bluuebunny/crossref_metadata_2025_split huggingface dataset:
Analysis of tumor immune protein expression and clinical outcomes in gastric adenocarcinoma.
Authors: Blakely Andrew M. , Matoso Andres , Miner Thomas J. 
Published: March 2017

177 Background: Up- and down-regulation of various immunomodulating proteins may reflect gastric tumor aggressiveness, possibly correlating with disease progression. Although a growing focus of investigation, literature is still lacking on which proteins may be predictors of patient outcomes. Methods: Retrospective review of a prospective database was performed of patients who underwent gastrectomy for adenocarcinoma with curative intent, 2003 to 2013. Patient demographics, operative details, pathology data, and outcomes were captured. Results: 86 of 105 gastrectomy patients had sufficient tissue for microarray analysis. Patients were mostly males (65.1%); median age was 74 years. 31 patients (36.0%) underwent total gastrectomy; the remainder underwent subtotal resection. 59 specimens (68.6%) had ≥ 15 lymph nodes harvested. Median tumor size was 4.9 cm; 55 (64.0%) were at least stage T3 and 63 (73.3%) had nodal involvement. 13 margins (15.1%) were positive, 50 had lymphovascular invasion (LVI, 58.1%), and 43 had perineural invasion (PNI, 50.0%). Median follow-up was 43 months; 28 patients (32.6%) died in follow-up. 9 patients (10.5%) developed local recurrence while 27 (31.4%) had regional/distant recurrence; median time to recurrence was 12 months. Recurrence was associated with LVI (50.0% vs. 25.0%, p = 0.028) and PNI (53.5% vs. 30.2%, p = 0.029). LVI was associated with microsatellite instability (MSI) (70.0% vs. 20.0%, p = 0.021). PNI was associated with suppressed programmed death-ligand 1 (PD-L1) expression in epithelium (73.1% vs. 41.4%, p = 0.0072) and lymphocytes (60.0% vs. 37.1%, p = 0.038). PD-L1 positive lymphocytes were associated with positive margins (21% vs 2%, p = 0.004). Epithelial indoleamine dioxygenase (IDO) expression was associated with lower recurrence (30.0% vs. 57.1%, p = 0.012). Conclusions: Histopathologic analysis of gastric cancer specimens may help identify which patients are more likely to develop recurrent disease. Downregulation of immunosuppressive proteins such as PD-L1 and IDO and MSI suggest more aggressive tumor biology. Knowledge of tumor protein expression profiles could be used to tailor adjuvant therapy to improve long-term oncologic outcomes.
Gastrointestinal stromal tumors (GISTs) of the esophagus and gastroesophageal junction (GEJ).
Authors: Briggler Andrew M. , Graham Rondell P , Westin Gustavo Figueiredo Marcondes , Folpe Andrew , Jaroszewski Dawn E. , Okuno Scott H. , Halfdanarson Thorvardur Ragnar 
Published: March 2017

179 Background: GISTs arise from interstitial cells of Cajal anywhere within the gastrointestinal tract, but those of the esophagus and GEJ are exceedingly rare ( < 1% of cases). Our aim was to characterize clinicopathological features and outcomes of esophageal and GEJ GISTs and compare survival with a population-based registry (SEER). Methods: 28 cases were identified using the Mayo Clinic Cancer Registry from 1997 to 2016, and 378 cases from the SEER 18 registry from 2000 to 2013. Mayo cases were re-reviewed by Mayo pathologists. We analyzed patient characteristics, tumor location, TNM staging, mitotic index, molecular diagnostics, IHC staining, and histomorphology. JMP software was used to calculate time to recurrence (TTR) and overall survival (OS) utilizing Kaplan-Meier and log-rank. Results: At Mayo, 60% of tumors arose in the distal esophagus. Mean tumor size was 5.73 cm. 42% of cases were low grade. None had nodal involvement. Five cases were metastatic at diagnosis, all to the liver. 86.7% had spindle cell morphology. IHC staining was positive for KIT in 92%, followed by CD34 (52%), DOG-1 (24%), and actin (16%). Mutational analysis was done on 10 cases and KIT mutation was found in 8 cases; 2 were wild-type. Two-thirds of patients underwent surgery, mostly esophagectomy. 14 patients received adjuvant imatinib. Median time to diagnosis from symptom onset was 2 months; median time to surgery from diagnosis was 1 month. Of 10 patients with complete follow-up, 2 had recurrences: 1at the anastomotic site and 1 in the liver. Median TTR from surgery was 36.5 months. Median follow-up time was 31.5 months. Median OS from diagnosis for the Mayo cohort was 129.5 months (95% CI 55.7-x). SEER cohort median OS was 81 months (95% CI 63-101), and females had superior OS compared to males (HR 0.67; 95% CI 0.48-0.93, p = 0.016). Conclusions: Patients undergoing surgical resection for esophageal and GEJ GISTs had a favorable prognosis, but recurrences occurred. The superior OS seen in the Mayo cohort suggests early resection and adjuvant imatinib may improve outcomes.
The impact of new-onset atrial fibrillation on short- and long-term outcomes after esophagectomy for esophageal cancer.
Authors: Booka Eisuke , Takeuchi Hiroya , Fukuda Kazumasa , Suda Koichi , Nakamura Rieko , Wada Norihito , Kawakubo Hirofumi , Kitagawa Yuko 
Published: March 2017

