bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy of laser capture microdissection plus RT-PCR technique in analyzing gene expression levels of human gastric cancer
Authors: Uetake H. , Shitara K. , Sugihara K. 
Published: August 2020

e15669 Background: We reported the efficacy of laser capture microdissection plus RT-PCR (LCM+RT-PCR) technique in analyzing gene expression levels of human colon cancer (Makino, BMC cancer, 2008). In the present study, gene expression level of angiogenic factors, such as vascular endothelial growth factor (VEGF), thymidine phosphorylase (TP) and cyclooxygenase-2 (COX-2) in human gastric cancer was studies using LCM+RT-PCR methods. Methods: Gene expression level of VEGF, TP and COX-2 were separately quantified in cancer cells and in cancerous stroma of 51 gastric cancers specimen by LCM+RT-PCR methods (Danenberg Tumor Profile). Results: All the gene expressions were successfully estimated separately in cancer cells and cancerous stroma. VEGF and TP gene higher expressed in cancer cell than in cancerous stroma (P<0.0001, Wilcoxon), whereas COX-2 gene expression was higher in cancerous stroma (P=0.0004, Wilcoxon). Only in TP, positive correlation of gene expression was observed between in cancer cells and in cancerous stroma (rs=0.494, P=0.0014, Spearman). And a linear relationship was observed between VEGF and TP gene expression in cancerous stroma (rs=0.768, P<0.0001, Spearman). Conclusions: Gene expression level of angiogenic factor was different between in cancer cells and cancerous stroma. By using LCM+RT-PCR method, gene expression level of angiogenic factors can be separately estimated in cancer cells and cancerous stroma. No significant financial relationships to disclose.
Study to see the efficacy and toxicity profile of docetaxel-based chemotherapy in advanced stomach cancer in Bangladeshi patient population
Authors: Hoque E. , Karim S. , Hossen M. , Ahmed T. U. 
Published: August 2020

e15687 Background: Gastric cancer is the second most common cause of cancer death worldwide. In Bangladesh it is one of the major causes of cancer death. Advanced gastric cancer patients have a poor prognosis of 3 to 5 months. Docetaxel has shown activity against gastric cancer as monotherapy and in combination with other agents. The purpose of this study was to investigate the efficacy and toxicity profile of docetaxel based chemotherapy in advanced stomach cancer in Bangladeshi patient population. Methods: From January 2004 to December 2006, thirty patients with advanced inoperable gastric cancer (Gastric or esophagogastric adenocarcinoma) were included in the study. Patients received no prior chemotherapy. Patients were given docetaxel 75mg/m2 I/V in 1 hour infusion and Cisplatin 75mg/m2 (d1) plus 5-fluorouracil 750mg/m2/d (days 1 to 5) I/V with adequate hydration every 3 weeks. The primary end point was time to tumour progression. Secondary end point was overall survival and toxicity profile. Results: Among the 30 evaluable patients time to tumour progression was 11.5 months. Overall response rate was 87% (26 patients). Complete response rate was 20% (6 patients), 27% (8 patients) had stable disease, 7% (2 patients) had developed progressive disease. Two-year survival rate was 21%. Grade 3 to 4 treatment related adverse events occurred in 63%. Among the toxicities there were: neutropenia (80%), stomatitis (19%), and diarrhea (15%). There was no treatment related death. Conclusions: Adding docetaxel to CF regimen significantly improved time to tumour progression and survival rate in advanced gastric cancer patients. In context with the survival benefit the toxicities of this regimen are acceptable. Docetaxel in combination with Cisplatin and 5-fluorouracil is a very safe and active in patients of Bangladesh with advanced gastric cancer. Larger studies involving higher number of patients are needed to evaluate these results in case of Bangladeshi patient population. No significant financial relationships to disclose.
Bone marrow recovery and subsequent chemotherapy following radiolabeled anti-prostate-specific membrane antigen (PSMA) monoclonal antibody J591 in patients (pts) with metastatic castration-resistant prostate cancer (metCRPC)
Authors: Tagawa S. T. , Parmar S. , Pena J. , Petrillo K. , Matulich D. , Selzer J. , Vallabhajosula S. , Goldsmith S. J. , Bander N. H. , Nanus D. M. 
Published: August 2020

