Cancer Science, EarlyView.
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Cancer Medicine by Alexandros G.Sfakianakis,Anapafseos 5 Agios Nikolaos,Crete 72100,Greece,tel :00302841026182 & 00306932607174
Πέμπτη 19 Απριλίου 2018
Anti‐epidermal growth factor receptor therapy concurrently with induction chemotherapy in locoregionally advanced nasopharyngeal carcinoma
Anti‐epidermal growth factor receptor therapy concurrently with induction chemotherapy in locoregionally advanced nasopharyngeal carcinoma
Cancer Science, EarlyView.
https://ift.tt/2JYoplE
Representation of Obese Participants in Obesity-Related Cancer Randomized Trials
Abstract
Background
Obesity is a risk factor for numerous cancer types, and may influence cancer treatment outcomes. Underrepresentation of obese patients in obesity-related cancer randomized controlled trials (RCTs) may affect generalizability of results. We aimed to assess the reporting of information about eligibility and enrollment of obese participants in obesity-related cancer RCTs. Methods
We conducted a systematic review of RCTs of 10 obesity-related cancer types (esophagus, colon/rectum, liver, gallbladder, pancreas, postmenopausal breast, endometrium, ovary, kidney, and thyroid cancer). We selected RCTs published between 2013 and 2016 in 5 major journals. For each trial, we examined the article, the protocol, and the registration record. We assessed if eligibility criteria limiting the enrollment of obese participants were reported, the proportion of obese participants that were enrolled, and if a subgroup analysis according to obesity status was reported. We systematically contacted corresponding authors and asked for information about eligibility of obese participants and the proportion of obese participants. Results
We included 76 RCTs. Colon/rectum (n = 20), postmenopausal breast (n = 11), and kidney (n = 11) cancers were the most frequent types. Based on publicly available sources, information on the eligibility of obese participants was available in 5 (7%) trials. The proportion of obese participants could be estimated in 9 (12%) trials only. We found a subgroup analysis in only one RCT. When considering unpublished information, the eligibility of obese participants was explicitly stated in 31 (41%) trials but it was unclear if the remaining 59% trials considered obese participants as eligible and what proportion of obese participants was included. Across 22 trials, the median proportion of obese participants included was 18% [Q1-Q3 11-23]. Conclusion
Information on the eligibility and enrollment of obese participants in cancer RCTs is dramatically underreported. More transparency is needed to understand the applicability of obesity-related cancer RCT results to obese patients with cancer.from Cancer via ola Kala on Inoreader https://ift.tt/2K1p85N
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Primary Tumor Sidedness and Benefit from FOLFOXIRI plus Bevacizumab as Initial Therapy for Metastatic Colorectal Cancer
Abstract
Background
Right-sided metastatic colorectal cancer (mCRC) patients have poor prognosis and achieve limited benefit from first-line doublets plus a targeted agent. In this unplanned analysis of the TRIBE study, we investigated the prognostic and predictive impact of primary tumor sidedness in mCRC patients and the differential impact of the intensification of the chemotherapy in subgroups defined according to both primary tumor sidedness and RAS and BRAF mutational status. Patients and methods
Patients were randomized to receive upfront 5-fluoruracil, leucovorin, and irinotecan (FOLFIRI) plus bevacizumab or 5-fluoruracil, leucovorin, oxaliplatin, and irinotecan (FOLFOXIRI) plus bevacizumab. Tumors were defined as right- or left-sided if they originated from the caecum to the transverse colon or within the splenic flexure and beyond, respectively. Patients with available information about both primary sidedness and RAS and BRAF status were included in the present analysis. Progression-free survival (PFS), overall survival (OS) and RECIST response rate were assessed according to tumor location and RAS and BRAF mutational status. Results
Information about primary sidedness and RAS and BRAF status was available for 358 (70.5%) out of 508 randomized patients. Patients with right-sided tumors (N = 173) presented shorter OS (23.7 vs 31.0 months, HR = 1.42 [95%CI, 1.09-1.84], P=0.010) and a trend toward shorter PFS (10.2 vs 11.5 months, HR = 1.24 [95%CI:0.98-1.56], P=0.083) than those with left-sided tumors (N = 185), but these associations were no longer evident when adjusting for RAS and BRAF status. Patients with right-sided tumors achieved more relative benefit from the intensification of the chemotherapy backbone in terms of both PFS (HR = 0.59 vs. 0.89, P-for-interaction=0.099) and OS (HR = 0.56 vs. 0.99, P-for-interaction=0.030) and this advantage was independent of their RAS and BRAF status. Conclusions
FOLFOXIRI plus bevacizumab may be regarded as a preferred first-line treatment option for clinically selected patients with right-sided metastatic colorectal cancer irrespective of their RAS and BRAF mutational status. Trial registration: clinicaltrials.gov identifier NCT00719797.from Cancer via ola Kala on Inoreader https://ift.tt/2Hekijz
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Representation of Obese Participants in Obesity-Related Cancer Randomized Trials
Abstract
Background
Obesity is a risk factor for numerous cancer types, and may influence cancer treatment outcomes. Underrepresentation of obese patients in obesity-related cancer randomized controlled trials (RCTs) may affect generalizability of results. We aimed to assess the reporting of information about eligibility and enrollment of obese participants in obesity-related cancer RCTs. Methods
We conducted a systematic review of RCTs of 10 obesity-related cancer types (esophagus, colon/rectum, liver, gallbladder, pancreas, postmenopausal breast, endometrium, ovary, kidney, and thyroid cancer). We selected RCTs published between 2013 and 2016 in 5 major journals. For each trial, we examined the article, the protocol, and the registration record. We assessed if eligibility criteria limiting the enrollment of obese participants were reported, the proportion of obese participants that were enrolled, and if a subgroup analysis according to obesity status was reported. We systematically contacted corresponding authors and asked for information about eligibility of obese participants and the proportion of obese participants. Results
We included 76 RCTs. Colon/rectum (n = 20), postmenopausal breast (n = 11), and kidney (n = 11) cancers were the most frequent types. Based on publicly available sources, information on the eligibility of obese participants was available in 5 (7%) trials. The proportion of obese participants could be estimated in 9 (12%) trials only. We found a subgroup analysis in only one RCT. When considering unpublished information, the eligibility of obese participants was explicitly stated in 31 (41%) trials but it was unclear if the remaining 59% trials considered obese participants as eligible and what proportion of obese participants was included. Across 22 trials, the median proportion of obese participants included was 18% [Q1-Q3 11-23]. Conclusion
Information on the eligibility and enrollment of obese participants in cancer RCTs is dramatically underreported. More transparency is needed to understand the applicability of obesity-related cancer RCT results to obese patients with cancer.https://ift.tt/2K1p85N
Primary Tumor Sidedness and Benefit from FOLFOXIRI plus Bevacizumab as Initial Therapy for Metastatic Colorectal Cancer
Abstract
Background
Right-sided metastatic colorectal cancer (mCRC) patients have poor prognosis and achieve limited benefit from first-line doublets plus a targeted agent. In this unplanned analysis of the TRIBE study, we investigated the prognostic and predictive impact of primary tumor sidedness in mCRC patients and the differential impact of the intensification of the chemotherapy in subgroups defined according to both primary tumor sidedness and RAS and BRAF mutational status. Patients and methods
Patients were randomized to receive upfront 5-fluoruracil, leucovorin, and irinotecan (FOLFIRI) plus bevacizumab or 5-fluoruracil, leucovorin, oxaliplatin, and irinotecan (FOLFOXIRI) plus bevacizumab. Tumors were defined as right- or left-sided if they originated from the caecum to the transverse colon or within the splenic flexure and beyond, respectively. Patients with available information about both primary sidedness and RAS and BRAF status were included in the present analysis. Progression-free survival (PFS), overall survival (OS) and RECIST response rate were assessed according to tumor location and RAS and BRAF mutational status. Results
Information about primary sidedness and RAS and BRAF status was available for 358 (70.5%) out of 508 randomized patients. Patients with right-sided tumors (N = 173) presented shorter OS (23.7 vs 31.0 months, HR = 1.42 [95%CI, 1.09-1.84], P=0.010) and a trend toward shorter PFS (10.2 vs 11.5 months, HR = 1.24 [95%CI:0.98-1.56], P=0.083) than those with left-sided tumors (N = 185), but these associations were no longer evident when adjusting for RAS and BRAF status. Patients with right-sided tumors achieved more relative benefit from the intensification of the chemotherapy backbone in terms of both PFS (HR = 0.59 vs. 0.89, P-for-interaction=0.099) and OS (HR = 0.56 vs. 0.99, P-for-interaction=0.030) and this advantage was independent of their RAS and BRAF status. Conclusions
FOLFOXIRI plus bevacizumab may be regarded as a preferred first-line treatment option for clinically selected patients with right-sided metastatic colorectal cancer irrespective of their RAS and BRAF mutational status. Trial registration: clinicaltrials.gov identifier NCT00719797.https://ift.tt/2Hekijz
Mohs Micrographic Surgery Volume and Payment Patterns Among Dermatologists in the Medicare Population, 2013
Objectives: Mohs micrographic surgery (MMS) has expanded markedly in recent years but there is limited information on volume, practice patterns or reimbursement. This study characterizes MMS utilization in the Medicare population. Materials and Methods: We analyzed the Medicare Provider Utilization and Payment Data: Physician and Other Supplier Public Use File Calendar Year 2013 data set for provider service volume and reimbursement for dermatologists who did and did not perform MMS procedures. Results: Total Medicare-funded MMS procedures increased 25% from 2009 (558,447) to 2013 (700,262). Dermatologists who performed MMS had significantly more average services per provider (5419.4 vs. 3627.1, r=0.16, P
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Characterization of PD-L1 and PD-1 Expression and CD8+ Tumor-infiltrating Lymphocyte in Epstein-Barr Virus-associated Nasopharyngeal Carcinoma
Objectives: Immunotherapies that target the programmed death-1/ programmed death-1 ligand (PD-1/PD-L1) immune checkpoint pathway have shown promise in nasopharyngeal carcinoma (NPC) in early phases clinical studies. Here, we evaluated PD-1 and PD-L1 expression and CD8+ tumor-infiltrating lymphocytes (TILs) in NPC patients. Materials and Methods: Newly diagnosed NPC patients were identified through the institutional database between January 2007 and December 2012. PD-L1 and PD-1 expression, Epstein-Barr virus (EBV) status, and CD8+ TIL numbers were measured in archival tumor samples at diagnosis and their correlations with clinicopathologic features, including survival, were evaluated. Results: A total of 114 NPC patients were analyzed. Most patients (96%) were EBV positive. PD-L1 was expressed in ≥1% of tumor cells (TCs) in 69% of patients, in ≥50% of TCs in 12% of patients, and in ≥5% of either TCs or infiltrating immune cells in 71% of patients. CD8+ TILs were present in tumors from all patients, whereas only 11% of tumors expressed PD-1. There were no correlations between PD-L1 expression and CD8+ TIL abundance, PD-1 expression, or survival. Conclusions: Approximately 70% of EBV-positive NPC expressed PD-L1, but this did not correlate with patient survival or clinicopathologic features. The findings of this study represent the immune biomarker profile of confirmed EBV-associated NPC in an endemic region. Since the current clinical development of immune checkpoint inhibitor for NPC is mostly focusing on an EBV-associated tumor, differences in immune biomarker profiles and EBV status of endemic and nonendemic regions should be further explored. N.L. and K.M. contributed equally. Supported by the Ramathibodi Cancer Center grant. N.N. received funding from the Research University Network (RUN) and Talent Management Program of Mahidol University, and the Ramathibodi Grant for Research Development from Ramathibodi Hospital. An abstract of this work was presented at the 2015 ASCO Annual Meeting, May 29 to June 2, 2015, Chicago, IL. The authors declare no conflicts of interest. Reprints: Nuttapong Ngamphaiboon, MD, Department of Medicine, Division of Medical Oncology, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, 270 Rama VI Road, Ratchathewi, Bangkok 10400, Thailand. E-mail: nuttapong.nga@mahidol.ac.th. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.
