bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical implication of peritoneal cytology in the pancreatic cancer patients who underwent curative resection followed by adjuvant gemcitabine or s-1 chemotherapy.
Authors: Katayama Yusuke , Aoyama Toru , Murakawa Masaaki , Asari Masahiro , Yamaoku Koichiro , Kanazawa Amane , Higuchi Akio , Shiozawa Manabu , Ueno Makoto , Morimoto Manabu , Akaike Makoto , Oshima Takashi , Rino Yasushi , Masuda Munetaka , Morinaga Soichiro 
Published: February 2017

252 Background: The clinical implications of peritoneal lavage cytology (CY) status in the patients who received curative resection and adjuvant chemotherapy have not been established. The clinical implications of peritoneal lavage cytology (CY) status in the patients who received curative resection and adjuvant chemotherapy have not been established. Methods: We retrospectively analyzed clinical data from 143 consecutive patients who underwent macroscopically curative resection and received adjuvant gemcitabine or S-1 chemotherapy for pancreatic cancer from 2005 to 2014 in our institution. Correlations between CY status and survival and clinicopathological features were investigated. Results: Of the 143 patients, 21 patients were peritoneal washing cytology positive (CY+) (14.7%). Although significant difference was observed in the tumor size, no other correlation between cytology status and clinicopathological parameter existed (age, gender, histology, UICC T status, LN metastasis, lymphovascular invasion). The recurrence free survival (RFS) rates at 3 and 5 years after surgery were 5.1% and 0% in CY+ patients, respectively, and were 21.5% and 16.1% in peritoneal washing cytology negative (CY-) patients, respectively, which were significantly different (p<0.001). On the other hands, the OS rates at 3 and 5 years after surgery were 17.1% and 8.6% in CY+ patients, respectively, and were 26.1% and 16.1% in CY- patients, respectively, which were trend to worse in the CY+ patients. However, there was not significantly different (p=0.254). Conclusions: The patients with CY+ are likely to experience recurrence, even after they received curative resection and adjuvant Gemcitabine or S-1adjuvant chemotherapy. To improve the patient’s survival, it is necessary to develop efficient treatment for CY+ patients.
Significance of serum interleukin-6 in patients treated with radiotherapy for hepatocellular carcinoma.
Authors: Cha Hyejung , Lee Eun Jung , Seong Jinsil 
Published: February 2017

254 Background: Interleukin-6 (IL-6) is reported to contribute to aggressive tumor growth and resistance to treatment. In several cancers including esophagus, head and neck, and pancreas, high IL-6 is associated with poor treatment outcome after radiotherapy (RT). However, reports about significance of IL-6 in RT for HCC were rare. The aim of this study was to investigate the significance of serum IL-6 with treatment outcome in patients treated with RT for HCC. Methods: For patients treated with RT for HCC, blood samples were collected prospectively, before start and after completion of RT schedule. Serum IL-6 levels were measured with enzyme-linked immunosorbent assay kit. Patients’ clinical profiles were recorded. Results: Between September 2008 and October 2009, 51 patients were included in this study. Median follow-up duration was 12.3 months (range, 0.5-62.3). Baseline serum IL-6 level was 31.63 pg/ml and patients who had treatment history before RT showed higher baseline serum IL-6 levels than treatment (Tx)-naïve patients (53.09 vs. 15.35, p=0.028). Baseline IL-6 levels were higher in patients showing infield failure (59.70 vs. 14.96, p=0.022) and extrahepatic failure (40.50 vs. 17.88, p=0.072). In patients who had treatment history before RT, higher baseline IL-6 levels were associated with both infield and extrahepatic failure (p=0.014, p=0.032, respectively) in. However, this significance was not found in Tx-naïve patients. Higher baseline IL-6 levels were associated with short infield PFS (p<0.0001) in entire patients and in patients who had treatment history before RT. After RT, serum IL-6 level decreased but it was not significant (29.54 pg/ml, p=0.794). And variation of serum IL-6 level was not associated with treatment failure. Conclusions: Baseline serum IL-6 levels seem significant in predicting treatment outcome in patients treated with RT for HCC. High baseline serum IL-6 levels were associated with infield and extrahepatic failure, especially in patients who had treatment history before RT.
Accuracy of diagnosing pancreatic ductal adenocarcinoma by EUS-FNA at a single institution.
Authors: Beal Hannah , Shea Jill E. , Witt Benjamin , Adler Douglas G. , Mulvihill Sean J. , Downs-Kelly Erinn , Firpo Matthew A. , Scaife Courtney L. 
Published: February 2017

