bluuebunny/crossref_metadata_2025 huggingface dataset:
HCC incidence in patients treated with DAA for chronic hepatitis C compared to PEG-interferon/ribavirin treated patients: HORRID study.
Authors: Siebenhuener Alexander Rheinhard
Published: January 2019

219

Background: Direct antiviral agents (DAA) have revolutionized the treatment of chronic hepatitis C (CHC) and have quickly become the standard of care. Despite this effective treatment CHC patients are known to have an increased risk to develop hepatocellular carcinoma (HCC). The incidence of HCC is about 3-5% in this population and regular surveillance is highly recommended. To date the correlation between eradication of viral hepatitis and the risk of HCC development in CHC patients is not well understood. Surprisingly several studies show a frequent incidence of HCC after DAA treatment. The aim of this study is to demonstrate treatment of CHC with DAA or PEG-INF/RBV and patients' outcome into context of HCC development and success of CHC treatment. Methods: We performed a retrospective analysis of 300 patients that received treatment with PEG-IFN and RBV and 346 patients that received DAA treatment for CHC in our institution. HCC viral load, genotype, treatment type, duration and outcome, fibrosis grade, age, gender, BMI as well as AFP and serum albumin were recorded. A Cox-proportional hazard model was fit to compare survival in patients treated with PEG-IFN and patients that received DAA regarding HCC, need for liver transplantation and death. Results: While death and need for liver transplantation was not different in both groups, there was a significant difference in the incidence of HCC. Patients that received DAA developed HCC post-treatment significantly earlier than PEG-IFN/RBV treated patients. In a Cox-proportional hazard model, DAA treatment remained a significant predictor for occurrence of HCC after adjusting for confounders. Conclusions: Our data demonstrates a significantly increased incidence of HCC in patients that were cured from CHC with DAA compared to patients after PEG-IFN/RBV treatment. In contrast to earlier studies using historic data, our study limited confounders by directly comparing HCC differential incidence of HCC after PEG-INF/RBV and DAA treatment within the same institution. Further prospective studies are warranted to precisely determine the HCC risk in patients that receive DAA for CHC.
The impact of C-reactive protein to albumin ratio on survivals in patients with esophageal cancer.
Authors: Hayashi Masato , Kawakubo Hirofumi , Mayanagi Shuhei , Nakamura Rieko , Fukuda Kazumasa , Suda Koichi , Wada Norihito , Kitagawa Yuko
Published: January 2019

22

Background: C-reactive protein to albumin (CRP/Alb) ratio is a novel inflammation-based prognostic score. It was originally reported as a prognostic score in septic patients, however, recent reports show CRP/Alb can be a prognostic score in some cancer patients. There are a few reports about CRP/Alb in patients with esophageal cancer. The usefulness of CRP/Alb in patients with esophageal cancer is still unclear. Methods: The aim of this study is to ensure the evidence of CRP/Alb in patients with esophageal cancer as a prognostic score. One hundred and sixty patients with esophageal cancer were reviewed in the current study. CRP/Alb was calculated before the treatment: In neoadjuvant chemotherapy (NAC) patients, CRP/Alb was calculated before NAC, in non-NAC patients, CRP/Alb was calculated before surgery. CRP/Alb was divided into high group and low group, using cut off value 0.035. The number of 0.035 was determined, referred from other reports of CRP/Alb. Results: The distributions of postoperative pathologic stages 0, 1, 2, 3, and 4 were respectively 4, 51, 33, 56, and 16. The number of high CRP/Alb group was 58 (36.3%). That of low CRP/Alb group was 102 (63.7%). In the survival analysis, the patients with high CRP/Alb showed a significantly shorter overall survival. In the multivariate analysis with pathological stage, neoadjuvant treatment, field of lymph node dissection, and CRP/Alb as covariates, CRP/Alb was detected as a significantly independent prognostic score (hazard ratio 2.602; P < 0.001). Conclusions: In this study, CRP/Alb was thought to be a prognostic score with statistical significance in esophageal cancer. Therefore, further investigation of reducing preoperative inflammation and increasing preoperative nutrition in esophageal cancer is needed.
Microsatellite instability in resectable colorectal liver metastasis: An international multi-institutional analysis.
Authors: Margonis Georgios Antonios , Buettner Stefan , Wagner Doris , McVey John , Andreatos Nikolaos , Beer Andrea , Sasaki Kazunari , He Jin , Kaczirek Klaus , Poultsides George A. , Cameron John L. , Mischinger Hans Jörg , Aucejo Federico , Wolfgang Christopher Lee , Weiss Matthew J.
Published: January 2019