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The Impact of Epidemiological Factors and Treatment Interventions on Survival in Patients With Signet Ring Cell Carcinoma of the Pancreas
Objectives: Primary pancreatic signet ring cell carcinoma (SRCC) is a rare histologic variant of pancreatic carcinoma. A population-based analysis of pancreatic SRCC was performed to determine the predictive effects of epidemiological factors and treatment interventions on overall survival (OS) and disease-specific survival (DSS). Materials and Methods: The Surveillance, Epidemiology, and End Results registry was searched for pancreatic SRCC cases diagnosed between January 1, 1973 and December 31, 2013. Statistical analysis was performed using the Fisher exact test, χ2 analysis, Kaplan-Meier method, log-rank test, and Cox proportional hazards regression. Results: The mean age among 497 patients was 66.6 years (SD, 11.9). Most patients were white (82.7%) and male (54.5%). The 1-, 2-, and 5-year OS rates were 17%, 9%, and 4%, respectively, while the corresponding 1-, 2-, and 5-year rates for DSS were 18%, 10%, and 5%, respectively. On univariable analysis; age, site, grade, stage, and treatment were predictive of OS and DSS (P
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https://ift.tt/2qKm7id
Mohs Micrographic Surgery Volume and Payment Patterns Among Dermatologists in the Medicare Population, 2013
Objectives: Mohs micrographic surgery (MMS) has expanded markedly in recent years but there is limited information on volume, practice patterns or reimbursement. This study characterizes MMS utilization in the Medicare population. Materials and Methods: We analyzed the Medicare Provider Utilization and Payment Data: Physician and Other Supplier Public Use File Calendar Year 2013 data set for provider service volume and reimbursement for dermatologists who did and did not perform MMS procedures. Results: Total Medicare-funded MMS procedures increased 25% from 2009 (558,447) to 2013 (700,262). Dermatologists who performed MMS had significantly more average services per provider (5419.4 vs. 3627.1, r=0.16, P
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Characterization of PD-L1 and PD-1 Expression and CD8+ Tumor-infiltrating Lymphocyte in Epstein-Barr Virus-associated Nasopharyngeal Carcinoma
Objectives: Immunotherapies that target the programmed death-1/ programmed death-1 ligand (PD-1/PD-L1) immune checkpoint pathway have shown promise in nasopharyngeal carcinoma (NPC) in early phases clinical studies. Here, we evaluated PD-1 and PD-L1 expression and CD8+ tumor-infiltrating lymphocytes (TILs) in NPC patients. Materials and Methods: Newly diagnosed NPC patients were identified through the institutional database between January 2007 and December 2012. PD-L1 and PD-1 expression, Epstein-Barr virus (EBV) status, and CD8+ TIL numbers were measured in archival tumor samples at diagnosis and their correlations with clinicopathologic features, including survival, were evaluated. Results: A total of 114 NPC patients were analyzed. Most patients (96%) were EBV positive. PD-L1 was expressed in ≥1% of tumor cells (TCs) in 69% of patients, in ≥50% of TCs in 12% of patients, and in ≥5% of either TCs or infiltrating immune cells in 71% of patients. CD8+ TILs were present in tumors from all patients, whereas only 11% of tumors expressed PD-1. There were no correlations between PD-L1 expression and CD8+ TIL abundance, PD-1 expression, or survival. Conclusions: Approximately 70% of EBV-positive NPC expressed PD-L1, but this did not correlate with patient survival or clinicopathologic features. The findings of this study represent the immune biomarker profile of confirmed EBV-associated NPC in an endemic region. Since the current clinical development of immune checkpoint inhibitor for NPC is mostly focusing on an EBV-associated tumor, differences in immune biomarker profiles and EBV status of endemic and nonendemic regions should be further explored. N.L. and K.M. contributed equally. Supported by the Ramathibodi Cancer Center grant. N.N. received funding from the Research University Network (RUN) and Talent Management Program of Mahidol University, and the Ramathibodi Grant for Research Development from Ramathibodi Hospital. An abstract of this work was presented at the 2015 ASCO Annual Meeting, May 29 to June 2, 2015, Chicago, IL. The authors declare no conflicts of interest. Reprints: Nuttapong Ngamphaiboon, MD, Department of Medicine, Division of Medical Oncology, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, 270 Rama VI Road, Ratchathewi, Bangkok 10400, Thailand. E-mail: nuttapong.nga@mahidol.ac.th. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.
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The Impact of Epidemiological Factors and Treatment Interventions on Survival in Patients With Signet Ring Cell Carcinoma of the Pancreas
Objectives: Primary pancreatic signet ring cell carcinoma (SRCC) is a rare histologic variant of pancreatic carcinoma. A population-based analysis of pancreatic SRCC was performed to determine the predictive effects of epidemiological factors and treatment interventions on overall survival (OS) and disease-specific survival (DSS). Materials and Methods: The Surveillance, Epidemiology, and End Results registry was searched for pancreatic SRCC cases diagnosed between January 1, 1973 and December 31, 2013. Statistical analysis was performed using the Fisher exact test, χ2 analysis, Kaplan-Meier method, log-rank test, and Cox proportional hazards regression. Results: The mean age among 497 patients was 66.6 years (SD, 11.9). Most patients were white (82.7%) and male (54.5%). The 1-, 2-, and 5-year OS rates were 17%, 9%, and 4%, respectively, while the corresponding 1-, 2-, and 5-year rates for DSS were 18%, 10%, and 5%, respectively. On univariable analysis; age, site, grade, stage, and treatment were predictive of OS and DSS (P
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Germline Genetic IKZF1 Variation and Predisposition to Childhood Acute Lymphoblastic Leukemia
Publication date: Available online 19 April 2018
Source:Cancer Cell
Author(s): Michelle L. Churchman, Maoxiang Qian, Geertruy te Kronnie, Ranran Zhang, Wenjian Yang, Hui Zhang, Tobia Lana, Paige Tedrick, Rebekah Baskin, Katherine Verbist, Jennifer L. Peters, Meenakshi Devidas, Eric Larsen, Ian M. Moore, Zhaohui Gu, Chunxu Qu, Hiroki Yoshihara, Shaina N. Porter, Shondra M. Pruett-Miller, Gang Wu, Elizabeth Raetz, Paul L. Martin, W. Paul Bowman, Naomi Winick, Elaine Mardis, Robert Fulton, Martin Stanulla, William E. Evans, Mary V. Relling, Ching-Hon Pui, Stephen P. Hunger, Mignon L. Loh, Rupert Handgretinger, Kim E. Nichols, Jun J. Yang, Charles G. Mullighan
Somatic genetic alterations of IKZF1, which encodes the lymphoid transcription factor IKAROS, are common in high-risk B-progenitor acute lymphoblastic leukemia (ALL) and are associated with poor prognosis. Such alterations result in the acquisition of stem cell-like features, overexpression of adhesion molecules causing aberrant cell-cell and cell-stroma interaction, and decreased sensitivity to tyrosine kinase inhibitors. Here we report coding germline IKZF1 variation in familial childhood ALL and 0.9% of presumed sporadic B-ALL, identifying 28 unique variants in 45 children. The majority of variants adversely affected IKZF1 function and drug responsiveness of leukemic cells. These results identify IKZF1 as a leukemia predisposition gene, and emphasize the importance of germline genetic variation in the development of both familial and sporadic ALL.
Graphical abstract
Teaser
Churchman et al. identify 28 unique germline IKZF1 coding variants in 45 children with acute lymphoblastic leukemia. Many of these variants are not predicted to be damaging using in silico prediction tools, but functional tests reveal that the majority of them have deleterious effects on IKAROS function.from Cancer via ola Kala on Inoreader https://ift.tt/2qLxeHI
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A Glial Signature and Wnt7 Signaling Regulate Glioma-Vascular Interactions and Tumor Microenvironment
Publication date: Available online 19 April 2018
Source:Cancer Cell
Author(s): Amelie Griveau, Giorgio Seano, Samuel J. Shelton, Robert Kupp, Arman Jahangiri, Kirsten Obernier, Shanmugarajan Krishnan, Olle R. Lindberg, Tracy J. Yuen, An-Chi Tien, Jennifer K. Sabo, Nancy Wang, Ivy Chen, Jonas Kloepper, Louis Larrouquere, Mitrajit Ghosh, Itay Tirosh, Emmanuelle Huillard, Arturo Alvarez-Buylla, Michael C. Oldham, Anders I. Persson, William A. Weiss, Tracy T. Batchelor, Anat Stemmer-Rachamimov, Mario L. Suvà, Joanna J. Phillips, Manish K. Aghi, Shwetal Mehta, Rakesh K. Jain, David H. Rowitch
Gliomas comprise heterogeneous malignant glial and stromal cells. While blood vessel co-option is a potential mechanism to escape anti-angiogenic therapy, the relevance of glial phenotype in this process is unclear. We show that Olig2+ oligodendrocyte precursor-like glioma cells invade by single-cell vessel co-option and preserve the blood-brain barrier (BBB). Conversely, Olig2-negative glioma cells form dense perivascular collections and promote angiogenesis and BBB breakdown, leading to innate immune cell activation. Experimentally, Olig2 promotes Wnt7b expression, a finding that correlates in human glioma profiling. Targeted Wnt7a/7b deletion or pharmacologic Wnt inhibition blocks Olig2+ glioma single-cell vessel co-option and enhances responses to temozolomide. Finally, Olig2 and Wnt7 become upregulated after anti-VEGF treatment in preclinical models and patients. Thus, glial-encoded pathways regulate distinct glioma-vascular microenvironmental interactions.
