Predictors of a successful outcome for infants with short bowel syndrome: a 30-year single-institution experience

Abstract

Purpose

Short-bowel syndrome (SBS) is associated with high morbidity and mortality. We conducted this study to establish the predictors of survival and weaning off parenteral nutrition (PN).

Methods

We reviewed the medical records of 16 SBS infants treated at our institution within a 30-year period. SBS was defined as a residual small-bowel length (RSBL) of <75 cm. Loss of the ileocecal valve (ICV), cholestasis (D-Bil >2.0 mg/dl), enterostomy, and RSBL were all evaluated. Kaplan–Meier analysis was used to analyze the predictors.

Results

The mean RSBL was 34.9 ± 22.9 cm. Six patients died (37.5%) and nine patients were weaned off PN (56.3%). Significant differences were observed in cholestasis (p < 0.03), enterostomy (p < 0.01), an absolute RSBL of <30 cm (p < 0.04), and a percentage of expected RSBL of <10% (p < 0.04) as survival predictors. Significant differences were also observed for cholestasis (p < 0.01), loss of the ICV (p < 0.04), an absolute RSBL of <20 cm (p < 0.01), and a percentage of expected RSBL of <10% (p < 0.03) as predictors of weaning off PN.

Conclusion

These predictors may help us select the optimal treatments for pediatric patients with SBS.

http://ift.tt/2p4JjWg

Senior general surgery residents can be trained to perform focused assessment with sonography for trauma patients accurately

Abstract

Purposes

Researchers studying trauma have found that physicians are able to perform a focused assessment with sonography for trauma (FAST) with minimal training and achieve ideal accuracy. However, there are currently no consensus or standard guidelines regarding the performance of this assessment. The aim of our study was to clarify the value of FAST performed by well-qualified senior general surgery residents in cases of suspected blunt abdominal trauma, which presents an important diagnostic problem in emergency departments.

Methods

This was a retrospective study in the emergency department (ED) of our hospital performed from January 2011 to September 2013. Patients were included if they (1) had undergone a FAST examination performed by qualified residents and (2) had received subsequent formal radiographic or surgical evaluations. The results were compared against subsequent surgical findings or formal Department of Radiology reference standards.

Results

Among the 438 patients enrolled, false-negative results were obtained in 8 and false-positive results in 5. Only one patient was missed and required laparotomy to repair a small intestine perforation. The sensitivity and specificity were 87 and 99%, respectively; the accuracy was 97%.

Conclusions

Senior general surgery residents can be trained to perform accurate FAST examinations on trauma patients.

http://ift.tt/2pS3cCI

Predictive risk factors for peritoneal recurrence after pancreatic cancer resection and strategies for its prevention

Abstract

Purpose

To evaluate the risk factors for peritoneal recurrence (PR) of pancreatic adenocarcinoma and to discuss the appropriate management strategies.

Methods

We reviewed the medical records of 236 patients who underwent pancreatectomy for pancreatic adenocarcinoma. We then compared the clinicopathological characteristics of patients with vs. those without PR. The independent risk factors for PR were defined using the Cox proportional hazards regression model.

Results

The median survival of patients with PR was 13.3 months after surgical treatment. The PR group had a significantly higher incidence of portal vein resection, longer operative time (≥648 min), greater blood loss (≥2179 mL), blood transfusion, tumor size, portal vein invasion, artery invasion, pancreatic nerve plexus invasion, and histological grade. Multivariate analysis revealed that excessive blood loss (≥2179 mL; P = 0.010), artery invasion (P = 0.025), pancreatic nerve plexus invasion (P = 0.001), and histological grade 3 (P = 0.011) were independent risk factors for PR. Excessive blood loss was also strongly related to tumor size (P = 0.018).

Conclusions

Local invasion and tumor size-related factors suggested the possibility of intraoperative dissemination at the time of tumor resection. Preoperative treatment and an operative procedure to prevent tumor exposure may help prevent PR.

http://ift.tt/2p4PeKQ

The outcomes of pediatric liver retransplantation from a living donor: a 17-year single-center experience

Abstract

Purpose

Liver retransplantation is the only therapeutic option for patients with graft failure after liver transplantation. The aim of this study is to evaluate the outcomes of pediatric retransplantation from living donor at a single center.

Methods

Between December 1998 to August 2015, retransplantation from a living donor was performed for 14 children (<18 years of age) at Kumamoto University Hospital. The characteristics of the retransplantation recipient and the clinicopathological factors between primary transplantation and retransplantation were analyzed to detect the prognostic factors.

Results

In retransplantation, the operative time was longer and the amount of blood loss was greater in comparison to primary transplantation. The 1-, 3-, and 5-year survival rates from the date of retransplantation were 85.7, 85.7, and 78.6%, respectively. The rates of re-laparotomy after primary transplantation, bile leakage and postoperative bleeding after retransplantation were higher than after primary transplantation. Among the three patients who died after retransplantation, the operative time, the rate of re-laparotomy after primary transplantation and the incidence of gastrointestinal complications were higher in comparison to the surviving patients.

Conclusion

Pediatric retransplantation from a living donor is an acceptable procedure that could save the lives of recipients with failing allografts when organs from deceased donors are scarce. To ensure good results, it is essential to make an appropriate assessment of the cardiopulmonary function and the infectious state of the patients before Re-LDLT.

http://ift.tt/2p4Sxlz

Predictors of a successful outcome for infants with short bowel syndrome: a 30-year single-institution experience

Abstract

Purpose

Short-bowel syndrome (SBS) is associated with high morbidity and mortality. We conducted this study to establish the predictors of survival and weaning off parenteral nutrition (PN).

Methods

We reviewed the medical records of 16 SBS infants treated at our institution within a 30-year period. SBS was defined as a residual small-bowel length (RSBL) of <75 cm. Loss of the ileocecal valve (ICV), cholestasis (D-Bil >2.0 mg/dl), enterostomy, and RSBL were all evaluated. Kaplan–Meier analysis was used to analyze the predictors.

Results

The mean RSBL was 34.9 ± 22.9 cm. Six patients died (37.5%) and nine patients were weaned off PN (56.3%). Significant differences were observed in cholestasis (p < 0.03), enterostomy (p < 0.01), an absolute RSBL of <30 cm (p < 0.04), and a percentage of expected RSBL of <10% (p < 0.04) as survival predictors. Significant differences were also observed for cholestasis (p < 0.01), loss of the ICV (p < 0.04), an absolute RSBL of <20 cm (p < 0.01), and a percentage of expected RSBL of <10% (p < 0.03) as predictors of weaning off PN.

Conclusion

These predictors may help us select the optimal treatments for pediatric patients with SBS.

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Senior general surgery residents can be trained to perform focused assessment with sonography for trauma patients accurately

Abstract

Purposes

Researchers studying trauma have found that physicians are able to perform a focused assessment with sonography for trauma (FAST) with minimal training and achieve ideal accuracy. However, there are currently no consensus or standard guidelines regarding the performance of this assessment. The aim of our study was to clarify the value of FAST performed by well-qualified senior general surgery residents in cases of suspected blunt abdominal trauma, which presents an important diagnostic problem in emergency departments.

Methods

This was a retrospective study in the emergency department (ED) of our hospital performed from January 2011 to September 2013. Patients were included if they (1) had undergone a FAST examination performed by qualified residents and (2) had received subsequent formal radiographic or surgical evaluations. The results were compared against subsequent surgical findings or formal Department of Radiology reference standards.

Results

Among the 438 patients enrolled, false-negative results were obtained in 8 and false-positive results in 5. Only one patient was missed and required laparotomy to repair a small intestine perforation. The sensitivity and specificity were 87 and 99%, respectively; the accuracy was 97%.

Conclusions

Senior general surgery residents can be trained to perform accurate FAST examinations on trauma patients.

from Cancer via ola Kala on Inoreader http://ift.tt/2pS3cCI
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Predictive risk factors for peritoneal recurrence after pancreatic cancer resection and strategies for its prevention

Abstract

Purpose

To evaluate the risk factors for peritoneal recurrence (PR) of pancreatic adenocarcinoma and to discuss the appropriate management strategies.

Methods

We reviewed the medical records of 236 patients who underwent pancreatectomy for pancreatic adenocarcinoma. We then compared the clinicopathological characteristics of patients with vs. those without PR. The independent risk factors for PR were defined using the Cox proportional hazards regression model.

Results

The median survival of patients with PR was 13.3 months after surgical treatment. The PR group had a significantly higher incidence of portal vein resection, longer operative time (≥648 min), greater blood loss (≥2179 mL), blood transfusion, tumor size, portal vein invasion, artery invasion, pancreatic nerve plexus invasion, and histological grade. Multivariate analysis revealed that excessive blood loss (≥2179 mL; P = 0.010), artery invasion (P = 0.025), pancreatic nerve plexus invasion (P = 0.001), and histological grade 3 (P = 0.011) were independent risk factors for PR. Excessive blood loss was also strongly related to tumor size (P = 0.018).

Conclusions

Local invasion and tumor size-related factors suggested the possibility of intraoperative dissemination at the time of tumor resection. Preoperative treatment and an operative procedure to prevent tumor exposure may help prevent PR.

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The outcomes of pediatric liver retransplantation from a living donor: a 17-year single-center experience

Abstract

Purpose

Liver retransplantation is the only therapeutic option for patients with graft failure after liver transplantation. The aim of this study is to evaluate the outcomes of pediatric retransplantation from living donor at a single center.

Methods

Between December 1998 to August 2015, retransplantation from a living donor was performed for 14 children (<18 years of age) at Kumamoto University Hospital. The characteristics of the retransplantation recipient and the clinicopathological factors between primary transplantation and retransplantation were analyzed to detect the prognostic factors.

Results

In retransplantation, the operative time was longer and the amount of blood loss was greater in comparison to primary transplantation. The 1-, 3-, and 5-year survival rates from the date of retransplantation were 85.7, 85.7, and 78.6%, respectively. The rates of re-laparotomy after primary transplantation, bile leakage and postoperative bleeding after retransplantation were higher than after primary transplantation. Among the three patients who died after retransplantation, the operative time, the rate of re-laparotomy after primary transplantation and the incidence of gastrointestinal complications were higher in comparison to the surviving patients.

Conclusion

Pediatric retransplantation from a living donor is an acceptable procedure that could save the lives of recipients with failing allografts when organs from deceased donors are scarce. To ensure good results, it is essential to make an appropriate assessment of the cardiopulmonary function and the infectious state of the patients before Re-LDLT.

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Recurrent glioblastoma: a single-institution experience with reirradiation and temozolomide

Abstract

Background

Glioblastoma is an aggressive disease with poor prognosis. Outcomes following recurrences are dismal despite the use of multimodality treatment. Surgery is usually not a viable option, and even in those who do undergo surgery, adjuvant radiation therapy with or without concurrent chemotherapy may be viable options depending on several factors such as performance status, disease volume, and time since prior therapy. We intended to assess the efficacy of high precision reirradiation with temozolomide as a salvage modality in patients with recurrent glioblastoma.

