bluuebunny/crossref_metadata_2025_split huggingface dataset:
KRAS mutations and relation to prognosis in patients operated for localized pancreatic cancer and other periampullary cancers
Authors: Schultz N. A. , Roslind A. , Christensen I. J. , Gaustadnes M. , Johansen J. S. , Kruhøffer M. , Horn T. , Wøjdemann M. 
Published: August 2020

e15618 Background: Prognostic biomarkers in patients with pancreatic cancer might direct patients to optimal treatment. We studied the prognostic value of KRAS mutations in patients operated for pancreatic and other periampullary cancers. Methods: Retrospective study of 328 patients who were operated with a Whipples procedure at a single HBP-center during the period August 1976 to May 2008. For the present pilot study cancer tissue blocks were collected from 58 patients (31 men, 27 women, median age 64, range 33–81 years, ASA 1–3). All had localized pancreatic (n=26), ampullary (n=26) or duodenal cancer (n=6) and were operated during the period June 2001 to May 2008. 32 patients died (3 within the first month after operation and were excluded). Median follow-up time was 41 months (range 7–90). KRAS mutations in exon 1 and 2 were determined by LightScanner analysis (Idaho Technology). Results: KRAS mutations were found in 32 (55%) of the patients; 16 (62%) patients with pancreatic cancer, 13 (50%) with ampullary cancer and in 3 (50%) with duodenal cancer. KRAS status was neither associated with type of cancer (p=0.68), TNM stage (T stage p=0.64, N stage p=0.31). The median survival time for all patients was 22 months (KRAS mutation: 21, 95% CI: 10–40; Wildtype: not reached yet). Univariate Cox analysis showed that T stage (TNM) (1: HR=0.09, 95% CI: 0.02–0.48 p=0.004; 2: HR=0.18, 0.06- 0.51, p=0.0013; 3: HR=0.26, 0.09–0.71, p=0.0089) was a prognostic factor of OS. KRAS status (HR=0.70, 0.33–1.49, p=0.36) and N stage (TNM) (HR=0.53, 0.25–1.11, p=0.09) were not significant factors of OS, but there is a strong tendency for both factors. Conclusions: KRAS mutations are frequent in patients with localized pancreatic, ampullary and duodenal cancers. Preliminary analysis of 58 patients out of our cohort of 328 patients indicate that KRAS mutations may be a marker of overall survival and time to progression. No significant financial relationships to disclose.
A single institution experience with neoadjuvant chemoradiation (CRT) with irinotecan (I) and cisplatin (C) in locally advanced esophageal carcinoma (LAEC)
Authors: Sharma R. , Yang G. Y. , Nava H. R. , Demmy T. L. , Nwogu C. E. , Yendamuri S. S. , Lamonica D. , Tan W. , Iyer R. V. , Khushalani N. I. 
Published: August 2020

e15619 Background: Multimodal therapy is considered standard for LAEC with cisplatin and 5FU-based CRT being commonly used, though with significant toxicity. Novel agents are needed to improve pathologic response (pCR) which predicts for better prognosis. We analyzed our experience with CRT using I + C in LAEC. Methods: LAEC patients (PTS) who underwent surgery preceded by CRT with I + C were identified from the Roswell Park tumor registry. Treatment consisted of Day 1,8 of C 30mg/m2 and I 65mg/m2in a 21 day cycle. PTS concurrently received 45–50.4 Gy radiation in1.8Gy fractions. Data retrieved included toxicity, pCR rate and survival. Results: 44 eligible PTS, median age 61 yr, 43 males and 1 female. Histology included adenocarcinoma (n=38), squamous cell (n=4), mixed (n=2); 12 PTS had signet-ring cell features. 29 PTS had poorly differentiated tumors. Clinical stage was II (n=5), III (n=24), IVa(n=6), IVb(n=1), not available (n=8). ECOG PS was 0 (n=34) and 1 (n=10). Most common toxicities observed were fatigue (n=24), diarrhea (n=19), vomiting (n=15), hematologic (n=11), constipation (n=11) and neurologic (n=7). Dose delay or reduction was required in 10 PTS, usually from hematologic toxicity. Of these,1 week delay in 45% and 2 weeks in 36%; 1 PT discontinued treatment due to toxicity. There was no CRT-related mortality. 2 PTS died post-operatively (anastamotic leak and sepsis). Dyphagia improved in 33/35 (94%) PTS following CRT. All PTS underwent R0 resection and pCR rate was 25% (11/44). 15 PTS have experienced recurrence. The median disease-free and overall survival is 24 months and 34 months, respectively; 3-yr overall survival is 46%. Available pre- and post-CRT FDG uptake on PET imaging in 28 PTS did not correlate with pCR status (p=0.77). Conclusions: Neo-adjuvant CRT with I + C has modest efficacy in the treatment of LAEC and can be given safely in the out-patient setting. PTS should be monitored closely for toxicity, specifically diarrhea that requires prompt intervention. Efficacy results appear better than those reported in ECOG 1201. This regimen is being evaluated in CALGB 80302 and results are awaited. No significant financial relationships to disclose.
Pharmacokinetics of intraperitoneal docetaxel and S-1 in patients with gastric cancer with peritoneal carcinomatosis
Authors: Kamikozuru H. , Hayashi K. , Kuramochi H. , Nakajima G. , Yamamoto M. 
Published: August 2020