Teaser
Griveau et al. show that Olig2+ glioma cells invade by single-cell vessel co-option, whereas Olig2− glioma cells promote angiogenesis and that anti-VEGF treatment selects for the Olig2+/Wnt7+ phenotype. Wnt7 is necessary for vessel co-option, and Wnt inhibition enhances the response to temozolomide treatment.from Cancer via ola Kala on Inoreader https://ift.tt/2F226I8
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Germline Genetic IKZF1 Variation and Predisposition to Childhood Acute Lymphoblastic Leukemia
Publication date: Available online 19 April 2018
Source:Cancer Cell
Author(s): Michelle L. Churchman, Maoxiang Qian, Geertruy te Kronnie, Ranran Zhang, Wenjian Yang, Hui Zhang, Tobia Lana, Paige Tedrick, Rebekah Baskin, Katherine Verbist, Jennifer L. Peters, Meenakshi Devidas, Eric Larsen, Ian M. Moore, Zhaohui Gu, Chunxu Qu, Hiroki Yoshihara, Shaina N. Porter, Shondra M. Pruett-Miller, Gang Wu, Elizabeth Raetz, Paul L. Martin, W. Paul Bowman, Naomi Winick, Elaine Mardis, Robert Fulton, Martin Stanulla, William E. Evans, Mary V. Relling, Ching-Hon Pui, Stephen P. Hunger, Mignon L. Loh, Rupert Handgretinger, Kim E. Nichols, Jun J. Yang, Charles G. Mullighan
Somatic genetic alterations of IKZF1, which encodes the lymphoid transcription factor IKAROS, are common in high-risk B-progenitor acute lymphoblastic leukemia (ALL) and are associated with poor prognosis. Such alterations result in the acquisition of stem cell-like features, overexpression of adhesion molecules causing aberrant cell-cell and cell-stroma interaction, and decreased sensitivity to tyrosine kinase inhibitors. Here we report coding germline IKZF1 variation in familial childhood ALL and 0.9% of presumed sporadic B-ALL, identifying 28 unique variants in 45 children. The majority of variants adversely affected IKZF1 function and drug responsiveness of leukemic cells. These results identify IKZF1 as a leukemia predisposition gene, and emphasize the importance of germline genetic variation in the development of both familial and sporadic ALL.
Graphical abstract
Teaser
Churchman et al. identify 28 unique germline IKZF1 coding variants in 45 children with acute lymphoblastic leukemia. Many of these variants are not predicted to be damaging using in silico prediction tools, but functional tests reveal that the majority of them have deleterious effects on IKAROS function.https://ift.tt/2qLxeHI
A Glial Signature and Wnt7 Signaling Regulate Glioma-Vascular Interactions and Tumor Microenvironment
Publication date: Available online 19 April 2018
Source:Cancer Cell
Author(s): Amelie Griveau, Giorgio Seano, Samuel J. Shelton, Robert Kupp, Arman Jahangiri, Kirsten Obernier, Shanmugarajan Krishnan, Olle R. Lindberg, Tracy J. Yuen, An-Chi Tien, Jennifer K. Sabo, Nancy Wang, Ivy Chen, Jonas Kloepper, Louis Larrouquere, Mitrajit Ghosh, Itay Tirosh, Emmanuelle Huillard, Arturo Alvarez-Buylla, Michael C. Oldham, Anders I. Persson, William A. Weiss, Tracy T. Batchelor, Anat Stemmer-Rachamimov, Mario L. Suvà, Joanna J. Phillips, Manish K. Aghi, Shwetal Mehta, Rakesh K. Jain, David H. Rowitch
Gliomas comprise heterogeneous malignant glial and stromal cells. While blood vessel co-option is a potential mechanism to escape anti-angiogenic therapy, the relevance of glial phenotype in this process is unclear. We show that Olig2+ oligodendrocyte precursor-like glioma cells invade by single-cell vessel co-option and preserve the blood-brain barrier (BBB). Conversely, Olig2-negative glioma cells form dense perivascular collections and promote angiogenesis and BBB breakdown, leading to innate immune cell activation. Experimentally, Olig2 promotes Wnt7b expression, a finding that correlates in human glioma profiling. Targeted Wnt7a/7b deletion or pharmacologic Wnt inhibition blocks Olig2+ glioma single-cell vessel co-option and enhances responses to temozolomide. Finally, Olig2 and Wnt7 become upregulated after anti-VEGF treatment in preclinical models and patients. Thus, glial-encoded pathways regulate distinct glioma-vascular microenvironmental interactions.
Teaser
Griveau et al. show that Olig2+ glioma cells invade by single-cell vessel co-option, whereas Olig2− glioma cells promote angiogenesis and that anti-VEGF treatment selects for the Olig2+/Wnt7+ phenotype. Wnt7 is necessary for vessel co-option, and Wnt inhibition enhances the response to temozolomide treatment.https://ift.tt/2F226I8
Antigen Presentation Keeps Trending in Immunotherapy Resistance
Through a gain-of-function kinome screen, MEX3B was identified as a mediator of resistance to T cell immunotherapy not previously identified using CRISPR based screens. MEX3B is a post-transcriptional regulator of HLA-A, validating the critical role of tumor-intrinsic antigen presentation in T cell immunotherapy and indicating a new putative molecular target.
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Combined BRAF and HSP90 inhibition in patients with unresectable BRAF V600E mutant melanoma
Purpose: BRAF inhibitors are clinically active in patients with advanced BRAFV600-mutant melanoma, although acquired resistance remains common. Preclinical studies demonstrated that resistance could be overcome using concurrent treatment with the HSP90 inhibitor XL888. Methods: Vemurafenib (960 mg PO BID) combined with escalating doses of XL888 (30, 45, 90 or 135 mg PO twice weekly) was investigated in 21 patients with advanced BRAFV600-mutant melanoma. Primary endpoints were safety and determination of a maximum tolerated dose. Correlative proteomic studies were performed to confirm HSP inhibitor activity. Results: Objective responses were observed in 15/20 evaluable patients (75%; 95% CI: 51-91%), with 3 complete and 12 partial responses. Median progression-free and overall survival were 9.2 months (95% CI: 3.8-not reached) and 34.6 months (6.2-not reached), respectively. The most common grade 3/4 toxicities were skin toxicities such as rash (n=4, 19%) and cutaneous squamous cell carcinomas (n=3, 14%), along with diarrhea (n=3, 14%). Pharmacodynamic analysis of patients' PBMCs showed increased day 8 HSP70 expression compared to baseline in the three cohorts with XL888 doses ≥45 mg. Diverse effects of vemurafenib-XL888 upon intratumoral HSP-client protein expression were noted, with the expression of multiple proteins (including ERBB3 and BAD) modulated on therapy. Conclusion. XL888 in combination with vemurafenib has clinical activity in patients with advanced BRAFV600-mutant melanoma, with a tolerable side-effect profile. HSP90 inhibitors warrant further evaluation in combination with current standard-of-care BRAF plus MEK inhibitors in BRAFV600-mutant melanoma.
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Tamoxifen Resistance Trumped and Oral Selective Estrogen Receptor Degraders Arrive
Predictive tests, to refine the estrogen receptor assay, for the adjuvant treatment of breast cancer with tamoxifen and oral Selective Estrogen Receptor Degraders (SERDs) are required. A splice variant of the corepressor NCOR2, BQ2313636.1 predicts tamoxifen resistence to adjuvant tamoxifen and AZ9496, the first oral SERD, completes phase one studies
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Antigen Presentation Keeps Trending in Immunotherapy Resistance
Through a gain-of-function kinome screen, MEX3B was identified as a mediator of resistance to T cell immunotherapy not previously identified using CRISPR based screens. MEX3B is a post-transcriptional regulator of HLA-A, validating the critical role of tumor-intrinsic antigen presentation in T cell immunotherapy and indicating a new putative molecular target.
https://ift.tt/2K1bMGH
Combined BRAF and HSP90 inhibition in patients with unresectable BRAF V600E mutant melanoma
Purpose: BRAF inhibitors are clinically active in patients with advanced BRAFV600-mutant melanoma, although acquired resistance remains common. Preclinical studies demonstrated that resistance could be overcome using concurrent treatment with the HSP90 inhibitor XL888. Methods: Vemurafenib (960 mg PO BID) combined with escalating doses of XL888 (30, 45, 90 or 135 mg PO twice weekly) was investigated in 21 patients with advanced BRAFV600-mutant melanoma. Primary endpoints were safety and determination of a maximum tolerated dose. Correlative proteomic studies were performed to confirm HSP inhibitor activity. Results: Objective responses were observed in 15/20 evaluable patients (75%; 95% CI: 51-91%), with 3 complete and 12 partial responses. Median progression-free and overall survival were 9.2 months (95% CI: 3.8-not reached) and 34.6 months (6.2-not reached), respectively. The most common grade 3/4 toxicities were skin toxicities such as rash (n=4, 19%) and cutaneous squamous cell carcinomas (n=3, 14%), along with diarrhea (n=3, 14%). Pharmacodynamic analysis of patients' PBMCs showed increased day 8 HSP70 expression compared to baseline in the three cohorts with XL888 doses ≥45 mg. Diverse effects of vemurafenib-XL888 upon intratumoral HSP-client protein expression were noted, with the expression of multiple proteins (including ERBB3 and BAD) modulated on therapy. Conclusion. XL888 in combination with vemurafenib has clinical activity in patients with advanced BRAFV600-mutant melanoma, with a tolerable side-effect profile. HSP90 inhibitors warrant further evaluation in combination with current standard-of-care BRAF plus MEK inhibitors in BRAFV600-mutant melanoma.
https://ift.tt/2qLpFAO
Tamoxifen Resistance Trumped and Oral Selective Estrogen Receptor Degraders Arrive
Predictive tests, to refine the estrogen receptor assay, for the adjuvant treatment of breast cancer with tamoxifen and oral Selective Estrogen Receptor Degraders (SERDs) are required. A splice variant of the corepressor NCOR2, BQ2313636.1 predicts tamoxifen resistence to adjuvant tamoxifen and AZ9496, the first oral SERD, completes phase one studies
https://ift.tt/2Hi7LMp
Blockade of myeloid-derived suppressor cell expansion with all-trans retinoic acid increases the efficacy of anti-angiogenic therapy
Intrinsic and adaptive resistance hamper the success of anti-angiogenic therapies (AAT), especially in breast cancer where this treatment modality has proven largely ineffective. Therefore, novel strategies to improve the efficacy of AAT are warranted. Solid tumors such as breast cancer are characterized by a high infiltration of myeloid-derived suppressor cells (MDSC) which are key drivers of resistance to AAT. Therefore, we hypothesized that all-trans retinoic acid (ATRA), which induces differentiation of MDSC into mature cells, could improve the therapeutic effect of AAT. ATRA increased the efficacy of anti-VEGFR-2 antibodies alone and in combination with chemotherapy in preclinical breast cancer models. ATRA reverted the anti-VEGFR-2-induced accumulation of intratumoral MDSC, alleviated hypoxia, and counteracted the disorganization of tumor microvessels. Mechanistic studies indicate that ATRA treatment blocked the AAT-induced expansion of MDSC secreting high levels of vessel-destabilizing S100A8. Thus, concomitant treatment with ATRA holds the potential to improve AAT in breast cancer and possibly other tumor types.
