bluuebunny/crossref_metadata_2025_split huggingface dataset:
The differences in the stage classification for node-positive colorectal cancer between the United States and Japan: A single institution experience.
Authors: Sugimoto Kiichi , Sato Koichi , Orita Hajime , Maekawa Hiroshi , Sakurada Mutsumi , Ito Tomoaki , Sakamoto Kazuhiro 
Published: March 2020

e14139 Background: In the United States, the stage classification by the number of lymph node metastasis (LNM) is adopted in TNM classification 7th edition. In Japan, the stage classification by the distribution of LNM was modified to that by the number of LNM in order to integrate with TNM classification in Japanese classification of colorectal carcinoma second English edition. We retrospectively examined the possibility of predicting prognosis by the number of LNM and considered the differences between TNM classification and Japanese classification. Methods: Two hundred and seventy-five patients with LNM who underwent curative surgery for colorectal cancer at our department between January 1992 and December 2004 were enrolled in this study. All patients were followed for 5 years after the operation. At first, we calculated cancer-specific survivals according to the number of LNM in order to examine whether the stratifications of prognosis by the number of LNM is appropriate or not. Secondary, clinicopathological factors and survival data were analyzed to determine prognostic factors. Finally, we considered the differences between TNM classification and Japanese classification. Results: When comparing cancer-specific survivals between the patients with the number of LNM of 1 and 2-3 and 4 or more, cancer-specific survivals were well stratified (both; p=0.006). According to the multivariate analysis using clinicopathological factors, invasion depth (T4) (p=0.007, odds ratio=2.230), venous invasion (moderate-severe) (p=0.003, odds ratio=2.577) and the number of LNM (p=0.0002, odds ratio=1.201) were significantly independent prognostic factors. In Japanese classification, there was a significant difference in cancer-specific survivals between Stage IIIa and IIIb (p<0.0001). On the other hand, in TNM classification, cancer-specific survivals in Stage IIIA, IIIB and IIIC were stratified into three groups with significant differences (IIIA vs IIIB; P=0.01, IIIB vs IIIC; p<0.0001). Conclusions: In comparison of Japanese classification and TNM classification, TNM classification seems to be superior to Japanese classification.
FOLFOX as adjuvant chemotherapy after curative resection of distant metastatic lesions in patients with colorectal cancer.
Authors: Kitayama Joji , Nozawa Hiroaki , Watanabe Toshiaki , Sunami Eiji 
Published: March 2020

e14142 Background: Although FOLFOX regimen is shown to be effective to suppress the recurrence of stage III colorectal cancer (CRC) who received curative resection, the prophylactic effect of has not fully been investigated in adjuvant setting of stage IV CRC cases, namely, after curative resection of distant metastases. Methods: This is a retrospective study including 116 CRC patients with synchronous metastases and 91 with metachronous metastases who received curative resection in our hospital between 2000 and 2009. Pathological parameters of primary CRC, postoperative chemotherapeutic regimen, relapse-free survival (RFS) were analyzed retrospectively. Results: After resection of CRC and synchronous metastases, 53 (84%) out of 63 patients without chemotherapy, and 38 (83%) out of 46 that received oral or intravenous 5-fluorouracil (5-FU) alone or with leucovorin (LV) developed recurrent tumors. By contrast, only single patient (17%) among 6 who underwent FOLFOX showed recurrence. With a median follow-up period of 775 days, the FOLFOX group exhibited a significantly improved RFS as compared to the 5-FU(+LV) or surgery alone group (p=0.03, p=0.007, respectively). The 5-year OS rates of the surgery alone, 5-FU(+LV), and FOLFOX group were 67%, 75%, and 100%. In CRC cases with metachronous metastases, on the other hand, the recurrence rate of the group without chemotherapy was 63%, and that of the 5-FU (+LV) group 55%. In 7 patients who underwent FOLFOX chemotherapy (5 cases of FOLFOX4 and 2 cases of mFOLFOX6, no antibody therapy) after metastasectomy, 71% (5 patients) relapsed afterward. Thus, the tumor-relapse rate after metastasectomy was similar among patients who received no postoperative chemotherapy. The median RFSs of the surgery alone, 5-FU(+LV), and FOLFOX groups were 323, 917, and 322 days, respectively. Conclusions: Adjuvant FOLFOX is certainly beneficial for stage IV CRC patients with synchronous metastasis who received curative resection. In contrast, the prophylactic effect of FOLFOX is not superior to other follow-up strategies in patients who received complete resection of metachronous metastases.
Use and findings of K-ras in colorectal cancer (CRC) testing in administrative and electronic medical records (EMR) data from 2005 through 2010.
Authors: Valluri Satish , Sullivan Sean D , Ramsey Scott David , Kreilick Charles , Foltz Boklage Susan H , Haislip Sally , Gilmore James W. , Szabo Stephen , Sarma Syam , Asche Carl V , Seal Brian S. 
Published: March 2020

