for MIE with robotic assisted approaches. Methods: Utilizing a prospective esophagectomy database we identified patients who underwent (MIE) via Ivor Lewis(TT), transhiatal(TH) or robotic assisted Ivor Lewis(RAIL) techniques. Patient demographics, tumor characteristics and complications were analyzed via ANOVA, Chi-Square, and Fisher Exact where appropriate. Results: We identified 302 patients who underwent MIE: TT 95(31.5%), TH 63(20.8%), and RAIL 144(47.7%) with a mean age of 65±9.6. The length of operation was longer in the RAIL: TT(299±87), TH(231±65), RAIL(409±104 minutes), p < 0.001. However the EBL was lower in the RAIL patients: TT(189±188ml), TH(242±380ml), RAIL(155±107ml), p = 0.03. Conversion to open was also lower in the RAIL group: TT 7(7.4%), TH 8(12.7%), RAIL 0, p < 0.001. The R0 resection rate and lymph node (LN) harvest also favored the RAIL cohort :TT 86(93.5%), TH 60(96.8%), and RAIL 144(100%), p = 0.01. LN:TT 14±7, TH 9±6, and RAIL 20±9, p < 0.001. The overall morbidity was lower in RAIL patients: TT 29(30.5%), TH 39(61.9%), RAIL 34(23.6%), p < 0.001. Mortality was lower in the TT and RAIL approaches compared to TH but was not significant: TT 2 (2.1%), TH 2 (3.2%), and RAIL 2 (1.4%), p = 0.6. Conclusions: RAIL demonstrates lower EBL, conversion to open, and morbidity than other MIE techniques. Additionally the oncologic outcomes measured by R0 resections and LN harvest also favored the patients who underwent RAIL.
Role of surgery for gastric cancer with liver limited multiple metastases.
Authors: Shirasu Hiromichi , Tsushima Takahiro , Tanizawa Yutaka , Hamauchi Satoshi , Todaka Akiko , Yokota Tomoya , Machida Nozomu , Yamazaki Kentaro , Fukutomi Akira , Terashima Masanori , Uesaka Katsuhiko , Yasui Hirofumi 
Published: March 2017

170 Background: Although it has been suggested that surgery provides favorable outcome for gastric cancer (GC) patients (pts) with liver limited multiple metastases (LLM), the survival benefit of surgery comparing to systemic chemotherapy (CTx) has yet to be elucidated, especially in pts with LLM. The aim of this study was to explore the role of surgery for GC with LLM. Methods: We retrospectively reviewed the data of consecutive GC pts with LLM who underwent hepatectomy or received systemic CTx as initial therapy at Shizuoka Cancer Center between Dec. 2004 and Dec. 2015. Inclusion criteria were as follows: ECOG PS 0-1; histologically proven adenocarcinoma; synchronous or metachronous LLM; 2 or 3 LLM technically resectable disease; no prior CTx or radiotherapy Pts who were refractory to adjuvant CTx were excluded. Results: Nine of 24 pts who met the inclusion criteria underwent hepatectomy, and 15 pts received CTx. Pts’ background who received hepatectomy versus (vs) CTx was as follows: median age (range), 74 (64-81) vs 59 (42-76) years; male/female, 8/1 vs 14/1 pts; Histology intestinal/diffuse, 9/0 vs 10/5 pts; HER2 positive/negative/unknown 0/0/9 vs 2/5/8 pts; number of liver metastases 2/3, 9/0 vs 9/6; unilobar/bilobar, 5/4 vs 5/10 pts. In hepatectomy group, all 9 pts underwent radical hepatectomy (with gastrectomy for synchronous metastases), and 3 pts received adjuvant CTx. No in-hospital death or severe complication was observed. In CTx group, 11 pts received fluoropyrimidine plus cisplatin therapy, and trastuzumab was combined in 2 pts with HER2 positive tumor. Three pts underwent radical hepatectomy after CTx. Eight pts in hepatectomy group had recurrence. Recurrent sites were remnant liver (7), lymph node (1), and peritoneum (2). With median follow-up time of 47.9 months, median progression free survival was 8.0 months in hepatectomy group and 27.9 months in CTx group (p = 0.02). In CTx group, 3 pts who underwent subsequent radical hepatectomy after CTx had no recurrence or death. Median overall survival was 24.1 months in hepatectomy group and 38.4 months in CTx group (p = 0.15). Conclusions: Initial surgery for GC pts with LLM did not show survival benefit. But radical hepatectomy subsequent to CTx may associate with preferable outcome.
Clinical outcomes of elderly patients with esophageal cancer treated with chemoradiotherapy in the modern era.
Authors: Xu Cai , Xi Mian , Moreno Amy , Shraishi Yutaka , Komaki Ritsuko , Lin Steven H. 
Published: March 2017