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Blockade of myeloid-derived suppressor cell expansion with all-trans retinoic acid increases the efficacy of anti-angiogenic therapy
Intrinsic and adaptive resistance hamper the success of anti-angiogenic therapies (AAT), especially in breast cancer where this treatment modality has proven largely ineffective. Therefore, novel strategies to improve the efficacy of AAT are warranted. Solid tumors such as breast cancer are characterized by a high infiltration of myeloid-derived suppressor cells (MDSC) which are key drivers of resistance to AAT. Therefore, we hypothesized that all-trans retinoic acid (ATRA), which induces differentiation of MDSC into mature cells, could improve the therapeutic effect of AAT. ATRA increased the efficacy of anti-VEGFR-2 antibodies alone and in combination with chemotherapy in preclinical breast cancer models. ATRA reverted the anti-VEGFR-2-induced accumulation of intratumoral MDSC, alleviated hypoxia, and counteracted the disorganization of tumor microvessels. Mechanistic studies indicate that ATRA treatment blocked the AAT-induced expansion of MDSC secreting high levels of vessel-destabilizing S100A8. Thus, concomitant treatment with ATRA holds the potential to improve AAT in breast cancer and possibly other tumor types.
https://ift.tt/2qKQ01Z
Consumption of Sugars, Sugary Foods and Sugary Beverages in Relation to Adiposity-Related Cancer Risk in the Framingham Offspring Cohort (1991-2013)
Background: Higher sugar consumption may increase cancer risk by promoting insulin-glucose dysregulation, oxidative stress, hormonal imbalances, and excess adiposity. This prospective study investigates the association between dietary sugars(fructose and sucrose) and sugary foods and beverages in relation to combined and site-specific (breast, prostate, colorectal) adiposity-associated cancers. Methods: The analytic sample consisted of 3,184 adults, aged 26-84y, from the Framingham Offspring cohort. Diet data was first collected between 1991-1995 using a food frequency questionnaire. Intakes of fructose, sucrose, sugary foods and sugary beverages (fruit juice and sugar-sweetened beverages) were derived. Participants were followed up until 2013 to ascertain cancer incidence; 565 doctor-diagnosed adiposity-related cancers, including 124 breast, 157 prostate and 68 colorectal cancers occurred. Multivariable-adjusted Cox proportional hazards models were used to evaluate associations. Tests for interaction with BMI and waist circumference were conducted. Results: No associations were observed between fructose, sucrose, sugary food consumption and combined incidence of adiposity-related cancers or the examined site-specific cancers. While total consumption of sugary beverages was not associated with site-specific cancer risk, higher intakes of fruit juice were associated with 58% increased prostate cancer risk(HR:1.58;95%CI:1.04-2.41) in multivariable-adjusted models. In exploratory stratified analyses, higher sugary beverage intakes increased overall adiposity-related cancer risk by 59% in participants with excessive central adiposity(HR:1.59;95%CI:1.01-2.50)(p-trend=0.057). Conclusions: In this cohort of American adults, higher sugary beverage consumption was associated with increased cancer risk among participants with central adiposity. Impact: These analyses suggest that avoiding sugary beverages represents a simple dietary modification that may be used as an effective cancer control strategy.
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Pectoral I Block Does Not Improve Postoperative Analgesia After Breast Cancer Surgery: A Randomized, Double-Blind, Dual-Centered Controlled Trial
Background and Objectives General anesthesia for breast surgery may be supplemented by using a regional anesthetic technique. We evaluated the efficacy of the first pectoral nerve block (Pecs I) in treating postoperative pain after breast cancer surgery. Methods A randomized, double-blind, dual-centered, placebo-controlled trial was performed. One hundred twenty-eight patients scheduled for unilateral breast cancer surgery were recruited. A multimodal analgesic regimen and surgeon-administered local anesthetic infiltration were used for all patients. Ultrasound-guided Pecs I was performed using bupivacaine or saline. The primary outcome was the patient pain score (numerical rating scale [NRS]) in the recovery unit 30 minutes after admission or just before the morphine administration (NRS ≥4/10). The secondary outcomes were postoperative opioid consumption (ie, in the recovery unit and after 24 hours). Results During recovery, no significant difference in NRS was observed between the bupivacaine (n = 62, 3.0 [1.0–4.0]) and placebo (n = 65, 3.0 [1.0–5.0]) groups (P = 0.55). However, the NRS was statistically significantly different, although not clinically significant, for patients undergoing major surgeries (mastectomies or tumorectomies with axillary clearance) (n = 29, 3.0 [0.0–4.0] vs 4.0 [2.0–5.0], P = 0.04). Morphine consumption during recovery did not differ (1.5 mg [0.0–6.0 mg] vs 3.0 mg [0.0–6.0 mg], P = 0.20), except in the major surgery subgroup (1.5 mg [0.0–6.0 mg] vs 6.0 mg [0.0–12.0 mg], P = 0.016). Intraoperative sufentanil and cumulative morphine consumption up to 24 hours did not differ between the 2 groups. Three patients experienced complications related to the Pecs I. Conclusions Pecs I is not better than a saline placebo in the presence of multimodal analgesia for breast cancer surgery. However, its role in extended (major) breast surgery may warrant further investigation. Clinical Trial Registration This study was registered at ClinicalTrials.gov, identifier NCT01670448. Accepted for publication December 13, 2017. Address correspondence to: Jérôme Cros, MD, MSc, Département d'Anesthésie-Réanimation, Hôpital de la mère et de l'enfant, 8, avenue Dominique Larrey, 87000 Limoges, France (e-mail: jerome.cros@chu-limoges.fr). Funding was provided by Réseau Québécois de Recherche sur la Douleur, Québec, Canada; Fondation d'Anesthésiologie et Réanimation du Québec, Canada; Fonds de Développement du Département d'anesthésiologie de l'Université de Montréal, Québec, Canada; and Fondation de France, Paris, France. This work has been presented in part at Euroanesthesia 2016, London, United Kingdom, May 29, 2016 (presented by J.C., abstract no. 03AP04-3); at the French Society of Anesthesia & Intensive Care Medicine (SFAR) 2016 Annual Meeting, Paris, France, September 24, 2016 (presented by J.C., abstract no. R480 [in French]); and at the World Congress of Pain 2016, Yokohama, Japan, September 27, 2016 (presented by P.B., abstract no. 943). The authors declare no conflict of interest. Copyright © 2018 by American Society of Regional Anesthesia and Pain Medicine.
https://ift.tt/2qNXG2v
https://ift.tt/2qNXG2v
Knowledge and Beliefs About Oncofertility and Associations with Quality of Life Among Adolescent and Young Adult Survivors of Pediatric Cancer
Journal of Adolescent and Young Adult Oncology, Ahead of Print.
https://ift.tt/2qNEzWa
Knowledge and Beliefs About Oncofertility and Associations with Quality of Life Among Adolescent and Young Adult Survivors of Pediatric Cancer
Journal of Adolescent and Young Adult Oncology, Ahead of Print.
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Systematic review of the mesopancreas: concept and clinical implications
Abstract
Background
In 2007, Gockel et al. coined the term mesopancreas (MP). In the next 10 years, a limited number of publications about MP have been published, but little is known about the oncological benefit of MP resection. We performed a systematic review of the literature on MP.
Methods
An electronic search was performed in PubMed, EMBASE, Cochrane, Latindex, Scielo, and Koreamed databases until 15 June 2017 to identify all published articles dealing with the subject of MP. Some language restriction was done (Chinese and Rumanian).
Results
The search yielded 51 articles; 28 articles were selected as relevant. All were retrospective studies focused more on describing technical variants, feasibility and safety than on the cancer results. The R0 rate in patients with MP resection ranged between 57 and 96.7%. In all the articles with a control group, the R0 rate was higher in the MP excision group. Survival data were explicitly stated only in five series.
Conclusion
MP is a difficult-to-excise retropancreatic area. In theory, it is agreed that MP excision raises the rate of R0 resections, which in turn reflected in an improvement in the oncological results; however, at present there are no randomized studies to prove this. Achieving a worldwide consensus on its concept, landmarks, excision technique and oncological results is essential.
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Systematic review of the mesopancreas: concept and clinical implications
Abstract
Background
In 2007, Gockel et al. coined the term mesopancreas (MP). In the next 10 years, a limited number of publications about MP have been published, but little is known about the oncological benefit of MP resection. We performed a systematic review of the literature on MP.
Methods
An electronic search was performed in PubMed, EMBASE, Cochrane, Latindex, Scielo, and Koreamed databases until 15 June 2017 to identify all published articles dealing with the subject of MP. Some language restriction was done (Chinese and Rumanian).
Results
The search yielded 51 articles; 28 articles were selected as relevant. All were retrospective studies focused more on describing technical variants, feasibility and safety than on the cancer results. The R0 rate in patients with MP resection ranged between 57 and 96.7%. In all the articles with a control group, the R0 rate was higher in the MP excision group. Survival data were explicitly stated only in five series.
Conclusion
MP is a difficult-to-excise retropancreatic area. In theory, it is agreed that MP excision raises the rate of R0 resections, which in turn reflected in an improvement in the oncological results; however, at present there are no randomized studies to prove this. Achieving a worldwide consensus on its concept, landmarks, excision technique and oncological results is essential.
https://ift.tt/2qKoXnv
Licorice-induced apparent mineralocorticoid excess compounded by excessive use of terbutaline and high water intake
This case highlights the clinical course of a 54-year-old male patient presenting with hypertension and long-term refractory hypokalaemia. He reported long-term malaise, fatigue and physical discomfort. Diarrhoea, vomiting, over-the-counter drugs, dietary supplements and any kind of medical abuse were all denied. Physical examination was normal. Suppressed plasma renin activity along with a low aldosterone level and elevated urinary cortisone/cortisol metabolite excretion ratio raised the suspicion of apparent mineralocorticoid excess (AME). The patient started treatment with spironolactone, but serum potassium levels were persistently fluctuating and the patient was hospitalised for further evaluation. During hospitalisation, repeated medical history and diagnostic examinations revealed licorice-induced AME complicated by excessive use of terbutaline and massive water intake. Licorice discontinuation, reduction of terbutaline and normalisation of water intake led to fully normalised potassium levels. Despite careful clinical history and diagnostic work-up, hospitalisation may be necessary in selected patients with long-term hypokalaemia.
https://ift.tt/2JXqHl8
Localised perforation of locally advanced transverse colon cancer with spontaneous colocutaneous fistula formation: a clinical challenge
Colon cancer can present with complications such as obstruction, perforation and bleeding. The clinical presentation has been recognised as an independent prognostic factor for morbidity and mortality.1 We present a rare case of localised perforation of a locally advanced colon cancer arising from mid-transverse colon in an elderly woman in the absence of widely metastatic disease with eventual cutaneous involvement of the overlying skin by direct extension, resulting in formation of colocutaneous fistula. The management of such cases is complex as usually tailored to the situation encountered.2 This case was a clinical challenge to choose between initial palliative resection and curative R0 resection following neoadjuvant chemotherapy.