Methods

Twenty-five patients with recurrent glioblastoma who received reirradiation (with or without concurrent temozolomide) for recurrence at our department between 2010 and 2015 were included in this retrospective analysis. Treatment decisions are taken following recommendations of multidisciplinary tumor board. Treatment details were noted from respective case records. Survival time was calculated using Kaplan-Meier method. Univariate and multivariate analyses were performed using Cox regression analysis.

Results

Eighteen men and seven women with a mean age of 52 years (range, 20–65 years) received reirradiation during the given period. Median Karnofsky Performance Score (KPS) was 70% (range, 40–90). Twelve patients underwent surgery before reirradiation, while 13 patients were deemed inoperable and direct taken for reirradiation. The reirradiation methods included stereotactic radiosurgery (2), hypofractionated stereotactic radiation therapy (15–40 Gy in 3–5 fractions; 14 patients), or conventionally fractionated stereotactic radiation therapy (45–54 Gy in 25–27 fractions; 9 patients). Patients who received conventional fractionated radiation also received concurrent temozolomide at 75 mg/m². All patients completed the planned course of radiation therapy and also received adjuvant temozolomide. MGMT methylation status was available for 15 patients; 7 had MGMT methylated while 8 had non-methylated tumors.

Median follow-up from recurrence was 12 months (range, 1–47.8 months). Median overall survival (OS) from recurrence was 15.2 months (95% confidence interval [CI], 10–20.33 months). None of the factors analyzed (age, sex, gross tumor volume at time of recurrence, KPS, MGMT, time of recurrence) were significant for outcomes. No grade 3 or above acute or late complications were noted following reirradiation.

Conclusions

Our results suggest that reirradiation with high precision radiotherapy along with temozolomide is an effective option in patients with recurrent glioblastoma.

http://ift.tt/2ogVRfY

Recurrent glioblastoma: a single-institution experience with reirradiation and temozolomide

Abstract

Background

Glioblastoma is an aggressive disease with poor prognosis. Outcomes following recurrences are dismal despite the use of multimodality treatment. Surgery is usually not a viable option, and even in those who do undergo surgery, adjuvant radiation therapy with or without concurrent chemotherapy may be viable options depending on several factors such as performance status, disease volume, and time since prior therapy. We intended to assess the efficacy of high precision reirradiation with temozolomide as a salvage modality in patients with recurrent glioblastoma.

Methods

Twenty-five patients with recurrent glioblastoma who received reirradiation (with or without concurrent temozolomide) for recurrence at our department between 2010 and 2015 were included in this retrospective analysis. Treatment decisions are taken following recommendations of multidisciplinary tumor board. Treatment details were noted from respective case records. Survival time was calculated using Kaplan-Meier method. Univariate and multivariate analyses were performed using Cox regression analysis.

Results

Eighteen men and seven women with a mean age of 52 years (range, 20–65 years) received reirradiation during the given period. Median Karnofsky Performance Score (KPS) was 70% (range, 40–90). Twelve patients underwent surgery before reirradiation, while 13 patients were deemed inoperable and direct taken for reirradiation. The reirradiation methods included stereotactic radiosurgery (2), hypofractionated stereotactic radiation therapy (15–40 Gy in 3–5 fractions; 14 patients), or conventionally fractionated stereotactic radiation therapy (45–54 Gy in 25–27 fractions; 9 patients). Patients who received conventional fractionated radiation also received concurrent temozolomide at 75 mg/m². All patients completed the planned course of radiation therapy and also received adjuvant temozolomide. MGMT methylation status was available for 15 patients; 7 had MGMT methylated while 8 had non-methylated tumors.

Median follow-up from recurrence was 12 months (range, 1–47.8 months). Median overall survival (OS) from recurrence was 15.2 months (95% confidence interval [CI], 10–20.33 months). None of the factors analyzed (age, sex, gross tumor volume at time of recurrence, KPS, MGMT, time of recurrence) were significant for outcomes. No grade 3 or above acute or late complications were noted following reirradiation.

Conclusions

Our results suggest that reirradiation with high precision radiotherapy along with temozolomide is an effective option in patients with recurrent glioblastoma.

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FKBP51s signature in peripheral blood mononuclear cells of melanoma patients as a possible predictive factor for immunotherapy

Abstract

The inhibitory immune checkpoint PD-L1/PD1 promotes the alternative splicing of the FKBP5 gene, resulting in increased expression of its variant 4 in the peripheral blood mononuclear cells of melanoma patients. The variant 4 transcript is translated into the truncated FKBP51s protein. Given the importance of co-inhibitory signalling in tumour immune escape, here we tested the potential for using FKBP51s expression to predict immunotherapy outcomes. To do this, we immunophenotyped PBMCs from 118 melanoma patients and 77 age- and sex-matched healthy controls. Blood samples were collected before patients underwent ipilimumab treatment. In 64 of the 118 patients, FKBP51s expression was also assessed in regulatory T cells (Tregs). We found that each PBMC subset analysed contained an FKBP51s^pos fraction, and that this fraction was greater in the melanoma patients than healthy controls. In CD4 T lymphocytes, the FKBP51s^neg fraction was significantly impaired. Tregs count was increased in melanoma patients, which is in line with previous studies. Also, by analyses of FKBP51s in Tregs, we identified a subgroup of ipilimumab nonresponder patients (p = 0.002). In conclusion, FKBP51s-based immunophenotyping of melanoma patients revealed several profiles related to a negative immune regulatory control and identified an unknown Treg subset. These findings are likely to be useful in the selection of the patients that are candidate for immunotherapy.

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FKBP51s signature in peripheral blood mononuclear cells of melanoma patients as a possible predictive factor for immunotherapy

Abstract

The inhibitory immune checkpoint PD-L1/PD1 promotes the alternative splicing of the FKBP5 gene, resulting in increased expression of its variant 4 in the peripheral blood mononuclear cells of melanoma patients. The variant 4 transcript is translated into the truncated FKBP51s protein. Given the importance of co-inhibitory signalling in tumour immune escape, here we tested the potential for using FKBP51s expression to predict immunotherapy outcomes. To do this, we immunophenotyped PBMCs from 118 melanoma patients and 77 age- and sex-matched healthy controls. Blood samples were collected before patients underwent ipilimumab treatment. In 64 of the 118 patients, FKBP51s expression was also assessed in regulatory T cells (Tregs). We found that each PBMC subset analysed contained an FKBP51s^pos fraction, and that this fraction was greater in the melanoma patients than healthy controls. In CD4 T lymphocytes, the FKBP51s^neg fraction was significantly impaired. Tregs count was increased in melanoma patients, which is in line with previous studies. Also, by analyses of FKBP51s in Tregs, we identified a subgroup of ipilimumab nonresponder patients (p = 0.002). In conclusion, FKBP51s-based immunophenotyping of melanoma patients revealed several profiles related to a negative immune regulatory control and identified an unknown Treg subset. These findings are likely to be useful in the selection of the patients that are candidate for immunotherapy.

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Associations of self-reported smoking, cotinine levels and epigenetic smoking indicators with oxidative stress among older adults: a population-based study

Abstract

Tobacco smoking and oxidative stress (OS) are both related to a wide spectrum of adverse age-related health outcomes, but their association is not yet well-established. We examined the associations of self-reported smoking indicators, serum cotinine levels and smoking-related DNA methylation biomarkers with two urinary proxy markers of OS, 8-isoprostane (8-iso) and 8-hydroxy-2′-deoxyguanosine (8-oxodG), in two independent subsets of older adults recruited in Germany (discovery set: n = 978, validation set: n = 531). We obtained DNA methylation profiles in whole blood samples by Illumina Human Methylation450K Beadchip and measured the urinary levels of both OS markers using commercial ELISA kits. After controlling for potential confounders, current smoking, cumulative smoking exposure (pack-years) and serum cotinine levels (ng/ml) were strongly associated with 8-iso levels (p values <0.0001, 0.004 and 0.001, respectively). Of 151 previously identified smoking-related CpG sites, 71 loci were associated with 8-iso levels after correction for multiple testing (FDR < 0.05) in the validation phase and were designated as loci related to 8-iso levels defined OS. In addition, serum cotinine levels, cumulative smoking exposure and a smoking index (SI) based on the 71 identified loci manifested monotonic associations with 8-iso levels. However, we did not observe any associations between these smoking indicators and 8-oxodG levels. In conclusion, this study suggests that smoking-related epigenetic alterations are closely correlated with smoking-induced OS. The identified CpG sites could potentially be prognostic epigenetic markers of OS and OS-related health outcomes. Our findings and the underlying mechanisms should be followed up in further, preferably longitudinal studies.

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Mesenteric Cystic Teratoma Masquerading as Acute Abdomen

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Left Versus Right: Does Location Matter for Refractory Metastatic Colorectal Cancer Patients in Phase 1 Clinical Trials?

Abstract

Purpose

Location of the primary tumor is prognostic and predictive of efficacy with VEGF-inhibitors (I) versus EGFR-I given first-line to metastatic colorectal cancer (mCRC) patients. However, little is known regarding the effect of location on prognosis and prediction in refractory mCRC. We assessed the efficacy of VEGF-I and EGFR-I in regards to location of the primary tumor in patients with refractory mCRC enrolled in early phase studies.

Methods

A historical cohort analysis of mCRC patients, including 44 phase I trials our institution, from March 2004 to September 2012. Median Progression free survival (mPFS) and overall survival (mOS) were estimated from Kaplan-Meier curves and groups were statistically compared with the log-rank test.

Results

One hundred thirty-nine patients with a median age 59 (33–81). 73.9% received 3+ lines of therapy. All KRAS wild-type patients had received prior EGFR-I. Location: right 20.9%, left 61.9%, and transverse 4.3%. For survival analysis, transverse CRC were included with right. Of the 112 patients, mOS was left (N = 80) 6.6 months versus right (N = 32) 5.9 months, P = 0.18. mPFS was left (n = 86) 2.0 months versus right (N = 35) 2.0 months, P = 0.76. In subgroup analysis, survival was significant for KRAS wild-type patients with left-sided mCRC had mOS of 6.2 months with other agents versus 9.4 months with EGFR-I (P = 0.03).

Conclusions

In phase 1 clinical trials, although location alone was not prognostic in heavily pretreated patients, left-sided mCRC had improved survival with EGFR-I. Despite progression on EGFR-I, left-sided KRAS wild mCRC patients should be considered for phase 1 studies of agents targeting growth factor pathways.

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Mesenteric Cystic Teratoma Masquerading as Acute Abdomen

http://ift.tt/2ogeZe3

Left Versus Right: Does Location Matter for Refractory Metastatic Colorectal Cancer Patients in Phase 1 Clinical Trials?

Abstract

Purpose

Location of the primary tumor is prognostic and predictive of efficacy with VEGF-inhibitors (I) versus EGFR-I given first-line to metastatic colorectal cancer (mCRC) patients. However, little is known regarding the effect of location on prognosis and prediction in refractory mCRC. We assessed the efficacy of VEGF-I and EGFR-I in regards to location of the primary tumor in patients with refractory mCRC enrolled in early phase studies.