174 Background: The optimal treatment approach is not clearly defined for elderly patients with esophageal cancer. We retrospectively analyzed the clinical outcomes of elderly patients ≥ 80 years old treated at a single institution in the modern era. Methods: Patients 80 years or greater with thoracic esophageal cancer who were treated consecutively with conventional modern radiotherapy (intensity-modulated radiation therapy or proton beam therapy) and concurrent chemotherapy between 2004 and 2016 were identified and included in this study. The one patient who had surgery was excluded. Toxicity was assessed using the CTCAE v.4.0. The rates of overall survival (OS) and recurrence free survival (RFS) were calculated with the Kaplan-Meier method. A p-value less than 0.05 indicated statistical significance. Results: Of the 1617 patients, 47 patients met the eligibility criteria. The median age was 81 years (range, 80-92 years). Most patients had some comorbid illnesses, with 81%, 9%, and 11% of patients having some cardiac, pulmonary, or diabetic related diseases, respectively. Twelve of 47 patients (26%) were given induction chemotherapy. The median dose was 50.4 Gy (range, 45 Gy-50.4 Gy). The clinical complete rate was 86%. With a median follow-up of 18 months (ranges, 1.9-117.6 months), the 2-year and 5-year OS was 54.5% and 27.7%, respectively, and the 2-year RFS was 63.6%. Three patients (6.4%) developed grade 3-5 radiation pneumonitis, with 2 (4.2%) being grade 5. Eighteen patients (38%) developed grade 1 pleural effusion, and 1 was grade 3. Three patients had grade 2 arrhythmia. Six patients had grades 1-2 pericardial effusion. One patient died from myocardial infarction. Four (9%) patients developed ≥ grade 3 esophagitis, with 7 patients having grade 3 esophageal stricture. Conclusions: The treatment of esophageal cancer patients 80 years or older with concurrent chemoradiotherapy was associated with an acceptable disease outcome, but the acute and late toxicities were higher than expected, which may be due to accompanying comorbidities. More research is needed to validate our observations and to better select patients who can optimally benefit from concurrent chemoradiotherapy.
Predictive value of Surgical Apgar Score for long-term outcome in patients with gastric cancer.
Authors: Tokunaga Masanori , Irino Tomoyuki , Makuuchi Rie , Tanizawa Yutaka , Bando Etsuro , Kawamura Taiichi , Terashima Masanori 
Published: March 2017

178 Background: Recently, a simple and easy complication prediction system, the surgical Apgar score (SAS) calculated according to three intraoperative parameters (estimated blood loss, lowest mean arterial pressure, and lowest heart rate), has been proposed for general surgery. We previously reported on the predictive power of SAS for severe complications after gastrectomy. However, the impact of SAS on long-term survival is still unclear. The aim of the present study was to clarify the relationship between SAS and survival outcome in patients with gastric cancer undergoing curative gastrectomy. Methods: This study included 302 patients who underwent curative gastrectomy at the Shizuoka Cancer Center in 2010. Clinical data, including intraoperative parameters, were collected retrospectively. When the SAS score was ≤ 6, patients were classified into an L-SAS group (n = 82), otherwise, they were classified into an H-SAS group (n = 220). Clinicopathological characteristics and survival outcomes were compared between the groups. Results: There was no difference in demographic data including sex and age between the groups. Total gastrectomy was more frequently performed in the L-SAS group (43%) than in the H-SAS group (21%; P < 0.001). The L-SAS group included patients with higher pT and pN stage. Five-year overall survival rate was worse in the L-SAS group (65.4%) than in the H-SAS group (82.7%; P < 0.001). Multivariate analysis, which included age, sex, histology, pT, pN, type of surgery and SAS as covariates, identified lower SAS (HR, 1.71, 95% C.I., 1.04-2.80) as well as age (HR, 1.62, 95% C.I., 1.10-2.40) and pN (HR, 2.05, 95% C.I., 1.19-3.52) as independent prognostic factors. Conclusions: The SAS was found to be a predictive factor for survival. Intraoperative bleeding and vital signs may affect survival of patients, and therefore warrant special attention from surgeons and anesthesiologists.
Laparoscopic D2 gastrectomy with complete mesogastrium excision (D2+CME) to reduce cancer leak from mesogastrium in patients with advanced gastric cancer.
Authors: Xie Daxing , Gong Jianping 
Published: March 2017

