scholarly journals Survival and Recurrence in Pancreatobiliary Versus Intestinal Histology of Ampullary Carcinoma

2021 ◽  
pp. 1-7
Author(s):  
Sanjay S. Reddy ◽  
Maitham A. Moslim ◽  
Hailan Liu ◽  
Max Lefton ◽  
Karen Ruth ◽  
...  
Keyword(s):  
Survival Benefit ◽  
Ampullary Carcinoma ◽  
Ampullary Cancer ◽  
Ductal Adenocarcinoma ◽  
Intestinal Histology ◽  
Significant Survival ◽  
Histological Variants ◽  
Histological Variant ◽  
Pathological Review ◽  
Mixed Histology

Background: Ampullary carcinoma is rare with a more favourable prognosis compared to pancreatic ductal adenocarcinoma. The role of histological classification, including pancreatobiliary (PB) and intestinal (INT), on survival and recurrence outcomes in ampullary cancer is still debatable. Methods: 42 patients were identified between 1996-2010. Results: Nineteen classic pancreatoduodenectomies (PD) and 23 pylorus-preserving PDs were performed. Pathological review revealed 23, 18 and 1 patients with the PB, INT and mixed histology, respectively. Adjuvant chemoradiation (ACRT), chemotherapy, and radiation were given to 14 (33.3%), 4 (9.5%) and 2 (4.8%) patients, respectively. Recurrence-free survival (RFS) and overall survival (OS) from time of surgery were higher in the PB histological variant compared to INT (p=0.005 and 0.012, respectively). A landmark (LM) analysis found higher survival in the PB variant patients compared to INT (RFS p=0.023; OS p=0.048). There was no difference in RFS between both histological variants for patients who underwent surgery alone (p=0.42). However, the PB had higher RFS compared to the INT histology for patients who underwent ACRT (p=0.008). Conclusion: Ampullary carcinoma with PB histological variant was associated with significant survival benefit. The PB versus INT survival benefit was seen in the setting of ACRT, but not with surgery alone.

Treatment of GM2 Gangliosidosis in Adult Sandhoff Mice using an Intravenous Self-Complementary Hexosaminidase Vector

2021 ◽  
Vol 21 ◽  
Author(s):  
Karlaina JL. Osmon ◽  
Patrick Thompson ◽  
Evan Woodley ◽  
Subha Karumuthil-Melethil ◽  
Cliff Heindel ◽  
...  
Keyword(s):  
Survival Benefit ◽  
High Dose ◽  
Lysosomal Storage ◽  
Gm2 Gangliosidosis ◽  
Α Subunit ◽  
Significant Survival ◽  
Virus Serotype ◽  
Novel Variant ◽  
Hexosaminidase A

Background: GM2 gangliosidosis is a neurodegenerative, lysosomal storage disease caused by the deficiency of β-hexosaminidase A enzyme (HexA), an α/β-subunit heterodimer. A novel variant of the human hexosaminidase α-subunit, coded by HEXM, has previously been shown to form a stable homodimer, HexM, that hydrolyzes GM2 gangliosides (GM2) in vivo. Materials & Methods: The current study assessed the efficacy of intravenous (IV) delivery of a self-complementary adeno-associated virus serotype 9 (scAAV9) vector incorporating the HEXM transgene, scAAV9/HEXM, including the outcomes based on the dosages provided to the Sandhoff (SD) mice. Six-week-old SD mice were injected with either 2.5E+12 vector genomes (low dose, LD) or 1.0E+13 vg (high dose, HD). We hypothesized that when examining the dosage comparison for scAAV9/HEXM in adult SD mice, the HD group would have more beneficial outcomes than the LD cohort. Assessments included survival, behavioral outcomes, vector biodistribution, and enzyme activity within the central nervous system. Results: Toxicity was observed in the HD cohort, with 8 of 14 mice dying within one month of the injection. As compared to untreated SD mice, which have typical survival of 16 weeks, the LD cohort and the remaining HD mice had a significant survival benefit with an average/median survival of 40.6/34.5 and 55.9/56.7 weeks, respectively. Significant behavioral, biochemical and molecular benefits were also observed. The second aim of the study was to investigate the effects of IV mannitol infusions on the biodistribution of the LD scAAV9/HEXM vector and the survival of the SD mice. Increases in both the biodistribution of the vector as well as the survival benefit (average/median of 41.6/49.3 weeks) were observed. Conclusion: These results demonstrate the potential benefit and critical limitations of the treatment of GM2 gangliosidosis using IV delivered AAV vectors.

scholarly journals Impact of Neoadjuvant Therapy in Resected Pancreatic Ductal Adenocarcinoma of the Pancreatic Body or Tail on Surgical and Oncological Outcome: A Propensity-Score Matched Multicenter Study