e14146 Background: The use of K-ras testing in clinical decision-making has grown over the past few years. The objective of this study was to evaluate, in a real world context, the trends and diagnostic findings of K-ras testing using managed care and EMR data. Methods: The Georgia Cancer Specialists Database EMR (2005-2010) and administrative data from the MarketScan and IMPACT database(s) was used to select patients with newly diagnosed colorectal cancer (CRC). We looked for trends in use of K-ras in relation to timing of chemotherapy administration. The EMR data provided information on k-ras mutation type. Results: In MarketScan, of the 23,548 patients with a diagnosis of CRC, 1,730 (7.3%) patients had a test ordered for K-ras between 2005 and 2010. The number of patients receiving K-ras increased with line of therapy: first line 336 patients (8.2%) of 4,098 treated, second line 455 patients (15.2%) of 2,984 treated, and third line 529 patients (33%) of 1,603 treated. We found similar results using the IMPACT database: 2,256 (7.8%) CRC patients had a test ordered for K-ras between 2005 and 2010. K-ras testing increased with line of therapy: first line 244 patients (7.8%), second line 510 (14.6%), and third line 650 patients (33.1%). EMR lab results from stage IV disease (n=349) consisted of 15% mutated type, 60% unknown and 25% wild type. For confirmed test results wild type represented 62.5% and mutated type 37.5%. Conclusions: Over the last six years, use of K-ras testing has increased in use in patients with CRC. The increase has occurred in later lines of therapy. The timing occurring late in therapy may limit the use of agents specific for this test.
Prevalence of low-penetrance KRAS (codons 12/13 and 61) and BRAF mutations in metastatic colorectal carcinoma.
Authors: Rojo Federico , Caldes Trinidad , Zazo Sandra , de la Hoya Miguel , Carames Cristina , Romero Atocha , Serrano Gloria , Bando Inmaculada , Leon Ana , Sastre Javier , Martin-Valades Jose Ignacio , Cillero Lourdes , Campos Angel , Gavina Belen , Lendinez Alberto , Bausela Cristina , Ferrandez Dolores , Ramos Teresa , Garcia-Foncillas Jesus , Diaz-Rubio Eduardo 
Published: March 2020

e14147 Background: In patients with metastatic colorectal cancer (mCRC), activating mutations within KRAS, which result in EGFR-independent intracellular signal transduction activation, are found in approximately 35-40% of patients with mCRC have been significantly associated with lack of response to cetuximab or panitumumab therapy. Although current guidelines recommend testing for frequent KRAS codons 12/13 mutations, emerging data indicate that additional KRAS and BRAF mutations are also predictive of non-responsiveness to anti-EGFR antibodies in mCRC. This study is aimed to analyze the prevalence of low-penetrance KRAS and BRAF V600 mutations in caucasian mCRC population. Methods: A two-institution retrospective cohort of 1,238 consecutive KRAS wild type mCRC patients previously studied for 7 mutations in codons 12/13 (G12D, G12A, G12V, G12S, G12R, G12C and G13D) by the CE-IVD marked ARMS-scorpion real-time polymerase chain reaction PCR (Therascreen, Qiagen) was assayed by the diagnostic TaqMelt PCR assay cobas KRAS mutation and cobas BRAF V600 mutation tests (Roche), which are designed to detect 19 mutations in KRAS codons 12, 13 and 61 (including G12F, G13C, G13R, G13S, G13A, G13V, G13I, Q61H, Q61K, Q61R, Q61L, Q61E and Q61P) and BRAF V600 (V600E, V600K and V600D) mutations. An additional cohort of 146 KRAS mutated patients by ARMS-scorpion PCR was studied. DNA was obtained by cobas DNA preparation kit from one single 5µm formalin-fixed paraffin-embedded tissue section. Results: In all samples, sufficient DNA was obtained for KRAS and BRAF mutational studies. Among 1238 KRAS codons 12/13 wild-type patients by ARMS-scorpion PCR,166 (13.4%) showed KRAS mutations, 117 (9.5%) in codons 12/13, and 49 (4%) in codon 61. BRAF V600 mutations were detected in 9% cases. In ARMS-scorpion PCR KRAS mutated patients, mutations were confirmed by cobas in all cases. Conclusions: The cobas mutation tests are robust and reproducible assays that, 1) detects a higher incidence (13.4%) of mutations in codons 12, 13, and 61 of the KRAS gene in wild-type mCRC population, 2) a relevant rate of BRAF mutations is present in the same population, and 3) requires a very small amount of tissue.
Incidence of colorectal premalignant and malignant neoplasm on colonoscopy in an in-patient setting.
Authors: Khan Manji Samira , Feinberg Zachery , Manji Gulam Abbas 
Published: March 2020

