bluuebunny/crossref_metadata_2025_split huggingface dataset:
The prognostic value of P53 in the nodal metastization of gastric cancer.
Authors: Quaresma Luisa , Fradique Antonio CALDEIRA , Cabrita Fernanda , Pupo Alexandra , DA Silva Guedes , Silva Gualdino , Esteves Jorge , Marques Mateus , Oliveira Mario , Pina Filomena , Bruno Da Costa Ligia 
Published: March 2020

e14673 Background: Lymph node Metastases play a major role as an independent prognostic factor in gastric cancer. Presence of distal lymph node metastases assumes a pejorative prognostic significance, and represents a problem in terms of therapeutic approach. For this reason it’s of major interest to find predictive markers of distal lymph node chain involvement. The P53 tumor suppressor gene, a product of the TP53 gene works normally as a brake on DNA replication, as suppressor of angiogenesis and triggering of apoptosis. The gene most frequently mutated in gastric cancer is the TP53, that is responsible for the production of P53 mutant protein, which forms inactive complex with the native protein, and manifest by the overexpression of p53 in immunocytochemistry. The overexpression of P53 gene has been considered a bad prognostic factor associated mainly with lymph node metastases. Methods: This study seeks to determine the relation between the expression of P53 and the presence of distal lymph node metastases as an indicator for an extended lymphadenectomy. A total of 50 patients undergoing surgery with D2 lymphadenectomy for gastric carcinoma with curative intent were enrolled in this work. Therefore it was evaluated in 1,786 lymph nodes the correlation between the P53 expression with tumor location, size, histological type, depth , number of nodes involved, number of distal lymph node metastases and the TNM stage. Results: In all parameters, mutant P53 protein related with indicators of poor prognosis. In particular has demonstrated a statistical significant correlation (p=0.019) with the presence of distal lymph node metastases. The main objective of this study which was finding a prognostic predictor of distal nodal metastases has been reached. Conclusions: Mutant P53 protein is a good prognostic indicator, for the presence of distal lymph node involvement in gastric carcinoma.
Diffusion weighted MR imaging versus F18 FDG PETC CT in identifying small hepatic metastases.
Authors: Govindarajan Mallarajapatna , Nagaraj Kanakapura Ramanna , Kallur Kumar G , Prashanth Gothlu Ramachandra , Shivakumar Swamy , Sudhakar S , Rajkumar Krishnappa , Indresh Desai , Sridhar P S , Ajaikumar Basavalinga S. 
Published: March 2020

e14675 Background: This exploratory study assessed the ability of diffusion weighted MRI imaging in identifying small liver metastases as compared to F18- FDG PETCT. Methods: Patients with diagnosis of carcinoma of breast, lung, colorectal, pancreas, neuroendocrine and HCC who were staged for their disease using PET CT and MRI were included in the study. We randomly analyzed and compared PETCT and MRI images of 40 patients with hepatic metastases for sensitivity in detection of metastatic lesions in the liver on PETCT and MRI. Where possible, biopsy was performed if MRI/PET CT showed one or two small lesions in the liver. We performed ANCOVA to detect differences between PETCT and MRI controlling for primary sites of disease as a covariate. Results: The mean number of small lesions detected on PETCT was 0.92 where as it was 3.96 in MRI. There was a significant increase in small (p=0.02) and total number of lesions (p=0.01) seen on MRI compared to PET CT but not in large lesions. MRI was able to detect subcentimeter lesions more accurately than PET CT. Random biopsies done on small lesions found on MRI were positive for disease. MRI was able to detect small subcentimeter lesions three times more accurately than PET CT. Conclusions: MR diffusion is more sensitive in indentifying subcentimeter metastatic deposits in the liver that could help in accurate staging when PET CT is negative for liver metastases or when locoregional treatment for oligometastases is contemplated. However, pixels of DWI MRI (like reduced Signal to noise ratio at high b value, artefacts at liver edges and left lobe due to exaggerated susceptibility weighting and spin dephasing) need to be addressed by using other morphological images.
Sixty-eight consecutive cases of neuroendocrine tumor treated with somatostatin analogues: A 20-year single-center experience.
Authors: Savvoukidis Theodoros , Cameron Silke , Ramadori Giuliano 
Published: March 2020