2019 ◽  
Vol 27 (6) ◽  
pp. 1986-1996 ◽  
Author(s):  
Sanne Lof ◽  
◽  
Maarten Korrel ◽  
Jony van Hilst ◽  
Adnan Alseidi ◽  
...  
Keyword(s):  
Overall Survival ◽  
Pancreatic Fistula ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Neoadjuvant Therapy ◽  
Survival Benefit ◽  
Pancreatic Head ◽  
Ductal Adenocarcinoma ◽  
Rank Test ◽  
Pancreatic Body ◽  
International Multicenter

Abstract Background Several studies have suggested a survival benefit of neoadjuvant therapy (NAT) for pancreatic ductal adenocarcinoma (PDAC) in the pancreatic head. Data concerning NAT for PDAC located in pancreatic body or tail are lacking. Methods Post hoc analysis of an international multicenter retrospective cohort of distal pancreatectomy for PDAC in 34 centers from 11 countries (2007–2015). Patients who underwent resection after NAT were matched (1:1 ratio), using propensity scores based on baseline characteristics, to patients who underwent upfront resection. Median overall survival was compared using the stratified log-rank test. Results Among 1236 patients, 136 (11.0%) received NAT, most frequently FOLFIRINOX (25.7%). In total, 94 patients receiving NAT were matched to 94 patients undergoing upfront resection. NAT was associated with less postoperative major morbidity (Clavien–Dindo ≥ 3a, 10.6% vs. 23.4%, P = 0.020) and pancreatic fistula grade B/C (9.6% vs. 21.3%, P = 0.026). NAT did not improve overall survival [27 (95% CI 14–39) versus 31 months (95% CI 19–42), P = 0.277], as compared with upfront resection. In a sensitivity analysis of 251 patients with radiographic tumor involvement of splenic vessels, NAT (n = 37, 14.7%) was associated with prolonged overall survival [36 (95% CI 18–53) versus 20 months (95% CI 15–24), P = 0.049], as compared with upfront resection. Conclusion In this international multicenter cohort study, NAT for resected PDAC in pancreatic body or tail was associated with less morbidity and pancreatic fistula but similar overall survival in comparison with upfront resection. Prospective studies should confirm a survival benefit of NAT in patients with PDAC and splenic vessel involvement.

scholarly journals P14.56 Recurrent Glioblastomas: Should we operate a second and even a third time

2019 ◽  
Vol 21 (Supplement_3) ◽  
pp. iii80-iii80
Author(s):  
M Yahia-Cherif ◽  
O De Witte ◽  
C Mélot ◽  
F Lefranc
Keyword(s):  
Overall Survival ◽  
Survival Benefit ◽  
Standard Of Care ◽  
Recurrent Glioblastoma ◽  
Kaplan Meier ◽  
Significant Survival ◽  
Significant Difference ◽  
Second Surgery ◽  
Second Resection ◽  
Initial Resection

Abstract BACKGROUND The aim of this study was i) to analyse the effect of repeat surgeries on the survival of patients with focally recurrent glioblastoma who have benefited from temozolomide treatment and ii) to identify potential prognostic factors for survival. MATERIAL AND METHODS Cases from 2005 to 2014 in the glioblastoma database of our department were retrospectively reviewed. The Kaplan-Meier method was used to estimate overall survival (OS) as a function of time after one, two and three surgical resections. All patients received the standard of care after the first surgery (temozolomide during and after radiotherapy) and adjuvant treatment after repeat surgeries. RESULTS One hundred-thirty-two glioblastoma patients (median age: 57 years) were included in the study. Among them, 68, 53 and 11 patients underwent one, two and three surgical resections, respectively. The median OS was 11, 16 and 18 months, respectively, for patients who underwent one, two and three surgical resections. Patients who underwent two (p<0.001) or three (p<0.01) surgeries survived significantly longer than patients who underwent only one. No significant difference was observed between patients who underwent two versus three surgeries (p=0.76). A second resection performed more than 6 months after the initial resection was the only factor associated with prolonged survival (p=0.008). CONCLUSION Glioblastoma patients who benefited from temozolomide treatment and underwent surgery for recurrent glioblastoma exhibited a significant increase in survival compared with patients who did not undergo a second surgery. By contrast, a third surgery for a second recurrence did not contribute to any significant survival benefit.

scholarly journals 2-Nitroimidazoles induce mitochondrial stress and ferroptosis in glioma stem cells residing in a hypoxic niche

2020 ◽  
Vol 3 (1) ◽  
Author(s):  
Naoyoshi Koike ◽  
Ryuichi Kota ◽  
Yoshiko Naito ◽  
Noriyo Hayakawa ◽  
Tomomi Matsuura ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stress Responses ◽  
Survival Benefit ◽  
Brain Slices ◽  
Glioma Stem Cells ◽  
Hypoxic Conditions ◽  
Significant Survival ◽  
Radiation Induced ◽  
Effects Of Radiation ◽  
Oxidative Stress Responses