183 Background: AF is common after thoracic and esophageal surgical procedures. The full spectrum of risk factors, associations, and implications are unclear. Objective:The aim of this study was to assess the impact of new-onset atrial fibrillation (AF) after esophagectomy on short- and long-term outcome. Methods: A retrospective analysis was performed on patients with esophageal cancer who underwent esophagectomy with thoracotomy and laparotomy, with R0 or R1 resection between January 1997 and December 2012. For the 402 patients included in this study, we analyzed the stage of disease, neoadjuvant therapies, surgical approaches, surgical complications, postoperative medical complications, and overall and relapse-free survivals using medical records. Results: The median age was 62 (range 34-82). Most patients were male (90.0%) and had squamous cell carcinoma (90.3%). Pathological staging of the esophageal cancers according to UICC 7th TNM classification system was categorized as follows: 17 (4.2%), 96 (23.9%), 16 (4.0%), 43 (10.7%), 57 (14.2%), 78 (19.4%), 39 (9.7%), 37 (9.2%), and 19 (4.7%) patients were designated as stage 0, ⅠA, ⅠB, ⅡA, ⅡB, ⅢA, ⅢB, ⅢC and Ⅳ respectively. Of the 402 patients studied, 42 (10.6%) had AF, 87 (21.6%) had pneumonia, 80 (20.0%) had anastomotic leakage, and 69 (17.2%) had recurrent laryngeal nerve paralysis. At a median follow-up of 133 months, the median survival was 49 months, and 5-year survival was 48% in the AF group, compared with 138 months and 60% in the non-AF group (p = 0.212). AF was significantly associated with recurrent laryngeal nerve paralysis (p = 0.001), but not with pneumonia or anastomotic leakage. Conclusions: New-onset AF is common, mostly associated with recurrent laryngeal nerve paralysis, but not with pneumonia or anastomotic leakage. AF has no impact on oncologic outcomes.
Analysis of predictive factors of ramucirumab plus paclitaxel for advanced gastric cancer.
Authors: Fukuda Naoki , Takahari Daisuke , Osumi Hiroki , Matsushima Tomohiro , Nakayama Izuma , Wakatsuki Takeru , Ogura Mariko , Ichimura Takashi , Ozaka Masato , Suenaga Mitsukuni , Shinozaki Eiji , Chin Keisho , Yamaguchi Kensei 
Published: March 2017

185 Background: Ramucirumab (RAM) is a novel anti-VEGF antibody approved in 2015 in Japan. Predictive factors for RAM in combination with paclitaxel (PTX) remain largely unknown. Methods: We reviewed 77 consecutive advanced gastric cancer patients who were treated with RAM plus PTX between June 2015 and June 2016 in our institution. We evaluated treatment outcome and analyzed potential predictive factors by univariate and multivariate analyses. Results: Median age was 67 years (range 35-83) and 51 % of the patients were male. The ECOG performance status (PS) was ≥ 2 in 8 patients. 89% (69/77) patients were treated as second line chemotherapy. Objective response rate (ORR) in patients who have measurable disease was 52 % (17/33). Median progression free survival (PFS) and overall survival (OS) and was 6.0 months (95% confidence interval [CI] = 4.3-7.1) and 10.4 months (95% CI 6.8-13.6), respectively. The most frequent adverse events were peripheral neuropathy (44%), G3 ≥ neutropenia (34%), hypertension (32%) and bleeding (27%). At multivariate analysis, hypertension was independent factor for OS (Hazard ratio [HR] = 0.35, 95% CI = 0.14-0.90, P = 0.03). Also, bleeding (HR = 0.23, 95% CI = 0.09-0.55, P = 0.001) was independent factor for PFS and hypertension (HR = 0.47, 95% CI = 0.22-1.02, P = 0.06) had trend toward to show better PFS. Conclusions: RAM plus PTX showed promising efficacy for advanced gastric cancer. RAM related toxicities such as hypertension and bleeding/hemorrhage were independent factors for better outcome. Further investigation is warranted to verify our analysis.
Association between markers of malnutrition (MN) and toxicity (T) during neoadjuvant chemoradiotherapy (nCRT) for esophageal cancer (EC).
Authors: Jain Rishi , Shaikh Talha , Yee Jia-Llon , Au Cherry , Handorf Elizabeth , Dotan Efrat , Meyer Joshua E. 
Published: March 2017