https://ift.tt/2Hi7YyM
Massive haemoptysis secondary to mycotic pulmonary artery aneurysm in subacute invasive aspergillosis
A 68-year-old man, presented with 3 week history of infective symptoms and mild haemoptysis. Past medical history included severe emphysema and a chronic right upper lobe (RUL) cavity. He was discharged from follow-up a year ago in view of clinical and radiological stability; previous bronchoscopic examinations yielded no specific diagnosis. CT scan on admission confirmed complex cavitary consolidation of RUL. He developed massive haemoptysis requiring intubation and ventilation. CT pulmonary angiogram (CTPA) revealed 16 mm RUL pulmonary artery (PA) aneurysm which was successfully embolized. Sputum cultures, aspergillus antigen and rapidity of clinical progression suggested a diagnosis of subacute invasive aspergillosis (SAIA), prompting treatment with Voriconazole. Bronchoscopy showed blood ooze from RUL even after embolization. Unfortunately, patient continued to deteriorate and succumbed to profound septicaemia.
https://ift.tt/2JYji52
Laparoscopic management of an internal hernia in a pregnant woman with Roux-en-Y gastric bypass
Management of abdominal pain in a pregnant patient with a history of Roux-en-Y gastric bypass presents unique challenges. A misdiagnosis or delay in management can result in lethal maternal–fetal outcomes. We present a 30-year-old woman at 21 weeks of pregnancy presented with abdominal pain. She had a history of laparoscopic Roux-en-Y gastric bypass performed 3 years earlier. The clinical examination was remarkable for epigastric pain and tenderness. The vital signs and laboratory examinations were unremarkable. The CT scan was suggestive of an internal hernia. On an exploratory laparoscopy, the distal common small bowel was found to be herniating through the jejunojejunostomy mesenteric defect, causing intestinal obstruction with dilatation of the Roux limb and the biliopancreatic limb. The internal hernia was reduced, and no bowel resection was required. The mesenteric defect was closed with 3-0 silk sutures in a continuous fashion. The patient was discharged after 3 days and delivered a healthy baby at 40 weeks of gestation.
https://ift.tt/2JZwPJv
Unexpected case of pneumomediastinum and subcutaneous emphysema: primary or secondary aetiology?
A 77-year-old man was admitted with a relapse of antineutrophil cytoplasmic antibody-positive vasculitis with pulmonary involvement and acute kidney injury. There was a background of pulmonary fibrosis (non-specific interstitial pneumonia type pattern) and superadded pulmonary haemorrhage, acute pulmonary oedema and sepsis. The patient was intubated for 4 days and remained dependent on high flow oxygen and continuous positive airway pressure after extubation. A chest radiograph performed 2 weeks after extubation demonstrated unexpected, extensive pneumomediastinum and subcutaneous emphysema. This was confirmed on CT which raised the possibility of a tracheal defect at the level of the prior endotracheal tube cuff position. Tracheal injury was considered clinically unlikely due to the considerable interval since extubation and a short, uneventful intubation period. The cardiothoracic team recommended a diagnostic bronchoscopy but this was felt too high risk by the clinical team. The cause of pneumomediastinum and subcutaneous emphysema remained indeterminate.
https://ift.tt/2HdWLzm
Recognition of supraduodenal artery from hepatic artery is essential to avoid untoward complications at HAIC: two cases
Description
Supraduodenal artery (SDA) supplies the proximal duodenum, which originates most commonly from gastroduodenal artery (GDA), followed by common and proper hepatic artery.1 2 Origination from left hepatic artery (LHA) is relatively rare and only few articles have addressed this anatomic variation.3 Recognition of such an aberrant artery and proper coiling before liver-directed therapy are essential to prevent non-target organ injury. Herein, we report two rare cases of SDA that originated from the LHA.
Case 1A 56-year-old man had a massive type hepatocellular carcinoma (HCC) in right hepatic lobe with right portal vein tumour thrombosis (figure 1). He had one episode of massive upper gastrointestinal bleeding at 2nd hepatic arterial infusion chemotherapy (HAIC) and panendoscope revealed haemorrhagic duodenitis with duodenal bulb ulcer. In our hospital, a SDA that originated from the LHA was found at angiography, which was successfully embolised with a minicoil (
https://ift.tt/2J7z8cq
Intestinal granulomatous disease: what is the first call
A 15-year-old girl presented with erythema nodosum and mild abdominal complaints. Her intestinal granulomatous disease was erroneously diagnosed as Crohn's disease despite the fact that the possibility of tuberculosis was considered. The final diagnosis of tuberculosis was made only when an anti-tumour necrosis factor therapy resulted in further deterioration. The patient was treated with isoniazid, rifampin, pyrazinamide and ethambutol, with slow and steady clinical improvement until complete recovery was achieved.
https://ift.tt/2K0TaXk
Cutaneous lymphangitis carcinomatosa made cervicofacial oedema intractable in a patient with superior vena cava syndrome
Cutaneous lymphangitis carcinomatosa (CLC) is a rare form of cutaneous metastasis that causes lymphoedema and various eruptions. We report a case of lung cancer with CLC that caused both superior vena cava (SVC) stenosis and cervicofacial oedema, suggestive of SVC syndrome. A 64-year-old woman with lung adenocarcinoma presented with cervicofacial oedema and erythema, followed by severe dyspnoea 2 months after four cycles of carboplatin, pemetrexed and bevacizumab triplet therapy. Although chest CT indicated SVC stenosis, cervicofacial oedema remained despite treating the SVC stenosis via balloon dilation. A skin biopsy of the erythematic sample confirmed CLC as the cause of the patient's symptoms. CLC should be considered as a differential diagnosis of cervicofacial oedema in addition to SVC syndrome, especially when it is observed in combination with skin erythema and induration. Moreover, a skin biopsy should be performed promptly for accurate diagnosis of CLC and to decide on appropriate treatment.
https://ift.tt/2HgsWhA
Liver chemistry abnormalities and leg oedema in rheumatoid arthritis
A 66-year-old man with seronegative, erosive rheumatoid arthritis for 12 years presented with malaise, elevated alkaline phosphatase and gamma-glutamyl transferase, and leg oedema. He subsequently developed ascites. No liver pathology was found, but cardiac analysis including right heart catheterisation revealed constrictive pericarditis. Rheumatoid constrictive pericarditis is a rare condition, but, despite current effective treatment for rheumatoid arthritis, still occurs. Diagnostic delay is frequent. Although mortality of the intervention is high, pericardiectomy is needed for most patients.
https://ift.tt/2JZ8BPy
Gas in the right hemiscrotum? Amyands hernia in a neonate
Description
A 10-day-old boy, born at 36 weeks' gestation, was brought to our emergency department (ED) with irritability. He was able to suck as usual, but his temperature was 37.9°C and his right inguinal region was slightly erythematous. Laboratory data showed leucocytosis with a total leucocyte count of 23x109/L (neutrophils 72.5%), but a low C reactive protein (<0.10 mg/dL). Urinalysis showed no pyuria and no organisms. Abdominal X-ray was unremarkable. Initial inguinal ultrasonography by a paediatric surgeon revealed no suggestion of testicular torsion or incarcerated hernia. The neonate was discharged home with a tentative diagnosis of acute epididymitis.
Six hours after discharge, he returned to ED with high fever of 38.7°C and extreme redness of the scrotum (figure 1). Repeat abdominal X-ray demonstrated gas in the right hemiscrotum (figure 2) and abdominal sonography revealed what appeared to be a bright cord in the right hemiscrotum (figure 3),...
https://ift.tt/2J9wq62
Spontaneous rupture of seminoma in undescended testis with hemoperitoneum: a rare presentation
Cryptorchidism is associated with increased risk of malignancy and infertility. We present a case of a 30-year-old man who presented to the Emergency Department of our tertiary care hospital with spontaneous intra-abdominal rupture of the seminoma in undescended testis with hemoperitoneum. This is a rare presentation of seminoma and emphasises the importance of scrotal examination in young men presenting with acute abdomen. Surgical management is the definitive treatment and should be instituted as soon as possible, after appropriate resuscitation.
https://ift.tt/2K0nKQI
Bilateral tension pneumothorax after acupuncture
Acupuncture is an ancient complementary medicine which is currently used worldwide. Many serious adverse events have been reported which include a spectrum of mild-to-fatal complications. However, the level of awareness with regard to complications is still low both to physicians and patients. We report a 63-year-old who presented with acute shortness of breath 2 hours after having had acupuncture. On examination, there was absent breath sound heard on the left lung and slightly reduced breath sound on the right lung. She had type 1 respiratory failure. Urgent chest radiograph confirmed bilateral pneumothorax which was more severe on the left with tension pneumothorax and mediastinal shift. Chest tubes were inserted bilaterally after failed needle aspiration attempts. Subsequently, the pneumothoraces resolved, and she was discharged well. The bilateral pneumothoraces caused by acupuncture were curable but could have been potentially fatal if diagnosis was delayed. This case report adds to the limited current literature on the complications of acupuncture leading to bilateral pneumothoraces.
https://ift.tt/2Jal2qJ
Systematic review of the mesopancreas: concept and clinical implications
Abstract
Background
In 2007, Gockel et al. coined the term mesopancreas (MP). In the next 10 years, a limited number of publications about MP have been published, but little is known about the oncological benefit of MP resection. We performed a systematic review of the literature on MP.
Methods
An electronic search was performed in PubMed, EMBASE, Cochrane, Latindex, Scielo, and Koreamed databases until 15 June 2017 to identify all published articles dealing with the subject of MP. Some language restriction was done (Chinese and Rumanian).
Results
The search yielded 51 articles; 28 articles were selected as relevant. All were retrospective studies focused more on describing technical variants, feasibility and safety than on the cancer results. The R0 rate in patients with MP resection ranged between 57 and 96.7%. In all the articles with a control group, the R0 rate was higher in the MP excision group. Survival data were explicitly stated only in five series.
Conclusion
MP is a difficult-to-excise retropancreatic area. In theory, it is agreed that MP excision raises the rate of R0 resections, which in turn reflected in an improvement in the oncological results; however, at present there are no randomized studies to prove this. Achieving a worldwide consensus on its concept, landmarks, excision technique and oncological results is essential.
from Cancer via ola Kala on Inoreader https://ift.tt/2qKoXnv
via IFTTT
Systematic review of the mesopancreas: concept and clinical implications
Abstract
Background
In 2007, Gockel et al. coined the term mesopancreas (MP). In the next 10 years, a limited number of publications about MP have been published, but little is known about the oncological benefit of MP resection. We performed a systematic review of the literature on MP.
Methods
An electronic search was performed in PubMed, EMBASE, Cochrane, Latindex, Scielo, and Koreamed databases until 15 June 2017 to identify all published articles dealing with the subject of MP. Some language restriction was done (Chinese and Rumanian).
Results
The search yielded 51 articles; 28 articles were selected as relevant. All were retrospective studies focused more on describing technical variants, feasibility and safety than on the cancer results. The R0 rate in patients with MP resection ranged between 57 and 96.7%. In all the articles with a control group, the R0 rate was higher in the MP excision group. Survival data were explicitly stated only in five series.