e14707 Background: Neuroendocrine tumours (NET) arise from enterochromaffine and related cells found in epithelial organs throughout the body. Hormone related symptoms in neuroendocrine tumours are well treated with somatostatin analogues. Previous experience has demonstrated some antiproliferative activity of somatostatin analogues in the treatment of NET. Methods: In the last 20 years 68 patients with histologically proven NET were treated: primaries in small bowel (27), pancreas (17), rectum (9), appendix (5), lung (4), unknown (3), extra- adrenal abdominal paragangliomas (2) and stomach (1). The mean age of first diagnosis was 56 years. All of them received somatostatin analogues in long acting depot administration (or combination interferon/somatostatin analogues) for a minimum period of two months and a maximum of 139 months. Somatostatin therapy was started in patients with endocrine-active tumours immediately after the diagnosis and in patients with endocrine-inactive tumours after an observation time of 3 months without therapy if progress was observed. Tumor size was assessed every 3 months after begin of therapy. Results: Best responses were a stable disease in 46 of 68 patients (68%) and a partial remission in 2 (3%). Twenty of 68 patients (29%) showed progress. The responses achieved were in small bowel 20/27; pancreas 14/17; rectum 7/9; appendix 4/5 and lung 3/4. The median duration of response was 34 months. Conclusions: Our results document that treatment with somatostatin analogues prolongs time to progression in NET. Stabilisation of tumour mass itself is a relevant outcome for patients with NET. The benefit of somatostin analogues is indipendent to use of chemotherapy. Because of its efficacy and the good tolerability somatostatin analogues can be considered a first line treatment option.
Neoadjuvant chemotherapy (NACT) with DCF regimen in stage III, squamous cell cancer: Esophagus followed by oesophagectomy—Indian experience.
Authors: Somashekhar S. P. , Rauthan Amit , Zaveri Shabber , Patil Poonam , Holla Soumya 
Published: March 2020

e14710 Background: Despite improved surgical techniques and peri-operative care in cancer of the esophagus, the 5 yr OS is 10%. Additional therapy could improve prognosis. At least 10 RCTs comparing NACT to surgery alone have demonstrated a significant increase in median survival of 17 months in the former, compared to 13 months in the latter. We aimed at studying impact of NACT in Indian patients and its impact on surgery and outcome. Methods: The study – Prospective non-randomised study. Between 2007-12, 20 patients were included to analyze the benefit of NACT with DCF (docetaxel 75mg/m2 day 1, cisplatin 75mg/m2 day 1, 5-FU 750mg/m2 per day 1-4) regimen, in stage III Ca. Esophagus, assessed by EUS and PET-CT scan , pre-chemo and post-chemo, in biopsy proven Squamous cell Carcinoma Oesophagus. Prophylactic growth factors were used in all cycles. Results: Post NACT, Partial response of 58.8%, and a complete pathological response of 17.6% were observed with response rage of 76.4%. NACT x 3 cycles used. 4 pt.s had mucositis, but none had grade 3 toxicity, neutropenia in 4 pt.s and febrile neutropenia in only one pt., vomiting and fatige in 5 pt.s . Surgery post NACT was, very easy and there was no significant morbidity, or surgical complication nor any mortality observed due to NACT. On follow-up, two patients died due to systemic recurrence and progression disease progression. Two patients had regional and one patient had , non-regional lymph node disease recurrence. In remaining 16 patients, till to date there is no recurrences and are disease free. All but 2 patients are alive to date. Conclusions: The response rate to NACT (TPF-Regimen) is 76.4%, with maximum benefit in the complete responders. NACT has no adverse impact on the surgical outcome. Surgery is done with acceptable morbidity and very low mortality. Surgical resection post NACT was easy. Impact of this regimen on DFS and OS, have to be ascertained over time.
Comorbidity, characteristics, and survival of gastric cancer patients at a VA medical center.
Authors: Wang Trent P. , Barnes Tanganyika , Gandhi Arpita , Zhong Fengming , Chang Victor Tsu-Shih , Gonzalez Melanie L. , Cheng Lucy , Duque Lourdes , Cogswell Janet , Kasimis Basil 
Published: March 2020