AbstractUnder hypoxic conditions, nitroimidazoles can replace oxygen as electron acceptors, thereby enhancing the effects of radiation on malignant cells. These compounds also accumulate in hypoxic cells, where they can act as cytotoxins or imaging agents. However, whether these effects apply to cancer stem cells has not been sufficiently explored. Here we show that the 2-nitroimidazole doranidazole potentiates radiation-induced DNA damage in hypoxic glioma stem cells (GSCs) and confers a significant survival benefit in mice harboring GSC-derived tumors in radiotherapy settings. Furthermore, doranidazole and misonidazole, but not metronidazole, manifested radiation-independent cytotoxicity for hypoxic GSCs that was mediated by ferroptosis induced partially through blockade of mitochondrial complexes I and II and resultant metabolic alterations in oxidative stress responses. Doranidazole also limited the growth of GSC-derived subcutaneous tumors and that of tumors in orthotopic brain slices. Our results thus reveal the theranostic potential of 2-nitroimidazoles as ferroptosis inducers that enable targeting GSCs in their hypoxic niche.

scholarly journals Individualized eHealth Support for Oncological Therapy Management

Breast Care ◽  
2019 ◽  
Vol 14 (3) ◽  
pp. 130-134 ◽  
Author(s):  
Timo Schinköthe
Keyword(s):  
Survival Benefit ◽  
Routine Care ◽  
Physical Activities ◽  
Substantial Evidence ◽  
Symptom Monitoring ◽  
Therapy Management ◽  
Oncological Therapy ◽  
Significant Survival ◽  
Direct Support

eHealth support for oncological therapy management has different faces. In addition to the direct support of therapy-supportive measures such as the promotion of physical activities, monitoring of the diet and observation of the quality of life through eHealth approaches are possible. Many solutions are now in transition between research and routine use. The most substantial evidence today is in the area of symptom monitoring. Independent studies have shown a significant survival benefit among other advantages as well. There is also a good overlap in eHealth and physical activity. More and more solutions are coming onto the market, which also has an impact for cancer patients. In the field of nutrition, there are only a few successful approaches both within and outside oncology. In contrast, the application of eHealth for the detection of disease-related malnutrition seems promising. Innovative approaches involving “artificial intelligence” or “Internet of Things” are slowly finding their place in both research and routine. For routine care, it will be necessary for doctors, nurses, and patients to know what a real medical eHealth application is and which are just lifestyle products without the needed quality for professional medical usage.

scholarly journals P1630IS THERE ALWAYS A SURVIVAL BENEFIT WITH KIDNEY TRANSPLANTATION? RESULTS FROM A BELGIAN COHORT

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Rachel Hellemans ◽  
Anneke Kramer ◽  
Johan De Meester ◽  
Dirk Kuypers ◽  
Michel Jadoul ◽  
...  
Keyword(s):  
Kidney Transplantation ◽  
Survival Benefit ◽  
Age Groups ◽  
Deceased Donor ◽  
Risk Levels ◽  
Significant Survival ◽  
Recipient Age ◽  
Expanded Criteria ◽  
Deceased Donor Kidney Transplant ◽  
Dialysis Outcomes

Abstract Background and Aims Older studies have shown a survival benefit with kidney transplantation compared to dialysis, even for patients older than 60 years. However, due to important evolutions such as older recipient age and the use of less-than-optimal quality donors, it is unclear if the survival benefit with transplantation still holds true nowadays. Method Patient survival was analyzed for 3808 Belgian patients waitlisted for a first deceased donor kidney transplant between 2000 to 2012. Patients were divided into age categories (20-44y, 45-64y, ≥65y). Primary outcome was the comparison of mortality during median waiting time plus 3 years follow-up, either after transplantation or when remaining on dialysis. Outcomes were analyzed separately for those receiving a standard criteria donor (SCD) or an expanded criteria donor (ECD) transplant. The survival analyses were adjusted for age, sex and primary renal disease. Results Among patients ≥ 65 years old, only SCD transplantation provided a significant survival benefit compared to dialysis: mortality was 16.3 % (95 % CI: 13.2–19.9 %) with SCD transplantation, 20.5 % (16.1–24.6 %) with ECD transplantation, and 24.6 % (19.5–29.5 %) when remaining on dialysis. Relative mortality risk was increased in the first months after transplantation compared to dialysis, with equal risk levels being reached earlier for SCD than ECD transplantations in all age groups. Conclusion This study suggests that older patients have a survival benefit with SCD transplantation versus dialysis, but the survival benefit with ECD transplantation versus dialysis may be small or non-existent.

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