Conclusion
MP is a difficult-to-excise retropancreatic area. In theory, it is agreed that MP excision raises the rate of R0 resections, which in turn reflected in an improvement in the oncological results; however, at present there are no randomized studies to prove this. Achieving a worldwide consensus on its concept, landmarks, excision technique and oncological results is essential.
https://ift.tt/2qKoXnv
Retreatment with pembrolizumab in advanced non-small cell lung cancer patients previously treated with nivolumab: emerging reports of 12 cases
Abstract
Purpose
After approval of anti-programmed cell death (PD)-1 antibodies, treatment for non-small cell lung cancer (NSCLC) has drastically changed. However, even in patients with favorable effects, therapeutic efficacy does not last long. Recently, retreatment with anti-PD-1 antibody has received attention. The aim of this study was to evaluate the efficacy and safety of retreatment with pembrolizumab in NSCLC patients previously treated with nivolumab.
Patients and methods
We retrospectively reviewed NSCLC patients retreated with pembrolizumab who were previously treated with nivolumab. We collected the following data: patient characteristics, number of cycles of nivolumab and pembrolizumab, treatment interval between nivolumab and pembrolizumab, best response, and immune-related adverse events.
Results
Twelve patients were reviewed. The median number of cycles of nivolumab was 12.5 (range 2–32 cycles). Seven patients (58.3%) achieved a partial response (PR) and two patients (16.7%) achieved stable disease (SD). Eight patients (66.7%) received cytotoxic chemotherapy between nivolumab and pembrolizumab. The median number of cycles of chemotherapy treatment was 4 (range 1–9 cycles). The median number of cycles of pembrolizumab was 3.5 (range 1–17 cycles). One patient (8.3%) achieved PR and four patients (33.3%) achieved SD as their best response to pembrolizumab. All patients showing response to pembrolizumab had very high (≥ 80%) tumor PD-Ligand 1 expression.
Conclusions
This study suggested that retreatment with anti-PD-1 antibody is a reasonable option for selected NSCLC patients.
https://ift.tt/2qHlQvA
Retreatment with pembrolizumab in advanced non-small cell lung cancer patients previously treated with nivolumab: emerging reports of 12 cases
Abstract
Purpose
After approval of anti-programmed cell death (PD)-1 antibodies, treatment for non-small cell lung cancer (NSCLC) has drastically changed. However, even in patients with favorable effects, therapeutic efficacy does not last long. Recently, retreatment with anti-PD-1 antibody has received attention. The aim of this study was to evaluate the efficacy and safety of retreatment with pembrolizumab in NSCLC patients previously treated with nivolumab.
Patients and methods
We retrospectively reviewed NSCLC patients retreated with pembrolizumab who were previously treated with nivolumab. We collected the following data: patient characteristics, number of cycles of nivolumab and pembrolizumab, treatment interval between nivolumab and pembrolizumab, best response, and immune-related adverse events.
Results
Twelve patients were reviewed. The median number of cycles of nivolumab was 12.5 (range 2–32 cycles). Seven patients (58.3%) achieved a partial response (PR) and two patients (16.7%) achieved stable disease (SD). Eight patients (66.7%) received cytotoxic chemotherapy between nivolumab and pembrolizumab. The median number of cycles of chemotherapy treatment was 4 (range 1–9 cycles). The median number of cycles of pembrolizumab was 3.5 (range 1–17 cycles). One patient (8.3%) achieved PR and four patients (33.3%) achieved SD as their best response to pembrolizumab. All patients showing response to pembrolizumab had very high (≥ 80%) tumor PD-Ligand 1 expression.
Conclusions
This study suggested that retreatment with anti-PD-1 antibody is a reasonable option for selected NSCLC patients.
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Incidence, pattern and prognosis of brain metastases in patients with metastatic triple negative breast cancer
Abstract
Background
To identify the incidence, recurrence pattern and prognosis of brain metastases (BM) among women with metastatic triple negative breast cancer (mTNBC) treated consecutively at a single institution during a 7-year period.
Methods
Patients with histologically confirmed mTNBC were retrospectively identified. The incidence of BM as first site of recurrence and the cumulative BM incidence were computed. We used the Cox proportional hazards model to identify the univariate and multivariate factors associated with survival.
Results
Four hundred thirty three patients were included with a median overall survival (OS) of 21.6 months after median follow-up for 48.1 months. BM was found in 29% (127/433) of the patients and about a quarter (32/127) of BM was first recurrence. The cumulative incidence of BM at 1 and 2 years was 17 and 25%, respectively. The median time from the diagnosis of extracranial metastases to BM was 10 months. Median OS following a diagnosis of BM was 7.3 months. The longer median OS from time of first recurrent BM was noted compared with those of subsequent recurrent (17.3 vs 6.3 months, p = 0.008). However, patients with first recurrent BM were associated with shorter OS compared with those without BM (17.3 vs 22.1 months, p = 0.006). The independent factors that increased BM death risk were > 3 brain lesions, no BM-directed treatment, subsequent recurrent BM, symptomatic BM and uncontrolled extracranial metastasis.
Conclusions
Patients with mTNBC have a high incidence of early BM with subsequent poor survival. The findings lend support to consideration of screening imaging of the brain for mTNBC patients.
https://ift.tt/2HcfefI
Dietary patterns, BCMO1 polymorphisms, and primary lung cancer risk in a Han Chinese population: a case-control study in Southeast China
Abstract
Background
We investigated whether BCMO1 variants and dietary patterns are associated with lung cancer risk.
Methods
Case-control study including 1166 lung cancer cases and 1179 frequency matched controls was conducted for three BCMO1 variants (rs6564851, rs12934922, and rs7501331) and four dietary patterns were investigated. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs).
Results
The rs6564851, rs12934922, and rs7501331 were not found to be associated with lung cancer risk (P > 0.05). In multivariable-adjusted models, compared to the lowest quartile of the score on the "fruits and vegetables" pattern, the highest quintile was associated with a 78.4% decreased risk (OR Q4 vs. Q1 = 0.216; 95% CI, 0.164–0.284; P for trend < 0.001). Other patterns were not found the association. The "fruits and vegetables" pattern was associated with a reduced risk of lung cancer with all 3 SNPs irrespective of genotypes (all P for trend< 0.001). The association for the "Frugal" pattern was associated with increased risk of lung cancer among smokers (P for interaction = 0.005). The protective effects of the "cereals/wheat and meat" pattern was more evident for squamous cell carcinoma and other histological type.
Conclusions
We did not observe associations of BCMO1 variants and lung cancer. Diets rich in fruits and vegetables may be protective against lung cancer.
https://ift.tt/2K0LGDI
AB0 blood groups and rhesus factor expression as prognostic parameters in patients with epithelial ovarian cancer – a retrospective multi-centre study
Abstract
Background
AB0 blood groups and Rhesus factor expression have been associated with carcinogenesis, response to treatment and tumor progression in several malignancies. The aim of the present study was to test the hypothesis that AB0 blood groups and Rhesus factor expression are associated with clinical outcome in patients with epithelial ovarian cancer (EOC).
Methods
AB0 blood groups and Rhesus factor expression were evaluated in a retrospective multicenter study including 518 patients with EOC. Their association with patients' survival was assessed using univariate and multivariable analyses.
Results
Neither AB0 blood groups nor Rhesus factor expression were associated with clinico-pathological parameters, recurrence-free, cancer-specific, or overall survival. In a subgroup of patients with high-grade serous adenocarcinoma, however, blood groups B and AB were associated with a better 5-year cancer-specific survival rate compared to blood groups A and 0 (60.3 ± 8.6% vs. 43.8 ± 3.6%, p = 0.04). Yet, this was not significant in multivariable analysis.
Conclusions
AB0 blood groups and Rhesus factor expression are both neither associated with features of biologically aggressive disease nor clinical outcome in patients with EOC. Further investigation of the role of the blood group B antigen on cancer-specific survival in the subgroup of high-grade serous should be considered.
https://ift.tt/2HgNhTV
Incidence, pattern and prognosis of brain metastases in patients with metastatic triple negative breast cancer
Abstract
Background
To identify the incidence, recurrence pattern and prognosis of brain metastases (BM) among women with metastatic triple negative breast cancer (mTNBC) treated consecutively at a single institution during a 7-year period.
Methods
Patients with histologically confirmed mTNBC were retrospectively identified. The incidence of BM as first site of recurrence and the cumulative BM incidence were computed. We used the Cox proportional hazards model to identify the univariate and multivariate factors associated with survival.
Results
Four hundred thirty three patients were included with a median overall survival (OS) of 21.6 months after median follow-up for 48.1 months. BM was found in 29% (127/433) of the patients and about a quarter (32/127) of BM was first recurrence. The cumulative incidence of BM at 1 and 2 years was 17 and 25%, respectively. The median time from the diagnosis of extracranial metastases to BM was 10 months. Median OS following a diagnosis of BM was 7.3 months. The longer median OS from time of first recurrent BM was noted compared with those of subsequent recurrent (17.3 vs 6.3 months, p = 0.008). However, patients with first recurrent BM were associated with shorter OS compared with those without BM (17.3 vs 22.1 months, p = 0.006). The independent factors that increased BM death risk were > 3 brain lesions, no BM-directed treatment, subsequent recurrent BM, symptomatic BM and uncontrolled extracranial metastasis.
Conclusions
Patients with mTNBC have a high incidence of early BM with subsequent poor survival. The findings lend support to consideration of screening imaging of the brain for mTNBC patients.
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Dietary patterns, BCMO1 polymorphisms, and primary lung cancer risk in a Han Chinese population: a case-control study in Southeast China
Abstract
Background
We investigated whether BCMO1 variants and dietary patterns are associated with lung cancer risk.
Methods
Case-control study including 1166 lung cancer cases and 1179 frequency matched controls was conducted for three BCMO1 variants (rs6564851, rs12934922, and rs7501331) and four dietary patterns were investigated. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs).
Results
The rs6564851, rs12934922, and rs7501331 were not found to be associated with lung cancer risk (P > 0.05). In multivariable-adjusted models, compared to the lowest quartile of the score on the "fruits and vegetables" pattern, the highest quintile was associated with a 78.4% decreased risk (OR Q4 vs. Q1 = 0.216; 95% CI, 0.164–0.284; P for trend < 0.001). Other patterns were not found the association. The "fruits and vegetables" pattern was associated with a reduced risk of lung cancer with all 3 SNPs irrespective of genotypes (all P for trend< 0.001). The association for the "Frugal" pattern was associated with increased risk of lung cancer among smokers (P for interaction = 0.005). The protective effects of the "cereals/wheat and meat" pattern was more evident for squamous cell carcinoma and other histological type.
Conclusions
We did not observe associations of BCMO1 variants and lung cancer. Diets rich in fruits and vegetables may be protective against lung cancer.
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AB0 blood groups and rhesus factor expression as prognostic parameters in patients with epithelial ovarian cancer – a retrospective multi-centre study
Abstract
Background
AB0 blood groups and Rhesus factor expression have been associated with carcinogenesis, response to treatment and tumor progression in several malignancies. The aim of the present study was to test the hypothesis that AB0 blood groups and Rhesus factor expression are associated with clinical outcome in patients with epithelial ovarian cancer (EOC).