e16004 Background: Reversible myelosuppression is the dose-limiting toxicity of radioimmunotherapy (RIT). Cases of marrow damage, including myelodysplasia and acute leukemia have been reported with the RIT most used to date (that targeting CD20 in Non- Hodgkin's lymphoma), though no statistically significant association exists. In addition, post-RIT chemotherapy (chemo) may theoretically be limited. We have treated metCRPC pts with anti-PSMA RIT since 2000 and analyzed post-therapy outcomes. Methods: Follow-up across 4 prospective phase I and II trials utilizing 177Lu-J591 and 90Y-J591 was performed. Quality of hematologic recovery from post-RIT myelosuppression was documented. Administration of pre- and post-RIT chemo was analyzed. Specific searches for subsequent myelodysplasia and/or leukemia were performed. Results: Median age of the 109 treated pts is 70 (range 47–88). Entry criteria for all trials included progressive metCRPC, PS < 2, normal baseline neutrophil and platelet counts, and hemoglobin > 10 g/dL. 80 received 177Lu-J591 at cumulative doses ranging from 10–120 mCi/m2 and 29 received 90Y-J591 at cumulative doses of 5–40 mCi/m2. 43% received at least 1 line of pre-RIT chemo, 53% received at least 1 line of post-RIT chemo, and 20% have never received chemo to date. All pts with adequate performance status received chemo except per pt choice. Excluding re-treated pts, 98% and 87% of assessable pts had full recovery of neutrophils and platelets respectively. Of the remaining, all but 4 recovered to Gr 1 neutropenia and/or thrombocytopenia. The most common reason for lack of complete hematologic recovery was CRPC progression in bone marrow (16 pts with persistent or recurrent myelosuppression underwent bone marrow biopsy). No cases of post-RIT myelodysplasia and/or leukemia were discovered. Conclusions: Anti-PSMA radioimmunotherapy is well-tolerated with efficacy previously reported. While follow-up is ongoing, reports of irreversible bone marrow damage appear unfounded and all patients with intact performance status willing to undergo post-RIT chemotherapy are able to receive it. [Table: see text]
Micropapillary urothelial carcinoma of the urinary bladder: Early surgery or neoadjuvant chemotherapy?
Authors: Ghoneim I. , Stephenson A. , Gong M. , Campbell S. , Fergany A. 
Published: August 2020

e16007 Background: Micropapillary bladder carcinoma is a rare variant of urothelial carcinoma (UC) of the urinary bladder. As a particularly aggressive variant, patients are often urged to undergo up-front radical cystectomy. Though data is scarce on the treatment outcomes of patients with this entity, we present the case for neoadjuvant chemotherapy as opposed to early cystectomy in the setting of clinically localized micropapillary UC. Methods: A review of records of all patients evaluated at our institution for UC was conducted to identify micropapillary UC of the bladder over the period from 2000–2007. A total of 24 cases were found, and were evaluated for preoperative pathology and clinical stage, treatment course, pathological stage and cancer specific survival. Results: Mean patient age was 67.9 years with 19 males and 5 females. Twenty-one (87.5%) patients had clinically organ confined micropapillary UC at the time of diagnosis, three had minimally enlarged lymph nodes on pelvic CAT scans. Half of our patients had BCG refractory high grade non-muscle invasive UC. Twenty-two patients (91.67%) were offered radical cystectomy as first line management. Extended lymph node dissection was performed in eleven patients (45.83%). Final pathologic examination diagnosed metastatic lymph node involvement in 20 patients (83.33%), with 4 patients (20%) having positive LN outside the standard (pelvic) template of dissection. A stage upgrade was noticed in 95.23% of cases. Median cancer specific survival was 13 months. Survival at one year was 44% and 50% at 2years, with only one patient alive at 5 years. Conclusions: Our results suggest that clinically localized micropapillary UC is often metastatic to LN at the time of presentation. This setting of frequent systemic disease should encourage standard neoadjuvant chemotherapy rather than early surgical management for these patients. Extended LN dissection is warranted in these cases due to the high incidence of nodal involvement outside the standard template. No significant financial relationships to disclose.
Expression of the CDK inhibitor p27kip1 and oxidative DNA damage in renal cell carcinoma
Authors: Sgambato A. , Camerini A. , De Luca F. , Valsuani C. , Siclari O. , Genovese G. , Boninsegna A. , Cecchi M. , Cittadini A. , Amoroso D. 
Published: August 2020