258 Background: Endoscopic ultrasound-directed fine needle aspiration (EUS-FNA) in combination with imaging is currently the standard preoperative diagnostic method for pancreatic ductal adenocarcinoma (PDA). Previous studies have reported sensitivities and specificities ranging from 80%-90% and accuracies of approximately 85%. Our goal was to determine the accuracy of EUS-FNA for detecting PDA in individual patients at our institution. Methods: We conducted a retrospective chart review using the Clinical Cancer Research Database at Huntsman Cancer Institute (HCI). We included all cases in which pancreatic lesions were evaluated by EUS-FNA and a subsequent surgical resection was performed. All patients that met these criteria at HCI between March 1999 and April 2014 were included. Descriptive variables were calculated by comparing EUS-FNA results to final surgical diagnoses. The variables used to determine these values were; false positive = PDA by EUS-FNA and negative at resection, true positive = PDA for both, false negative = negative for PDA at EUS-FNA and positive at resection, true negative = negative for both. We considered atypical cells positive for PDA since their presence mandates aggressive intervention by the treating clinician. Results: Of the 242 patients that met the inclusion criterion, 139 were female with an average age of 58 +/- 15 (mean +/- standard deviation) and 103 were male with an average age of 62 +/- 13. In terms of diagnosing PDA by EUS-FNA we determined the sensitivity 89% (81%-94%; 95% confidence interval), specificity 76% (68%-83%), positive predictive value of 74% (66%-82%), and negative predictive value 89% (82%-94%). Conclusions: Although our findings are relatively consistent with the current literature, there is discernible potential for inappropriate treatment of patients based purely on EUS-FNA evaluation. Limitations of this study are the appraisal at a single institution and the necessity to evaluate only cases that ultimately had surgical resection of the pancreatic lesion.
Association of pancreatic metastasectomy for melanoma with long-term overall survival: A single-institution experience.
Authors: Doepker Matthew , Juan TzuHua , Chen Dung-Tsa , Nguyen Phuong , Sarnaik Amod , Pimiento Jose Mario , Hodul Pamela Joy , Malafa Mokenge Peter 
Published: February 2017

264 Background: Isolated metastatic melanoma to the pancreas is extremely rare. A recent pooled analysis evaluated 11 patients(pts) with metastatic melanoma to the pancreas and reported a median disease free interval(DFI) between the diagnosis of the primary cancer to the diagnosis of the isolated pancreatic metastasis of 48 months and a 5-year overall survival(OS) of 27%. The purpose of this study was to review our experience with resection of metastatic melanoma to the pancreas and compare it to the more common metastatic renal cell carcinoma(RCC) to the pancreas. Methods: Pts with pancreatic metastasis followed by metastasectomy were identified at a single institution from 1998 to 2013. The Kaplan-Meier method was used to report 5-year OS and disease-specific survival (DSS). Results: We identified24 pts with isolated metastasis to the pancreas that underwent curative resections. Eighteen (75%) were males and the overall median age was 64. Eleven RCC (45.8%), 4 melanomas (16.7%), and 9 other histologies (37.5%) were noted. The median DFI between the diagnosis of the primary cancer to the diagnosis of the isolated pancreatic metastasis for RCC, melanoma, and other histologies was 91.3 months (range, 2.0-361.6), 77.8 months (range, 65.3-97.4), and 55.4 months (range, 7.6-154.8) respectively. Nineteen distal pancreatectomies (79.2%) and 5 pancreaticoduodenectomies (20.8%) were performed. Five-year OS and DSS were 51% and 65%. Pts with metastatic melanoma to the pancreas had a 5-year OS of 67% (95% CI=0.05, 0.95) compared to 65% and 30% for RCC and other histologies respectively. The 5-year DSS for pts with melanoma was 67% (95% CI=0.05, 0.95) vs 100% for RCC and 34% for other histologies. After a median follow up of 39.9 months, all melanoma pts recurred after resection, with a median time to recurrence of 17.7 months. Of the 24, 10 died of disease. Conclusions: We report the largest series on pancreatic metastasectomy for melanoma. Our data show comparable DFI and survival to RCC, along with higher OS compared to previously reported data. Pancreatic metastasectomy for melanoma should be considered as evidenced by prolonged DFI and higher OS.
Initial evaluation of patients diagnosed with pancreatic cancer within a community health system.
Authors: Chen Kathryn Tzung-Kai 
Published: February 2017