Methods
AB0 blood groups and Rhesus factor expression were evaluated in a retrospective multicenter study including 518 patients with EOC. Their association with patients' survival was assessed using univariate and multivariable analyses.
Results
Neither AB0 blood groups nor Rhesus factor expression were associated with clinico-pathological parameters, recurrence-free, cancer-specific, or overall survival. In a subgroup of patients with high-grade serous adenocarcinoma, however, blood groups B and AB were associated with a better 5-year cancer-specific survival rate compared to blood groups A and 0 (60.3 ± 8.6% vs. 43.8 ± 3.6%, p = 0.04). Yet, this was not significant in multivariable analysis.
Conclusions
AB0 blood groups and Rhesus factor expression are both neither associated with features of biologically aggressive disease nor clinical outcome in patients with EOC. Further investigation of the role of the blood group B antigen on cancer-specific survival in the subgroup of high-grade serous should be considered.
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Optimization of training periods for the estimation model of three-dimensional target positions using an external respiratory surrogate
Abstract
Background
During therapeutic beam irradiation, an unvisualized three-dimensional (3D) target position should be estimated using an external surrogate with an estimation model. Training periods for the developed model with no additional imaging during beam irradiation were optimized using clinical data.
Methods
Dual-source 4D-CBCT projection data for 20 lung cancer patients were used for validation. Each patient underwent one to three scans. The actual target positions of each scan were equally divided into two equal parts: one for the modeling and the other for the validating session. A quadratic target position estimation equation was constructed during the modeling session. Various training periods for the session—i.e., modeling periods (TM)—were employed: TM ∈ {5,10,15,25,35} [s]. First, the equation was used to estimate target positions in the validating session of the same scan (intra-scan estimations). Second, the equation was then used to estimate target positions in the validating session of another temporally different scan (inter-scan estimations). The baseline drift of the surrogate and target between scans was corrected. Various training periods for the baseline drift correction—i.e., correction periods (TCs)—were employed: TC ∈ {5,10,15; TC ≤ TM} [s]. Evaluations were conducted with and without the correction. The difference between the actual and estimated target positions was evaluated by the root-mean-square error (RMSE).
Results
The range of mean respiratory period and 3D motion amplitude of the target was 2.4–13.0 s and 2.8–34.2 mm, respectively. On intra-scan estimation, the median 3D RMSE was within 1.5–2.1 mm, supported by previous studies. On inter-scan estimation, median elapsed time between scans was 10.1 min. All TMs exhibited 75th percentile 3D RMSEs of 5.0–6.4 mm due to baseline drift of the surrogate and the target. After the correction, those for each TMs fell by 1.4–2.3 mm. The median 3D RMSE for both the 10-s TM and the TC period was 2.4 mm, which plateaued when the two training periods exceeded 10 s.
Conclusions
A widely-applicable estimation model for the 3D target positions during beam irradiation was developed. The optimal TM and TC for the model were both 10 s, to allow for more than one respiratory cycle.
Trial registration
UMIN000014825. Registered: 11 August 2014.
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Prognostic factors of radiation dermatitis following passive-scattering proton therapy for breast cancer
Abstract
Background
To identify prognostic factors for grade 3 radiation dermatitis following passive-scattering proton therapy for breast cancer.
Methods
This retrospective study included data on 23 (11 post-mastectomy and 12 post-lumpectomy) breast cancer patients who underwent proton therapy with the passive scattering technique in our institute from 2012 to 2016. Each patient received 50–50.4 cobalt Gy equivalent (CGE) at 1.8 or 2 CGE per daily fraction. Logistic regression analysis was performed to identify prognostic factors for grade 3 skin toxicity. Receiver operating characteristic (ROC) curve analysis and the area under the curve (AUC) were used to evaluate the performance of the models.
Results
43% of the studied patients developed grade 3 radiation dermatitis. The dose-volume histogram (DVH) parameters of V52.5CGE and D10cm3 to skin5mm were correlated with grade 3 radiation dermatitis in both univariate and multivariate logistic regression analyses. Univariate logistic regression analysis suggested that D10cm3 to skin5mm (AUC = 0.69) and V52.5CGE to skin5mm (AUC = 0.70) were prognostic for grade 3 skin toxicity. The models using the combination of D10cm3 to skin5mm or V52.5CGE to skin5mm with breast volume marginally increased the AUC to 0.72 and 0.73, respectively. Models using the combination of D10cm3 to skin5mm or V52.5CGE to skin5mm with history of smoking increased the AUC to 0.75 and 0.83, respectively.
Conclusion
In the current study, we identified prognostic factors for grade 3 radiation dermatitis in patients treated with passive-scattering proton therapy for breast cancer. This study provides promising tool for identifying high risk patients for whom treatment plan adjustment could be done to reduce the risk of radiation-induced grade 3 skin toxicity.
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Optimization of training periods for the estimation model of three-dimensional target positions using an external respiratory surrogate
Abstract
Background
During therapeutic beam irradiation, an unvisualized three-dimensional (3D) target position should be estimated using an external surrogate with an estimation model. Training periods for the developed model with no additional imaging during beam irradiation were optimized using clinical data.
Methods
Dual-source 4D-CBCT projection data for 20 lung cancer patients were used for validation. Each patient underwent one to three scans. The actual target positions of each scan were equally divided into two equal parts: one for the modeling and the other for the validating session. A quadratic target position estimation equation was constructed during the modeling session. Various training periods for the session—i.e., modeling periods (TM)—were employed: TM ∈ {5,10,15,25,35} [s]. First, the equation was used to estimate target positions in the validating session of the same scan (intra-scan estimations). Second, the equation was then used to estimate target positions in the validating session of another temporally different scan (inter-scan estimations). The baseline drift of the surrogate and target between scans was corrected. Various training periods for the baseline drift correction—i.e., correction periods (TCs)—were employed: TC ∈ {5,10,15; TC ≤ TM} [s]. Evaluations were conducted with and without the correction. The difference between the actual and estimated target positions was evaluated by the root-mean-square error (RMSE).
Results
The range of mean respiratory period and 3D motion amplitude of the target was 2.4–13.0 s and 2.8–34.2 mm, respectively. On intra-scan estimation, the median 3D RMSE was within 1.5–2.1 mm, supported by previous studies. On inter-scan estimation, median elapsed time between scans was 10.1 min. All TMs exhibited 75th percentile 3D RMSEs of 5.0–6.4 mm due to baseline drift of the surrogate and the target. After the correction, those for each TMs fell by 1.4–2.3 mm. The median 3D RMSE for both the 10-s TM and the TC period was 2.4 mm, which plateaued when the two training periods exceeded 10 s.
Conclusions
A widely-applicable estimation model for the 3D target positions during beam irradiation was developed. The optimal TM and TC for the model were both 10 s, to allow for more than one respiratory cycle.
Trial registration
UMIN000014825. Registered: 11 August 2014.
https://ift.tt/2qF95T9
Prognostic factors of radiation dermatitis following passive-scattering proton therapy for breast cancer
Abstract
Background
To identify prognostic factors for grade 3 radiation dermatitis following passive-scattering proton therapy for breast cancer.
Methods
This retrospective study included data on 23 (11 post-mastectomy and 12 post-lumpectomy) breast cancer patients who underwent proton therapy with the passive scattering technique in our institute from 2012 to 2016. Each patient received 50–50.4 cobalt Gy equivalent (CGE) at 1.8 or 2 CGE per daily fraction. Logistic regression analysis was performed to identify prognostic factors for grade 3 skin toxicity. Receiver operating characteristic (ROC) curve analysis and the area under the curve (AUC) were used to evaluate the performance of the models.
Results
43% of the studied patients developed grade 3 radiation dermatitis. The dose-volume histogram (DVH) parameters of V52.5CGE and D10cm3 to skin5mm were correlated with grade 3 radiation dermatitis in both univariate and multivariate logistic regression analyses. Univariate logistic regression analysis suggested that D10cm3 to skin5mm (AUC = 0.69) and V52.5CGE to skin5mm (AUC = 0.70) were prognostic for grade 3 skin toxicity. The models using the combination of D10cm3 to skin5mm or V52.5CGE to skin5mm with breast volume marginally increased the AUC to 0.72 and 0.73, respectively. Models using the combination of D10cm3 to skin5mm or V52.5CGE to skin5mm with history of smoking increased the AUC to 0.75 and 0.83, respectively.
Conclusion
In the current study, we identified prognostic factors for grade 3 radiation dermatitis in patients treated with passive-scattering proton therapy for breast cancer. This study provides promising tool for identifying high risk patients for whom treatment plan adjustment could be done to reduce the risk of radiation-induced grade 3 skin toxicity.
https://ift.tt/2vsv44F
Colorectal dysplasia and adenocarcinoma in patients with ulcerative colitis: an experience from a tertiary care hospital
Abstract
Background
The rationale behind this study was to find out the frequency of dysplasia and colorectal cancer (CRC) in young patients with ulcerative colitis (UC) using histopathological examination. This facilitated early detection of dysplasia and CRC by regular endoscopic biopsies and also guided physicians on appropriate surveillance and management, thus improved outcome.
Methods
It was a prospective cross-sectional study conducted at the Department of Pathology, PIMS, Islamabad. Seventy-six biopsies of already diagnosed cases of UC of young patients aged between 15 and 40 years of either gender were included. Specimens were fixed in 10% buffer formalin, paraffin embedded followed by cutting, slide preparation, and staining with hematoxylin and eosin (H&E) stain, and examined under light microscope. Statistical package for social sciences (SPSS 21) was used for data compilation and analysis. Mean and standard deviation were calculated for quantitative variables. Frequency and percentage were calculated for qualitative variables.
Results
There were 13 (17.2%) patients who were diagnosed with colorectal dysplasia, 3 (4.0%) with indefinite for dysplasia, 8 (10.5%) with low-grade dysplasia, and 2 (2.6%) with high-grade dysplasia. There were three (3.9%) patients who were diagnosed for colorectal carcinoma, one (1.3%) with grade 1, one (1.3%) with grade 2, and one (1.3%) with grade 3 CRC.
Conclusion
Routine biopsies can identify dysplastic epithelium, which is an established sign for synchronized carcinoma with ulcerative colitis, and give the rationale for surveillance of the patients.
https://ift.tt/2qJAGBO
Colorectal dysplasia and adenocarcinoma in patients with ulcerative colitis: an experience from a tertiary care hospital
Abstract
Background
The rationale behind this study was to find out the frequency of dysplasia and colorectal cancer (CRC) in young patients with ulcerative colitis (UC) using histopathological examination. This facilitated early detection of dysplasia and CRC by regular endoscopic biopsies and also guided physicians on appropriate surveillance and management, thus improved outcome.
Methods
It was a prospective cross-sectional study conducted at the Department of Pathology, PIMS, Islamabad. Seventy-six biopsies of already diagnosed cases of UC of young patients aged between 15 and 40 years of either gender were included. Specimens were fixed in 10% buffer formalin, paraffin embedded followed by cutting, slide preparation, and staining with hematoxylin and eosin (H&E) stain, and examined under light microscope. Statistical package for social sciences (SPSS 21) was used for data compilation and analysis. Mean and standard deviation were calculated for quantitative variables. Frequency and percentage were calculated for qualitative variables.
