Professor Fulton's View of Phenomenology

Paper by Ramakrishna Puligandl

Validation of a new prognostic model to easily predict outcome in renal cell carcinoma: The GRANT score applied to the ASSURE trial population

Background: Prognostic scores have been developed to estimate the risk of recurrence and the probability of survival after nephrectomy for renal cell carcinoma (RCC). The use of these tools, despite being helpful to plan a customized schedule of follow-up, to the patient's tailored counselling and to select individuals who could potentially benefit from adjuvant treatment, currently is not routine, due to their relative complexity and to the lack of histological data (i.e. necrosis).Patients and methods: We developed a simple score called GRade, Age, Nodes and Tumor (GRANT) based on four easily obtained parameters: Fuhrman grade, age, pathological nodal status and pathological tumor size. Patients with 0 or 1 factor are classified as favorable risk, whereas patients with two or more risk factors as unfavorable risk. The large population of RCC patients from the ASSURE adjuvant trial was used as independent dataset for this external validation, to investigate the prognostic value of the new score in terms of disease-free survival and overall survival and to evaluate its possible application as predictive tool. Statistical analyses were carried out by the Department of Biostatistics & Computational Biology, Dana-Farber Cancer Institute (Boston, USA) for the ASSURE trial patients' population.Results: The performance of the new model is similar to that of the already validated score systems, but its strength, compared with the others already available, is the ease and clarity of its calculation, with great speed of use during the clinical practice. Limitations are the use of the Fuhrman nuclear grade, not valid for rare histologies, and the TNM classification modifications over time.Conclusion: The GRANT score demonstrated its potential usefulness for clinical practice

From Path-Segment Tiles to Loops and Labyrinths

Abstract We explain how to use integer programs to assemble a collection of path-segment tiles-squares decorated with path segments-on a grid so that the path segments join together to form a single closed loop or a single open path through the centers of the squares of the grid. We describe how to optimize (maximize or minimize) the number of bends (90-degree turns) in the loop or path. We show how to force loops to be symmetric and to encourage paths to be as close to symmetric as possible. We conclude by displaying laser-cut and 3D-printed artwork designed with our integer programs

Imaging, radiation exposure, and attributable cancer risk for neonates with necrotizing enterocolitis

Abstract Purpose: Neonates with necrotizing enterocolitis (NEC) receive numerous radiologic investigations that potentially increase their lifetime cancer mortality risk. We evaluated our radiologic practice pattern for patients with NEC and estimated cumulative radiation exposure and lifetime cancer risk. Methods: Infants with NEC in a tertiary care NICU had patient demographics, imaging, treatments/ interventions, and outcomes analyzed over 3 years. The number and type of imaging were recorded, including NEC-related imaging (thoraco-abdominal "babygrams" and abdominal radiographs), and all other imaging modalities. Patients were stratified by birth weight: group 1 (b 750 g); group 2 (751-1500 g); and group 3 (N 1501 g). Pre-existing normative data were used to calculate radiation exposure, absorption, and attributable cancer risk from NEC-related imaging. Results: Sixty-four neonates with 72 episodes of NEC were identified. Overall survival was 75.0%. When stratified by birth weight, mean abdominal radiographs and babygrams comprised 51%, 60%, and 74% of total imaging, giving median mGy doses of 2.1, 0.4, and 0.2, respectively. Compared to normative data, radiation dosing, and median cumulative cancer lifetime mortality risk increased by an average of 4.3 × from baseline, with two cases documenting a 20-fold increase. Conclusion: Neonates with NEC are exposed to significant amounts of radiation directly attributable to disease surveillance. Non-radiologic surveillance methods could significantly reduce radiation exposure and cancer risk in these infants

Adenocarcinoma Arising in a Duplication of the Cecum

Intestinal duplications are rare developmental abnormalities that may occur anywhere in the gastrointestinal tract. The possibility of a malignant change occurring in these duplications is very low. We present a case of adenocarcinoma arising in a duplication of the cecum. A 41-year-old male patient was admitted because of a palpable abdominal mass. Abdominal computed tomography revealed a 6-cm, peripheral wall-enhanced, round, cystic mass in the cecal area. Excision of the mesenteric mass and a right hemicolectomy was performed. Upon histologic examination, the patient was diagnosed with adenocarcinoma arising in a duplication of the cecum

Tumor Microvessel Density as a Prognostic Marker in High-Risk Renal Cell Carcinoma Patients Treated on ECOG-ACRIN E2805

Purpose—Increased vascularity is a hallmark of renal cell carcinoma (RCC). Microvessel density (MVD) is one measurement of tumor angiogenesis; however, its utility as a biomarker of outcome is unknown. ECOG-ACRIN 2805 (E2805) enrolled 1,943 resected high-risk RCC patients randomized to adjuvant sunitinib, sorafenib, or placebo. We aimed to determine the prognostic and predictive role of MVD in RCC. Experimental Design—We obtained pretreatment primary RCC nephrectomy tissues from 822 patients on E2805 and constructed tissue microarrays. Using quantitative immunofluorescence, we measured tumor MVD as the area of CD34-expressing cells. We determined the association with disease-free survival (DFS), overall survival (OS), treatment arm, and clinicopathologic variables. Results—High MVD (above the median) was associated with prolonged OS for the entire cohort (p = 0.021) and for patients treated with placebo (p = 0.028). The association between high MVD and OS was weaker in patients treated with sunitinib or sorafenib (p = 0.060). MVD was not associated with DFS (p = 1.00). On multivariable analysis, MVD remained independently associated with improved OS (p = 0.013). High MVD correlated with Fuhrman grade 1–2 (p \u3c 0.001), clear cell histology (p \u3c 0.001), and absence of necrosis (p \u3c 0.001) but not with gender, age, sarcomatoid features, lymphovascular invasion, or tumor size. Conclusions—High MVD in resected high-risk RCC patients is an independent prognostic, rather than predictive, biomarker of improved OS. Further studies should assess whether incorporating MVD into clinical models will enhance our ability to predict outcome and if low MVD can be used for selection of high-risk patients for adjuvant therapy trials