e14727 Background: This is to study whether comorbidity indices predict survival in gastric cancer patients (pts). Methods: In an IRB approved protocol, we reviewed the records of pts diagnosed with gastric cancer at a VA Medical Center from 3/1/2000 to 3/31/2011. Comorbidity was assessed with four comorbidity indices, the Charlson Comorbidity Index (CMI), the Kaplan-Feinstein Index (KFI), the Cumulative Illness Rating Scale (CIRS), and VA Comorbidity Scale (VACS). Demographics, stage, histology, grade, weight (wt) loss, hemoglobin (HGB), ALB, Total bilirubin (TBili), creatinine at diagnosis, alcohol or tobacco use, past gastric surgery (pSx), and surgical resection (Sx) were also reviewed. COX survival analysis was performed. Results: There were 49 patients. All were men. 23 (46.9%) pts were Caucasian, 25 (51%) African American and 1 (2%) Hispanic. The median (M) age at diagnosis was 70 years (range 43-90). Median survival was 321 days (4-4221). 17 (35.5%) pts has localized disease (stage I/II), and 31 (64.5 %) advanced disease (stage III/IV). 2 (4%) pts had grade1, 12 (26%) grade 2, 32 (68%) grade 3, and 1 (2.1%) grade 4. M HGB was 12.1 g/dl (range 5.5-16.9), MCV 85.4 fl (59-104), albumin 3.6 g/dl (1.8-4.6), TBili 0.5 mg/dl (0.2-5.1) and creatinine 1 mg/dl (0.7-1.6). M CMI 4.7 (1.1-10.8), CIRS15 5 (0-12), CIRS16 9 (0-19), CIRS17 1.6 (0-2.5), CIRS18 0 ( 0-4), CIRS19 0 (0-1), KFI 3 (0-3), VACS 4 (0-12) Demographic features included alcohol use (51%), M tobacco use 25 PPY (0-80), and M wt loss 9% (0-25) and pSX 5 (10%). 22 pts (47%) has Sx. In univariate survival analysis, only wt loss (p<0.013), stage (p<0.001), grade (p<0.001), Tbil (p<0.003), and Sx (p<0.003) were significant in predicting survival. In multivariate survival analyses, none were significant for predicting survival. Conclusions: Comorbidity did not contribute to the survival of gastric ca pts in this population. More research in a larger sample is needed. Supported by the New Jersey Commission for Cancer Research.
Impact of first-line platinum therapy on survival in patients with platinum-refractory advanced transitional cell carcinoma of the urothelium (TCCU) treated with vinflunine.
Authors: Fougeray Ronan , Choueiri Toni K. , Pons Francesc , Schutz Fabio Augusto Barros , Salhi Yacine , Rosenberg Jonathan E. , Bellmunt Joaquim 
Published: March 2020

e15007 Background: Standard first-line therapy of advanced TCCU is based on cisplatin-based combinations. In patients deemed unfit to receive CISPLATIN, carboplatin-based or non-platinum combinations are considered. A phase III trial comparing vinflunine (VFL) and best supportive care (BSC) with BSC alone for second-line treatment of advanced TCCU patients demonstrated a survival advantage for VFL+BSC. We studied the impact of the first-line platinum therapy on overall survival in second line setting. Methods: Eligible 357 patients of the phase III study were split in the two following subsets: CISPLATIN (Patients with prior CISPLATIN administration) and NO CISPLATIN (patients without prior CISPLATIN administration). Survival was measured from the date of random assignment. Overall Survival (OS) was calculated using Kaplan-Meier method, with log-rank comparisons. Multivariate Analysis of OS was analyzed with the Cox proportional hazards model, including prognostic factors for second-line setting previously identified (Bellmunt, 2010). Updated survival data in 11/2008 cut-off date was used. Results: CISPLATIN group represented 70.3% (n=251) and NO CISPLATIN 29,7% (n= 106). CISPLATIN group had less Liver involvement (25% vs 43%, p=0.0007) and better WHO-PS (>1: 66% vs 76%; p=0.0478). OS was higher in CISPLATIN group for all eligible patients (HR: 0.77; CI 95% 0.61-0.97; p=0.0294), for VFL+BSC arm (HR: 0.78; CI 95% 0.59-1.02; p=0.0693) and for BSC arm (HR: 0.68; CI 95% 0.42-1.08; p=0.0978). Multivariate analysis including prognostic factors (liver involvement, hemoglobin, PS) and prior platinum administration, did not show effect of CDDP on OS. VFL reduced the risk of death by 24% in CDDP-group (HR: 0.76; CI 95% 0.58-0.99; p=0.043) and by 35% in NO CDDP –group (HR: 0.65; CI 95% 0.41-1.04; p=0.0724). Conclusions: Differences in prognostic factors between CISPLATIN and NO CISPLATIN groups may explain the differences in OS in patients who undergo 2nd line therapy. The choice of Cisplatin or no Cisplatin chemotherapy in the first line did not impact subsequent benefit of vinflunine over best supportive care.
The impact of regional anesthesia on bladder cancer outcomes.
Authors: RiChard Jamie , Lipsky Michael , Whalen Michael , Motamedinia Piruz , Finkelstein Julia , Hruby Gregory , DeCastro Guarionex , Curry Saundra , Benson Mitchell C. , McKiernan James M. 
Published: March 2020