e16008 Background: Deregulation of the normal cell cycle is a frequent event in human tumors and plays an important role in malignant transformation. p27kip1 is a negative regulator of the G1 phase, is frequently lost in tumor cells and, in some cases, its alteration is coupled with oxidative DNA damage. Methods: We evaluated the expression of p27kip1 and the extent of endogenous oxidative DNA damage (by means of 8-hydroxydeoxyguanosine [8-OHdG] levels) by immunostaining in a series of 125 (median age 64[range23–86]yrs) renal cell carcinomas (RCCs); furthermore, the prognostic significance of their alterations was tested. Median values of expression were used as cut-off. p27kip1 expression was also evaluated by Western Blot in a second series of 34 fresh-frozen RCCs. Results: to date, median follow-up is 29[range 4 - 104] months. p27kip1expression was lost in a significant fraction of tumors (55%) with a median percentage of positive cells of 20% [range 0–60%). Loss of p27kip1 staining correlated with higher tumor grade (p=0.049). Recurrence (p=0.007) and death (p=0.006) from RCCs were significantly more frequent in patients p27kip1-negative compared with positive ones. Kaplan-Meier analysis showed a significant separation between high vs low p27kip1 expression groups for both disease-free (p=0.011) and overall (p=0.002) survival. At multivariate analysis, loss of p27kip1expression was the only independent risk predictor for recurrence (HR=4.326, p=0.014) and death (HR=4.915, p=0.012) from RCCs when tumor size, tumor grade and stage were included. No significant correlation with clinical or pathological parameters and outcome was found for 8- OHdG. p27kip1 total protein levels showed a variable behaviour at WB analysis with a modest trend toward a global reduction but an elevation in some cases. Conclusions: loss of p27kip1 is frequent in human RCCs and is a powerful predictor of poor outcome. p27kip1 alteration are not related to endogenous oxidative DNA damage. The behaviour of p27kip1at WB analysis is probably related to the elevation of the cytoplasmatic (and inactive) fraction. No significant financial relationships to disclose.
Somatic malignant differentiation in adult male germ-cell tumors (GCTs): Preliminary evidences from the INTera database (International Project for Teratoma with Malignant Transformation)
Authors: Necchi A. , Colecchia M. , Nicolai N. , Mego M. , De Giorgi U. , Mikuz G. , Sava T. , Di Nicola M. , Pastorino U. , Salvioni R. 
Published: August 2020

e16013 Background: Malignant transformation (MT) is a rare phenomenon characterized by a neoplastic somatic differentiation within a GCT. Little is known concerning its clinical implications. An international registry (INTera Project) has been established to collect all past and new cases worldwide. Methods: Patients (pts) with a MT within GCT have been retrospectively identified from registries of contributing Institutions. Significant clinical and pathological data have been collected and data files gathered at the Fondazione IRCCS Istituto Nazionale dei Tumori, Milan. Results: 47 pts have been identified as well as a variety of 12 histologies. 25 pts had MT in primary tumor: 14 of them had no metastases (11 underwent primary retroperitoneal lymph-node dissection - RPLND), and 11 underwent chemotherapy (CT) ± surgery due to metastatic disease. All 14 pts with no metastases remain disease-free (DF) following a median follow-up (f-up) of 72 months (2–236+ months). 6 of 11 pts undergoing chemotherapy remain disease-free following a median f-up of 155 months (8–297+). 22 pts had MT in metastases only and 20 of them are evaluable. Following CT, 7 underwent radical surgery and 5 of them remain DF following a median f-up of 77 months (19–166+ months), while 13 could not undergo radical removal of disease, and 3 of them have been rescued by further CT and are DF at 37+, 41+ and 79+ months. So far, all 14 pts with no metastases as well as 7/9 (78%) who had radical removal of disease are alive and DF versus only 7/22 pts (32%) who could not receive a radical excision of residual masses. Median disease-free survival of pts with MT in primary only versus distant sites only was 54 (0–326+) and 2.5 (0–166+) months respectively (p=0.064 - at Log-rank test). No relevant outcome differences have been observed according to histology. Conclusions: Ongoing INTera project is a collaborative effort of MT case- collection worldwide. Stage of disease and radical surgery seem to associate with outcome. The growing number of cases and a centralized pathology review would help to increase knowledge on this rare disease. No significant financial relationships to disclose.
Long-term effects of a program of bladder preservation using chemotherapy plus radiotherapy in muscle invasive bladder cancer (BC). Analysis of biologic predictive factors and health-related quality of life (QOL)
Authors: Passalacqua R. , Brighenti M. , Naldi N. , Potenzoni D. , Monica B. , Fumagalli M. , Lazzarelli S. , Caminiti C. 
Published: August 2020