220

Background: Microsatellite instability (MSI) is associated with favorable prognosis and distinct response to chemotherapy and immunotherapy for non-metastatic colorectal cancer (CRC). However, studies suggest that MSI may have minimal prognostic impact for widely metastatic CRC. Whether MSI is prognostic for the subset of patients with resectable colorectal liver metastases (CRLM) remains unknown. In this study, we analyze the impact of MSI status on patients with CRLM in the largest cohort reported to date. Methods: Patients who underwent curative-intent resection for CRLM between 2003 and 2017 in five participating tertiary centers and had available data on MSI status were included. Standard clinicopathologic and outcome data were collected. Survival was calculated using Kaplan-Meier analysis. Results: A total of 332 patients who met inclusion criteria were identified, of which 198 (59.6%) were male and 133 (40.7%) had rectal primary tumors. Sixteen patients (4.8%) were MSI positive. The majority of patients had T3 tumors (n = 193; 61.3%) and lymph node metastasis were present in 202 patients (64.5%). The median number of hepatic lesions was 1 [inter-quartile range (IQR):1-3] and median tumor diameter was 2.0 cm (1.2-3.5). Extrahepatic disease was present in 51 (15.7%) patients. Preoperative chemotherapy was administered to 220 (68.8%) patients. Of note, data on KRAS mutation status were available for the majority of the patients (95.5%). Baseline characteristics were similar between MSI positive and negative patients. At a median follow-up of 22.1 months, 154 (47.5%) patients experienced disease recurrence and 70 (21.1%) died. Importantly, neither disease-free survival (DFS, p = 0.168) nor overall survival (OS) were associated with MSI status (p = 0.759). Conclusions: MSI status did not appear to impact survival for patients with resectable CRLM. Additional research in larger cohorts from additional participating institutions is currently underway to assess these preliminary findings.
Survival after surgery for metastatic small bowel compared to pancreatic neuroendocrine tumors.
Authors: Concors Seth Jason , Ecker Brett , Sinnamon Andrew , Fraker Douglas L. , Karakousis Giorgos , Vollmer Charles M. , Roses Robert
Published: January 2019

221

Background: Surgical management of small bowel (mSBNET) and pancreatic (mPNET) neuroendocrine tumors with hepatic metastases remains controversial. Previous studies, often drawn from single institution experiences, combine outcomes mSBNET and mPNET cohorts, despite ample evidence indicating discreet biology and natural history. This study aimed to define and contrast survival outcomes after surgery in patients with mSBNET and mPNET using a large national dataset. Methods: Patients with hepatic metastases from SBNET and PNET who underwent surgical (n = 1063; n = 556, respectively) or non-surgical management (n = 456; n = 2593, respectively) were identified in the National Cancer Database (1998-2014). Surgical and non-surgical cohorts were matched (1:1) by propensity scores based on the likelihood of receiving surgery and survival hazard. Kaplan-Meier estimates of overall survival (OS) were compared. Results: After adjustment for potential cofounders (age, Charleston comorbidity index, tumor differentiation and administration of chemotherapy or radiotherapy), nonsurgical management was associated with poorer survival in SBNET (HR 2 95%CI 1.5-2.7) and in PNET (HR 3.6, 98%CI 2.8-4.5). In the propensity matched cohort, there was a significant survival advantage for patients who received surgery for both SBNET and PNET (p < 0.001). In SBNET, mean survival in the non-surgical cohort was 33.9 months (SD 1.3, 95%CI 31.5-36.4), and 39.3 months in the surgical cohort (SD 0.8, 95%CI 36.1-39.1). In PNET, mean survival in the non-surgical cohort was 32.7 months (SD 1.6, 95%CI 29.5-35.8), and 55.1 months in the surgical cohort (SD 1.4, 95%CI 52.4-57.7). Conclusions: Surgical selection or management are associated with a survival advantage in both mPNET and mSBNET; this advantage is greater in mPNET. The relative contributions of patient selection and therapeutic benefit require further elucidation.
Survival for small, well-differentiated PNETs in relation to treatment.
Authors: Julian bao-Quynh , Ituarte Philip HG , Jutric Zeljka , Singh Gagandeep , Paz Isaac Benjamin , Lewis Aaron G
Published: January 2019

222

Background: Management of small well-differentiated pancreatic neuroendocrine tumors (PNETs) is controversial, and the malignant potential remains uncertain. Treatment options include observation (OB), enucleation (ENUC), and formal resection (Distal pancreatectomy – DP, Whipple/Total pancreatectomy – PD). Our objective was to analyze the association between treatment types of small PNETs and overall survival (OS). Methods: The California Cancer Registry linked with the Office of Statewide Health Planning and Development inpatient database was queried from 2000-2012 for patients with < 3 cm, nonfunctional, stage I–II PNETs. Exclusion: poorly-differentiated PNETs or metastases within 6 months. Non-parametric statistics (Kruskal-Wallis) or Fisher’s exact test were used to determine if any patient characteristics were associated with type of treatment (surgery or observation). Ten-year OS was estimated by the Kaplan-Meier method. A multivariate model was performed using Cox proportional hazards. Results: Of 1,862 patients with PNETs, 204 were small, well-differentiated. Treatments include: OB n = 41, EN n = 20, DP n = 106, or PD n = 67. Few patients developed distant recurrences past 6 months (OB, n = 0; EN, n = 0; DP, n = 2; PD, n = 1). On bivariate analysis, comorbidities (2 or more, p = 0.024), insurance type (p = 0.018), and mean number of lymph nodes retrieved (EN = 1.8 +/- 4.1; DP = 6.3 +/- 7.63; PD = 11.0 +/-8.5) were associated with treatment. Patient gender, race, socio-economic status, hospital type, tumor size, grade (well vs. moderate), and lymph node status at diagnosis were not associated with treatment type. On multivariate analysis, treatment type was not associated with worse OS (p = 0.098). Ten-year OS was similar between treatment groups (OB = 92%, EN = 100%, DP = 95%, PD = 95%, p= 0.1828). Conclusions: In this unique study accounting for time of metastasis in patients who present with early stage, well-differentiated PNETs, observation, enucleation, and resection are equally associated with long-term survival. In the appropriately selected patient group, enucleation or observation may be alternatives to more aggressive surgery.
Tumor-normal sequencing to reveal frequency of false positive error rates with tumor-only sequencing in GI cancers and with RNA sequencing as a new standard of precision molecular profiling.
Authors: Garner Chad , Reddy Sandip , Sanborn John Z , Benz Stephen Charles , Soon-Shiong Patrick , Rabizadeh Shahrooz
Published: January 2019