Methods

A historical cohort analysis of mCRC patients, including 44 phase I trials our institution, from March 2004 to September 2012. Median Progression free survival (mPFS) and overall survival (mOS) were estimated from Kaplan-Meier curves and groups were statistically compared with the log-rank test.

Results

One hundred thirty-nine patients with a median age 59 (33–81). 73.9% received 3+ lines of therapy. All KRAS wild-type patients had received prior EGFR-I. Location: right 20.9%, left 61.9%, and transverse 4.3%. For survival analysis, transverse CRC were included with right. Of the 112 patients, mOS was left (N = 80) 6.6 months versus right (N = 32) 5.9 months, P = 0.18. mPFS was left (n = 86) 2.0 months versus right (N = 35) 2.0 months, P = 0.76. In subgroup analysis, survival was significant for KRAS wild-type patients with left-sided mCRC had mOS of 6.2 months with other agents versus 9.4 months with EGFR-I (P = 0.03).

Conclusions

In phase 1 clinical trials, although location alone was not prognostic in heavily pretreated patients, left-sided mCRC had improved survival with EGFR-I. Despite progression on EGFR-I, left-sided KRAS wild mCRC patients should be considered for phase 1 studies of agents targeting growth factor pathways.

http://ift.tt/2oxIqV4

Is adjuvant chemotherapy necessary in pT1N1 gastric cancer?

Abstract

Background

Due to a lack of consensus on adjuvant treatments for pT1N1 gastric cancer, surgeons face a dilemma when deciding treatments for patients with pT1N1 gastric cancer after gastrectomy. The objective of this study was to determine survival benefits of adjuvant chemotherapy and risk factors for tumor recurrence in gastric cancer patients with pT1N1.

Methods

Between 1996 and 2010, 510 patients who underwent curative resection for pT1N1 gastric cancer at three institutes were divided into two groups: adjuvant chemotherapy group (N = 150) and surgery-only group (N = 360). Disease-free survival rates and risk factors for tumor recurrence were analyzed.

Results

During the median follow-up of 78 months, 7.5% of patients experienced tumor recurrence (7.3% in adjuvant chemotherapy group and 7.5% in surgery-only group). The 5-year disease-free survival rate was 91.8% in the adjuvant chemotherapy group and 94.6% in the surgery-only group without significant difference between the two. In univariate analysis, older age (>65 years), male gender, body mass index <25 kg/m², elevated gross type, and differentiated histology were associated with tumor recurrence. Multivariate analysis showed that advanced age and male gender were independent risk factors for tumor recurrence. In addition, adjuvant chemotherapy showed no benefitial effect on tumor recurrence in pT1N1 gastric cancer.

Conclusions

Adjuvant chemotherapy did not show any oncologically benefitial effect on tumor recurrence, it might be unnecessary for pT1N1 gastric cancer after curative surgery.

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Is adjuvant chemotherapy necessary in pT1N1 gastric cancer?

Abstract

Background

Due to a lack of consensus on adjuvant treatments for pT1N1 gastric cancer, surgeons face a dilemma when deciding treatments for patients with pT1N1 gastric cancer after gastrectomy. The objective of this study was to determine survival benefits of adjuvant chemotherapy and risk factors for tumor recurrence in gastric cancer patients with pT1N1.

Methods

Between 1996 and 2010, 510 patients who underwent curative resection for pT1N1 gastric cancer at three institutes were divided into two groups: adjuvant chemotherapy group (N = 150) and surgery-only group (N = 360). Disease-free survival rates and risk factors for tumor recurrence were analyzed.

Results

During the median follow-up of 78 months, 7.5% of patients experienced tumor recurrence (7.3% in adjuvant chemotherapy group and 7.5% in surgery-only group). The 5-year disease-free survival rate was 91.8% in the adjuvant chemotherapy group and 94.6% in the surgery-only group without significant difference between the two. In univariate analysis, older age (>65 years), male gender, body mass index <25 kg/m², elevated gross type, and differentiated histology were associated with tumor recurrence. Multivariate analysis showed that advanced age and male gender were independent risk factors for tumor recurrence. In addition, adjuvant chemotherapy showed no benefitial effect on tumor recurrence in pT1N1 gastric cancer.

Conclusions

Adjuvant chemotherapy did not show any oncologically benefitial effect on tumor recurrence, it might be unnecessary for pT1N1 gastric cancer after curative surgery.

http://ift.tt/2pQs8aU

Reply to Offiah et al.: The triad of shaken baby syndrome

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Reply to Offiah et al.: The triad of shaken baby syndrome

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Quality of Death, Rumination and Posttraumatic Growth among Bereaved Family Members of Cancer Patients in Home Palliative Care

Abstract

Objective

The current study was designed to test the hypothesis that quality of death (QOD) and intrusive and deliberate rumination are associated with posttraumatic growth (PTG) among bereaved family members of cancer patients in home palliative care.

Methods

Data were collected from 805 bereaved family members of cancer patients who died at home in Japan. We used a cross-sectional design and participants completed Good Death Inventory, Event-Related Rumination Inventory and PTG Inventory. Structural equation modeling was used to test the hypothesized relationships.

Results

A direct pathway from QOD to PTG was significant. We also found significant indirect pathways between QOD and PTG via deliberate rumination soon after the death and recent deliberate rumination.

Conclusions

Clinicians should provide high-quality end-of-life care with the goals of achieving a good death for terminally ill cancer patients and supporting the experience of PTG in bereaved family members after their loss.

http://ift.tt/2pQ5e3s

A systematic review of psychotherapeutic interventions for women with metastatic breast cancer: Context matters.

Abstract

Objectives

To summarise the evidence-base of psychological interventions for women with metastatic breast cancer (MBC), by mode of delivery (group, individual, or low-intensity interventions). To synthesise data regarding core intervention-elements (e.g., intervention duration) and context factors (trial setting, uptake and adherence, demographic characteristics).

Methods

Four databases were searched (inception – May 2016): MEDLINE (OvidSP), PsycINFO (OvidSP), CINAHL (EBSCO), and SCOPUS; reference lists were examined for additional publications. Grey literature was excluded. Outcome data were extracted for survival, distress, quality of life, coping, sleep, fatigue, and/or pain, and summarised through narrative synthesis.

Results

Fifteen randomised clinical trials (RCTs), reported across 23 articles, met inclusion criteria: seven group, four individual, and four low-intensity interventions. Overall, interventions improved distress (8/13 RCTs); coping (4/5 RCTs); and pain (4/5 RCTs). No evidence of survival benefit was found. For remaining outcomes, evidence was either insufficient, or too mixed to draw conclusions. Group programs had the strongest evidence-base for efficacy; individual and low-intensity therapy had insufficient evidence to form conclusions. Group interventions had longest intervention durations and lowest uptake and adherence; low-intensity interventions had shortest durations and highest uptake and adherence. Disparities in uptake, adherence and reach were evident, with the demographic profile of participants polarised to young, Caucasian, English-speaking, partnered women.

Conclusions

There remains a paucity of psychological interventions for women with MBC. Those that exist have an inconsistent evidence-base across the range of patient-reported outcomes. Further research is needed to evaluate accessible delivery formats that ensure efficacy as well as uptake.

http://ift.tt/2p7tzDY

Quality of Death, Rumination and Posttraumatic Growth among Bereaved Family Members of Cancer Patients in Home Palliative Care

Abstract

Objective

The current study was designed to test the hypothesis that quality of death (QOD) and intrusive and deliberate rumination are associated with posttraumatic growth (PTG) among bereaved family members of cancer patients in home palliative care.

Methods

Data were collected from 805 bereaved family members of cancer patients who died at home in Japan. We used a cross-sectional design and participants completed Good Death Inventory, Event-Related Rumination Inventory and PTG Inventory. Structural equation modeling was used to test the hypothesized relationships.

Results

A direct pathway from QOD to PTG was significant. We also found significant indirect pathways between QOD and PTG via deliberate rumination soon after the death and recent deliberate rumination.

Conclusions

Clinicians should provide high-quality end-of-life care with the goals of achieving a good death for terminally ill cancer patients and supporting the experience of PTG in bereaved family members after their loss.

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A systematic review of psychotherapeutic interventions for women with metastatic breast cancer: Context matters.

Abstract

Objectives

To summarise the evidence-base of psychological interventions for women with metastatic breast cancer (MBC), by mode of delivery (group, individual, or low-intensity interventions). To synthesise data regarding core intervention-elements (e.g., intervention duration) and context factors (trial setting, uptake and adherence, demographic characteristics).

Methods

Four databases were searched (inception – May 2016): MEDLINE (OvidSP), PsycINFO (OvidSP), CINAHL (EBSCO), and SCOPUS; reference lists were examined for additional publications. Grey literature was excluded. Outcome data were extracted for survival, distress, quality of life, coping, sleep, fatigue, and/or pain, and summarised through narrative synthesis.

Results

Fifteen randomised clinical trials (RCTs), reported across 23 articles, met inclusion criteria: seven group, four individual, and four low-intensity interventions. Overall, interventions improved distress (8/13 RCTs); coping (4/5 RCTs); and pain (4/5 RCTs). No evidence of survival benefit was found. For remaining outcomes, evidence was either insufficient, or too mixed to draw conclusions. Group programs had the strongest evidence-base for efficacy; individual and low-intensity therapy had insufficient evidence to form conclusions. Group interventions had longest intervention durations and lowest uptake and adherence; low-intensity interventions had shortest durations and highest uptake and adherence. Disparities in uptake, adherence and reach were evident, with the demographic profile of participants polarised to young, Caucasian, English-speaking, partnered women.

Conclusions

There remains a paucity of psychological interventions for women with MBC. Those that exist have an inconsistent evidence-base across the range of patient-reported outcomes. Further research is needed to evaluate accessible delivery formats that ensure efficacy as well as uptake.

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A 4-year phase II study of everolimus in NF2 patients with growing vestibular schwannomas

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IDH mutation and 1p19q codeletion distinguish two radiological patterns of diffuse low-grade gliomas

Abstract

Diffuse low-grade gliomas (DLGG) prognosis is variable, depending on several factors, including the isocitrate dehydrogenase (IDH) mutation and the 1p19q codeletion. A few studies suggested associations between these parameters and tumor radiological characteristics including topography. Our aim was analyzing the correlations between the IDH and 1p19q statuses and the tumor intracerebral distribution (at the lobar and voxel levels), volume, and borders. We conducted a retrospective, monocentric study on a consecutive series of 198 DLGG patients. The IDH and 1p19q statuses were recorded. The pre-treatment magnetic resonance FLAIR imagings were reviewed for determination of lobar topography, tumor volume, and characterisation of tumor borders (sharp or indistinct). We conducted a voxel-based lesion-symptom mapping analysis to investigate the correlations between the IDH and 1p19q statuses and topography at the voxel level. The IDH mutation and 1p19q statuses were correlated with the tumor topography defined using lobar anatomy (p < 0.001 and p = 0.004, respectively). Frontal tumors were more frequently IDH-mutant (87.1 vs. 57.4%) and 1p19q codeleted (45.2 vs. 17.0%) than temporo-insular lesions. At the voxel level, these associations were not found. Tumors with sharp borders were more frequently IDH-mutant (p = 0.001) while tumors with indistinct borders were more frequently IDH wild-type and 1p19q non-codeleted (p < 0.001). Larger tumors at diagnosis (possibly linked to a slower growth rate) were more frequently IDH-mutant (p < 0.001). IDH wild-type, 1p19q non-codeleted temporo-insular tumors are distinct from IDH-mutant, 1p19q codeleted frontal tumors. Further studies are needed to determine whether the therapeutic strategy should be adapted to each pattern.