e15626 Background: One of the most causes of death from gastric cancer is peritoneal cartinomatosis. Intraperitoneal docetaxel infusion is expected to be a new strategy for a treatment of peritoneal carcinomatosis. The purpose of this study is to evaluate the plasma and peritoneal pharmacokinetic of intraperitoneal docetaxel infusion in combination with oral administration of S-1. Methods: Eight patients with peritoneal carcinomatosis of advanced gastric cancer were enrolled. Docetaxel was dissolved in an isotonic saline to a final 1 liter solution and administered in 2 hour via an implanted intraperitoneal catheter at dosage of 40mg/m2. Five of eight patients were administered S-1 orally at dosage of 80mg/m2. Blood and peritoneal fluid were collected before administration, on completion of the docetaxel infusion(hour 0) and at hours 1,2,4,6,12,24,48,and 72 after completion of the infusion of the docetaxel. Plasma and peritoneal fluid concentrations of docetaxel and 5FU were evaluated. Results: The mean peak peritoneal and plasma concentrations of docetaxel were 18.6×103 ng/ml (at hour 0) and 45 ng/ml (at hour 0 to 2), respectively. The peritoneal concentrations of docetaxel were remained even after 24 and 72 hours (24 hours: 1150ng/ml, 72 hours: 74ng/ml). In seven out of eight patients, plasma concentrations of docetaxel were disappeared after 24 hours, but in only one patient with severe ascites, concentration of plasma docetaxel at hour 24 could be obtained (20 ng/ml). The mean peritoneal and plasma areas under the curves (AUC) of docetaxel were 141×103 ng/ml×hr and 480 ng/ml×hr, respectively. The mean peritoneal concentrations of 5FU kept over 60% of plasma concentrations (plasma: 164.3ng/ml, peritoneal: 105ng/ml). Conclusions: Intaperitoneal docetaxel kept relatively high concentrations even after 72hours. 5FU concentrations were well transfered in peritoneal fluid from plasma via oral S-1 administration. Intraperitoneal docetaxel in combination with S-1 orally may be a useful regimen to the patients with carcinomatosis of advanced gastric cancer. No significant financial relationships to disclose.
Chemotherapy for patients with advanced gastric cancer with performance status 2
Authors: Muro K. , Shitara K. , Ura T. , Takahari D. , Yokota T. , Sawaki A. , Kawai H. , Munakata M. , Sakata Y. 
Published: August 2020