224

Background: Tumor-only sequencing to identify somatic tumor genomic variants increases the risk of mistakenly identifying germline mutations as somatically derived driver mutations. Simultaneous bioinformatics analysis of both normal germline and the tumor genome with RNA analysis is necessary for precise identification of molecular targets for cancer therapy. The objective of this study was to compare the accuracy and precision of tumor somatic SNV calling with a 45-gene GI cancer molecular actionability panel, analyzing tumor tissue alone versus analyzing tumor DNA with normal germline DNA and tumor RNA. Methods: The study included 204 cancer patients with 11 GI cancer types with whole genome sequencing of tumor and normal genomes. True positive and false positive rates were measured for single nucleotide variants (SNVs). RNA sequencing was available for 139 patients to determine SNVs expressed in messenger RNA. SNVs were identified using well-established and published bioinformatics methods. False positive results were SNVs identified as being somatic origin that were of germline origin. Results: 92% SNVs identified from sequencing tumor genomes alone were of germline origin (false positives) rather than true somatic mutations. Filtering the SNVs using a public database with reported population allele frequencies < 0.001 still resulted in a false positive rate of 41%. Furthermore, 71% of GI cancer patients had at least one false positive SNV after filtering. RNA analysis showed 10% of true somatic variants were not expressed and 17% of patients had at least one true somatic variant that was not expressed. Conclusions: Simultaneous sequencing and analysis of both normal germline and tumor genomes is necessary for accurate identification of molecular targets. Analysis of tumor genome alone results in a high false positive rate. Higher precision is achieved with simultaneous tumor-normal DNA and RNA sequencing analysis. Treatment decisions based on tumor-only DNA analysis or in the absence of RNA analysis can result in administration of ineffective therapies and increasing risk of negative drug-related side effects.
Emerging value of multigene panels for germline testing in patients with neuroendocrine tumors.
Authors: Whitman Julia , Shih Brandon , Blanco Amie , Chan Salina , Paciorek Alan , Desjardin Jacqueline , Dhawan Mallika Sachdev , Zhang Li , Bergsland Emily
Published: January 2019

226

Background: Neuroendocrine tumors (NETs) are known to be associated with hereditary syndromes stemming from MEN1, VHL, SDH or TSC mutations. Recent data suggest that additional germline mutations may be relevant, implying a role of germline testing with multigene panels. We examined genetic counseling (GC) referral and testing patterns, test results, and their changes over time in NET patients (pts). Methods: Retrospective chart review was conducted in 236 NET pts referred to UCSF Cancer Genetics and Prevention Program 2004-2017. Univariate logistic models were used to assess relationship between binary outcome and covariate. STATA was used for analysis and statistical significance was based on p < 0.05. Results: 139 referred pts (59%) followed up with GC. Pts with >1 family members diagnosed with cancer were more likely to attend GC [OR=2.75, p=0.010]. Among 107 pts tested, small bowel NETs were less associated with testing than pancreatic NETs [OR=0.15, p=0.001]. Single-gene tests were routine until 2015, when panels up to 130 genes became standard. Overall, 31 pts (29% of 107 tested) had a pathogenic/likely pathogenic (P/LP) result. There was no significant difference between single and multi-gene tests in identifying P/LP mutations (likely due to changes in threshold for testing over time), but greater diversity in P/LP mutations was noted with larger panels. Functional tumors showed lower rate of P/LP mutations than non-functional [OR=0.17, p=0.037]. Conclusions: Only 59% of referred pts followed up with GC, suggesting significant barriers to testing exist. Of those tested, 29% harbored a P/LP mutation. Germline mutations not traditionally associated with NETs were identified, highlighting the potential importance of larger panels to detect rare mutations. [Table: see text]
The short-term and long-term prognostic risk stratification of patients with resectable gastric cancer.
Authors: Amada En , Kawakubo Hirofumi , Mayanagi Shuhei , Fukuda Kazumasa , Nakamura Rieko , Suda Koichi , Wada Norihito , Kitagawa Yuko
Published: January 2019

23

Background: Some studies suggest anastomotic leakage (AL) may adversely affect long-term survival in patients undergoing radical gastrectomy (RG) for gastric cancer (GC). Therefore, we assume that common risk evaluation system for short-term and long-term prognosis can be devised in patients with GC that have undergone RG. Methods: Five hundred and twenty patients undergone RG against GC during May 2012 to March 2017 were enrolled. Patients’ characteristics, preoperative laboratory data, operative information and pathological factors were analyzed. Also AL with Clavien-Dindo classification Grade≥III (AL≥III), disease free survival (DFS) and disease specific survival (DSS) were examined. Results: By bringing patients under classification of “with or without relapse” and “with or without AL≥III”, we identified preoperative body weight (BW), serum C-reactive protein (CRP) and albumin (Alb) level were independent risk factors of both relapse and AL≥III. Stratifying patients with recurrence, we obtained crude hazard ratio (HR) of 1.04 (95% CI: 1.02-1.06) for 1kg-increase of BW, 1.51 (95% CI: 1.08-1.40) for 1mg/dl-increase of CRP and 1.23 (95% CI: 1.34-1.64) for 1g/dl-decrease of Alb. With these HR and median value of each parameters of none-relapse group, we defined ABC score (ABCs) is calculated by following formula; ABCs = (4.1-Alb)*51+(58.5-BW)*4+(CRP-0.05)*23. AL≥III were observed in 3.1% of the cases and ABCs of patients with AL≥III was significantly low (with AL≥III; -22.4, without AL≥III; 9.03, p = 0.045). We determine a cut off value of ABCs to -7 on the basis of the ROC curve. Patients with ABCs≤-7 had significantly high risk of AL≥III and we found ABCs≤-7 is an independent risk factor of AL≥III (HR 1.775, p = 0.003). Also, we stratified patients as Low group (L), Mid group (M), High group (H), by approximate tertile value of ABCs, -20 and 30. We found significant shortening of DFS and DSS in order of L, M and H (DFS; L vs M p = 0.006, Mid vs High p = 0.03, DSS; L vs M p = 0.002, L vs H p < 0.001). Moreover, HR for disease specific death for ABCs≥-20 was 4.2 (p = 0.003) in multivariate analysis. Conclusions: ABCs can be a risk evaluation system for short-term and long-term prognosis in patients with GC that have undergone RG.
Role of stereotactic body radiation therapy in patients with hepatocellular carcinoma extensively pretreated with transarterial chemoembolization or yttrium-90.
Authors: Tanimoto Kayo , Rusu Iris , Martin Brendan , Price Jennifer , Thomas Tarita
Published: January 2019