e15021 Background: Studies in breast and prostate surgery show reduced cancer recurrence after regional (RA) versus general anesthesia (GA). Mechanisms include RAÕs reduced post-operative opioid use and cortisol-mediated immunosuppression. RA may be used alone during transurethral resection of bladder tumors (TURBT) and in combination with GA during radical cystectomy (RC). We assess the impact of RA on short-term bladder urothelial cell carcinoma (UCC) recurrence after TURBT or RC. Methods: From 8/2001 and 6/2006 to 6/2011, 151 patients underwent RC and 488 patients underwent TURBT for bladder UCC, respectively. Those with incomplete resection on TURBT were excluded. Anesthesia included RA or GA for TURBT, and GA alone or GA + RA for RC. Multivariate logistic regression was performed to identify significant predictors of biopsy- or radiography-confirmed UCC recurrence. Results: TURBT. Of 252 patients, 211 received GA and 41 received RA during TURBT. Patient and operative characteristics were similar between groups. Recurrence was 56% at 12 months for GA and RA. Multivariate analysis revealed clinical stage to be the only predictor of UCC recurrence (HR=1.8, p<0.0001). Anesthesia had no affect on 6 or 12 month RFS, DSS or OS (see table). RC. GA was used in 114 patients and 37 patients had GA + RA at RC. There were no between group differences in patient or tumor characteristics. After follow-up of 18 months, 25.9% and 21.6% recurred in GA and GA+RA groups, respectively (p>0.05). There were no differences in RFS, DSS, or OS (see Table). Conclusions: Contrary to other malignancies, our data suggest anesthesia type at TURBT or RC does not affect bladder cancer outcomes. Anesthesia modality should be based on patient comorbidities and procedure type. [Table: see text]
Hypoxia-inducible factor 1α: A screening tool for predicting development of castrate resistant prostate cancer.
Authors: Ranasinghe Weranja Kalana Bodhisiri , Xiao Lin , Kovac Suzana , Chang Mike , Shulkes Arthur , Bolton Damien M , Baldwin Graham , Patel Oneel 
Published: March 2020

e15117 Background: Currently there is no method to determine which patients starting androgen deprivation therapy (ADT) for prostate cancer (PC) will progress to castrate resistant prostate cancer (CRPC) while the reasons for early metastases and chemoresistance in CRPCs are unknown. We aimed to investigate the potential role of hypoxia inducible factor 1α (HIF1α), a key transcription factor in the cell mediated adaptive response to changes in tissue oxygenation, in predicting the development of CRPC. Methods: 100 prostate tumour samples were divided into Gleason ≤7 (38) and Gleason >7 (62) and stained for HIF1α using immunohistochemistry, blinded to the outcomes. The outcomes of CRPC, metastases and PC specific death were measured and correlated with HIF1α expression. In vitro, the effects of HIF1α on proliferation, survival and migration of PC cells were assessed by cell count and Boyden chamber assays. Results: HIF1α expression in PC was independent of Gleason grade and tumour stage. HIF1α was an independent risk factor for development of CRPC (Hazard Ratio (HR) 10.4), progression to metastases (HR 9.8) and PC specific death (HR 13.4) at median times of 23, 24 and 25 months respectively, from the start of ADT on a multivariate Cox regression analysis (all p<0.05) adjusted for Gleason score, PSA and age. CRPC free survival, metastases free survival and PC specific survival were all significantly decreased in patients with HIF1α on Kaplan Meier analyses. The presence of HIF1α was highly sensitive (all 100%) with excellent negative predictive values (all 100%) for all 3 outcomes, but had poor specificity. HIF1α over-expressing PC3 cells (CRPC) were compared with androgen sensitive LNCaP cells in vitro. PC3 cells were resistant to cytotoxic agents including H2O2 (oxidative stress) and 5-fluorouracil (chemotherapy agent) and had higher rates of migration compared to LNCaP cells. HIF1α knockdown in PC3 cells reversed these effects. Protein translation efficiency in PC3 cells was significantly higher than LNCaP cells. Conclusions: HIF1α is a good screening tool for CRPC. HIF1α expression is likely to contribute to metastases and chemoresistance of CRPCs and is likely upregulated at protein translation in PC cells.
A phase II trial of neoadjuvant metformin in prostatic adenocarcinoma with serum and tissue biomarker evaluation.
Authors: Joshua Anthony Michael , Evren Sevan , Zannella Vanessa E. , Bowes Barbara , Fleshner Neil Eric , Jewett Michael A. S. , Finelli Antonio , Evans Andrew , Koritzinsky Marianne , Sweet Joan , Pollak Michael N. 
Published: March 2020