e16014 Background: Long-term effects of a combined approach of transurethral resection (TUR) plus chemotherapy (CT) and pelvic radiotherapy (RT) in terms of bladder preservation, survival, QOL are largely unknown. Moreover we investigated whether p53, Ki67, bcl-2, c-erbB-2 protein expression predict the achievement of a complete response (CR). Methods: From March 1994 to June 2000, 75 pts with muscle invasive BC were treated with a bladder sparing approach including an initial TUR, 3 cycles of CT (cisplatin + 5- FU) alternating with pelvic RT (40 Gy). At the response evaluation, pts with biopsy proven residual disease were considered incomplete responders (IR) and underwent immediate cystectomy. Pts with CR were treated with two additional CT cycles plus a bladder RT boost (20- 24 Gy). Paraffin embedded blocks of the primary tumors were collected and Ki67, p53, bcl-2 and c-erbB-2 protein expression were evaluated in a blind fashion. The Expanded Prostate Cancer Index Composite (EPIC) scores for urinary function, (especially storage, voiding symptoms and bowel function) was used to explore QOL in bladder preserved and compared with a group of matched patients treated by radical cystectomy only. Results: Median age was 67 yrs (range 42–80); T2a-T2b: 42%; T3a-T3b: 47%; T4a: 11%; G3: 88%; hydronephrosis: 32%. Overall, 56 (74.7%) pts achieved a CR and the achievement of a CR was significantly related to lower T stage (p= 0.002), high Ki67 (p=0.001), absence of hydronephrosis (p= 0.007) and high p53 overexpression (p=0.007). Multivariate analysis showed that only a low T stage (p=0.002) and high p53 expression (p=0.043) predict the obtaining of a CR. At 5 years of follow-up, 44 (59%) were alive and in 33 of them (75%) bladder was preserved; after 10-years 28 (37.3%) were alive and in 23 of them (82%) bladder was preserved. Analysis of QOL scores is ongoing. Conclusions: This approach induces a long term survival similar to radical cystectomy with a high rate of bladder preservation and represents a valid treatment for muscle invasive BC. Overexpression of p53 is a predictive marker for the obtaining of CR and for bladder preservation. No significant financial relationships to disclose.
Identification of factors predicting loss of renal differential function on the operated kidney after laparoscopic partial nephrectomy
Authors: Pouliot F. , Pantuck A. J. , Calimlim B. , Dujardin T. 
Published: August 2020

e16015 Background: Partial nephrectomy (PN) is now the gold standard for small renal mass of less than 4 cm since it prevents renal insufficiency that may occur with radical nephrectomy. The impact of warm ischemis time (WIT) on the operated kidney's renal differential function (RDF) have been poorly studied in the litterature, especially when WIT is less than 30 minutes. We evaluated the effect of WIT and other perioperative factors on RDF function assessed by pre- and post-operative renal scintigraphy. Methods: Between 2003 and 2008, 182 laparoscopic PN were performed by a single surgeon on patients with two kidneys. Among those, 56 had a MAG3-lasix renal scintigraphy pre- and post-operatively between 7 and 14 days. Data were collected prospectively. Loss in RDF is calculated as follow: Loss in RDF=(RDF preoperatively-RDF postoperatively/RDF preoperatively) × 100. Results: Medians for age, pre- op creatinine, pre-op GFR (Cockroft formula) and tumor CT-size were 61 years, 83 μM, 83,2 ml/min and 26 mm, respectively. Median WIT and pre-operative RDF were 30 minutes and 50%. Median loss of RDF after surgery was 24%. In multivariate analysis, low pre-operative RDF, WIT and intrarenal location of the tumor were associated with a statistically significant loss of RDF (p<0.05). Age, pre-op GFR, tumor CT-size, diabetes and HTN did not predict loss in RDF. Fitting the relative RDF loss versus WIT to a polynomial curve suggests that the rate of loss in RDF increase with WIT. The point of inflection of the polynomial curve (reflecting the maximal change in rates of loss in RDF) was estimated to be at 32 minutes. Linear regression curves show that loss in RDF rate is 0.8% per minute when WIT is less than 32 minutes and 1.3 % per minute when WIT is more or equal to 32 minutes. Conclusions: We show that a WIT of less than 32 minutes optimizes the chances of preserving RDF of the operated kidney and that the rate of loss in RDF is higher above 32 minutes. Finally, higher loss in RDF must be expected if the patient has a low pre-operative RDF and intrarenal location of the tumor. No significant financial relationships to disclose.
Incidence and long term prognosis of papillary renal cell carcinoma
Authors: Schrader A. J. , Rauer-Bruening S. , Olbert P. J. , Hegele A. , Rustemeier J. , Hofmann R. 
Published: August 2020