233

Background: Hepatocellular carcinoma (HCC) is an aggressive disease with dismal outcomes. Patients who are not surgical candidates are routinely treated with local therapies such as TACE, Y90, or SRBT among others. The study aimed to assess treatment response and treatment related toxicity to SBRT in patients who received prior TACE or Y90 at our institution, some of whom subsequently underwent orthotopic liver transplantation. Methods: IRB approval was obtained to retrospectively review 26 medical records of patients who received SBRT at the Loyola University Medical Center from 9/9/14-12/28/16. GI toxicities were analyzed using the Common Terminology Criteria for Adverse Events (CTAE) version 4.0 following SBRT. Skin, pharyngeal/esophageal, thorax, lung, GU, and GI toxicities were included in toxicity analysis. Patients received radiation dose from 36 Gy - 50 Gy in 5 fractions using RTOG 1112 dose constraints for dosimetric plan evaluation. Fisher’s exact tests and Wilcoxon Rank Sum tests were used for statistical analysis. Results: Of the 26 patients, 21 patients had prior TACE (median 3 TACE procedures; ranging from 1-5). 6 patients had prior Y90 with or without prior TACE. Median follow up for the cohort was 51 weeks. No patient showed GI toxicities above grade 1 during SBRT, with fatigue and nausea being the most common. One patient who previously received Y90 developed fatal duodenal perforation. Pathology demonstrated this was related to tumor infiltration of the duodenum and was not related to post radiation necrosis. 6 patients went on to undergo OLT with all patients having treatment response on surgical pathology with 4 patients having complete treatment response. Conclusions: SBRT was shown to safely treat patients after prior therapies including Y90 and TACE. Furthermore, SBRT showed favorable outcomes in post-OLT patients. To our knowledge, this is the first study to assess the effects of SBRT following extensive local therapies for HCC including Y90. Prospective data is needed to evaluate these findings further with longer follow up.
A population-based study of morbidity after pancreatic cancer diagnosis.
Authors: Sarkar Reith , Fero Katherine Elaine , Panjwani Neil , Matsuno Rayna , Murphy James Don
Published: January 2019

236

Background: Pancreatic cancer is characterized by early and relentless tumor spread. This leads healthcare providers to consider pancreatic cancer a “distant disease.” However, local tumor progression within the pancreas can lead to substantial morbidity. This study defines the long-term morbidity from local and non-local disease progression in a large population-based cohort. Methods: We identified 21,500 Medicare beneficiaries diagnosed with pancreatic cancer between 2000-2011 in the Survival, Epidemiology and End Results database. Hospitalizations identified from Medicare claims were attributed to complications either local (biliary, upper GI ulcer/bleed, pain, pancreatic, radiation toxicity) or non-local (thromboembolic events, any cytopenia, dehydration, nausea/vomiting/motility, malnutrition and cachexia, ascites, pathologic fracture, chemotherapy toxicity) in nature. Competing risk analyses were used to determine the cumulative incidence of complications from local, and non-local disease. Multivariable Fine-Gray models were used to identify the impact of chemotherapy or radiotherapy on the risk of hospitalization. Results: Of the total cohort 9,347 (43.5%) patients were hospitalized for a local complication, and 13,101 (52.4%) for a non-local complication. After adjusting for the competing risk of death, complication due to local disease at 24-months post-diagnosis was highest in non-metastatic non-resection (55.1%), followed by non-metastatic resection (44%) and metastatic (34.5%) patients. Non-local complications were highest in non-metastatic non-resection (60.6%), followed by metastatic (58.6%) and non-metastatic resection (52.5%) patients. Predictors of hospitalization for local and non-local complications included age, race-ethnicity, location, patient group, tumor size and diagnosis year. Radiation and chemotherapy had minimal impact on risk of hospitalization. Conclusions: Despite the widely-known predilection of distant disease spread in pancreatic cancer, local tumor progression also leads to substantial morbidity and hospitalization. Radiation and chemotherapy did not decrease the rates of hospitalization for local complications.
Implications of pancreatic cancer with diabetes mellitus on patient outcomes and care: A matched case-control study.
Authors: Karlin Nina J. , Amin Shailja , Buras Matthew , Kosiorek Heidi E. , Verona Patricia M. , Cook Curtiss B.
Published: January 2019