191 Background: EC is associated with significant MN. Resultant weight loss (WL) can be further exacerbated by toxicity of nCRT. We evaluated the association of surrogates of MN and T during nCRT for EC. Methods: A retrospective analysis of EC patients (pts) treated with nCRT as part of tri-modality therapy between 2002-2014 was performed. The following pre and post-CRT factors were assessed: presence of jejunostomy tube (J-tube), weight change (gain, loss of < 5%, 5-10%, ≥ 10%) and albumin change (decrease by < 0.5 or ≥ 0.5). We recorded rates of chemotherapy (ctx) dose reduction/interruption (DRI), hospitalizations (H), grade 3/4 T (G3+T), any grade non-hematologic (NHT) or hematologic T (HT). Multivariate regression analyses (MVA) were used to determine associations between MN and T, adjusting for age, gender, smoking status, stage, CRT regimen, performance status, and co-morbidities. Results: 125 patients were identified. Median age was 63 (range 35-80). Pre-CRT body mass index ranged from 17-45 kg/m2, with 74% overweight or obese. Mean WL during nCRT was 10 lbs (5%). Increased WL was noted in pts who received cisplatin/5-FU as compared to other ctx (p < 0.001) or ≥ 50 Gy (p = 0.025). In MVA, increased NHT was noted in pts with ≥ 5% WL (p < 0.05) and more G3+T was noted in pts with ≥ 10% WL (p = 0.002). A decrease in albumin by ≥ 0.5 was associated with increased DRI (p = 0.043), NHT (p = 0.004), HT (p = 0.002), and G3+T (p = 0.004). Sixty-three pts (50%) had a J-tube prior to nCRT. Pts with a J-tube had reduced mean WL (8 lbs vs 13 lbs) during nCRT. No differences in T were noted based on J-tube status. No associations between MN and H rates were observed. Conclusions: Hypoalbuminemia and WL during nCRT were associated with multiple T endpoints. The presence of a prophylactic J-tube did not reduce T rates. Other methods to prevent MN and reduce T during nCRT should be studied.
The impact of dose modification or termination of S-1 as adjuvant therapy on survival of locally advanced gastric cancer underwent curative gastrectomy.
Authors: Kawakami Takeshi , Machida Nozomu , Bando Etsuro , Hayashi Kaori , Shirasu Hiromichi , Kawahira Masahiro , Kawai Sadayuki , Kito Yosuke , Yoshida Yukio , Hamauchi Satoshi , Todaka Akiko , Tsushima Takahiro , Yokota Tomoya , Yamazaki Kentaro , Fukutomi Akira , Terashima Masanori , Yasui Hirofumi 
Published: March 2017