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Precision knockdown of EGFR gene expression using radio frequency electromagnetic energy

Abstract

Electromagnetic fields (EMF) in the radio frequency energy (RFE) range can affect cells at the molecular level. Here we report a technology that can record the specific RFE signal of a given molecule, in this case the siRNA of epidermal growth factor receptor (EGFR). We demonstrate that cells exposed to this EGFR siRNA RFE signal have a 30–70% reduction of EGFR mRNA expression and ~60% reduction in EGFR protein expression vs. control treated cells. Specificity for EGFR siRNA effect was confirmed via RNA microarray and antibody dot blot array. The EGFR siRNA RFE decreased cell viability, as measured by Calcein-AM measures, LDH release and Caspase 3 cleavage, and increased orthotopic xenograft survival. The outcomes of this study demonstrate that an RFE signal can induce a specific siRNA-like effect on cells. This technology opens vast possibilities of targeting a broader range of molecules with applications in medicine, agriculture and other areas.

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The risk of radiation necrosis following stereotactic radiosurgery with concurrent systemic therapies

Abstract

To investigate late toxicity among patients with newly-diagnosed brain metastases undergoing stereotactic radiosurgery (SRS) with concurrent systemic therapies with or without whole-brain radiation therapy (WBRT). Patients with newly-diagnosed brain metastasis who underwent SRS at a single tertiary-care institution from 1997 to 2015 were eligible for inclusion. The class and timing of all systemic therapies were collected for each patient. The primary outcome was the cumulative incidence of radiographic radiation necrosis (RN). Multivariable competing risks regression was used to adjust for confounding. During the study period, 1650 patients presented with 2843 intracranial metastases. Among these, 445 patients (27%) were treated with SRS and concurrent systemic therapy. Radiographic RN developed following treatment of 222 (8%) lesions, 120 (54%) of which were symptomatic. The 12-month cumulative incidences of RN among lesions treated with and without concurrent therapies were 6.6 and 5.3%, respectively (p = 0.14). Concurrent systemic therapy was associated with a significantly increased rate of RN among lesions treated with upfront SRS and WBRT (8.7 vs. 3.7%, p = 0.04). In particular, concurrent targeted therapies significantly increased the 12-month cumulative incidence of RN (8.8 vs. 5.3%, p < 0.01). Among these therapies, significantly increased rates of RN were observed with VEGFR tyrosine kinase inhibitors (TKIs) (14.3 vs. 6.6%, p = 0.04) and EGFR TKIs (15.6 vs. 6.0%, p = 0.04). Most classes of systemic therapies may be safely delivered concurrently with SRS in the management of newly-diagnosed brain metastases. However, the rate of radiographic RN is significantly increased with the addition of concurrent systemic therapies to SRS and WBRT.

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Dendritic cell based vaccination strategy: an evolving paradigm

Abstract

Malignant gliomas (MG), tumors of glial origin, are the most commonly diagnosed primary intracranial malignancies in adults. Currently available treatments have provided only modest improvements in overall survival and remain limited by inevitable local recurrence, necessitating exploration of novel therapies. Among approaches being investigated, one of the leading contenders is immunotherapy, which aims to modulate immune pathways to stimulate the selective destruction of malignant cells. Dendritic cells (DCs) are potent initiators of adaptive immune responses and therefore crucial players in the development and success of immunotherapy. Clinical trials of various DC-based vaccinations have demonstrated the induction of anti-tumor immune responses and prolonged survival in the setting of many cancers. In this review, we summarize current literature regarding DCs and their role in the tumor microenvironment, their application and current clinical use in immunotherapy, current challenges limiting their efficacy in anti-cancer therapy, and future avenues for developing successful anti-tumor DC-based vaccines.

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Associations of self-reported smoking, cotinine levels and epigenetic smoking indicators with oxidative stress among older adults: a population-based study

Abstract

Tobacco smoking and oxidative stress (OS) are both related to a wide spectrum of adverse age-related health outcomes, but their association is not yet well-established. We examined the associations of self-reported smoking indicators, serum cotinine levels and smoking-related DNA methylation biomarkers with two urinary proxy markers of OS, 8-isoprostane (8-iso) and 8-hydroxy-2′-deoxyguanosine (8-oxodG), in two independent subsets of older adults recruited in Germany (discovery set: n = 978, validation set: n = 531). We obtained DNA methylation profiles in whole blood samples by Illumina Human Methylation450K Beadchip and measured the urinary levels of both OS markers using commercial ELISA kits. After controlling for potential confounders, current smoking, cumulative smoking exposure (pack-years) and serum cotinine levels (ng/ml) were strongly associated with 8-iso levels (p values <0.0001, 0.004 and 0.001, respectively). Of 151 previously identified smoking-related CpG sites, 71 loci were associated with 8-iso levels after correction for multiple testing (FDR < 0.05) in the validation phase and were designated as loci related to 8-iso levels defined OS. In addition, serum cotinine levels, cumulative smoking exposure and a smoking index (SI) based on the 71 identified loci manifested monotonic associations with 8-iso levels. However, we did not observe any associations between these smoking indicators and 8-oxodG levels. In conclusion, this study suggests that smoking-related epigenetic alterations are closely correlated with smoking-induced OS. The identified CpG sites could potentially be prognostic epigenetic markers of OS and OS-related health outcomes. Our findings and the underlying mechanisms should be followed up in further, preferably longitudinal studies.

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Associations of self-reported smoking, cotinine levels and epigenetic smoking indicators with oxidative stress among older adults: a population-based study

Abstract

Tobacco smoking and oxidative stress (OS) are both related to a wide spectrum of adverse age-related health outcomes, but their association is not yet well-established. We examined the associations of self-reported smoking indicators, serum cotinine levels and smoking-related DNA methylation biomarkers with two urinary proxy markers of OS, 8-isoprostane (8-iso) and 8-hydroxy-2′-deoxyguanosine (8-oxodG), in two independent subsets of older adults recruited in Germany (discovery set: n = 978, validation set: n = 531). We obtained DNA methylation profiles in whole blood samples by Illumina Human Methylation450K Beadchip and measured the urinary levels of both OS markers using commercial ELISA kits. After controlling for potential confounders, current smoking, cumulative smoking exposure (pack-years) and serum cotinine levels (ng/ml) were strongly associated with 8-iso levels (p values <0.0001, 0.004 and 0.001, respectively). Of 151 previously identified smoking-related CpG sites, 71 loci were associated with 8-iso levels after correction for multiple testing (FDR < 0.05) in the validation phase and were designated as loci related to 8-iso levels defined OS. In addition, serum cotinine levels, cumulative smoking exposure and a smoking index (SI) based on the 71 identified loci manifested monotonic associations with 8-iso levels. However, we did not observe any associations between these smoking indicators and 8-oxodG levels. In conclusion, this study suggests that smoking-related epigenetic alterations are closely correlated with smoking-induced OS. The identified CpG sites could potentially be prognostic epigenetic markers of OS and OS-related health outcomes. Our findings and the underlying mechanisms should be followed up in further, preferably longitudinal studies.

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Preoperative radiation therapy: The ‘new’ targeted breast cancer treatment?

Publication date: June 2017
Source:European Journal of Cancer, Volume 78
Author(s): Charlotte E. Coles, Alain Fourquet, Philip Poortmans




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Retrospective evaluation of the effectiveness of radiotherapy in patients with plantar fascitis (heel spurs)

Publication date: May–June 2017
Source:Reports of Practical Oncology & Radiotherapy, Volume 22, Issue 3
Author(s): Piotr Kędzierawski, Rafał Stando, Paweł Macek
AimThe aim of the study was the evaluation of the effectiveness of radiotherapy in patients with the feet pain caused by heel spurs.BackgroundTreatment options for patients reporting these symptoms include use of suitable orthopedic footwear, the use of general or topical non-steroidal anti-inflammatory drugs or steroids, physiotherapy, manual therapy, shock wave or appropriate surgical procedures. Radiotherapy is one of the method used in patients with chronic pain syndrome.Materials and methodsThe material consisted of 47 patients treated in Radiotherapy Department at the Holycross Cancer Center. The time of follow-up ranged from 1 to 129 months. After treatment patients were observed.ResultsDuring the first follow-up visit a complete relief of symptoms was observed in 37 patients, and the pain was felt by 10 patients for 4 months after the treatment. One patient was re-irradiated 6 months after treatment because of persistent pain. At 16 and 17 months after the onset of treatment, pain was reported by two patients. These patients were re-irradiated. One patient had recurrence of pain 48 months after completion of radiation. After the second irradiation the pain was relieved. The remaining patients, with the exception of two, experienced remission of pain, which has been documented. Tolerance of the treatment was very good. No complications of radiation were observed.ConclusionsRadiotherapy remains an attractive treatment for patients with inflammation of the heel fascia.



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CT- and MRI-based gross target volume comparison in vestibular schwannomas

Publication date: May–June 2017
Source:Reports of Practical Oncology & Radiotherapy, Volume 22, Issue 3
Author(s): Bhudevi Soubhagya N. Kulkarni, Harjot Bajwa, Mukka Chandrashekhar, Sunil Dutt Sharma, Rohith Singareddy, Dileep Gudipudi, Shabbir Ahmad, Alok Kumar, N.V.N. Madusudan Sresty, Alluri Krishnam Raju
AimThis study represents an enumeration and comparison of gross target volumes (GTV) as delineated independently on contrast-enhanced computed tomography (CT) and T1 and T2 weighted magnetic resonance imaging (MRI) in vestibular schwannomas (VS).BackgroundMultiple imaging in radiotherapy improves target localization.Methods and materials42 patients of VS were considered for this prospective study with one patient showing bilateral tumor. The GTV was delineated separately on CT and MRI. Difference in volumes were estimated individually for all the 43 lesions and similarity was studied between CT and T1 and T2 weighted MRI.ResultsThe male to female ratio for VS was found to be 1:1.3. The tumor was right sided in 34.9% and left sided in 65.1%. Tumor volumes (TV) on CT image sets were ranging from 0.251cc to 27.27cc. The TV for CT, MRI T1 and T2 weighted were 5.15±5.2cc, 5.8±6.23cc, and 5.9±6.13cc, respectively. Compared to MRI, CT underestimated the volumes. The mean dice coefficient between CT versus T1 and CT versus T2 was estimated to be 68.85±18.3 and 66.68±20.3, respectively. The percentage of volume difference between CT and MRI (%VD: mean±SD for T1; 28.84±15.0, T2; 35.74±16.3) and volume error (%VE: T1; 18.77±10.1, T2; 23.17±13.93) were found to be significant, taking the CT volumes as the baseline.ConclusionsMRI with multiple sequences should be incorporated for tumor volume delineation and they provide a clear boundary between the tumor and normal tissue with critical structures nearby.