269 Background: The management of pancreatic patients who are referred to a tertiary care center is well described. However, many patients receive their initial evaluation and care at community health systems. We sought to describe how patients present within the community, the patterns of initial evaluation, and the impact on management. Methods: In a period spanning 3 years (2010-2013), 82 patients were newly diagnosed with pancreatic cancer, as identified by a cancer registry at a community health system. Under IRB approval, data regarding patient characteristics, initial evaluation, and management were retrospectively collected from the electronic medical record (EMR) and analyzed. Results: Of the 82 patients, 68 patients had sufficient data available in the EMR for analysis. Thirty-two patients (47%) initially presented to outpatient clinic, and 36 patients (53%) presented to the emergency department. The presenting complaint was identified as abdominal pain in 33 patients (49%), jaundice in 20 patients (29%), and general malaise in 9 patients (13%). Patients who presented through outpatient clinic vs. emergency department received similar initial imaging studies upfront, including CT of the abdomen and pelvis (61% vs. 72%) and abdominal ultrasound (27% vs. 17%). Sixteen percent of those patients evaluated in outpatient clinic were subsequently admitted, compared to 94% of those patients evaluated in the emergency department. Finally, 31% of those presenting in outpatient clinic eventually underwent surgical resection, compared to 8% of those presenting through the ER, and the median time to surgery for the entire cohort was 1.1 months. Conclusions: Within the community, half of all patients present through the emergency department, and the majority of these are admitted for work up and management of symptoms. In contrast, those patients who present through outpatient clinic are less likely to be admitted, and are more likely to undergo definitive resection. This likely represents a disparity on several levels: the acuity of patients presenting to the emergency department vs. clinic, and how they are managed in each setting.
The efficacy of prophylactic GCSF for FOLFIRINOX.
Authors: Terazawa Tetsuji , Goto Masahiro , Takahiro Miyamoto , Asaishi Ken , Shimamoto Fukutaro , Kuwakado Shin , Nishitani Hitoshi , Kii Takayuki , Higuchi Kazuhide 
Published: February 2017

274 Background: Granulocyte Colony-Stimulating Factors (GCSF) is used as supportive care in cancer management when patients (pts) receive chemotherapy with high risk of febrile neutropenia (FN). Peg-GCSF is unapproved in Japan at the time of Aug 2014. Hence, phase II study of combination chemotherapy regimen consisting of oxaliplatin, irinotecan, fluorouracil, and leucovorin (FOLFIRINOX) for Japanese pts with advanced pancreatic cancer showed FN; 22% and severe neutropenia; 77.8%. Purpose of this retrospective study was to describe the incidence of FN and severe neutropenia during the first cycle of FOLFIRINOX with prophylactic GCSF (pGSF). Methods: Between January 2014 and August 2014, the pts who received FOLFIRINOX with pGCSF were examined retrospectively. The adverse events and detail of pGCSF administration during first cycle were investigated. Results: Among five pts administered FOLFIRINOX, 4 pts received pGSF in first cycle. All patients received FOLFIRINOX without dose reduction. The patient characteristics were as follows: median age (range), 58 (50-66); male/ female, 3/1; PS 0/1, 1/3. The detail of UTG1A1 (*6/ *28) was as follows: (wild type/ wild type), 2pts; (wild/ hetero), 1pt; (hetero/ hetero), 1pt. Hematological adverse events (grade 1/2/3/4) were as follows: leukopenia (0/1/2/0), neutropenia (0/1/0/1), thrombocytopenia (0/4/0/0), FN (0/0/1/0). The patient who occurred grade4 neutropenia and grade3 febrile neutropenia had UTG1A1 *6 hetero/ *28 hetero. Non-hematological adverse events (grade 1/2/3/4) were as follows: elevated GOT (2/1/0/0), elevated GPT (2/1/0/0), elevated T-Bil (0/0/0/0), anorexia (1/2/1/0), fatigue (2/1/0/0), nausea (0/1/2/0), diarrhea (1/1/0/0). The median starting date of pGSF administration was 4.5 (3-7). The median number of pGSF administration was 7.5 (6-9). Conclusions: Although this was retrospective and small study, pGSF appeared to be effective for prevention of severe neutropenia and FN. Hence pGSF might increase dose intensity of FOLFIRINOX.
Comprehensive multiplatform biomarker analysis of 313 hepatocellular carcinoma to identify potential therapeutic options.
Authors: Abou-Alfa Ghassan K. , Miura John Thomas , Gamblin T. Clark , Xiu Joanne , Millis Sherri Z. , Gatalica Zoran , Reddy Sandeep K. , Ang Celina , Yee Nelson S. 
Published: February 2017