e15118 Background: Metformin is an inhibitor of the complex 1 in the respiratory chain, and is widely used in diabetes due to its effect on reducing insulin resistance. It has also been recently described to have effects via AMPK on inhibiting the mTOR kinase. Significant preclinical and epidemiological studies suggest its role in chemoprevention. These actions provide significant rationale to evaluate its utility in prostate cancer. We conducted a phase II single centre study of neoadjuvant metformin in localised prostate cancer. Methods: Men were required to have histologically confirmed prostate cancer involving at least 20% of at least 1 unfragmented biopsy core. Exclusion criteria included patients who on initial assessment are found to be on treatment with any drug used for the treatment of any form of diabetes, or patients that begin treatment for any form of diabetes during the course of the study. Pts were treated with up to 500mg tid of metformin. Primary objectives were to demonstrate safety and tolerability of neoadjuvant metformin administration in men with prostate cancer and document changes in phospho-AKT signalling indices. Results: 24 patients were enrolled with 22 evaluable; median age was 64 yrs (range, 45-70 yrs). Baseline characteristics included median PSA 6 ng/mL (range, 3.22-36.11ng/mL). Median duration of drug treatment was 41 days (range 18-81). No grade 3 adverse events were reported, all patients underwent subsequent radical prostatectomy with adverse effects related to metformin. Final Gleason scores ranged form 6-8, and final stage ranged from pT2a-pT3b. Significant pre-and post changes were noted in serum IGF1 (p=0.02), fasting glucose (p=0.03), BMI (p<0.01) and waist/hip ratio (p<0.01). There was a trend for a PSA reduction (p=0.08), with 6/22 patients experiencing a PSA fall of greater than 20%. There were no correlations between any metabolic, morphometric or cancer-related serum indices.Tissue results are pending. Conclusions: Neoadjuvant metformin is well tolerated prior to radical prostatectomy. Data to date indicates promising effects on metabolic parameters, tissue results will be presented including proliferation indices and signaling pathway assessments.
Sarcopenia and altered body composition following abiraterone acetate (AA) and corticosteroid (C) treatment in men with castration-refractory prostate cancer (CRPC).
Authors: Mukherji Deborah , Pezaro Carmel Jo , Bianchini Diletta , Tunariu Nina , Mulick Cassidy Amy , Omlin Aurelius Gabriel , Sandhu Shahneen Kaur , Attard Gerhardt , De Bono Johann Sebastian 
Published: March 2020

e15134 Background: Sarcopenia, or skeletal muscle wasting, is an independent prognostic factor in advanced malignancy (Prado Lancet Onc 2008). Decreased muscle and increased fat are recognized side effects of androgen deprivation therapy. AA is a CYP17 inhibitor administered with corticosteroids (C), approved for treatment of advanced CRPC. AA reduces circulating androgens to ‘super-castrate’ levels; we hypothesized that AA + C would impact body composition. Methods: We retrospectively evaluated 54 CRPC pts treated on a Phase I/II trial. Pts received AA alone followed by combination AA + C on biochemical progression. CT scans at baseline, on AA alone and on AA + C were analyzed. Cross-sectional areas of fat and muscle were measured on 3 consecutive images at L4 using OsiriX 4.0. Muscle area was used to calculate skeletal muscle index (SMI); sarcopenia was defined as SMI <52.4 cm2/m2. Data were analyzed using t-tests and Kaplan-Meier analysis with overall survival (OS) measured from day 1 of AA. Results: Median duration on AA alone was 7.4 months (m; range 1.4-37.5); median duration on concurrent AA + C was 7.4m (range 0.9-46.2). Body composition did not change between two pre-treatment scans (n=29; median 3m apart). On AA alone there was a decrease in total fat (-8.5%, p=0.0001), visceral fat (-9.8%, p=0.0015) and muscle mass (-3.9%, p=0.0023) with a significant decrease in mean body mass index (BMI; -3.4 %, p=0.0118). Conversely AA + C was associated with increased total fat (+15.1%, p<0.0001) and visceral fat (+21.4%, p<0.0001) but no further change in muscle mass. Mean BMI significantly increased on the addition of C, returning to baseline levels (p< 0.0001). Overall, 13 pts (24%) were sarcopenic prior to commencing AA compared to 22 (41%) at the end of treatment. Pts who were sarcopenic at baseline had significantly reduced OS: 26.1m (95%CI 16.6 – 41) vs 46.5m (95%CI 28.6 – 57.5, p=0.0253). Conclusions: Treatment with AA alone resulted in decreased fat and muscle. AA + C increased body fat without further alteration in muscle mass. Changes in BMI did not reflect changes in body composition. Sarcopenia at baseline was a negative prognostic factor in this population.