239

Background: The aim of this case-control study was to determine the impact of DM on survival in pancreatic cancer patients, and to examine the impact of pancreatic cancer on glycemic control in DM. Methods: Ninety-two patients with newly diagnosed pancreatic cancer from 2007 to 2015 with DM were identified from the institutional Cancer Registry and matched to ninety-two pancreatic cancer patients without DM according to age, gender, and year of pancreatic cancer diagnosis. The file was linked to the electronic medical record to obtain information on DM and pancreatic cancer therapies, and laboratory results. Overall survival (OS) was estimated with the Kaplan-Meier method and compared by Cox regression analysis. Mixed models were used to compare hemoglobin A1c (HbA1c) and glucose over time. Results: Mean age of the entire pancreatic cancer cohort was 70 years, most (92%) were white, most common (88%) histology was adenocarcinoma, and majority (41%) were stage IV. No differences in age, race/ethnicity, histology, or tumor stage were detected between patients with and without DM, although DM patients had higher body mass index (P = 0.014). Mean ca 19-9 (U/ml) was 804 for diabetics, and 395 for non-diabetics. Among those with DM the mean HbA1c during the year following cancer diagnosis was 7.3%. Time (days since diagnosis) was significant in DM patients (p = 0.014) as HbA1c decreased over time. Mean glucose during the year following diagnosis among DM patients was significantly higher compared to non-DM patients [160.6 (SD = 38.0) versus 117.2 (SD = 19.0); p < 0.001]. Both groups had a decline in glucose over time (p = 0.008). In Kaplan-Meier survival analysis (median follow-up time of 11.9 months), 2 year overall survival was estimated at 15% [95% CI: 8-24%] for DM patients versus 26% [95% CI: 17-36%] in non-DM patients. Hazard ratio (for matched pairs) was 1.15 (95% CI: 0.75-1.77; p = 0.51). Conclusions: DM did not adversely impact survival in patients with pancreatic cancer. Pancreatic cancer did not affect glycemic control. Elevated ca 19-9 in diabetic patients may be an unreliable marker for gauging disease progression.
Prognostic impact of interval between diagnosis and surgery in patients with gastric cancer.
Authors: Kumazu Yuta , Hayashi Tsutomu , Hara Kentaro , Osakabe Hiroaki , Nagasawa Shinsuke , Nakazono Masato , Aoyama Toru , Yamada Takanobu , Sato Tsutomu , Rino Yasushi , Masuda Munetaka , Ogata Takashi , Yoshikawa Takaki
Published: January 2019

24

Background: Patients with gastric cancer should receive treatment for the cure as soon as possible because cancer cells are considered to grow and metastasize quickly. However, patients sometimes have to wait for the treatment because of further examinations of comorbidity, social background, and limited medical resources. It remained unclear whether interval between diagnosis and surgery is a risk factor for the survival. Methods: This retrospective single-center study examined 801 patients who visited outpatient clinic for gastric cancer and underwent curative surgery from 2006 to 2012 at Kanagawa Cancer Center in Japan. The patients who received neoadjuvant chemotherapy were excluded. Interval was defined as the time from the date of the first visit to the date of surgery. Interval was divided by the median and was classified to the early (less than median) and the late (exceeding the median) groups. Survival was analyzed by separating clinical T1 and T2-4. Results: 461 patients had clinical T1 and 340 had clinical T2-4. Median interval was 55 days (15-269 days) in clinical T1 and 35 days (10-148 days) in clinical T2-4, respectively. In clinical T1, 5-year survival rate was 93.1% in the early group and 91.2% in the late group (p = 0.456). In clinical T2-4, 5-year survival rate was 77.8% in the early group and 78.9% in the late group (p = 0.864). In the multivariate analysis, significant independent risk factors were over 75 years of age and clinical T4, and clinical N+, over 75 years of age in clinical T1, and over 75 years of age and clinical T4 in clinical T2-4. Interval was not significant factor both in clinical T1 (HR: 1.242, 95%CI 0.641-2.407 p = 0.522) and in clinical T2-4 (HR: 1.078, 95%CI 0.672-1.729 p = 0.756). Conclusions: Interval between diagnosis and surgery did not have a negative impact on the prognosis in patients with gastric cancer. Necessary interval for the clinical practice would be acceptable.
Points to keep in mind when carrying out clinical trials in Japan on advanced pancreatic cancer cases without alternative treatments: Analysis of 367 cases.
Authors: Tsurita Giichiro , Yasui Hiroshi , Kurokawa Tomohiro , Yoshioka Yuichiro , Yazawa Kentaro
Published: January 2019

243

Background: We commenced a physician-led clinical trial to examine the efficacy of a combined treatment of peptide vaccine therapy for advanced pancreatic cancer that has no effective treatment. During this trial, there were inquiries from 367 cases, of which 145 cases (40%) were examined at our outpatient clinic. The purpose of this study was to examine these cases in detail and to consider the points to be noted in executing clinical trials for poor prognosis cases. Methods: We examined the timing of inquiry, medical condition, the person(s) they inquired, and other relevant information regarding the 367 subjects who made inquiries. For the 145 cases visited the outpatient clinic of our hospital, we examined their medical condition, treatment and whether or not they have participated in a clinical trial. Results: 140 of the 367 cases (38%) of inquiry were concentrated within the first two months after the start. During these two months, there was a concentration of patients who had completed standard treatments and were a few months into BSC, but were unable to participate in the clinical trial due to deterioration of their general condition. Many of the inquiries were made by family members (spouse or child) of the patients, around twice the number of inquiries made by patients themselves. Even among the 145 subjects that were examined in the outpatient clinic of our hospital, severe cases, in particular, were seen several months after the start of the study. There were many cases that required urgent hospitalization during outpatient visits or patients whose general condition rapidly deteriorated during the screening tests. 23 cases (16%) underwent the clinical trial. Conclusions: In clinical trials such as this one, which handles cases with poor prognosis, many of the subjects are in poor general condition at the inquiry stage, and most of these inquiries are concentrated immediately after the start of the study. Therefore, it is very important to deal with inquiries and make judgments during the outpatient examination on whether or not clinical trial participation is possible.
Complications and seeding risk after percutaneous liver biopsy in an oncological setting.
Authors: De Paepe Katja , Bonne Lawrence , Fotiadis Nicos , Starling Naureen , Chau Ian , Gerlinger Marco , Rao Sheela , Watkins David J. , McCall James , Koh Dow-Mu , Brown Gina , Cunningham David
Published: January 2019