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Estimation of peripheral dose from Co60 beam in water phantom measured in Secondary Standard Dosimetry Laboratory, Pakistan

Publication date: May–June 2017
Source:Reports of Practical Oncology & Radiotherapy, Volume 22, Issue 3
Author(s): Muhammad Shahban, Babar Hussain, Khalid Mehmood, Shakeel Ur Rehman
BackgroundPeripheral or scatter dose harms neighbouring normal tissues during administration of dose to cancerous tissues, therefore, knowledge of peripheral dose is an important consideration in radiotherapy.AimIn present study, absorbed dose measurements in a water phantom were performed for three field sizes, 7×7cm², 10×10cm² and 15×15cm².Materials and methodsFor each field size, dose was measured at six depths below the front surface of the water phantom; 2.5–15cm with an interval of 2.5cm. Measurements were made at equal transverse distances along the horizontal axis, from 1cm to 6cm, on both sides of the central beam axis and normalized with central axis dose of each field. All measurements were made at the source to surface distance of 100cm.ResultsVariation of peripheral dose with lateral distance was analysed and an appropriate parametric equation for each field size and depth was constructed.ConclusionsThe peripheral radiation dose showed a strong dependence on field size and distance from field boundary.



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Prospective evaluation of anxiety, depression and quality of life in medically inoperable early stage non-small cell lung cancer patients treated with stereotactic ablative radiotherapy

Publication date: May–June 2017
Source:Reports of Practical Oncology & Radiotherapy, Volume 22, Issue 3
Author(s): Jacek Rutkowski, Magdalena Szymanik, Maciej Blok, Joanna Kozaka, Renata Zaucha
AimThe aim of this prospective study was to evaluate the level of anxiety, depression, and quality of life (QoL) in medically inoperable patients with early stage non-small cell lung cancer (NSCLC) treated with stereotactic ablative radiotherapy (SABR).BackgroundProlonged survival is equally important as maintaining high QoL and good psychological functioning during the treatment of lung cancer. Nowadays available SABR has markedly changed clinical care and outcomes in the group of medically inoperable patients. To our knowledge, analysis of QoL and psychological state has not been performed in Polish patients with early NSCLC treated with SABR.Materials and methodsResearch group consisted of medically inoperable, early NSCLC (T1-2aN0M0) patients qualified to SABR. Patients were asked to complete Polish versions of the European Organization for Research and Treatment of Cancer Quality of Life – Core Questionnaire (EORTC QLQ-C30) with the Lung Cancer Questionnaire (LC13) and Hospital Anxiety and Depression Scale (HAD). These questionnaires were repeated 2 weeks and then 3 months after treatment completion.ResultsWe enrolled 51 patients who met the inclusion criteria. SABR did not deteriorate QoL and psychological functioning. On the contrary, clinically meaningful improvement was observed in emotional functioning, level of insomnia, anxiety and depression. Significantly worse improvement was shown in patients with chronic obstructive pulmonary disease (COPD).ConclusionsOur results confirm that SABR is well tolerated and does not have a deleterious effect on QoL and psychological state. Results of our study indicate the importance of additional psychological care in the group of patients with COPD.



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Dosimetric impact in the dose–volume histograms of rectal and vesical wall contouring in prostate cancer IMRT treatments

Publication date: May–June 2017
Source:Reports of Practical Oncology & Radiotherapy, Volume 22, Issue 3
Author(s): Laura Gómez, Carlos Andrés, Antonio Ruiz
AimThe main purpose of this study was to evaluate the differences in dose–volume histograms of IMRT treatments for prostate cancer based on the delineation of the main organs at risk (rectum and bladder) as solid organs or by contouring their wall.BackgroundRectum and bladder have typically been delineated as solid organs, including the waste material, which, in practice, can lead to an erroneous assessment of the risk of adverse effects.Materials and methodsA retrospective study was made on 25 patients treated with IMRT radiotherapy for prostate adenocarcinoma. 76.32Gy in 36 fractions was prescribed to the prostate and seminal vesicles. In addition to the delineation of the rectum and bladder as solid organs (including their content), the rectal and bladder wall were also delineated and the resulting dose–volume histograms were analyzed for the two groups of structures.ResultsData analysis shows statistically significant differences in the main parameters used to assess the risk of toxicity of a prostate radiotherapy treatment. Higher doses were received on the rectal and bladder walls compared to doses received on the corresponding solid organs.ConclusionsThe observed differences in terms of received doses to the rectum and bladder based on the method of contouring could gain greater importance in inverse planning treatments, where the treatment planning system optimizes the dose in these volumes. So, one should take into account the method of delineating of these structures to make a clinical decision regarding dose limitation and risk assessment of chronic toxicity.



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The semiconductor diode detector response as a function of field size and beam angle of high-energy photons

Publication date: May–June 2017
Source:Reports of Practical Oncology & Radiotherapy, Volume 22, Issue 3
Author(s): Tomasz Koper, Anna Kowalik, Sebastian Adamczyk
AimThe measurements of semiconductor diode detector response as a function of field size and beam angle of high-energy photons.BackgroundIn vivo dosimetry plays an important role in the therapeutic process of the patient. Because of the different orientation of the beam relative to the patient and different sizes of irradiation fields, it is extremely important to take into account the response of the detector depending on the angle and the size of the beam.Materials and methodsIn this study we used a 30cm×30cm×25cm PMMA slab phantom. On the surface of the phantom, various semiconductor detectors were placed sequentially in two configurations, angle and tilt.ResultsFor the measurements of the calibration factor based on the different value of the angle, the correction coefficient value was close to 1.00 for smaller values of the angle for all the detectors used in the energy range of 6–12MV. For the measurements, the calibration factor based on the size of the field of irradiation to the value of the correction coefficient is 1.00 for the field of 8cm×8cm and 10cm×10cm. With the increase field size, the correction factor shows a linear relationship in the direction of value less than 1.00.ConclusionFlat Detectors – used for both photon beams generated by the accelerating potential of 6MV and 20MV show a greater angular dependence than the cylindrical detectors. Also, the repeatability of measurements made using the flat detector is less as evidenced by larger standard deviations for the results.



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Coping with loss of ability vs. acceptance of disease in women after breast cancer treatment

Publication date: May–June 2017
Source:Reports of Practical Oncology & Radiotherapy, Volume 22, Issue 3
Author(s): Katarzyna Cieślak, Wojciech Golusiński
AimTo answer the question: is there a correlation between copying with the loss of ability and the acceptance of disease?BackgroundThe loss of ability is the beginning of a process of dealing with a widely understood dysfunction and its consequences. This happens owing to the lifting of the barriers that emerged due to the loss of ability and through the acquisition of skills that help an individual find their way in the new reality.Materials and methodsThe study included 90 patients with history of breast cancer. They were divided into two groups- I: up to five years from diagnosis, II: more than five years from diagnosis. The study was conducted using the Questionnaire on Coping With Ability Loss by P. Wolski, Acceptance of Illness Scale – B.J. Felton, T.A. Revenson, G.A. Hinrichsen, adapted by: Z. Juczyński.ResultsGroup I: it is positive weak correlation, meaning that the higher level of acceptance in the QCAL test, the higher acceptance of illness. Group II: there is no relation between acceptance of illness and the QCAL test acceptance scale and no relation between depression and the level of acceptance.ConclusionsThe more depressed a patient is and the less successful they are in dealing with the loss of ability, the lower their level of acceptance of illness. On the other hand, in time, it is struggle with the disability that plays more important role in the acceptance of the disease than the impact of negative emotions.



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Is immunohistochemical evaluation of p16 in oropharyngeal cancer enough to predict the HPV positivity?

Publication date: May–June 2017
Source:Reports of Practical Oncology & Radiotherapy, Volume 22, Issue 3
Author(s): Paweł Golusiński, Jakub Pazdrowski, Mateusz Szewczyk, Maciej Misiołek, Wioletta Pietruszewska, Janusz Klatka, Sławomir Okła, Henryk Kaźmierczak, Andrzej Marszałek, Violetta Filas, Augusto Schneider, Michał M. Masternak, Katarzyna Stęplewska, Katarzyna Miśkiewicz-Orczyk, Wojciech Golusiński
AimOur goal was to determine the expression levels of p16 in the cohort of the OPSCC patients and evaluation of the pathological and clinical differences between these two groups including patients' survival.BackgroundHPV infection is the main causative factor of oropharyngeal cancer (OPSCC). Identification of HPV status in OPSCC requires positive evaluation of viral DNA integration into host cell however, p16 accumulation in the proliferating cell layers has been accepted as an alternative marker for HPV infection.Material and MethodsThe IHC staining for p16 has been performed in tumor tissue from 382 OPSCC patients. The sample was considered positive based on more than 70% of carcinoma tissue showing strong and diffused nuclear and cytoplasmic immunostaining. The clinicopathological characteristics of the patients including site, age, gender, tumor grade, tumor stage, the nodal status, smoking and survival have been analyzed when comparing p16 positive and p16 negative tumors.ResultsOut of our cohort in 38.2% cases positive staining for p16 has been recorded. Our analysis did not indicate significant differences in the distribution of the p16 positive patients and age of the patients, stage of the disease. Among the patients who have presented with the N+ neck, there were significantly more p16 positive tumors than in the group with N0 neck (p=0.0062). There was highly significant correlation between the expression of p16 and smoking (p<0.0001). The significant difference in survival (p<0.0001) with more favorable prognosis in the p16 positive group has been observed.ConclusionsOverexpression of p16 is accepted as a surrogate diagnostic marker for detecting HPV infection in oropharyngeal cancer. However, one should remember about existence of the small subgroups of p16 positive but HPV negative tumors, with relatively worse prognosis. Immunostaining for p16, however useful on everyday basis, should be complemented with other techniques in terms of reliable identification of the HPV infection.