193 Background: Adjuvant S-1 therapy for pStage II/III gastric cancer (GC) patients (pts) after curative resection is standard treatment in Japan, however, prognosis of pStage III is still poor. There are few reports investigating the association of treatment exposure with survival. Therefore, we investigated the impact of dose modification or termination of S-1 as adjuvant therapy on overall survival (OS). Methods: The data of locally advanced GC pts who underwent gastrectomy with D2 lymph-node dissection in Shizuoka Cancer Center between Jan 2007 and Aug 2013 were retrospectively collected. Inclusion criteria were as follows: age 20 to 80 years; ECOG PS 0 or 1; histologically proven adenocarcinoma; pStage III under TNM 7th edition; R0 resection; initiation of S-1 within 56 days after surgery. S-1 was administered for 4 weeks followed by a 2 weeks rest. We defined completion of planned S-1 therapy as continuation of S-1 one year after surgery. Results: One hundred and six pts satisfied inclusion criteria. Pts’ characteristics were as follows: median age, 67 years (range, 38-78); male/female, 77/29 pts; ECOG PS 0/1, 72/34 pts; primary tumor location EGJ/U/M/L, 1/27/45/33 pts; and pStage IIIA/IIIB/IIIC, 25/41/40 pts. Fifty-five pts (51%) needed dose modification (dose reduction and/or schedule alteration). Eighty-two pts (77%) achieved completion of planned S-1 therapy. Five year OS rate was 59.9%. Among potential prognostic factors for OS in univariate analysis (age, PS, pStage, completion of planned S-1 therapy, dose modification), completion of planned S-1 therapy (HR 0.26; 95% CI 0.13-0.51; p < 0.001) and PS 0 (HR 0.52; 95% CI 0.27-0.99; p = 0.048) were good prognostic factors and dose modification was not prognostic factor (HR 1.06; 95% CI 0.53-2.12; p = 0.876) for OS. Conclusions: This study suggested that completion of planned adjuvant S-1 therapy and PS 0 were good prognostic factors for OS and appropriate dose modification might not worsen their prognosis.
Application of very low dose-rate brachytherapy in gastrointestinal cancer.
Authors: Herskovic Arnold M. , Rivard Mark , Rothstein Richard I , Moodie Karen L , Corcoran Kathleen , Swanson Lynne , Clerc Claude 
Published: March 2017

201 Background: Despite treatment intensity escalation, the high local recurrence rate for esophageal cancer has frustrated clinicians for decades. Conventional High Dose Rate brachytherapy, particle therapies, and other sophisticated treatment methods are encouraging but often fiscally and/or biologically infeasible. Additionally, these technologies often burden patients with numerous hospital visits, decreasing patient quality of life. Very low dose-rate brachytherapy (vLDR), with sources emitting relatively low energy, can be more cost effective than conventional radiation treatments, particularly in underserved communities, and can replace many hospital visits with one procedure. The dose distribution advantages of vLDR are irrefutable, especially in regard to doses to other tissues. vLDR seeds are currently used regularly in the prostate and have been tested in several other anatomical sites with good safety results. In the present study, a radioactive(RA) stent platform was developed and tested to apply vLDR therapy to cancers of the gastrointestinal (GI) system. Methods: Monte Carlo simulations were used to guide design of a RA esophageal stent. A design was chosen that minimized surface dose variation while using commercially available RA seeds. RA stents loaded with 60 -125 Seed-in Carrier, GE Healthcare were endoscopically placed in the naïve esophagus of 3 Yucatan swine. Previously, mock treatments using dummy seeds were performed in three similar pigs. Stents were left in place for between 4 and 7 weeks and reaction of the mucosa was assessed macroscopically and histologically. Results: Porcine esophageal tissue received doses in the range of 132-160 Gy at the mucosal surface and 39-48 Gy at a distance of 5mm from the stent surface. Tissues were collected at 0, 1 and 10 weeks after stent removal. No macroscopic radiation damage was seen at autopsy and pathological analysis yielded no radiation-related damage in evaluable tissues. Conclusions: In this preliminary study, no local or systemic damage due to radiation was observed after treatment of normal esophageal tissue with a vLDR stent device. Ongoing research aims to determine dose tolerance in esophageal tissue and target application of vLDR in other locations in the GI tract.
CUSUM analysis of mortality following esophagectomy to allow for identification and intervention of quality problems.
Authors: McLaren Patrick James , Hart Kyle D , Dolan James P. , Hunter John G. 
Published: March 2017

203 Background: CUSUM analysis is an analytic tool for monitoring institutional quality and clinical outcomes. CUSUM is a summative plot of an event that occurs over time. The slope that is generated can be used to determine rates of occurrence and deviations from an accepted rate. CUSUM can be used to monitor mortality rates following esophagectomy. Methods: A single institution prospectively maintained esophageal disease registry was used to construct CUSUM plots for in-hospital and 30-day mortality. All patients undergoing esophagectomy with reconstruction from 1995-2015 were included for analysis. Time points that deviated from an accepted mortality rate of 5% were evaluated for cause analysis. Results: From 1995-2015, 485 esophagectomies were performed with a cumulative in-hospital mortality rate of 4.7%. In 2008 our institution shifted to a primarily minimally invasive approach. Prior to March 2008 in-hospital mortality was 7.4%. After this time, in-hospital mortality was 2.1%, corresponding with a decreased slope of the CUSUM plot. A second period was investigated from September 2012-October 2012. Eight esophagostomies were performed with 3 deaths for a 37.5% mortality rate. All 3 patients were deaths related to ARDS and multisystem organ failure; this prompted an institutional epidemiologic investigation, as well as review of our enhanced esophageal recovery pathway. Since this time frame in-hospital mortality has been 1%. Conclusions: CUSUM analysis offers a useful observational tool to monitor institutional quality following esophagectomy. Investigations into mortality can identify quality problems and can lead to implementation of improved process measures that may lead to improved future outcomes.
Toxicity and survival in older versus younger esophageal cancer (EC) patients (pts) treated with neoadjuvant chemoradiotherapy (nCRT).
Authors: Jain Rishi , Yee Jia-Llon , Shaikh Talha , Au Cherry , Handorf Elizabeth , Meyer Joshua E. , Dotan Efrat 
Published: March 2017