246

Background: Percutaneous biopsy of suspected liver metastases is a common practice for diagnostic purposes. Particularly, in the setting of oncological clinical trials, it is a relatively non-invasive method to obtain sufficient tissue for molecular analyses at regular set time points. However, various complications may occur, including seeding of the tumour along the biopsy tract. Only few reports exist on the actual incidence of seeding, on a limited number of tumor types. The aim of this study was to evaluate the technique’s safety and risk of seeding. Methods: All patients with an ultrasound or CT-guided liver biopsy between 2012-2016 were included. Medical records were reviewed retrospectively for post-biopsy complications and all follow-up imaging was re-assessed for the presence of seeding, defined as tumoral deposits in the biopsy needle tract. Results: In total 782 biopsies were performed in 550 patients (282 women, 268 men; mean age of 61 years), 43.9% (343/782) for trials and 56.1% (439/782) for diagnostic/molecular purposes, 93.7% (733/782) were diagnostic, revealing malignancy in 96.9% (710/733). Number of biopsies per patient ranged between 1 (n=387) to 7 (n=1), a co-axial system was used in 70.6% (552/782) and multiple passes in 29.4% (230/782). Complications were reported in 8.8% (69/782), more often pain (4.7%) and hypotension/vasovagal (2.3%). Admission and/or re-intervention were needed for more severe complications as bleeding (1.0%), sepsis/fever (1.1%), pulmonary embolism (0.3%) and pneumothorax (0.4%). Seeding was seen in 1.1% (8/782) of cases (2/44 melanoma, 1/11 GIST, 1/39 cholangiocarcinoma, 1/247 colorectal, 1/14 oesophagus, 1/97 breast, 1/31 prostate). Mean time for seeding was 208 days (range 43-469 d); mean post-biopsy survival time was 495 days in the seeding and 349 days in the non-seeding group. Conclusions: Percutaneous liver biopsy is a highly effective and safe method for tissue collection, with only a minimal risk of seeding.
Clinical features of hemobilia in unresectable pancreatic cancer (uPC).
Authors: Kimura Gen , Ohno Izumi , Inamura Kensuke , Watanabe Kazuo , Umemoto Kumiko , Suzuki Yuko , Sasaki Mitsuhito , Takahashi Hideaki , Hashimoto Yusuke , Imaoka Hiroshi , Mitsunaga Shuichi , Kobayashi Tatsushi , Ikeda Masafumi
Published: January 2019

247

Background: Hemobilia is a life-threatening, although rare event in uPC patient(pt)s. However, there are few reports about it. The purpose of this study was to identify it’s clinical features in uPC at our institute. Methods: Data of 2066 pts who received treatment for uPC between April 2008 and August 2017 were reviewed retrospectively from the electronic medical records. Hemobilia was determined when extravasation was detected from the biliary tree artery on contrast-enhanced computed tomography (CT) or angiography. Blood clot seen in the bile duct on endoscopy was also included. Pts whose bleeding was diagnosed due to tumor invasion of the stomach or duodenum by endoscopy were excluded. CT and angiography were reviewed by an experienced radiologist. Results: Eleven pts developed hemobilia; there were no pts before 2013. All of them received gemcitabine plus nab-paclitaxel (GnP) as first-line chemotherapy. Eight pts developed hemobilia during GnP, three had it after disease progression. Every pt had at least one symptom of Quinke’s triad; upper gastrointestinal hemorrhage (n = 8, 73%), biliary colic (n = 4, 36%), and jaundice (n = 6, 55%). The median time to hemobilia after the start of GnP was 198 days (range: 43-559 days). A covered self-expanding metal stent (cSEMS) was placed in the lower common bile duct in all pts. The median time to bleeding after cSEMS placement was 87 days (range: 30-467 days). Eight pts showed pseudoaneurysm(PA). In 7 of these pts, were diagnosed by CT, the remaining by interventional radiology(IR). IR was employed initially in 6 of the 8 pts, and hemostasis was successful in all. Two pts underwent cSEMS placement and was unsuccessful in both. Of these 2 pts, one underwent IR, with successful hemostasis. Of the remaining 3 pts, 2 pts had hemostasis without treatment, and one had cSEMS placement that was successful for hemostasis. Conclusions: In our study, hemobilia was only seen after 2014. Hemobilia developed after the start of GnP in all of the pts. Pts who showed PA, successful hemostasis was obtained in all cases that underwent IR. Hemobilia should be kept in mind as a cause of upper GI bleeding in uPC pts, especially those with a biliary stent and history of GnP. IR was effective for the management of hemobilia associated with PA.
Association of liquid biopsy and gastric cancer patients' prognosis: Comprehensive synopsis and a meta-analysis.
Authors: Chen Lin , Gao Yunhe , Xi Hongqing , Cui Jianxin , Cai Aizhen , Shen Weisong , Zhang Kecheng , Li Jiyang , Peng Zheng , Wei Bo
Published: January 2019