e14185 Background: Colorectal cancer (CRC) continues to be a leading cause of death and the third most common cancer in both genders. Numerous studies have shown that routine screening for colon cancer reduces CRC incidence and mortality by detecting premalignant lesions early. Hence screening colonoscopy in the outpatient setting has been the standard of care. In contrast, the incidence of pre-malignant (PMN) and malignant neoplasms (MN) identified during a colonoscopy due to an acute presentation in an in-patient setting is currently unknown. We evaluate the incidence of PMN and MN lesions identified in patients that underwent in-patient colonoscopy for anemia, gastrointestinal bleed (GIB), and or abdominal pain. Methods: A retrospective review of all gastrointestinal consultations (GIC) from January 1st, 2009 until December 31st, 2009 at a single institution. GIC as determined by the requesting provider for anemia, abdominal pain, and/or gastrointestinal bleed (GIB) were included. Results: There were 291 GICs for anemia, abdominal pain, GIB, or a combination thereof resulting in 218 colonoscopies. A total of 15 (6.9%) PMN and MN lesions were identified. Pathological evaluation reveled 13 (86.7%) of these lesions to be consistent with that of adenocarcinoma. The remaining 2 showed squamous cell cancer morphology. PMN/MNs were identified in patients with GIB and anemia (46.7%), anemia alone (20%), GIB and abdominal pain (20%), and GIB alone (13.3%). There was no significant difference in lesions found between genders (46.7% male). Conclusions: Routine outpatient screening colonoscopy is the standard of care with the goal of resecting early stage cancerous lesions resulting in cure. However, there is paucity of data on the incidence of these lesions being identified in an in-patient setting where colonoscopy is performed for GI bleed, anemia, abdominal pain, or a combination thereof. We demonstrate that colonoscopy resulted in identification of PMN/MNs in a significant proportion of patients with afore mentioned specific complaints. Interestingly, most lesions were identified in patients with GIB and anemia, suggesting that a thorough evaluation be undertaken as it may herald an underlying neoplasm.
Phase Ib study of gemcitabine and oxaliplatin with erlotinib in patients with advanced biliary tract cancer.
Authors: Ciombor Kristen Keon , Cardin Dana Backlund , Chan Emily , McClanahan Pamela , Fan Kang-Hsien , Flynn Jayme , Young Ruth T. , DeMers April , Smith Stephen James , Berlin Jordan , Goff Laura Williams 
Published: March 2020