204 Background: Trimodality therapy (TMT) for EC is associated with significant toxicity. Limited data are available on the safety of nCRT in vulnerable populations such as older pts. We evaluated the associations between age and toxicity as well as survival in pts treated with nCRT as part of TMT. Methods: A retrospective review of pts with EC treated with nCRT as part of TMT at an academic cancer center between 2002-2014 was conducted. We assessed the impact of age (<65 versus ≥65) on chemotherapy dose reduction/interruption (DRI), hospitalizations (H), and toxicity including grade 3/4 (G3+T), and composite number of any grade non-hematologic (NHT) or hematologic (HT) toxicity. Relapse free (RFS) and overall survival (OS) were assessed with the Kaplan-Meier (KM) method. Univariate (UVA) and multivariate regression analyses (MVA) were performed. Results: 125 pts were identified. The median age was 63 (range 35-80) with 46% of patients ≥65.There were increased co-morbidities in older pts and more active smokers in younger group. Otherwise,baseline characteristics were well balanced. In UVA, advanced age was associated with increased HT, and a trend towards increased G3+T (table 1). After adjusting for covariates in MVA, no differences in toxicity were noted between older and younger pts. There were no differences in RFS or OS between groups (table).Conclusions: Our study demonstrates similar rates of toxicity and outcomes among older and younger EC patients treated with nCRT as part of TMT. Advanced age alone should not be a barrier to nCRT. [Table: see text]
Predictive factors for long-term survival after conversion surgery for unresectable gastric cancer: A retrospective analysis.
Authors: Sagawa Tamotsu , Hamaguchi Kyoko , Sakurada Akira , Tamura Fumito , Hayashi Tsuyoshi , Fujikawa Koshi , Takahashi Yasuo , Sato Yasushi 
Published: March 2017

205 Background: Chemotherapy occasionally converts an initially unresectable gastric cancer to a resectable cancer. However, the association between clinical factors and long-term prognosis after conversion surgery for unresectable gastric cancer has not been investigated. Methods: We retrospective reviewed 36 gastric cancer patients who underwent conversion surgery at our institute between 2005 and 2015. Clinicopathologic characteristics and patient outcomes were analyzed, with particular focus on the potential to predict long-term survival. Results: The number of incurable factors was one in 31 patients and two in 5, including metastases to non-regional lymph node in 22, peritoneum in 10, liver in 6, and lung in 3. The regimen of chemotherapy was Docetaxel/CDDP/S-1 in 23 patients, Docetaxel/CDDP/S-1+Trastuzmab in 7, S-1/CDDP in 2, Docetaxel/S-1 in 1, CPT/CDDP in 1, and S-1 monotherapy in 1. Complete resection with no residual tumor (R0) was achieved in 25 of 36 patients, microscopic residual tumor status (R1) in 10, and macroscopic residual tumor (R2) in 1. The 3-year overall survival (OS) rate among the 36 patients who underwent conversion surgery was 60.3 % (median survival time, 1200 days). The 3-year OS rate among patients who underwent R0 resection was 70.8 % (median survival time, 1503 days). Patients who underwent R0 resection had significantly longer OS times than those who underwent R1 and R2 resection ( p=0.0124). We selected 16 variables in addition to residual tumor for Kaplan–Meier analysis. According to the log rank test, the following four variables were significantly associated with a better OS: clinical response to 1st line therapy (CR or PR vs. SD or PD)( p=0.0283), pathological response grade (1b-3 vs. 0-1a) ( p=0.0304), pathological tumor depth (CR or T1~T3 vs. T4) ( p=0.0261), and pathological nodal stage (N0〜2 vs. N3) ( p=0.0086). Conclusions: Our data indicates that clinical response to 1st line therapy in preoperative characteristics, R0 resection, pathological response grade, pathological tumor depth, pathological nodal stage in postoperative characteristics are predictive factors that can be expected to long-term survival.