e15627 Background: S-1 plus cisplatin is considered to be the standard chemotherapy for Japanese patients with advanced gastric cancer (AGC) according to the results of three phase III trials (JCOG9912/SPIRITS/TOP-002). However, since few patients with poor performance status (PS2) were included in these phase III trials (27 of 1317; 2%), the standard treatment of patients with PS2 has not been established yet. In also, the characteristics and prognosis of AGC patients with PS2 has not been reported in detail. Methods: We retrospectively analyzed 545 patients with AGC treated by chemotherapy during the period from January 2003 to June 2008. Patients characteristic and treatment results were compared between PS0–1 and PS2. Results: At the beginning of 1st-line chemotherapy, PS0–1/2/3–4 was 454/69/22 cases respectively. Patients with peritoneal/pleural dissemination was more common in PS2 than PS0–1 (75% vs. 43%, p<0.001). Patients with multiple metastatic places was more common in PS2 (62% vs. 43%; p=0.007). Fewer patients in PS2 were registered in clinical trial (1.4% vs. 25%, p<0.001). First-line chemotherapy using oral drug (S- 1/capecitabine) was significantly fewer in PS2 (43% vs. 75%, P<0.001). Median time to treatment failure was significantly shorter in PS2 (2.3 months vs. 4.2 months, p<0.001). Patients who could receive second-line chemotherapy were significantly fewer in PS2 (50% vs. 75%, p<0.001). With the median follow up time of 42 months, median survival time of patients with PS0–1 was 14.8 months (95% CI;13.1–16.5) and that of patients with PS2 was 6.1 months (4.3 to 7.4 months; hazard ratio for death 3.0: 95% CI2.3–4.0; p<0.001). Mortality rate within 30 days was higher in PS2 (3% vs. 0.2%; p<0.001). Conclusions: AGC patients with PS2 had not only had poor prognosis compared with PS0–1 but also had fewer chance of registration in the clinical trial, shorter time to treatment failure, and higher mortality rate within 30 days. Considering these different characteristics and treatment results of PS0–1 and PS2, clinical trial especially targeting AGC patients with PS2 is necessary to evaluate optimal chemotherapeutic regimens for PS2 patients. No significant financial relationships to disclose.
Use of partial liver resection according to carcinologic procedures as an alternative to liver transplantation for HCC
Authors: Herrero A. , Pulitano C. , Dondero F. , Dokmak S. , Aussilhou B. , Sauvanet A. , Farges O. , Faivre S. , Belghiti J. 
Published: August 2020

e15628 Background: There are some arguments showing that anatomic resection, anterior approach and preoperative transarterial chemoembolization (TACE) with portal vein embolization (PVE) before major resection improves long term survival after partial liver resection for HCC. This oncologic approach could compete with liver transplantation (LT) which remains poorly accessible in western countries and inaccessible in the greatest part of the world.The aim of this study was to evaluate in patients with good liver function.the result of partial liver resection with an intended carcinologic approach. Methods: Between 1998 and 2007, among 210 patients resected for HCC, we selected a subgroup of 36 patients with single and small HCC (< 6 cm) developed on chronic liver disease (CLD) who underwent anatomic partial resection and anterior approach and TACE and PVE in case of major resection. Results: These 36 patients aged 37 to 76 years included 26 males (72%). Underlying CLD included hepatitis C in 16 (44%); hepatitis B in 8 (22%); alcohol in 9 (25%) and other in 3 ( 8%). The mean size of the tumor was 5.2 cm and 86% (n=31) had major resection. Operative mortality was 2.7% (n=1) and the overall 1-, 3- and 5-year survival rate were 92%,85%,73% while the disease free 1-, 3-, 5-year survival was 80%, 74%, 58%. Tumor recurrence occurred in 16 cases( 44%) after a mean delay of 21 months (ranging from 5 to 58 months). Recurrence was located out of the resected location in 6 cases. Conclusions: Partial liver resection for small tumors in patients with good liver function according to carcinologic procedures allow an excellent overall and disease free survival which can challenge LT. In the case of single HCC <6cm on chronic liver disease, this surgical approach may therefore be considered as a valuable alternative to LT within a curative intent. No significant financial relationships to disclose.
The analysis of EGFR expression and EGFR mutations in advanced pancreatic cancer
Authors: Ueno M. , Ohkawa S. , Sakamoto Y. , Miyakawa K. , Miyagi Y. 
Published: August 2020

e15629 Background: The standard chemotherapy of advanced pancreatic cancer is still gemcitabine and recently gemcitabine + EGFR tyrosine kinase inhibitor (TKI)is noted to be positive on Phase III study. In lung cancer, EGFR mutations (the deletion of exon 19, the point mutation of exon 18, 21) have been reported to be correlated with the effect of EGFR TKI. On the other hand, such EGFR mutations were not reported to be recognized by the direct sequencing method in pancreatic cancer. This time we examined EGFR expressions and EGFR mutations in advanced pancreatic cancer. Methods: We examined EGFR expressions immunohistochemically and EGFR mutations by Loop-Hybrid Mobility Shift Assay (LH-MSA) which is more sensitive than the direct sequencing method in the tissue obtained from percutaneous biopsies in advanced pancreatic cancer patients. In addition we examined the correlation between EGFR expressions and survivals by the log-rank test. Results: The subjects were 31 inoperable pancreatic cancer patients. Patients received chemotherapy (gemcitabine: 10, S-1: 8, gemcitabine+S-1: 12, no treatment: 1).The UICC stages were as follows:stage II; 2, stage III; 6, stage IV; 23. The tissues were obtaind from liver; 12, pancreas; 19. EGFR expressions were positive; 15, negative; 16. EGFR expressions were not correlated with survival (p=0.386). Although LH-MSA were performed successfully in all patients, the same EGFR mutations as lung cancer were not detected. Conclusions: EGFR expressions were not correlated with survivals and the same EGFR mutations as lung cancer were not detected in inoperable advanced pancreatic cancer. No significant financial relationships to disclose.
Gastric submucosal tumors: Lessons learned from 10-year follow-up
Authors: Sawaki A. , Mizuno N. , Takagi T. , Hara K. , Nakamura T. , Tajika M. , Kawai H. , Matsumoto K. , Kobayashi Y. , Yamao K. 
Published: August 2020