18 Background: The mechanism underlying tumor recurrence following curative surgery remains unclear. It is believed that intraperitoneal free cancer cells leaked into peritoneal cavity during curative surgery play an important role. In gastric cancer, new strategies should be established towards preventing leakage of cancer cells from the primary tumor involved tissues. Our previous research demonstrated the existence of disseminated cancer cells in the mesogastrium, and we proposed laparoscopic D2 lymphadenectomy plus complete mesogastrium excision (D2+CME) as an optimized surgical procedure for advanced gastric cancer (AGC). By dissecting along the surgical planes and embryonic boundary of mesogastrium, D2+CME is repeatable with less blood lost and improved short-term surgical outcomes. In this study, we further evaluated the oncological effect of D2+CME based on the detection of “cancer leak”. Methods: The peritoneal washings were collected prior to and after tumor resection from 45 patients who underwent D2+CME (D2+CME group) and 46 patients who underwent conventional D2 lymphadenectomy (D2 group). RT-PCR was used to determine the presence of cancer cells. Positive samples are defined as those with CEA mRNA level over threshold (cutoff value). Results: Of 91 peritoneal washing samples obtained before gastrectomy, 84 (41 in D2+CME; 43 in D2 alone) showed no presence of cancer cell. After gastrectomy, CEA positive was detected in 17 of 43 (39.5%) samples with D2 group, however, only 5 of 41 (12.2%) samples in D2+CME group detected positive CEA. The average level of CEA expression in D2+CME group was also significant lower than that in D2 group after gastrectomy (p < 0.05). Presence of “cancer leak” was closely associated with pT stage and surgical procedures. The DFS of patients with CEA positive after gastrectomy was significantly poorer than that of patients with CEA negative (p < 0.05). Conclusions: LaparoscopicD2+CME could reduce the leakage of free cancer cells from the envelop of mesogastrium into the peritoneal cavity during radical gastrectomy, and thus, it might potentially increase the prognosis of AGC patients. Clinical trial information: NCT01978444.
Efficacy and safety of endoscopic submucosal dissection in elderly patients with esophageal squamous cell carcinoma.
Authors: Shin In Seub , Song Byeong Geun , Kim Doyeon , Lee Hyuk , Min Byung-Hoon , Lee Jun Haeng , Rhee Poong-Lyul , Kim Jae J. , Min Yang Won 
Published: March 2017

182 Background: Endoscopic submucosal dissection (ESD) has been widely applied to superficial esophageal squamous cell carcinoma (SCC) as a minimally invasive treatment, which has advantages over surgery especially in the elderly who are at high risk of surgery. This study elucidated the efficacy and safety of ESD for superficial esophageal SCC in the elderly. Methods: Between April 2007 and June 2016, a total of 176 patients with superficial esophageal SCC were studied. The short-term outcomes including En bloc resection, complete resection, and curative resection rate and procedure-related complication rates were compared between elderly group ( n = 20, ≥ 75 years of age) and non-elderly group ( n = 156, < 75 years of age). Results: The mean age of elderly group was 76.9 ± 1.5 years and that of non-elderly group was 62.9 ± 6.9 years ( p < 0.001). Sex, past medical history (hypertension and diabetes), body mass index, tumor characteristics (number, location, shape, maximal and circumferential size of tumor and resected specimen, and depth), and presence of stricture prevention did not differ between two groups. En bloc resection (95% vs 93.6%, p > 0.999), complete resection (85% vs 73.1%, p = 0.292), and curative resection rates (75% vs 56.4%, p = 0.149) did not differ significantly between two groups. Procedure time and hospital stay were also similar. Complications of ESD such as stricture (10% vs 12.8%, p > 0.999) and perforation (10% vs 7.7%, p = 0.587) occurred similarly. Conclusions: ESD for superficial esophageal SCC is effective and safe in elderly patients like in non-elderly patients.
Effect of extending the original eligibility criteria for the “CROSS” neoadjuvant chemoradiotherapy on toxicity and survival in esophageal cancer.
Authors: Hulshoff Jan-Binne , de Heer Ellen C. , Klerk Daphne H. , De Groot Derk Jan , Plukker John Theodorus , Hospers Geke 
Published: March 2017

187 Background: Patients with curable esophageal cancer (EC) which proceed beyond the original CROSS eligibility criteria are also treated with neoadjuvant chemoradiotherapy (nCRT). This study assessed the effect of extending the CROSS eligibility criteria for nCRT on treatment related toxicity and overall survival (OS) in EC. Methods: Included were 161 patients with locally advanced EC (T1N1-3/T2-4aN0-3/M0), treated with the CROSS schedule followed by esophagectomy. Group 1 (N = 90) consisted of patients which met the CROSS criteria and patients in group 2 (N = 71) met the extended eligibility criteria, i.e. including a tumor length of > 8 cm (N = 23), > 10% weight loss (N = 35), > 2 – 4 cm extension in the stomach (N = 21), celiac lymph node metastasis (N = 13), and/or age > 75 years (N = 2). We assessed the differences in hematologic toxicity (≥ grade 3) and 90-day postoperative mortality. Moreover, we assessed the prognostic value on OS with multivariate Cox regression analysis. Results: No difference was found in hematologic toxicity and 90-day mortality. The OS differed significantly (P = 0.003), with a median of 37.3 (95% CI 10.56 – 64.0) and 17.2 (95% CI 13.8 – 20.6) months in group I and II, respectively. Pathological N-stage (P = 0.024), ypT-stage (P = 0.044), and group II (P = 0.006) were independent prognostic factors for OS. Conclusions: Extension of the CROSS study eligibility criteria for nCRT did not affect hematologic toxicity and postoperative mortality, but was prognostic for OS.