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Management Options for Biochemically Recurrent Prostate Cancer

Prostate cancer is the most common solid tumor malignancy in men worldwide. Treatment with surgery and radiation can be curative in organ-confined disease. Unfortunately, about one third of men develop biochemically recurrent disease based only on rising prostate-specific antigen (PSA) in the absence of visible disease on conventional imaging. For these patients with biochemical recurrent prostate cancer, there is no uniform guideline for subsequent management. Based on available data, it seems prudent that biochemical recurrent prostate cancer should initially be evaluated for salvage radiation or prostatectomy, with curative intent. In selected cases, high-intensity focused ultrasound and cryotherapy may be considered in patients that meet very narrow criteria as defined by non-randomized trials. If salvage options are not practical or unsuccessful, androgen deprivation therapy (ADT) is a standard option for disease control. While some patients prefer ADT to manage the disease immediately, others defer treatment because of the associated toxicity. In the absence of definitive randomized data, patients may be followed using PSA doubling time as a trigger to initiate ADT. Based on retrospective data, a PSA doubling time of less than 3–6 months has been associated with near-term development of metastasis and thus could be used signal to initiate ADT. Once treatment is begun, patients and their providers can choose between an intermittent and continuous ADT strategy. The intermittent approach may limit side effects but in patients with metastatic disease studies could not exclude a 20% greater risk of death. In men with biochemical recurrence, large studies have shown that intermittent therapy is non-inferior to continuous therapy, thus making this a reasonable option. Since biochemically recurrent prostate cancer is defined by technological limitations of radiographic detection, as new imaging (i.e., PSMA) strategies are developed, it may alter how the disease is monitored and perhaps managed. Furthermore, patients have no symptoms related to their disease and thus many prefer options that minimize toxicity. For this reason, herbal agents and immunotherapy are under investigation as potential alternatives to ADT and its accompanying side effects. New therapeutic options combined with improved imaging to evaluate the disease may markedly change how biochemically recurrent prostate cancer is managed in the future.

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Lactobacillus paracasei strain 06TCa19 suppresses inflammatory chemokine induced by Helicobacter pylori in human gastric epithelial cells

Abstract

Helicobacter (H.) pylori infection is an important risk factor for gastric cancer that causes gastric inflammation. Inflammatory chemokines such as interleukin (IL)-8 and regulated on activation normal T cell expressed and secreted (RANTES) are elevated in the gastric mucosa by H. pylori. This study aimed to investigate the effects of Lactobacillus paracasei strain 06TCa19, a probiotic strain, on IL-8 and RANTES expression and production induced by H. pylori using human gastric epithelial cell lines. Strain 06TCa19 was shown to suppress H. pylori-mediated elevation of gene expression related to these chemokines in MKN45 cells. The strain also suppressed the increase in IL-8 and RANTES products induced by H. pylori in AGS cells as well as in MKN45 cells. In MKN45 cells inoculated with H. pylori, strain 06TCa19 was shown to downregulate the activation of NF-κB and p38 MAPK signaling pathways. Additionally, the level of the CagA virulence protein of H. pylori in the MKN45 cells and the number of viable H. pylori adhering to MKN45 cells decreased with the addition of strain 06TCa19. Moreover, the strain 06TCa19 notably increased lactic acid in the supernatant of MKN45 cells. Thus, lactic acid released from strain 06TCa19 might have inhibited the adhesion of H. pylori to MKN45 cells and prevented the insertion of H. pylori CagA into the cells, and elevation of IL-8 and RANTES genes and proteins might be suppressed by downregulating the NF-κB and p38 MAPK pathways. Therefore, use of strain 06TCa19 may prevent H. pylori-associated gastric inflammation.

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Establishment and characterization of novel epithelial-like cell lines derived from human periodontal ligament tissue in vitro

Abstract

In this study, novel human-derived epithelial-like cells (hEPLCs) lines were established from periodontal ligament (PDL) tissues, which were composed of a variety of cell types and exhibited complex cellular activities. To elucidate the putative features distinguishing these from epithelial rest of Malassez (ERM), we characterized hEPLCs based on cell lineage markers and tight junction protein expression. The aim of this study was, therefore, to establish and characterize hEPLCs lines from PDL tissues. The hEPLCs were isolated from PDL of third molar teeth. Cellular morphology and cell organelles were observed thoroughly. The characteristics of epithelial–endothelial-mesenchymal-like cells were compared in several markers by gene expression and immunofluorescence, to ERM and human umbilical-vein endothelial cells (HUVECs). The resistance between cellular junctions was assessed by transepithelial electron resistance, and inflammatory cytokines were detected by ELISA after infecting hEPLCs with periodontopathic bacteria. The hEPLCs developed into small epithelial-like cells in pavement appearance similar to ERM. However, gene expression patterns and immunofluorescence results were different from ERM and HUVECs, especially in tight junction markers (Claudin, ZO-1, and Occludins), and endothelial markers (vWF, CD34). The transepithelial electron resistance indicated higher resistance in hEPLCs, as compared to ERM. Periodontopathic bacteria were phagocytosed with upregulation of inflammatory cytokine secretion within 24 h. In conclusion, hEPLCs that were derived using the single cell isolation method formed tight multilayers colonies, as well as strongly expressed tight junction markers in gene expression and immunofluorescence. Novel hEPLCs lines exhibited differently from ERM, which might provide some specific functions such as metabolic exchange and defense mechanism against bacterial invasion in periodontal tissue.

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Peroxidatic cysteine residue of peroxiredoxin 2 separated from human red blood cells treated by tert -butyl hydroperoxide is hyperoxidized into sulfinic and sulfonic acids

Abstract

Peroxiredoxin 2 (Prx2) is a redox enzyme that is abundantly expressed in red blood cells (RBCs) and has been the focus of clinical attention for monitoring the oxidative status. We previously developed a method to quantify the reduced and hyperoxidized forms of Prx2 in human RBCs using reverse-phase high-performance liquid chromatography (HPLC). In the present study, we investigated the hyperoxidative status of Prx2 at the molecular level in a post-translational modification analysis using a liquid chromatography–tandem mass spectrometry (LC–MS/MS) system. The LC–MS/MS analysis of the trypsin digests of Prx2 fractionated by reverse-phase HPLC demonstrated that the cysteine-51 residue (Cys-51) of the protein was modified with the hyperoxidative functional groups, sulfinic acid (–SO₂H) and sulfonic acid (–SO₃H), in RBCs treated with tert-butyl hydroperoxide (t-BHP). Furthermore, a selected ion monitoring (SIM) analysis quantitatively showed that sulfinic acid- and sulfonic acid-induced modifications in Prx2 Cys-51 were increased by the treatment with the oxidant. It was demonstrated that the peroxidatic cysteine of Prx2 separated using our HPLC system for oxidative monitoring was hyperoxidized into sulfinic acid and sulfonic acid in RBCs under an oxidative stress condition.

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Lactobacillus paracasei strain 06TCa19 suppresses inflammatory chemokine induced by Helicobacter pylori in human gastric epithelial cells

Abstract

Helicobacter (H.) pylori infection is an important risk factor for gastric cancer that causes gastric inflammation. Inflammatory chemokines such as interleukin (IL)-8 and regulated on activation normal T cell expressed and secreted (RANTES) are elevated in the gastric mucosa by H. pylori. This study aimed to investigate the effects of Lactobacillus paracasei strain 06TCa19, a probiotic strain, on IL-8 and RANTES expression and production induced by H. pylori using human gastric epithelial cell lines. Strain 06TCa19 was shown to suppress H. pylori-mediated elevation of gene expression related to these chemokines in MKN45 cells. The strain also suppressed the increase in IL-8 and RANTES products induced by H. pylori in AGS cells as well as in MKN45 cells. In MKN45 cells inoculated with H. pylori, strain 06TCa19 was shown to downregulate the activation of NF-κB and p38 MAPK signaling pathways. Additionally, the level of the CagA virulence protein of H. pylori in the MKN45 cells and the number of viable H. pylori adhering to MKN45 cells decreased with the addition of strain 06TCa19. Moreover, the strain 06TCa19 notably increased lactic acid in the supernatant of MKN45 cells. Thus, lactic acid released from strain 06TCa19 might have inhibited the adhesion of H. pylori to MKN45 cells and prevented the insertion of H. pylori CagA into the cells, and elevation of IL-8 and RANTES genes and proteins might be suppressed by downregulating the NF-κB and p38 MAPK pathways. Therefore, use of strain 06TCa19 may prevent H. pylori-associated gastric inflammation.

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Establishment and characterization of novel epithelial-like cell lines derived from human periodontal ligament tissue in vitro

Abstract

In this study, novel human-derived epithelial-like cells (hEPLCs) lines were established from periodontal ligament (PDL) tissues, which were composed of a variety of cell types and exhibited complex cellular activities. To elucidate the putative features distinguishing these from epithelial rest of Malassez (ERM), we characterized hEPLCs based on cell lineage markers and tight junction protein expression. The aim of this study was, therefore, to establish and characterize hEPLCs lines from PDL tissues. The hEPLCs were isolated from PDL of third molar teeth. Cellular morphology and cell organelles were observed thoroughly. The characteristics of epithelial–endothelial-mesenchymal-like cells were compared in several markers by gene expression and immunofluorescence, to ERM and human umbilical-vein endothelial cells (HUVECs). The resistance between cellular junctions was assessed by transepithelial electron resistance, and inflammatory cytokines were detected by ELISA after infecting hEPLCs with periodontopathic bacteria. The hEPLCs developed into small epithelial-like cells in pavement appearance similar to ERM. However, gene expression patterns and immunofluorescence results were different from ERM and HUVECs, especially in tight junction markers (Claudin, ZO-1, and Occludins), and endothelial markers (vWF, CD34). The transepithelial electron resistance indicated higher resistance in hEPLCs, as compared to ERM. Periodontopathic bacteria were phagocytosed with upregulation of inflammatory cytokine secretion within 24 h. In conclusion, hEPLCs that were derived using the single cell isolation method formed tight multilayers colonies, as well as strongly expressed tight junction markers in gene expression and immunofluorescence. Novel hEPLCs lines exhibited differently from ERM, which might provide some specific functions such as metabolic exchange and defense mechanism against bacterial invasion in periodontal tissue.

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Peroxidatic cysteine residue of peroxiredoxin 2 separated from human red blood cells treated by tert -butyl hydroperoxide is hyperoxidized into sulfinic and sulfonic acids

Abstract

Peroxiredoxin 2 (Prx2) is a redox enzyme that is abundantly expressed in red blood cells (RBCs) and has been the focus of clinical attention for monitoring the oxidative status. We previously developed a method to quantify the reduced and hyperoxidized forms of Prx2 in human RBCs using reverse-phase high-performance liquid chromatography (HPLC). In the present study, we investigated the hyperoxidative status of Prx2 at the molecular level in a post-translational modification analysis using a liquid chromatography–tandem mass spectrometry (LC–MS/MS) system. The LC–MS/MS analysis of the trypsin digests of Prx2 fractionated by reverse-phase HPLC demonstrated that the cysteine-51 residue (Cys-51) of the protein was modified with the hyperoxidative functional groups, sulfinic acid (–SO₂H) and sulfonic acid (–SO₃H), in RBCs treated with tert-butyl hydroperoxide (t-BHP). Furthermore, a selected ion monitoring (SIM) analysis quantitatively showed that sulfinic acid- and sulfonic acid-induced modifications in Prx2 Cys-51 were increased by the treatment with the oxidant. It was demonstrated that the peroxidatic cysteine of Prx2 separated using our HPLC system for oxidative monitoring was hyperoxidized into sulfinic acid and sulfonic acid in RBCs under an oxidative stress condition.