e14503 Background: Gemcitabine (GEM) with a platinum agent such as oxaliplatin (OX) is standard therapy for advanced biliary tract cancers (ABTC). The epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) erlotinib has also shown modest benefit in ABTC. Erlotinib (E) induces G1/S cell cycle arrest and may exhibit sequence-specific synergy with GEM. Given continuously, it may antagonize the action of chemotherapy against cycling tumor cells but intermittent pulsatile dosing of EGFR TKIs in combination with chemotherapy may lead to maximum efficacy. The purpose of this study is to assess the tolerability of E when pulsed with GEM and OX (GEMOX). Methods: This investigator initiated, single institution phase Ib study (NCT00987766) used a standard 3+3 dose-escalation model in patients with ABTC, pancreas cancer or duodenal cancer. The primary endpoint was to evaluate the maximum tolerated dose (MTD) of pulsatile E in combination with GEMOX. Patients received escalating doses of E starting at 50 mg daily (given on D3-8) with GEM on D1 (dose rate 10 mg/m2/min) and OX on D2 every two weeks. Dose-limiting toxicity was defined as any treatment-related, first course (28 days) non-hematologic ≥Gr3 toxicity, except nausea/vomiting or Gr4 hematologic toxicity. Results: Nineteen patients have been enrolled and 4 dose levels have been explored. Two of two patients experienced DLT [Gr3 diarrhea (n=1), Gr4 anemia (n=1)] at a dose of 150 mg E + 1000 mg/m2 GEM + 85 mg/m2 OX, exceeding the MTD. Most frequent toxicities were nausea (68%), neuropathy (68%), fatigue (63%) diarrhea (52%) and rash (52%), most Gr1 or 2. Disease stabilization occurred in 12/17 (71%) evaluable patients (5/9 ABTC, 7/8 pancreas), and partial responses were seen in 4/17 evaluable patients (24%), all with ABTC (4/9). The rate of progression-free survival at 6 months was 75% in ABTC. Conclusions: The MTD and recommended phase 2 dose of E in combination with GEMOX was E 150 mg given on days 3-8 with GEM 800 mg/m2 and OX 85 mg/m2 in this population. Clinical activity of this combination was seen in the majority of patients. An expansion cohort of an additional ten patients with ABTC at the MTD is ongoing, and correlative studies on available tissue will be performed.
Impact of pretreatment thrombocytosis on blood-borne metastasis and prognosis of primary gastric cancer.
Authors: Kim Kyung Min , Cheong Jae-Ho , Hwang Seong-Geun , Kim Yu Min , Kim Hyoung-Il , Ahn Ji Yeong , Hyung Woo Jin , Noh Sung Hoon 
Published: March 2020

e14504 Background: Thrombocytosis has been associated with malignancies and poor prognostic implications in cancer patients. In the present study the prognostic significance of pretreatment platelet (PLT) level was assessed with regard to recurrence and survival in patients with primary gastric adenocarcinoma. Methods: The authors reviewed the prospective data of 1,593 gastric cancer patients who received curative gastrectomy with extended lymphadenectomy. The correlations of PLT level with recurrence and overall survival were evaluated by both univariate and multivariate analyses. Results: Thrombocytosis (≥ 40 x 104/μL) was present in 6.4% of the patients prior to curative surgery. Thrombocytosis was more frequently associated with advanced T and N stage, larger tumor size, anemia, and old age (p<0.05). The 5-year survival rate of patients with thrombocytosis was significantly worse than that of patients without thrombocytosis (56.9% vs. 65.5%; p=0.043). The recurrence rate was higher, mainly attributed to the frequent hematogenous spread, in patients with thrombocytosis than in those without thrombocytosis (51.0% vs. 34.5%; p<0.001). Furthermore, thrombocytosis was an independent risk factor of recurrence (Odds ratio 1.649 [95% CI 1.074 – 2.531], p=0.022), along with serosa invasion and nodal metastasis. Conclusions: Pretreatment thrombocytosis correlated significantly with poor prognosis and can be used as an independent predictor of recurrence by blood-borne metastasis in gastric cancer.
Novel methods of analyzing long-term trends in incidence and survival applied to gastroesophageal cancers.
Authors: Wang Zhensheng , Goodman Michael , Mahaseth Hemchandra , El-Rayes Bassel F 
Published: March 2020

e14512 Background: The incidence of esophageal squamous cell (ESC) carcinoma has been decreasing, while incidence of esophageal adenocarcinoma (EA) keeps increasing. The specific time periods during which incidence trends changed have not been examined. Secular trends in survival and changes of those trends need to be investigated. Methods: Incidence and survival were analyzed using joinpoint regression models, which are designed to examine long-term longitudinal data for a change in trend. We identified 75,497 patients with esophageal cancer and adenocarcinoma of the gastric cardia (GCA) in the Surveillance, Epidemiology, and End Results database between 1973 and 2008. Incidence and one-year survival rates for ESC, EA, and GCA were compared by race, gender and stage. Results were expressed in terms of identifiable inflexion points (joinpoints) with before-and-after estimates of annual percent changes (APC) with 95% confidence intervals (CI). Results: Incidence of ESC has demonstrated a clear inflexion point in the mid 1980s with accelerated decrease across race and gender categories. While incidence of EA has been increasing, the increase slowed down in mid 90s in all groups except blacks. For GCA, there was a clear increase in incidence up until early 80s followed by a plateau although in men there was a significant post-87 decrease. One-year survival of ESC patients has been improving; for local/regional disease the trend became less pronounced in late 80s whereas for distant disease the improvement appears to continue without identifiable inflexion points. The patterns of one-year survival for EA and GCA were similar. Local/regional diseases demonstrated a significant improvement in survival without changes in trend while survival of distant diseases showed an inflexion point in the mid 90s followed by a marked improvement. Conclusions: Joinpoint regression analysis is a valuable tool in assessing long-term trends of incidence and survival. The survival of ESC, EA, and GCA demonstrated significant improvement over the last 35 years. The inflexion points reflected introduction of combined modality therapy for regional disease and availability of newer chemotherapy agents for distant disease.
Peptide receptor radionuclide therapy for neuroendocrine tumors in Germany: Initial results of a multiinstitutional cancer registry.
Authors: Hörsch Dieter ,   AG PRRT of the DGN Germany
Published: March 2020