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Background: Liquid biopsy including circulating tumor cells (CTCs) and cell-free nucleic acids (cfNAs) has offered a minimally invasive approach for detection and measurement of gastric cancer (GC). Reports regarding associations between liquid biopsy and gastric cancer have been emerging rapidly in recent decades, yet their prognostic value still remains paradoxical. Methods: We searched Medline, Embase, Cochrane Central Register of Controlled Trials database for relevant studies that assessed the prognosis significance of CTCs and cfNAs in gastric cancer from peripheral blood(PB). Newcastle-Ottawa Scale (NOS) was used to assess the quality of evidence. Stata 12.0 was used for pooled analysis and subgroup analysis was performed to determine the association of CTCs or cfNAs’ presence and major clinical characteristics. Pooled results were displayed as hazard ratios (HRs) with their 95% confidence intervals (95% CI) with random effect models. Results: We identified 1258 studies, and then 43 were finally eligible for analysis. A total of 3792 patients were included for final evaluation. Pooled analysis showed that detection of certain CTCs, ctDNA or circulating miRNA was associated with poorer overall survival (OS) (CTCs, HR=2.05, 95%CI 1.65-2.55, p < 0.001; circulating miRNA HR=1.74, 95%CI 1.13-2.69, p=0.013; ctDNA, HR=1.77, 95%CI 1.28-2.44, p=0.001) and disease-free survival(DFS) (CTCs, HR=2.92, 95%CI 1.93-4.40, p < 0.001; circulating miRNA, HR=3.30, 95%CI 2.39-4.55, p < 0.001; ctDNA, HR=4.69, 95%CI 2.23-9.86, p < 0.001) of gastric cancer patients, regardless of the disease’s early or late stage. Conclusions: Several high-quality circulating biomarkers or detection methods for gastric cancer prognosis prediction were identified by subgroup analysis, including the Cellsearch system, cytokeratins, miR-20a, miR-200c, etc. Detection of these certain dysregulation circulating markers in patients’ PB indicates poor prognosis with advanced GC patients.
Method of diagnosis of pancreatic adenocarcinoma: A Nova Scotia experience.
Authors: Lees Caitlin , Hopman Wilma M , Younis Tallal , Lamond Nathan William Dana , Ramjeesingh Ravi
Published: January 2019

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Background: The gold standard for the diagnosis of pancreatic adenocarcinoma involves pathologic confirmation, as identified in consensus guidelines. Little is known about the care of patients with pancreatic cancer in Nova Scotia. This retrospective study intends to clarify the methods utilized in Nova Scotia to diagnose pancreatic adenocarcinoma and identify variables associated with pathologic confirmation of diagnosis. Methods: A provincial database, involving patients diagnosed with unresectable pancreatic adenocarcinoma between January 1, 2011 and December 31, 2014, was created as identified by the surveillance and epidemiology unit of the program of care for cancer. Pearson chi-square was used to determine significant differences between groups and logistic regression was used to identify those variables associated with a specific pathologic diagnosis. Results: Of the 264 patients identified, most were diagnosed by a combination of imaging and an elevated CA 19-9 level (n = 120, 45.5%) and 24.2% (n = 64) by imaging alone. Significant predictors of diagnosis by imaging alone included i) age 65 or more vs less than 65 (n = 55, 31.3% vs n = 9, 10.2%; p = 0.001), and ii) living in areas served by community hospitals (rather than a tertiary care centre) (n = 46, 28.6% vs n = 18, 17.5%; p = 0.014). A pathologic diagnosis was attempted (non-diagnostic or positive) in 40.2% of patients (n = 106), and a pathologic diagnosis was actually obtained in 30.3% of patients (n = 80). Patients were significantly less likely to have an attempted pathologic diagnosis if they were over 65 (OR = 1.95, 95% CI 1.13 – 3.38), female (OR = 1.78, 95% CI 1.05 – 3.01), or resided in a community with a tertiary care centre (OR = 2.02, 95% CI = 1.17 – 3.49). Conclusions: A significant majority of patients in Nova Scotia were diagnosed with pancreatic adenocarcinoma without pathological confirmation, and nearly a quarter of these patients were diagnosed on the basis of imaging alone. The lack of pathologic diagnosis does not conform to consensus guidelines of management of pancreatic cancer and suggests that more work needs to be done to improve care for these patients.
The expression of versican and its role in pancreatic neuroendocrine tumors.
Authors: Sun Zhao , Gao Heli , Gu Junjie , Cheng Yuejuan , Chen Yuanjia , Bai Chunmei
Published: January 2019