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A 4-year phase II study of everolimus in NF2 patients with growing vestibular schwannomas

http://ift.tt/2pR6m9P

IDH mutation and 1p19q codeletion distinguish two radiological patterns of diffuse low-grade gliomas

Abstract

Diffuse low-grade gliomas (DLGG) prognosis is variable, depending on several factors, including the isocitrate dehydrogenase (IDH) mutation and the 1p19q codeletion. A few studies suggested associations between these parameters and tumor radiological characteristics including topography. Our aim was analyzing the correlations between the IDH and 1p19q statuses and the tumor intracerebral distribution (at the lobar and voxel levels), volume, and borders. We conducted a retrospective, monocentric study on a consecutive series of 198 DLGG patients. The IDH and 1p19q statuses were recorded. The pre-treatment magnetic resonance FLAIR imagings were reviewed for determination of lobar topography, tumor volume, and characterisation of tumor borders (sharp or indistinct). We conducted a voxel-based lesion-symptom mapping analysis to investigate the correlations between the IDH and 1p19q statuses and topography at the voxel level. The IDH mutation and 1p19q statuses were correlated with the tumor topography defined using lobar anatomy (p < 0.001 and p = 0.004, respectively). Frontal tumors were more frequently IDH-mutant (87.1 vs. 57.4%) and 1p19q codeleted (45.2 vs. 17.0%) than temporo-insular lesions. At the voxel level, these associations were not found. Tumors with sharp borders were more frequently IDH-mutant (p = 0.001) while tumors with indistinct borders were more frequently IDH wild-type and 1p19q non-codeleted (p < 0.001). Larger tumors at diagnosis (possibly linked to a slower growth rate) were more frequently IDH-mutant (p < 0.001). IDH wild-type, 1p19q non-codeleted temporo-insular tumors are distinct from IDH-mutant, 1p19q codeleted frontal tumors. Further studies are needed to determine whether the therapeutic strategy should be adapted to each pattern.

http://ift.tt/2p3gWrB

Precision knockdown of EGFR gene expression using radio frequency electromagnetic energy

Abstract

Electromagnetic fields (EMF) in the radio frequency energy (RFE) range can affect cells at the molecular level. Here we report a technology that can record the specific RFE signal of a given molecule, in this case the siRNA of epidermal growth factor receptor (EGFR). We demonstrate that cells exposed to this EGFR siRNA RFE signal have a 30–70% reduction of EGFR mRNA expression and ~60% reduction in EGFR protein expression vs. control treated cells. Specificity for EGFR siRNA effect was confirmed via RNA microarray and antibody dot blot array. The EGFR siRNA RFE decreased cell viability, as measured by Calcein-AM measures, LDH release and Caspase 3 cleavage, and increased orthotopic xenograft survival. The outcomes of this study demonstrate that an RFE signal can induce a specific siRNA-like effect on cells. This technology opens vast possibilities of targeting a broader range of molecules with applications in medicine, agriculture and other areas.

http://ift.tt/2pR6hmz

The risk of radiation necrosis following stereotactic radiosurgery with concurrent systemic therapies

Abstract

To investigate late toxicity among patients with newly-diagnosed brain metastases undergoing stereotactic radiosurgery (SRS) with concurrent systemic therapies with or without whole-brain radiation therapy (WBRT). Patients with newly-diagnosed brain metastasis who underwent SRS at a single tertiary-care institution from 1997 to 2015 were eligible for inclusion. The class and timing of all systemic therapies were collected for each patient. The primary outcome was the cumulative incidence of radiographic radiation necrosis (RN). Multivariable competing risks regression was used to adjust for confounding. During the study period, 1650 patients presented with 2843 intracranial metastases. Among these, 445 patients (27%) were treated with SRS and concurrent systemic therapy. Radiographic RN developed following treatment of 222 (8%) lesions, 120 (54%) of which were symptomatic. The 12-month cumulative incidences of RN among lesions treated with and without concurrent therapies were 6.6 and 5.3%, respectively (p = 0.14). Concurrent systemic therapy was associated with a significantly increased rate of RN among lesions treated with upfront SRS and WBRT (8.7 vs. 3.7%, p = 0.04). In particular, concurrent targeted therapies significantly increased the 12-month cumulative incidence of RN (8.8 vs. 5.3%, p < 0.01). Among these therapies, significantly increased rates of RN were observed with VEGFR tyrosine kinase inhibitors (TKIs) (14.3 vs. 6.6%, p = 0.04) and EGFR TKIs (15.6 vs. 6.0%, p = 0.04). Most classes of systemic therapies may be safely delivered concurrently with SRS in the management of newly-diagnosed brain metastases. However, the rate of radiographic RN is significantly increased with the addition of concurrent systemic therapies to SRS and WBRT.

http://ift.tt/2p3wQ5o

Dendritic cell based vaccination strategy: an evolving paradigm

Abstract

Malignant gliomas (MG), tumors of glial origin, are the most commonly diagnosed primary intracranial malignancies in adults. Currently available treatments have provided only modest improvements in overall survival and remain limited by inevitable local recurrence, necessitating exploration of novel therapies. Among approaches being investigated, one of the leading contenders is immunotherapy, which aims to modulate immune pathways to stimulate the selective destruction of malignant cells. Dendritic cells (DCs) are potent initiators of adaptive immune responses and therefore crucial players in the development and success of immunotherapy. Clinical trials of various DC-based vaccinations have demonstrated the induction of anti-tumor immune responses and prolonged survival in the setting of many cancers. In this review, we summarize current literature regarding DCs and their role in the tumor microenvironment, their application and current clinical use in immunotherapy, current challenges limiting their efficacy in anti-cancer therapy, and future avenues for developing successful anti-tumor DC-based vaccines.

http://ift.tt/2pQTMHL

Pathological analysis of the surgical margins of resected glioblastomas excised using photodynamic visualization with both 5-aminolevulinic acid and fluorescein sodium

Abstract

During glioma resection, 5-aminolevulinic acid (5-ALA) and fluorescein sodium (Fl-Na) are used for photodynamic tumor visualization. The objective of this study was to evaluate the pathological findings of the boundary zone between the tumor and adjacent normal brain in glioblastoma patients undergoing simultaneous double staining with 5-ALA and Fl-Na during surgery. Eight patients received 5-ALA (20 mg/kg orally) before the induction of general anesthesia, and Fl-Na (20 mg/kg) was administered intravenously before the dural incision was performed. The tumor bulk was removed under the guidance of Fl-Na staining alone using conventional white light. Subsequently, residual tumor was removed under the guidance of both fluorescent agents within functionally safe limits until both were visibly undetectable. Twenty specimens exhibiting different staining intensities of both agents were obtained. The vessel index (VI) was calculated from CD31 immunohistochemistry (IHC) samples. Boundary zone tumor cells were detected by IHC for olig2, and were expressed as the olig2 index (OLI). The VI was significantly higher in Fl-Na-positive areas than in Fl-Na-negative areas (p = 0.0005). In contrast, the OLI was significantly higher in 5-ALA-positive areas than in 5-ALA-negative areas (p = 0.0149). 5-ALA-positive/Fl-Na negative areas were observed in 7 patients. These findings indicate that Fl-Na accumulates in areas with a disrupted blood–brain barrier, and that 5-ALA fluorescence is dependent on tumor cell protoporphyrin IX metabolism. In conclusion, 5-ALA was better for detecting tumor cells in the boundary zone than was Fl-Na. Of note, tumor cells existed outside the fluorescence-stained boundaries of both agents.

http://ift.tt/2pnI2wp

A 4-year phase II study of everolimus in NF2 patients with growing vestibular schwannomas

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IDH mutation and 1p19q codeletion distinguish two radiological patterns of diffuse low-grade gliomas

Abstract

Diffuse low-grade gliomas (DLGG) prognosis is variable, depending on several factors, including the isocitrate dehydrogenase (IDH) mutation and the 1p19q codeletion. A few studies suggested associations between these parameters and tumor radiological characteristics including topography. Our aim was analyzing the correlations between the IDH and 1p19q statuses and the tumor intracerebral distribution (at the lobar and voxel levels), volume, and borders. We conducted a retrospective, monocentric study on a consecutive series of 198 DLGG patients. The IDH and 1p19q statuses were recorded. The pre-treatment magnetic resonance FLAIR imagings were reviewed for determination of lobar topography, tumor volume, and characterisation of tumor borders (sharp or indistinct). We conducted a voxel-based lesion-symptom mapping analysis to investigate the correlations between the IDH and 1p19q statuses and topography at the voxel level. The IDH mutation and 1p19q statuses were correlated with the tumor topography defined using lobar anatomy (p < 0.001 and p = 0.004, respectively). Frontal tumors were more frequently IDH-mutant (87.1 vs. 57.4%) and 1p19q codeleted (45.2 vs. 17.0%) than temporo-insular lesions. At the voxel level, these associations were not found. Tumors with sharp borders were more frequently IDH-mutant (p = 0.001) while tumors with indistinct borders were more frequently IDH wild-type and 1p19q non-codeleted (p < 0.001). Larger tumors at diagnosis (possibly linked to a slower growth rate) were more frequently IDH-mutant (p < 0.001). IDH wild-type, 1p19q non-codeleted temporo-insular tumors are distinct from IDH-mutant, 1p19q codeleted frontal tumors. Further studies are needed to determine whether the therapeutic strategy should be adapted to each pattern.

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Precision knockdown of EGFR gene expression using radio frequency electromagnetic energy

Abstract

Electromagnetic fields (EMF) in the radio frequency energy (RFE) range can affect cells at the molecular level. Here we report a technology that can record the specific RFE signal of a given molecule, in this case the siRNA of epidermal growth factor receptor (EGFR). We demonstrate that cells exposed to this EGFR siRNA RFE signal have a 30–70% reduction of EGFR mRNA expression and ~60% reduction in EGFR protein expression vs. control treated cells. Specificity for EGFR siRNA effect was confirmed via RNA microarray and antibody dot blot array. The EGFR siRNA RFE decreased cell viability, as measured by Calcein-AM measures, LDH release and Caspase 3 cleavage, and increased orthotopic xenograft survival. The outcomes of this study demonstrate that an RFE signal can induce a specific siRNA-like effect on cells. This technology opens vast possibilities of targeting a broader range of molecules with applications in medicine, agriculture and other areas.

from Cancer via ola Kala on Inoreader http://ift.tt/2pR6hmz
via IFTTT

The risk of radiation necrosis following stereotactic radiosurgery with concurrent systemic therapies

Abstract

To investigate late toxicity among patients with newly-diagnosed brain metastases undergoing stereotactic radiosurgery (SRS) with concurrent systemic therapies with or without whole-brain radiation therapy (WBRT). Patients with newly-diagnosed brain metastasis who underwent SRS at a single tertiary-care institution from 1997 to 2015 were eligible for inclusion. The class and timing of all systemic therapies were collected for each patient. The primary outcome was the cumulative incidence of radiographic radiation necrosis (RN). Multivariable competing risks regression was used to adjust for confounding. During the study period, 1650 patients presented with 2843 intracranial metastases. Among these, 445 patients (27%) were treated with SRS and concurrent systemic therapy. Radiographic RN developed following treatment of 222 (8%) lesions, 120 (54%) of which were symptomatic. The 12-month cumulative incidences of RN among lesions treated with and without concurrent therapies were 6.6 and 5.3%, respectively (p = 0.14). Concurrent systemic therapy was associated with a significantly increased rate of RN among lesions treated with upfront SRS and WBRT (8.7 vs. 3.7%, p = 0.04). In particular, concurrent targeted therapies significantly increased the 12-month cumulative incidence of RN (8.8 vs. 5.3%, p < 0.01). Among these therapies, significantly increased rates of RN were observed with VEGFR tyrosine kinase inhibitors (TKIs) (14.3 vs. 6.6%, p = 0.04) and EGFR TKIs (15.6 vs. 6.0%, p = 0.04). Most classes of systemic therapies may be safely delivered concurrently with SRS in the management of newly-diagnosed brain metastases. However, the rate of radiographic RN is significantly increased with the addition of concurrent systemic therapies to SRS and WBRT.