Results
There were 13 (17.2%) patients who were diagnosed with colorectal dysplasia, 3 (4.0%) with indefinite for dysplasia, 8 (10.5%) with low-grade dysplasia, and 2 (2.6%) with high-grade dysplasia. There were three (3.9%) patients who were diagnosed for colorectal carcinoma, one (1.3%) with grade 1, one (1.3%) with grade 2, and one (1.3%) with grade 3 CRC.
Conclusion
Routine biopsies can identify dysplastic epithelium, which is an established sign for synchronized carcinoma with ulcerative colitis, and give the rationale for surveillance of the patients.
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Predictors of anxiety and depression 2 years following treatment in uveal melanoma survivors
Psycho-Oncology, EarlyView.
https://ift.tt/2HLJH5t
Relationship between individual and family characteristics and psychosocial factors in persons with familial pancreatic cancer
Psycho-Oncology, EarlyView.
https://ift.tt/2F0ylYd
Predictors of anxiety and depression 2 years following treatment in uveal melanoma survivors
Psycho-Oncology, EarlyView.
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Relationship between individual and family characteristics and psychosocial factors in persons with familial pancreatic cancer
Psycho-Oncology, EarlyView.
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Hormone Replacement Therapy After Oophorectomy and Breast Cancer Risk Among BRCA1 Mutation Carriers
This prospective cohort study examines the association between hormone replacement therapy use after oophorectomy and risk of breast cancer among women with a BRCA1 mutation.
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Validity in Propensity Score–Matched Estimates of Adjuvant Chemotherapy Effects in Rectal Cancer
Current treatment guidelines in the United States for patients with stage T3 or greater or N+ rectal cancer recommend neoadjuvant chemoradiation therapy (nCRT) and 6 months of perioperative chemotherapy. However, there exists a paucity of direct evidence to support the administration of adjuvant chemotherapy following nCRT and radical surgery. The indication for adjuvant chemotherapy in these patients is therefore an important clinical concern and the topic of debate. In this issue of JAMA Oncology, 2 separate observational cohort studies have used the National Cancer Database (NCDB) to evaluate the association between adjuvant chemotherapy and overall survival among patients with ypT0N0 rectal cancer following nCRT and surgery. They conclude that adjuvant chemotherapy may improve survival. So do these 2 reports finally provide adequate support for current treatment guidelines?
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Evaluating Treatment Effect Based on Duration of Response
This study evaluates the duration of response for crizotinib vs chemotherapy for patients with ALK-positive lung cancer using data from the PROFILE-1014 randomized clinical trial.
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Addressing Financial Barriers to Enrollment in Clinical Trials
This Viewpoint discusses the need to refine existing guidance to clarify the broad acceptability of offering all types of payment to research participants to reduce financial burden for patients.
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Patient’s Perception of Physicians’ Professionalism With vs Without Physician Computer Use
This randomized controlled crossover study compares patients' perception of physicians' compassion and patients' perception of physicians' communication skills and professionalism and patients' overall physician preference after watching two standardized scripted-video vignettes of physicians.
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Association of Adjuvant Chemotherapy With Survival in Patients With Rectal Cancer
This propensity score–matched cohort study examines whether adjuvant chemotherapy is associated with improved overall survival in patients with rectal cancer and pathological complete response following neoadjuvant chemoradiation therapy and resection.
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Misclassification of Upper Tract Urothelial Carcinoma in Patients With Lynch Syndrome
To the Editor As academic urologic oncologists with an interest in Lynch syndrome (LS)-related genitourinary cancers, we read with great interest the article by Samadder et al quantifying the prevalence of Utah families fulfilling Amsterdam criteria and the risk of colonic and extracolonic malignant neoplasms. The authors used the Utah Population Database and linked it to the Utah Cancer Registry. They described finding a high rate of kidney (standardized morbidity ratio [SMR], 3.22) and urinary bladder (SMR, 1.62) cancers in first-degree relatives of Amsterdam criteria pedigrees. The data are informative and we congratulate the authors on this effort, yet we have one concern.
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Adjuvant Chemotherapy and Rectal Cancer Survival With Response Following Neoadjuvant Chemotherapy
This propensity score matching cohort analysis compares the overall survival between adjuvant chemotherapy and postoperative observation in patients with rectal cancer with pathologic complete response following neoadjuvant chemoradiotherapy and resection.
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Misclassification of Upper Tract Urothelial Carcinoma in Patients With Lynch Syndrome—Reply
In Reply We thank Drs Matin and Coleman for their informative letter regarding our article. On review of the literature cited by the authors, we agree that there is confusion regarding the nomenclature describing genitourinary malignant neoplasms, especially as it applies to grouping of upper tract urothelial malignant neoplasms separately from renal cell carcinomas.
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SNAI1, an endothelial–mesenchymal transition transcription factor, promotes the early phase of ocular neovascularization
Abstract
Ocular neovascularization is a comprehensive process involved in retinal vascular development and several blinding diseases such as age-related macular degeneration and retinopathy of prematurity, with vascular endothelial growth factor (VEGF) regarded as the master regulator. However, the qualified effect of anti-VEGF therapy reveals that the underlying mechanisms are still not clearly identified. To initialize angiogenesis, endothelial cells undergo a phenotype switching to generate highly migratory and invasive cells. This process shares certain similar characters observed in endothelial–mesenchymal transition (EndMT). Here, we found that SNAI1, an EndMT transcription factor, was expressed by endothelial cells in both physiological and pathological ocular neovascularization. SNAI1 overexpression triggered cell morphological change and enhanced cell motility, while loss of SNAI1 attenuated migration, invasion and sprouting. RNA sequence analysis further revealed that SNAI1 knockdown decreased the expression of genes related to cytoskeleton rearrangement and ECM remodeling. Moreover, intravitreal injection of small interfering RNA of SNAI1 suppressed new vessel formation in developing retina as well as mice model of choroidal neovascularization and oxygen-induced retinopathy. Therefore, we propose that the EndMT transcription factor SNAI1 promotes the early phase of ocular neovascularization and may provide a potential therapeutic target.
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SNAI1, an endothelial–mesenchymal transition transcription factor, promotes the early phase of ocular neovascularization
Abstract
Ocular neovascularization is a comprehensive process involved in retinal vascular development and several blinding diseases such as age-related macular degeneration and retinopathy of prematurity, with vascular endothelial growth factor (VEGF) regarded as the master regulator. However, the qualified effect of anti-VEGF therapy reveals that the underlying mechanisms are still not clearly identified. To initialize angiogenesis, endothelial cells undergo a phenotype switching to generate highly migratory and invasive cells. This process shares certain similar characters observed in endothelial–mesenchymal transition (EndMT). Here, we found that SNAI1, an EndMT transcription factor, was expressed by endothelial cells in both physiological and pathological ocular neovascularization. SNAI1 overexpression triggered cell morphological change and enhanced cell motility, while loss of SNAI1 attenuated migration, invasion and sprouting. RNA sequence analysis further revealed that SNAI1 knockdown decreased the expression of genes related to cytoskeleton rearrangement and ECM remodeling. Moreover, intravitreal injection of small interfering RNA of SNAI1 suppressed new vessel formation in developing retina as well as mice model of choroidal neovascularization and oxygen-induced retinopathy. Therefore, we propose that the EndMT transcription factor SNAI1 promotes the early phase of ocular neovascularization and may provide a potential therapeutic target.
https://ift.tt/2K0tiLl
No influence of smoking status on the performance of urine markers for the detection of bladder cancer
Abstract
Purpose
The performance of urinary markers for detecting bladder cancer (BC) is influenced by various factors. The aim of the present study was to evaluate the influence of smoking habits on the performance of four commonly used urine markers.
Methods
Urine samples of 723 patients with suspected BC were analysed using urine cytology, fluorescence in situ hybridization (FISH), immunocytology (uCyt+ test), and quantitative nuclear matrix protein 22 (NMP22) immunoassay. The smoking habits of all patients were recorded and a cystoscopy performed within 2 weeks after urinary marker testing. Rates of false negative and false positive results were compared between non-smokers, former smokers, and current smokers by contingency analyses.
Results
We included 723 patients in this study, 431 (59.6%) of which were non-smokers, 215 former smokers (29.7%), and 77 (10.7%) current smokers. 148 patients (20.5%) had a tumour at the time of urinary marker testing. Respective rates of false positive test results among non-smokers, former smokers, and current smokers were: 16.3, 19.1, and 11.5% (p = 0.81) for urine cytology; 36.8, 42.0, and 32.7% for the uCyt+ test (p = 0.88); 18.0, 19.1, and 13.5% for FISH (p = 0.66); and 69.5, 71.6, and 71.2% for NMP22 (p = 0.67). Respective rates of false negatives among non-smokers, former smokers, and current smokers were: 31.4, 15.1, and 28.0% for cytology (p = 0.34); 21.4, 22.6, and 16.0% for uCyt+ test (p = 0.67); 24.3, 13.2, and 28.0% for FISH (p = 0.88); and 10.0, 18.9, and 8.0% for NMP22 (p = 0.80).
Conclusions
Our results strongly suggest that smoking habits do not affect performance characteristics of urinary markers in the diagnostics of BC.
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No influence of smoking status on the performance of urine markers for the detection of bladder cancer
Abstract
Purpose
The performance of urinary markers for detecting bladder cancer (BC) is influenced by various factors. The aim of the present study was to evaluate the influence of smoking habits on the performance of four commonly used urine markers.
Methods
Urine samples of 723 patients with suspected BC were analysed using urine cytology, fluorescence in situ hybridization (FISH), immunocytology (uCyt+ test), and quantitative nuclear matrix protein 22 (NMP22) immunoassay. The smoking habits of all patients were recorded and a cystoscopy performed within 2 weeks after urinary marker testing. Rates of false negative and false positive results were compared between non-smokers, former smokers, and current smokers by contingency analyses.
Results
We included 723 patients in this study, 431 (59.6%) of which were non-smokers, 215 former smokers (29.7%), and 77 (10.7%) current smokers. 148 patients (20.5%) had a tumour at the time of urinary marker testing. Respective rates of false positive test results among non-smokers, former smokers, and current smokers were: 16.3, 19.1, and 11.5% (p = 0.81) for urine cytology; 36.8, 42.0, and 32.7% for the uCyt+ test (p = 0.88); 18.0, 19.1, and 13.5% for FISH (p = 0.66); and 69.5, 71.6, and 71.2% for NMP22 (p = 0.67). Respective rates of false negatives among non-smokers, former smokers, and current smokers were: 31.4, 15.1, and 28.0% for cytology (p = 0.34); 21.4, 22.6, and 16.0% for uCyt+ test (p = 0.67); 24.3, 13.2, and 28.0% for FISH (p = 0.88); and 10.0, 18.9, and 8.0% for NMP22 (p = 0.80).
Conclusions
Our results strongly suggest that smoking habits do not affect performance characteristics of urinary markers in the diagnostics of BC.
https://ift.tt/2HdSFLR
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