Abscess formation of a spherical-shape duplication in the splenic flexure of the colon: case report and review of the literature

Gastrointestinal tract duplications are rare congenital malformations that may occur anywhere in the alimentary tract from the mouth to the anus, and vary greatly in presentation, size, location, and especially in symptoms. We present a case of an infected spherical colonic duplication, in a 20-day-old baby, located at the splenic flexure of the colon. The prominent symptom was acute abdomen, accompanied by bilious vomiting, intestinal obstruction, and high fever. We present this case, due to atypical clinical presentation and the inability of the imaging modality to establish the diagnosis preoperatively

Management of Gastroschisis: Results From the NETS2G Study, a Joint British, Irish, and Canadian Prospective Cohort Study of 1268 Infants.

OBJECTIVE: In infants with gastroschisis, outcomes were compared between those where operative reduction and fascial closure were attempted ?24?hours of age (PC), and those who underwent planned closure of their defect >24?hours of age following reduction with a pre-formed silo (SR). SUMMARY OF BACKGROUND DATA: Inadequate evidence exists to determine how best to treat infants with gastroschisis. METHODS: A secondary analysis was conducted of data collected 2006-2008 using the British Association of Pediatric Surgeons Congenital Anomalies Surveillance System, and 2005-2016 using the Canadian Pediatric Surgery Network.28-day outcomes were compared between infants undergoing PC and SR. Primary outcome was number of gastrointestinal complications. Interactions were investigated between infant characteristics and treatment to determine whether intervention effect varied in sub-groups of infants. RESULTS: Data from 341 British and Irish infants (27%) and 927 Canadian infants (73%) were used. 671 infants (42%) underwent PC and 597 (37%) underwent SR. The effect of SR on outcome varied according to the presence/absence of intestinal perforation, intestinal matting and intestinal necrosis. In infants without these features, SR was associated with fewer gastrointestinal complications [aIRR 0.25 (95% CI 0.09-0.67, P = 0.006)], more operations [aIRR 1.40 (95% CI 1.22-1.60, P < 0.001)], more days PN [aIRR 1.08 (95% CI 1.03-1.13, P < 0.001)], and a higher infection risk [aOR 2.06 (95% CI 1.10-3.87, P = 0.025)]. In infants with these features, SR was associated with a greater number of operations [aIRR 1.30 (95% CI 1.17-1.45, P < 0.001)], and more days PN [aIRR 1.06 (95% CI 1.02-1.10, P = 0.003)]. CONCLUSIONS: In infants without intestinal perforation, matting, or necrosis, the benefits of SR outweigh its drawbacks. In infants with these features, the opposite is true. Treatment choice should be based upon these features

Declining recurrence among ductal carcinoma in situ patients treated with breast-conserving surgery in the community setting

Introduction: Randomized trials indicate that adjuvant radiotherapy plus tamoxifen decrease the five-year risk of recurrence among ductal carcinoma in situ patients treated with breast-conserving surgery from about 20% to 8%. The aims of this study were to examine the use and impact of these therapies on risk of recurrence among ductal carcinoma in situ patients diagnosed and treated in the community setting. Methods: We identified 2,995 patients diagnosed with ductal carcinoma in situ between 1990 and 2001 and treated with breast-conserving surgery at three large health plans. Medical charts were reviewed to confirm diagnosis and treatment and to obtain information on subsequent breast cancers. On a subset of patients, slides from the index ductal carcinoma in situ were reviewed for histopathologic features. Cumulative incidence curves were generated and Cox regression was used to examine changes in five-year risk of recurrence across diagnosis years, with and without adjusting for trends in use of adjuvant therapies. Results: Use of radiotherapy increased from 25.8% in 1990-1991 to 61.3% in 2000-2001; tamoxifen increased from 2.3% to 34.4%. A total of 245 patients had a local recurrence within five years of their index ductal carcinoma in situ. The five-year risk of any local recurrence decreased from 14.3% (95% confidence interval 9.8 to 18.7) for patients diagnosed in 1990-1991 to 7.7% (95% confidence interval 5.5 to 9.9) for patients diagnosed in 1998-1999; invasive recurrence decreased from 7.0% (95% confidence interval 3.8 to 10.3) to 3.1% (95% confidence interval 1.7 to 4.6). In Cox models, the association between diagnosis year and risk of recurrence was modestly attenuated after accounting for use of adjuvant therapy. Between 1990-1991 and 2000-2001, the proportion of patients with tumors with high nuclear grade decreased from 46% to 32% (P = 0.03) and those with involved surgical margins dropped from 15% to 0% (P = 0.03). Conclusions: The marked increase in the 1990s in the use of adjuvant therapy for ductal carcinoma in situ patients treated with breast-conserving surgery in the community setting only partially explains the 50% decline in risk of recurrence. Changes in pathology factors have likely also contributed to this decline