e14513 Background: Peptide receptor radionuclide therapy is an effective treatment option for patients with well differentiated somatostatin receptor expressing neuroendocrine tumors. However, published data results mainly from retrospective monocentric studies. Methods: We initiated a multi-institutional, prospective and board reviewed registry for patients treated with Peptide receptor radionuclide therapy in Germany in 2009. Results: In five centers, 297 patients were registered. Primary tumors were mainly derived from pancreas (117/297), small intestine (80/297) whereas 56 were of unknown primary. Most tumors were well differentiated with a median Ki67 proliferation rate of 5% (range 0.9 to 70). Peptide receptor radionuclide therapy was performed using mainly Yttrium-90 and/or Lutetium-177 as radionuclides in 1-8 cycles. Mean overall survival was estimated at 213 months with a follow up between 1 and 230 months after initial diagnosis and 87 months with a follow up between 1 and 92 months after start of Peptide receptor radionuclide therapy. Median overall survival was not yet reached. Subgroup analysis demonstrated that best results were obtained in neuroendocrine tumors with a proliferation rate below 20%. Conclusions: Our results indicate that Peptide receptor radionuclide therapy is an effective treatment well and moderately differentiated neuroendocrine tumors irrespective of previous therapies and should be regarded a one of the primary treatment options for patients with neuroendocrine tumors.
Effect of three-dimensional collagen I and global histone acetylation on gemcitabine resistance in pancreatic cancer cells.
Authors: Dangi-Garimella Surabhi , Sahai Vaibhav , Shields Mario A. , Munshi Hidayatullah G. 
Published: March 2020

e14515 Background: Pancreatic ductal adenocarcinoma (PDAC) is associated with a pronounced collagen-rich stromal reaction that has been shown to contribute to chemo-resistance. PDAC is also associated with epigenetic changes. We have previously shown that PDAC cells are resistant to gemcitabine in the collagen microenvironment because of increased expression of the chromatin remodeling protein high mobility group A2 (HMGA2) and increased ERK1/2 signaling. Methods: Pancreatic tissue microarrays were stained with trichrome and for histone H3K9, H3K27 acetylation (Ac), and histone acetyltransferase (HATs) expression. PDAC cells were plated onto tissue culture plastic or in 3D collagen gels and protein expression was assessed by Western blotting. DNA damage response was assessed by comet and clonogenic assays. Results: Human PDAC tumors display in areas of fibrosis higher histone H3K9Ac and H3K27Ac. Moreover, PDAC cells upregulate H3K9Ac and H3K27Ac along with GCN5, PCAF and p300 HATs when grown in 3D collagen. Inhibiting ERK1/2 activity and/or decreasing HMGA2 expression attenuates the effect of collagen on H3Ac and HAT expression. Human PDAC tumors with HMGA2 also demonstrate H3Ac and HAT expression. Additionally, cells in 3D collagen demonstrate reduced tailing with the comet assay, increased clonogenic potential and increased γH2AX following gemcitabine treatment, suggesting an increased repair response to damaged DNA in the collagen microenvironment. Significantly, downregulation of HATs along with inhibition of ERK1/2 activity attenuates gemcitabine-induced γH2AX detected in 3D collagen. Conclusions: Collagen microenvironment limits the effectiveness of gemcitabine through ERK1/2 and HMGA2-dependent HAT expression. HMGA2 expression is associated with histone acetylation and HAT expression in human PDAC tumors, particularly in area of fibrosis, suggesting that fibrosis may contribute to chemo-resistance through increased HMGA2-HAT signaling. Given that very little progress has been made in the treatment of pancreatic cancer, targeting HATs could be a novel approach to sensitize pancreatic tumors to chemotherapy.