e15631 Background: Gastric Submucosal tumors (SMTs) were incidentally discovered esophagogastroduodenoscopy (EGD). However, they have not been studied in detail of epidemiology. Furthermore, no treatment strategy for SMTs has been established with few studies looking into long-term outcomes. The aim of this study is to clarify the clinical features and long-term outcomes of gastric SMT at a single institute for 10-year period. Methods: We performed a total of 5307 EGDs and detected 188 gastric SMTs during 1998. All clinical data including incidence, size and location in stomach were analyzed for the medical records. A retrospective review was conducted for 10-year period for 109 patients and 79 patients were excluded because of simultaneous surgery (3), disappear in follow- up EGD (27), lost of follow-up (49). Results: Gastric SMTs were detected 188 (81 males, 107 females) of 5307 patients (3.5%). Majority size of SMTs was less than 1cm (64%) and SMTs<2cm were 91%. 56% of SMTs located middle one third of stomach, and half (22%) of the remaining SMTs were detected at upper and lower one third, respectively. In 10-year follow-up, 83 of 109 patients were alive at December 2008. One patient was dead of SMT and the remaining 25 patients were dead of other disease till December 2008. Enlargement of SMT was observed in 2 of 109 SMTs (1.8%). Both of them underwent surgical resection and diagnosed as gastrointestinal stromal tumors (GIST). One patient was annually monitored by endoscopy, from 0.6cm to 1.5cm during 4 years, without recurrence for 6 years after surgical intervention. Another didn't undergo regular endoscopy, from 1.8cm to 8cm during 2 years, with recurrence, and consequently died of SMT. Conclusions: The incidence of SMTs is 3.5%, majority (91%) is small (<2cm), and frequent location is middle one third of stomach. Most of SMTs might be managed conservatively, but regular endoscopy is required. No significant financial relationships to disclose.
A phase II study of Halichondrin B analog eribulin mesylate (E7389) as second-line therapy for patients with advanced pancreatic cancer
Authors: Moore M. J. , Tang P. , Renouf D. , Major P. , Hedley D. , Paterson V. , Wang L. , Dhesy-Thind B. , Southwood B. , Doyle L. 
Published: August 2020

e15634 Background: Eribulin mesylate is a halichondrin B analog that inhibits microtubule dynamics by a mechanism that is distinct from other tubulin-targeted agents. Preclinical studies suggest that Eribulin may be effective in pancreatic cancer. The primary objective of this study was to determine the objective response rate (complete and partial) to Eribulin in patients with advanced, pancreatic adenocarcinoma that had progressed after gemcitabine based therapy. Methods: Eligibility criteria included histologically confirmed pancreatic adenocarcinoma; measurable locally advanced, or metastatic disease; disease progression after gemcitabine; and ECOG performance status 0–2. Patients (pts) received Eribulin mesylate 1.4 mg/m2 IV on days 1 and 8. Treatment was repeated every 3 weeks in the absence of disease progression or unacceptable toxicity. Response was assessed by CT scans every 6 weeks while on treatment. Initially 12 pts were to be accrued, if 1 or more pt(s) had an objective response the accrual would increase to a total of 37. Results: 15 pts were accrued,14 received treatment and 12 were evaluable for response. Median age 61; M:F = 8:7; ECOG 1:2 = 11:4; Median number of cycles 2 (1–15). Grade 3+ adverse events included neutropenia (29%), fatigue (14%), peripheral neuropathy (7%) and thrombosis (7%). There were no complete or partial responses, and therefore the study was closed at the first accrual cut off. The best response was stable disease (SD) in 5/12 (42%) pts. Of these 5 pts, 3 (42%) had SD for 12 cycles or greater. Survival data is pending. Conclusions: Eribulin was well tolerated and did not result in any objective responses in refractory pancreatic cancer. However, 42% of pts had stable disease and for 3 pts this was maintained for more than 9 months. Further studies of eribulin in pancreatic cancer may be warranted. No significant financial relationships to disclose.
Is there still place for endoscopic mucosal resection in patients with early oesophageal carcinomas?
Authors: Bogoevski D. , Schurr P. G. , Koenig A. M. , Busch P. , Kutup A. , Izbicki J. R. 
Published: August 2020