283 Background: Effective treatment strategies for hepatocellular carcinoma (HCC) remain limited. Identification of additional therapies remains paramount as currently available agents have resulted in marginal improvements in overall survival. Methods: 313 HCC sampleswere evaluated using a multiplatform profiling service (Caris Life Sciences, Phoenix, AZ), including gene sequencing (Sanger, NGS [N=79]), protein expression (IHC) and gene amplification (ISH). Results: Biomarker changes of interest are shown. See Table. TP53 was mutated in 28%, CTNNB1 in 23%, and BRCA2 in 20%; other gene mutation rates were < 5%.TP53-mutated tumors show significantly higher TOPO2A (89% vs. 39%, p<0.0001), TS (70% vs. 32%, p=0.0067) and RRM1 expression (40% vs. 12%, p=0.017), implying high rates of proliferation and DNA synthesis. CTNNB1-mutated tumors showed significantly higher SPARC (67% vs. 21%, p=0.0013) and AR expression (53% vs. 22%, p=0.025). Primary HCC (N=209) exhibited significantly higher PD-1 (89% vs. 33%, p=0.01) and TS expression (35% vs. 13%, p<0.0001) than metastatic (N=105). Patient history/outcomes relative to biomarker status are being evaluated. Conclusions: These data suggest potential therapeutic targets, such as tyrosine kinase inhibitors, anti-PD1 agents, or PI3 kinase pathway inhibitors. Although no evidence shows that cytotoxics are effective in patients with HCC, irinotecan, alkylating agents, fluoropyrimidines, anthracyclines, nab-paclitaxel, gemcitabine, or taxanes may be therapeutically relevant. The protein changes associated with CTNNB1-mutated tumors suggest potential benefit of targeting WNT pathway in combination with nab-paclitaxel or anti-androgens. Immuno-modulatory agents may be a therapeutic option in primary HCC, based on the higher levels of PD-1. Multiplatform tumor profiling reveals molecular heterogeneity HCC, similar overall to previous reports, and identifies different potential treatment options for molecular subtypes. [Table: see text]
Neuroendocrine gene transcript analysis of blood to define the completeness of surgical resection and identify stable or progressive neuroendocrine tumor disease.
Authors: Kidd Mark S. , Modlin Irvin Mark , Frilling Andrea , Alaimo Daniele , Callahan Stephen , Bodei Lisa , Drozdov Ignat 
Published: February 2017

293 Background: A critical requirement in NET management is a sensitive, specific, reproducible blood biomarker test. Surgery and somatostatin analogs (SSAs) are widely used but efficacy is difficult to determine. Imaging is relatively insensitive for residual/recurrent disease determination and symptoms remains the only way to determine SSA efficacy. We evaluated a PCR-based 51 transcript signature (NETest) comparing it to CgA to determine whether biomarkers were effective in defining surgical resection and SSA efficacy. Methods: GEP-NETs (n=50) [M:F 19:31; median age: 58 years, small intestine: n=35, pancreas n=9, rectum n=3, appendix: n=2, stomach n=1] were evaluated. Groups included surgery (n=15, R0-no disease), and SSA therapy (n=35). qRT-PCR was used for transcript measurement, ELISA (DAKO) for CgA and imaging (RECIST) for clinical status. NETest defined risk of disease activity (low disease activity risk <47%, high risk 47-100%). Results: Resection decreased NETest (pre-surgery: 80±6%; 1 post-surgery: 29±6%, p<0.0001). Thirteen (87%) were high risk before surgery; post-surgery two (13%) remained high risk (despite lowered score), 11 (74%) were low risk and 2 normal. Four (26%) developed recurrence at 6 months. CgA levels were non-informative. In the SSA group, the NETest was lower in clinically stable disease (32±3.7%; n=25) than in progressive disease (82±4.3%, n=10; p<0.0001). All patients in the latter were categorized as high risk disease activity. The accuracy for differentiating stable from active disease was 92% (sensitivity=100%, specificity=88%). Three SSA patients developed clinically progressive disease with concordant increases in NETest. CgA levels were not significant and were non-informative. Conclusions: NET transcript analysis accurately defined surgical cytoreduction and identified biochemical evidence of residual disease. NETest also accurately identified stable and progressive clinical disease activity during SSA treatment. Blood-based multigene analytic measurement will facilitate early detection of residual/recurrent disease and further define therapeutic efficacy for surgery and SSAs.
Effect of targeting tumor-infiltrating myeloid cells on tumor progression in pancreatic adenocarcinoma.
Authors: Nywening Timothy M. , Belt Brian , Cusworth Brian M , Panni Roheena Z. , Sanford Dominic E. , Goedegebuure Peter S. , Linehan David 
Published: February 2017