e16020 Background: Papillary renal cell carcinoma (pRCC) represents the largest subgroup of non clear-cell kidney cancer. In this study we assessed tumour characteristics and long-term prognosis of patients with pRCC in comparison with conventional clear-cell cancer (ccRCC). Methods: We evaluated 744 patients who had undergone renal surgery for RCC between 1990 and 2005. The mean follow-up was 5.6 years. Results: Both groups pRCC and ccRCC were alike concerning age, body mass index, and the incidence of regional lymph node or distant metastasis at diagnosis. The percentage of male patients was higher in pRCC than in ccRCC (73.8 vs. 60.3%, p = 0.006). Even though patients with pRCC presented more often with smaller (p = 0.039) and low grade tumours (p = 0.006), there was no statistically significant difference in tumour recurrence or tumour related death. Moreover, looking at the whole cohort Kaplan-Meier curves revealed no differences regarding tumour specific survival between pRCC and ccRCC (p = 0.94; 5-year survival 78% vs. 77%). However, we observed a trend towards an improved outcome for organ confined (pT1–2) cancer, but a significantly inferior prognosis for locally advanced stage (pT3–4) and/or metastatic papillary tumours at the time of renal surgery. However, applying multivariate analysis including age, sex, and tumour grade, histology could neither be retained as a significant independent prognostic marker in the metastatic setting (p = 0.068, cox regression analysis) nor in a subgroup analysis focussing on patients with advanced cancer (pT3–4 and/or N+/M+; p = 0.064, cox regression analysis). Conclusions: Even though pRCC and ccRCC differ significantly in many aspects including histology and genetic alterations, in all, their long term prognosis is comparable. As we could not confirm a favourable clinical course for pRCC in general, standardized aftercare programmes and - if necessary - systemic treatment, especially in the era of novel targeted drugs, are also needed for this common RCC subtype. In addition, routine histologic subtyping of pRCC is strongly recommended. No significant financial relationships to disclose.
Association of estimated glomerular filtration rate (eGFR) with odds of a renal lesion
Authors: Hruby G. , Van Batavia J. , Wosnitzer M. , Benson M. , Desai M. , McKiernan J. , Newhouse J. 
Published: August 2020

e16025 Background: Patients with ESRD on long term hemodialysis are known to be at an increased risk for renal cell carcinoma. We postulate that some component of chronic renal failure not corrected by dialysis might be the tumor-inducing factor. We sought to determine if chronic renal insufficiency is a risk factor for developing renal cell carcinoma. Methods: A case- control study was used to determine a relationship between renal carcinoma and glomerular filtration rate (MDRD) (eGFR) and using patients with prostate cancer as controls. 1,298 patients from the Columbia University Urologic Oncology Database were identified with either prostate or kidney cancer who had sufficient information to predict eGFR. eGFR calculations were performed for both groups. eGFR was divided into two groups based upon the cut-off value of ≥90. eGFR was also categorized according to the MDRD definitions of chronic kidney disease (CKD), CKD1–4 (values≥90, 60≤values<90, 30≤values<60, and values<30, respectively). Logistic regression techniques were used to quantify the association between pre-operative glomerular filtration rate and the presence of renal or prostate cancer. Results: The mean age of the prostate (n=713) and kidney (n=585) group was 59.9 and 61 years, respectively (p=0.041). The mean weight was 83.9 and 87 kg, respectively (p=0.005). The mean serum creatinine was 1.01 and 1.29 mg/dL, respectively (p<0.001). The mean eGFR was 85 and 73.8, respectively (p<0.001). Two models were fit to analyze the association of eGFR. The first model found eGFR <90 was significantly associated with the presence of a renal carcinoma when controlling for age and race (OR=1.93, CI=1.49–2.49). The second model investigated the eGFR-CKD categories while controlling for age and race and was able to predict the presence of renal cancer (p < 0.001). Patients with an eGFR value of 60≤X<90 had an OR of 1.47 (CI= 1.13–1.92) for renal cancer when compared to patients with normal eGFR levels. Patients with an eGFR value of 30≤X<60 and <30 had an OR of 6.26 (CI=4.10–9.55) and 21.11 (CI=4.87–91.42), respectively. Conclusions: Diminished renal function showed a significant association with the presence of renal cancer. Chronic renal insufficiency may be a risk factor for the development of renal carcinoma. No significant financial relationships to disclose.