e15640 Background: The objective of this study was to investigate whether limited resection of the oesophagogastric junction can be successfully used in the treatment of the patients with early oesophageal carcinomas. Methods: A total of 111 patients with early oesophageal cancer (57 adenocarcinomas, 54 squamous cell carcinomas) had surgical resection with systematic lymphadenectomy (41 thoracoabdominal-TA, 52 transhiatal-TH and 18 with limited resection of the oesophagogastric junction- LROGJ). Results: In all patients, regardless from the surgical procedure, a complete resection (R0) was achieved. The median lymph node yield was significantly higher (p=0.0001) in TA patients (24 LN), compared with TH (14LN) and LROGJ (16LN). The median in hospital and ICU stay were shorter in patients with the LROGJ (12 and 2 days, respectively) compared with the TA (24 and 8 days) and TH patients (23 and 4 days). None of the 43 patients with high grade intraepithelial neoplasia (HGIEN) or oesophageal carcinoma limited to the mucosa had lymphatic spread, as compared with 15 of 68 (22.1%) with affection of the submucosa. Although lymph node metastases were usually limited to locoregional lymph node stations, two patients had metastases in distant lymph nodes (pM1a) The infiltration of the submucosa was accompanied with significant worsening of the overall survival (pT1a vs. pT1b; p=0.002). Multifocal neoplasia was detected in three patients with SCC HGIEN (30%) but not in AC HGIEN! Nine out of 44 (20.4%) patients with early SCC had multifocal neoplasia, compared to 6 out of 53 (11.3%) patients in AC (p=0.322). The sensitivity of the preoperative tumour dept staging (endoscopic ultra sound - EUS; and CT) was astonishing low (only 50% for cT1b), as was the specificity (66.7% for cT1a and only 87.5% for cT1b). On multivariate analysis, only histological tumor type (AC) was independent predictor of survival. Conclusions: Considering the limitations and pitfalls of endoscopic and classical resectional procedures, the quest for alternative and “patient tailored” treatment in patients with early oesophageal carcinoma carries on. A valuable alternative can be the limited resection of the oesophago-gastric junction under sparing of the healthy oesophagus and stomach. No significant financial relationships to disclose.
Differential expression of human telomerase reverse transcriptase β-site remaining alternative splicing variants (hTERT β+ ASV) in gastric carcinogenesis
Authors: Geng X. 
Published: August 2020

e15641 Background: To investigate the changes of hTERT alternative splicing variants pattern in gastric cancer, precancerous lesions and normal gastric mucosa tissue. Methods: Three alternative splicing sites (α, β, γ) were selected and designed PCR primer. The expression of 8 hTERT alternative splicing variants (ASVs) in gastric cancer, precancerous lesions and normal gastric mucosa were detected by Semi-nested RT-PCR. The expression of β-site remaining ASV (β+ASV) in specimens of gastric cancer and specimens of precancerous lesions was detected by SYBER Green real-time PCR. Telomerase enzyme activity was evaluated associated with the different hTERT ASVs. Results: The positive rate of active full-length (α+β+γ+ ) ASV was significantly higher in gastric cancer than in precancerous lesions and normal mucosa (94.7% vs. 40.0% and 0, P<0.05). The positive rates of other ASVs were not different among the 3 groups(P>0.05). The positive rates of β+ ASVs (including α+β+γ+ASV, α-deletion ASV, γ-deletion ASV, αγ-deletion ASV) were 11.1% in normal mucosa,40.0% in precancerous lesions and 94.7% in gastric cancer (P<0.05). SYBR Green real-time RT-PCR showed that the expression level of β+ASV was 6.99 times higher in gastric cancer than in precancerous lesions. Further, increased telomerase enzyme activity was only associated with expression of the full-length hTERT isoform. Conclusions: hTERT alternative splicing pattern is different during gastric carcinogenesis. β+ASV was widely expressed in gastric carcinogenesis and may provide some information for diagnosis of gastric cancer or precancerous lesions. The gene expression patterns of hTERT alternative splicing variants may provide some useful information for diagnosis of gastric cancer and precancerous lesions. No significant financial relationships to disclose.