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Background: Pancreatic neuroendocrine tumor (pNET) is a group of rare and heterogeneous tumor. Prognostic biomarkers are essential to better predict patients’ prognosis and approve individualized chemotherapy. According to references, Versican(VCAN) expression plays an important role in the development of various tumors.Our previous study found VCAN had a tumor-specific expression in pNET tissues. Therefore, further study is performed to investigate the relationship between VCAN expression in pNET tissues and patients’ prognosis. Methods: Clinicopathological data of pNET patients who underwent surgery between 2005 and 2010 were collected, followed up and evaluated. VCAN expression was assessed by immunohistochemical (IHC) staining. The relationship between VCAN expression and clinicopathological characteristics of patients were analyzed by Chi square. The expression between VCAN expression and disease-free survival (DFS) of patients were analyzed by Kaplan-Meier. The relationship between patients’ DFS and relative clinicopathological characters were analyzed by Cox regression. Results: 174 pNET patients were enrolled in our research. Among them, 124 patients were VCAN positive and 50 were VCAN negative. VCAN expression was significantly associated with tumor stage. Better disease-free survival (DFS) was observed in patients with VCAN positive compared to those with VCAN negative (124.1±75.71m,99.35±12.14,respectively, p = 0.003).Multivariate analysis demonstrated that VCAN expression, Grade, tumor size were independent prognostic predictor for patients’ prognosis(p = 0.01,0.000,0.001,respectively). Subgroup analysis revealed that VCAN positive predicted a better DFS in patients with Grade 2, Tumor size > 2cm, and Non-functional tumor(p = 0.04,0.002,0.01,respectively). Conclusions: pNET patients with VCAN positive had a longer DFS.
A study of the combination of oxaliplatin, capecitabine, and trastuzumab and chemo-radiotherapy in the adjuvant setting in operated patients with HER2+ gastric or gastroesophageal junction cancer (TOXAG study).
Authors: Abali Huseyin , Yalcin Suayib , Onal Cem , Dane Faysal , Oksuzoglu Berna , Ozdemir Nuriye , Mertsoylu Huseyin , Artac Mehmet , Camci Celaletdin , Karabulut Bulent , Basal Fatma Bugdaycı , Budakoglu Burcin , Sendur Mehmet Ali Nahit , Goktas Burce , Ozdener Fatih , Baygul Arzu
Published: January 2019

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Background: We evaluated the safety and tolerability of trastuzumab (T) in combination with oxaliplatin (O), capecitabine (C) and chemo-radiotherapy in the adjuvant setting in operated, HER-2 positive gastric or gastroesophageal junction adenocarcinoma patients. Methods: We have screened 212 and enrolled 34 patients who were curatively resected (R0, R1 with partial or total gastrectomy, with D2 lymph node dissection) and were HER2-positive (IHC 2+/FISH+ or IHC 3+). The primary objectives were safety and tolerability of the treatment combination and secondary objectives were disease-free and overall survival rates. Patients received T 8 mg/kg intravenously (iv) on Day 1 of cycle 1 and 6 mg/kg iv on day 1 of every following 3-weekly cycle for 1 year as 17 cycles, O 100 mg/m2 iv on Day 1 of cycles 1-3 and C 850 mg/m2 orally twice daily on days 1-14 of cycles 1-3 and 5 days per week during chemo-radiotherapy. Radiotherapy was given at a total dose of 45 Gy divided into 25 doses 5 treatment days per week for 5 weeks starting from the 1st day of cycle 4. Results: The median age was 57 years and 73.5% were male, 97.0% had an ECOG PS score ≤ 1,33, 97.0% had D2 lymph node resection. Staging was 3A or higher at the time of diagnosis in 76.4% of patients. Patients had high rate of tolerability to the combination regimen (90.3%) and successfully completed 3 cycles of O+C+T plus chemoradiotherapy followed by continuation with T, achieving the primary goal of the study by showing a better tolerability rate as compared to tolerability reported for INT0116 study (p = 0.0068). After 25 months of follow-up confirmed through a telephone visit, 59.8% patients were still alive and median overall survival was not yet reached. Twelve patients died secondary to disease progression. There were no deaths due to toxicity and 6 dose reductions overall (1 for T, 2 for O and 3 for C). T was stopped in one patient; C was temporarily interrupted 11 times (mostly during radiotherapy) and stopped in 1 patient. Conclusions: T in combination with C, O and radiotherapy in the adjuvant setting for gastric or gastroesophageal junction adenocarcinoma seems safe and tolerable. Clinical trial information: NCT01748773.
Pancreatic adenocarcinoma in young adults (≤45 years old): Characteristics and clinical outcomes from a Canadian center.
Authors: Desilets Antoine , Aubin Francine , Amireault Carl , Ayoub Jean-Pierre M. , Letourneau Richard , Tehfe Mustapha
Published: January 2019

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Background: Clinical data concerning pancreatic adenocarcinoma (PAC) in young adults is restricted. Limited evidence might suggest a worse prognosis in terms of overall survival (OS) and progression-free survival (PFS), when compared to an older population. Methods: The studied population included adults ≤45 diagnosed with a PAC (stages I to IV) between January 2006 and December 2016 at University of Montreal Health Center (CHUM), a tertiary care referral center in Canada. Clinical data was retrospectively extracted from chart review. The Kaplan Meier estimator was used for survival analyses. Results: 36 patients were identified in the study (median age 41.6, 56% males). Most patients (61%) had localized disease at diagnosis, with 22% presenting with metastases. The head of the pancreas was the primary site involved in 75% of cases. Most patients (63%) had a positive smoking history, with a median number of pack-years of 15. A personal history of cancer was present in 20% (n = 7) and 14% had a positive family history of PAC. Surgery was performed in 58% of individuals and systemic chemotherapy was offered to 89%. First-line agents included gemcitabine-based treatments (72%), FOLFIRINOX (19%) and 5-FU (9%). Despite treatment, 33% showed evidence of disease progression on initial follow-up imaging. Second-line chemotherapy was ultimately offered to 18 patients, and third-line treatments to 5. Survival data is described in the table below. Conclusions: According to our results, young patients with localized PAC may benefit from prolonged OS when compared to the literature. This could be attributed to a favourable comorbidity profile and increased surgical eligibility. Advanced stages however demonstrated a worse prognosis, with shorter OS. Young patients with PAC may also harbor a specific genetic profile, based on increased prevalence of personal and familial cancers. [Table: see text]