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via IFTTT

Dendritic cell based vaccination strategy: an evolving paradigm

Abstract

Malignant gliomas (MG), tumors of glial origin, are the most commonly diagnosed primary intracranial malignancies in adults. Currently available treatments have provided only modest improvements in overall survival and remain limited by inevitable local recurrence, necessitating exploration of novel therapies. Among approaches being investigated, one of the leading contenders is immunotherapy, which aims to modulate immune pathways to stimulate the selective destruction of malignant cells. Dendritic cells (DCs) are potent initiators of adaptive immune responses and therefore crucial players in the development and success of immunotherapy. Clinical trials of various DC-based vaccinations have demonstrated the induction of anti-tumor immune responses and prolonged survival in the setting of many cancers. In this review, we summarize current literature regarding DCs and their role in the tumor microenvironment, their application and current clinical use in immunotherapy, current challenges limiting their efficacy in anti-cancer therapy, and future avenues for developing successful anti-tumor DC-based vaccines.

from Cancer via ola Kala on Inoreader http://ift.tt/2pQTMHL
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Pathological analysis of the surgical margins of resected glioblastomas excised using photodynamic visualization with both 5-aminolevulinic acid and fluorescein sodium

Abstract

During glioma resection, 5-aminolevulinic acid (5-ALA) and fluorescein sodium (Fl-Na) are used for photodynamic tumor visualization. The objective of this study was to evaluate the pathological findings of the boundary zone between the tumor and adjacent normal brain in glioblastoma patients undergoing simultaneous double staining with 5-ALA and Fl-Na during surgery. Eight patients received 5-ALA (20 mg/kg orally) before the induction of general anesthesia, and Fl-Na (20 mg/kg) was administered intravenously before the dural incision was performed. The tumor bulk was removed under the guidance of Fl-Na staining alone using conventional white light. Subsequently, residual tumor was removed under the guidance of both fluorescent agents within functionally safe limits until both were visibly undetectable. Twenty specimens exhibiting different staining intensities of both agents were obtained. The vessel index (VI) was calculated from CD31 immunohistochemistry (IHC) samples. Boundary zone tumor cells were detected by IHC for olig2, and were expressed as the olig2 index (OLI). The VI was significantly higher in Fl-Na-positive areas than in Fl-Na-negative areas (p = 0.0005). In contrast, the OLI was significantly higher in 5-ALA-positive areas than in 5-ALA-negative areas (p = 0.0149). 5-ALA-positive/Fl-Na negative areas were observed in 7 patients. These findings indicate that Fl-Na accumulates in areas with a disrupted blood–brain barrier, and that 5-ALA fluorescence is dependent on tumor cell protoporphyrin IX metabolism. In conclusion, 5-ALA was better for detecting tumor cells in the boundary zone than was Fl-Na. Of note, tumor cells existed outside the fluorescence-stained boundaries of both agents.

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Early whole brain radiotherapy in primary CNS lymphoma: negative impact on quality of life in the randomized G-PCNSL-SG1 trial

Abstract

Purpose

In the randomized G-PCNSL-SG-1 trial, the addition of whole brain radiotherapy (45 Gy) to high-dose methotrexate (HD-MTX)-based chemotherapy (early WBRT arm) did not prolong overall survival (OS) as compared to HD-MTX-based chemotherapy alone (no early WBRT arm) in primary CNS lymphoma (PCNSL) patients. To determine whether WBRT might lead to quality of life (QoL)-relevant late neurotoxicity, this trial prospectively monitored QoL.

Methods

QoL measurements were performed using the EORTC-QLQ-C30 and BN20 questionnaires and combined with repeated Mini Mental State Examinations (MMSE). Exploratory data analysis included the 318 patients in the per-protocol population.

Results

In year 2 after randomization, cognitive functioning and global health status were reduced in the early WBRT arm as compared to the no early WBRT arm (p = 0.004 and p = 0.022, respectively). Also, fatigue (p = 0.037), appetite loss (p = 0.006) and hair loss (p = 0.002) were more intense in the early WBRT arm. MMSE testing revealed lower values (p = 0.002) in the early WBRT arm. A mixed model analysis of longitudinal data additionally showed differences favoring the no early WBRT arm in 15 of 26 dimensions of QoL.

Conclusions

The analysis of subjective QoL questionnaires and objective MMSE testing revealed that QoL and cognition were conserved in the arm without early WBRT. Thus, even though it was an exploratory analysis, the results of G-PCNSL-SG1 challenge the place of WBRT in the primary therapy of PCNSL.

http://ift.tt/2ofTslK

Erratum to: Curcumin induces G2/M arrest, apoptosis, NF-κB inhibition, and expression of differentiation genes in thyroid carcinoma cells

http://ift.tt/2pQHVcx

Early whole brain radiotherapy in primary CNS lymphoma: negative impact on quality of life in the randomized G-PCNSL-SG1 trial

Abstract

Purpose

In the randomized G-PCNSL-SG-1 trial, the addition of whole brain radiotherapy (45 Gy) to high-dose methotrexate (HD-MTX)-based chemotherapy (early WBRT arm) did not prolong overall survival (OS) as compared to HD-MTX-based chemotherapy alone (no early WBRT arm) in primary CNS lymphoma (PCNSL) patients. To determine whether WBRT might lead to quality of life (QoL)-relevant late neurotoxicity, this trial prospectively monitored QoL.

Methods

QoL measurements were performed using the EORTC-QLQ-C30 and BN20 questionnaires and combined with repeated Mini Mental State Examinations (MMSE). Exploratory data analysis included the 318 patients in the per-protocol population.

Results

In year 2 after randomization, cognitive functioning and global health status were reduced in the early WBRT arm as compared to the no early WBRT arm (p = 0.004 and p = 0.022, respectively). Also, fatigue (p = 0.037), appetite loss (p = 0.006) and hair loss (p = 0.002) were more intense in the early WBRT arm. MMSE testing revealed lower values (p = 0.002) in the early WBRT arm. A mixed model analysis of longitudinal data additionally showed differences favoring the no early WBRT arm in 15 of 26 dimensions of QoL.

Conclusions

The analysis of subjective QoL questionnaires and objective MMSE testing revealed that QoL and cognition were conserved in the arm without early WBRT. Thus, even though it was an exploratory analysis, the results of G-PCNSL-SG1 challenge the place of WBRT in the primary therapy of PCNSL.

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Erratum to: Curcumin induces G2/M arrest, apoptosis, NF-κB inhibition, and expression of differentiation genes in thyroid carcinoma cells

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Molecular Alterations and Expression Dynamics of LATS1 and LATS2 Genes in Non-Small-Cell Lung Carcinoma

Abstract

Large tumor suppressor (LATS) is an important member of the Hippo pathway which can regulate organ size and cell proliferation. However, very little is known about the expression and clinical significance of LATS in lung cancer especially from this part of the world. We elucidated the frequency of LATS1 &LATS2 promoter hypermethylation (by methylation-specific PCR) and expression (by real-time PCR) in sixty nine (n = 69) Non-Small Cell Lung Cancer (NSCLC) patients and their corresponding normal lung tissue samples. We found promoter hypermethylation frequencies of LATS1 & LATS1to be 66.66% (46/69) and 71% (49/69) in NSCLC tissues. Decreased LATS1 & LATS2 mRNA expression was found in 55% and 66.66% of NSCLC patients. The LATS1 mRNA expression was significantly higher in normal lung tissues. Also, the mRNA levels of LATS1 and LATS2 NSCLC tissues with hypermethylation were significantly lower. Multivariable analysis confirmed that LATS1 under expression increased the hazard of death after adjusting for other clinicopathological factors. Importantly, the loss of LATS1 mRNA expression was associated with overall short survival. LATS1 is an independent prognostic factor and may play an important role in NSCLC progression and may serve as a novel therapeutic target of NSCLC.

http://ift.tt/2p7hi2D

General practitioner attitudes towards prescribing aspirin to carriers of Lynch Syndrome: findings from a national survey

Abstract

A dose non-inferiority study comparing 100 mg, 300 mg and 600 mg of aspirin for cancer prevention among Lynch Syndrome carriers is underway (Colorectal Adenoma/Carcinoma Prevention Programme trial 3, CaPP3). To guide implementation of the findings, we investigated general practitioner (GP) attitudes towards aspirin prescribing for Lynch Syndrome carriers. We surveyed 1007 UK GPs (9.6% response rate). Using a within-subjects design, GPs read a statement on harms and benefits of aspirin and indicated their willingness to prescribe aspirin at three doses (100 mg, 300 mg, 600 mg). Approximately two-thirds (70.8%) of GPs had heard of Lynch Syndrome or its associated names, and among those 46.7% were aware of the cancer preventive effects of aspirin among carriers. Two-thirds (68.1%) of GPs reported feeling comfortable discussing harms and benefits of aspirin with a Lynch Syndrome patient. Willingness to prescribe was 91.3% at 100 mg, and declined to 81.8% at 300 mg and 62.3% at 600 mg (p < 0.001). In multivariable analyses, willingness to prescribe (600 mg) was higher among GPs ≥50 years (OR 1.46, 95% CI 1.03–2.07), more experienced GPs (OR 1.50, 95% CI 1.10–2.04), GPs who were aware of the cancer preventive effects of aspirin (OR 1.58, 95% CI 1.20–2.09), and those who reported seeing a Lynch Syndrome patient in practice (OR 1.44, 95% CI 1.01–2.05, p = 0.045). GPs report limited awareness of Lynch Syndrome and the preventive effects of aspirin among carriers. To ensure the optimal dose identified in the CaPP3 trial is readily available to patients, prescribing guidance and strategies to educate GPs should be developed.

http://ift.tt/2pPNvJG