298 Background: Human pancreas cancer (PC) is associated with a heavy desmoplastic reaction and influx of bone marrow derived myeloid cells. Recruitment of these cells by the tumor allows for PC to create a favorable microenvironment that is immunosuppressive. Our work demonstrates that the most abundant type of myeloid cell in PC is granulocytes, which are positive for the chemokine receptor CXCR2. This receptor is vital for the trafficking of granulocytes from the peripheral blood to the tumor, therefore selective targeting of these cells via CXCR2 blockade may lead to potential clinical benefit in patients with PC. Methods: Human samples were obtained under IRB approved protocol at Washington University.C57BL/6 mice were injected subcutaneously or orthotopically with syngeneic PC (KCKO) cells and treated with vehicle or inhibitor daily. Tumor size was determined by caliper measurements and weight. Flow cytometry was performed and samples analyzed for myeloid markers. Results: Human PC patients have elevated levels of CXCR2+ granulocytes in the peripheral blood (p=0.02) and tumor microenvironment (p=0.002) compared to controls. In a murine model, CXCR2 inhibition reduces tumor infiltrating granulocytes (p=0.02) which was associated with a reduction in tumor growth in both a subcutaneous and orthotopic model (p=0.03). Our group has previously demonstrated that targeting the monocytic subset of myeloid cells in PC is an effective treatment strategy (p=0.02). Surprisingly, neither antagonist alone was effective at significantly decreasing the total tumor myeloid infiltrate and treatment with CCR2 inhibitor alone increased tumor infiltrating granulocytes (p=0.03). However, both therapies in combination resulted in a significant reduction in total tumor myeloid infiltrate (p<0.05) and was synergistic in regards to tumor reduction compared to either therapy alone (p<0.05). Conclusions: Human PC has an abundant CXCR2+ granulocytic infiltrate and blockade of CXCR2 may translate to potential clinically useful therapies.
Targeting the Rho-ROCK pathway to treat pancreatic cancer: The use of unique preclinical models to ascertain the effects on cancer growth and metastasis.
Authors: Chin Venessa T. , Conway James , Nagrial Adnan , Chantrill Lorraine A. , Chou Angela , Steinmann Angela , Gill Anthony , Pinese Mark , Wu Jiamin , Johns Amber , Dury Alison , Biankin Andrew , Timpson Paul , Pajic Marina 
Published: February 2017

312 Background: Pancreatic cancer (PC) is a highly lethal and genetically heterogenous disease. Genomic sequence data from the Australian Pancreatic Cancer Genome Initiative (APGI) has identified a subset of patients with ROCK-1 amplification. ROCK-1 is a downstream target of Rho, a small GTPase that plays an important role in regulating proliferation, invasion and metastasis of cancer cells. Our aim was to analyse the effects of inhibiting ROCK-1 using specific small molecule inhibitors (Fasudil and Y-27632) in well annotated and robust pre-clinical model systems generated as part of our APGI efforts. Methods: Patient derived cell lines (PDCL) and xenografts (PDX) were used to test the effectiveness of ROCK-1 inhibitors (RI). Colony formation and 3-D organotypic assays tested cellular proliferation and invasion. In vivo, pre-clinical trials assessed the effect gemcitabine (G) +/- RI on a range of PDXs with varying tumour ROCK expression, including one G resistant model. A PDCL shown to form metastases when injected orthotopically into mice has been labeled with firefly luciferase. The effect of RI on metastasis formation will be assessed in vivo using real time imaging. Results: ROCK inhibition has a differential effect on colony formation on PDCLs in vitro, and inhibits cellular invasion. A statistically significant increase in median survival in the G + RI group compared with G alone, was seen in 3 PDXs, including the G resistant tumour. 1 PDX showed a decrease in tumour size at 200 days in the G + RI group. Conclusions: ROCK inhibition has a differential effect in vitro, but an anti-tumour effect in vivo, including overcoming resistance to G. This suggests that effects on the tumour micro-environment are an important mechanism of action. RI have the potential to be an effective therapy in PC.